case study of obstructive jaundice

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The GE Portuguese Journal of Gastroenterology is the official publicatio of the Portuguese Society of Gastroenterology, Portuguese Society of Digestive Endoscopy and the Portuguese Association for the Study of the Liver. The GE Portuguese Journal of Gastroenterology publishes original manuscripts on on Gastroenterology, Digestive Endoscopy, Hepatology and related matters. Review articles, clinical cases, images, letters to the editor and other articles are also published and included in the structure of the journal (such as recommendations, articles on gastroenterology clinical practice and notifications of meetings of scientific societies). Articles must be written in English.

An 84-year-old woman presented with a 2-day history of jaundice, fever and abdominal pain. Physical examination showed scleral icterus and right upper quadrant tenderness without inspiratory arrest at palpation (absent Murphy's sign). Laboratory workup revealed leukocytosis (12.4 × 10 3 μL), elevated C-reactive protein (8.3 mg/dL) and cholestasis (bilirubin 5.4 mg/dL, alkaline phosphatase 893 U/L, gamma-glutamyl transferase 1143 U/L) with elevated liver enzymes (aspartate aminotransferase 231 U/L, alanine aminotransferase 178 U/L). Abdominal ultrasound demonstrated a scleroatrophic gallbladder with cholelithiasis and an impacted large gallstone in the common bile duct with dilated common and intrahepatic bile ducts.

We performed an endoscopic retrograde cholangiopancreatography (ERCP) that clearly showed common hepatic duct compression by a large gallstone (20 mm) impacted in the cystic duct ( Fig. 1 ), compatible with the diagnosis of Mirizzi syndrome. Successful biliary decompression was performed by internal stenting ( Fig. 2 ) with subsequent patient referral to surgery (cholecystectomy plus closure of the fistula).

ERCP: cholangiography.

ERCP: internal stenting.

The Mirizzi syndrome refers to common hepatic duct obstruction caused by an extrinsic compression from an impacted stone in the cystic duct or Hartmann's pouch of the gallbladder. 1 The majority of the patients present the clinical triad of jaundice, fever, and right upper quadrant pain, showing in the laboratory evaluation elevations in the serum concentrations of alkaline phosphatase and bilirubin. 2

The Mirizzi syndrome is part of the differential diagnosis of obstructive jaundice and therefore the diagnostic approach usually begins with ultrasonography complemented by ERCP or magnetic resonance cholangiography.

A useful classification system takes into account the presence and extent of a cholecystobiliary fistula, due to erosion of the anterior or lateral wall of the common bile duct by impacted stones. 3

Surgery is the mainstay of therapy for Mirizzi syndrome. 4 ERCP treatment can be effective as a temporizing measure before surgery and can be definitive treatment for unsuitable surgical candidates.

The authors declare that no experiments were performed on humans or animals for this study.

The authors declare that they have followed the protocols of their work center on the publication of patient data.

The authors declare that no patient data appear in this article.

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Ayurveda management of jaundice: A case study

Sinha, Nitu; Ojha, Nisha Kumari

Department of Kaumarbhritya, National Institute of Ayurveda, Deemed To Be University (De Novo), Jaipur, Rajasthan, India

Address for correspondence: Dr. Nitu Sinha, Department of Kaumarbhritya, National Institute of Ayurveda, Deemed to Be University (De Novo), Jaipur 302002, Rajasthan, India. E-mail: [email protected]

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

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Jaundice is a yellow discoloration of the body’s tissues from excess bilirubin (hyperbilirubinemia). According to the Ayurveda perspective, the clinical presentation of jaundice can be correlated with that of the disease Kamala . We present a case of a 10-year-old female patient who attained the outpatient department with complaints of anorexia, poor appetite, general weakness, abdominal pain, and hard stools since 10 days. The examination revealed yellow discoloration of the sclera, oral mucosa, skin, urine, and hard yellowish stool, and the blood investigation revealed elevated level of serum bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, and alkaline phosphatase. The case was managed with Tab Liv 52 DS, 1 tab twice a day and Tab Nirocil, 1 tab twice daily before food with lukewarm water . Mridu Virechana (mild purgation) was done using a combination of Avipatikar Churna 2 gm twice a day and Kutki Churna (powder of Picrorhiza kurrooa ) 1 gm twice a day with lukewarm water for 4 weeks. These medications effectively improved the clinical symptoms, and the appetite increased, the patient became more active, and the icterus decreased. The patient also started passing normal stool and urine. complete blood count, liver function test , and urine examination revealed that the values were within the reference range. This combination can be utilized for symptoms of Koshthashrita Kamala .

Introduction

The clinical features of jaundice are abdominal pain, nausea, and fatigue. Some clinical features are also explained in the case of Kamala . [ 1 ] So, based on common characteristics and pathology, Kamala (Jaundice) can be correlated with jaundice. Jaundice, also known as hyperbilirubinemia, is a yellow discoloration of the body tissue resulting from the accumulation of an excess of bilirubin. [ 2 ] In Ayurveda, Jaundice is associated with the Pitta Dosha because a person with Pandu Roga (anemia) may acquire jaundice if they continue to consume Pitta vitiating diet. [ 3 ] According to Acharya Sushrut, jaundice is a distinct illness that a further complication of anemia may also cause. [ 4 ] Ayurvedic classics have mentioned the treatment of jaundice and its complications. The present case study reports the treatment of a 10-year-old female child with jaundice.

Patient Information

A 10-year-old female patient visited Kaumarbhritya outpatient department, National Institute of Ayurveda, Jaipur on August 16, 2022 with complaints of yellowish discoloration of the body, anorexia, poor appetite, generalized weakness, abdominal pain, and hard stool since 10 days. There was no history of diarrhea/blood transfusions/contact with a patient with jaundice, or surgery. The patient had taken allopathic medication [tablet of ofloxacin 200 mg, one tablet twice a day for 7 days, a liver tonic, 5 mL thrice a day for 15 days, a syrup of Ornithine and Aspartate, 5 mL thrice a day for 15 days, a lactulose syrup, 20 mL twice a day for 15 days, Paracetamol (500 mg) syrup 5 mL Si Opus Sit (means as and when required)] since August 7, 2022. When symptoms were not relieved, the patient’s guardian brought her to take Ayurvedic treatment.

Clinical Finding

On examination, the child looked ill, weak, pale, hemodynamically stable, afebrile, well-oriented, and responding to commands. Her sclera was deep yellow; her skin was dry, lusterless, with a yellowish hue. The pulse was 86 per minute, regular, and the blood pressure was within normal range. Per abdominal examination revealed tenderness in the right upper quadrant, and the liver was palpable 1.5 cm below the costal margin, soft, with normal peristaltic sounds. There were no cutaneous markers like spider naevi, ascites, or palpable lymph nodes. On systemic examination, the respiratory sounds were bilaterally equal, clear chest, no added sound present, and no obvious deformity, and S1 and S2 were audible, with no murmur. Gastrointestinal tract findings, such as decreased appetite and constipation, were present, and the patient also reported yellowish discoloration of urine. Other systems were normal.

Personal history revealed that the child lost appetite with significantly less food intake and one kg weight loss since the onset of the illness. Her bowel habit was once on alternate days and 6–7 times per day urinary outputs. Sleep was slightly disturbed, mild irritability and on and off aversion and off aversion to food.

Ayurveda clinical assessment revealed, Nadi (pulse): 82/min; Mala (stool): yellowish, constipated; Mutra (urine): yellowish; Jihwa (tongue): Ishat Saam (slightly whitish coated); Agni (digestive fire): Mandagni ; Shabda (speech): normal; skin and eyes were slightly yellowish.

The patient was normal before 2 months of manifestation of illness. Symptoms such as anorexia, poor appetite, generalized weakness, abdominal pain, and hard stool started manifesting and increased gradually. The patient had taken allopathic medicines from August 7, 2022, to August 15, 2022, but had not felt satisfactory relief. The patient came for Ayurvedic treatment on August 16, 2022, and continued until September 27, 2022. The total duration of the treatment was 6 weeks [ Table 1 ].

Diagnostic Assessment

The diagnosis was made as jaundice based on clinical manifestations such as yellowish discoloration of skin and sclera of the eyes due to high levels of serum bilirubin; and the laboratory investigation, that is, liver function test [total bilirubin (5.41 mg/dL), indirect bilirubin (1.96 mg/dL), direct bilirubin (3.45 mg/dL), serum glutamic-oxaloacetic transaminase (SGOT) (1098.76 U/L), serum glutamic-pyruvic transaminase (SGPT) (1175.84 U/L), alkaline phosphate (628.07 U/L)]. According to Ayurveda, clinical signs such as yellowish eyes, urine, skin, weakness, and yellowish stool, described by Charaka, were present in this case. Thus, based on these symptoms, the diagnosis of Koshthashrita Kamala was confirmed.

Therapeutic Intervention

Deepana and Pachana (increasing appetite and digestion) were done by Tablet Liv 52 DS (1 tablet twice a day after food with lukewarm water) and Tablet Nirocil (1 tablet twice a day before food with lukewarm water). Both formulations have hepatoprotective action. Mild Virechana was done by Avipatikara Churna (2 gm twice a day before food and Kutaki Churna (1 gm twice a day before food) with lukewarm water for 4 weeks. The total duration of intervention was 4 weeks [ Table 2 ].

During this period, the patient was advised to avoid the Pitta Dosha vitiating diet, such as fried and fatty food, and take old rice ( Oryza sativa ), barley ( Hordeum vulgare ), Godhuma (Wheat), carbohydrate-rich diet bread, rice, potato, yam, custard, sugarcane juice, pulses such as Adhaki (Red gram- Cajanuscajan ), Kulattha (horse gram), and Mudga (green gram), Leafy vegetables such as lettuce and spinach, and fruits such as orange, watermelon, apple, Jambu ( Syzygium cumini ), Kapitha ( Feronia limonia ), grapes, pears, carrots, and beets.

Follow-up and Outcomes

Follow-up was done twice in the interval of 7 days. In the second follow-up, the patient has come 2 days before the follow-up period. So, the patient was kept only on oral medication for 12 days. Thus, after 12 days of treatment, the investigations including complete blood count, liver function test, and urine examination of the patient were done, and the liver function test showed improvement. During each follow-up, improvement was found clinically and by laboratory investigations. There is no recurrence of symptoms during follow-up. Medications were taken until September 14, 2022, but the subsequent investigation was done on September 27, 2022.

Clinically, icterus and yellowish discoloration of urine decreased. There was relief in the symptoms such as loss of appetite, weakness, and a reduction in serum bilirubin levels, SGOT, SGPT, alkaline phosphatase, and PT INR (Prothrombin Time) was obtained in laboratory parameters criteria [ Table 3 ]. Still, the child has not been cured entirely at 2nd follow-up. After 4 weeks of intervention, the child was cured completely and looked normal on clinical examination. The interventions have shown a positive effect on improving appetite and taste and reducing yellow discoloration of skin and urine [ Figure 1 ].

Jaundice occurs due to the excessive breaking of RBC, leading to the accumulation of bilirubin in the blood. According to Ayurveda, excessive Pitta must be excreted from the body; therefore, Pittavirechana is significant in managing Kamala . The liver has a vital role in the excretion of this bilirubin. Therefore, the Pittavirechana and hepatoprotective properties of the drug will be helpful. The given Ayurvedic medications have the quality to remove Pittadushti and treat Kamala (Jaundice).

The main ingredient of Avipattikara Churna is Nishotha ( Operculina turpethum ) which is mild purgative. [ 5 ] It increases gastric motility, enhances gastric secretion, and relieves hyperacidity and constipation. [ 6 ] It also has Triphala Churna as an ingredient, which is a mild laxative. Triphala is the most effective to pacify Pitta Dosha , which was found as a cause of liver disorders in the studied case. All the drug of Avipattikara Churna has Deepana - Pachanga (increase appetite and digestion) property which can improve digestion and metabolism and prevents Ama formation. Avipattikara Churna contains sugar, which also has Pitta pacifying properties. [ 7 ] Kutaki Churna is a strong purgative, liver stimulating, and Pittasaraka (helps excrete Pitta ). [ 8 ] It is helpful in liver problems, spleen disorders, and fever. [ 9 ] It also has hepato-protective, antioxidant, anti-inflammatory, anticancer, immunomodulator, anti-ulcerative colitis, and antimicrobial actions. [ 10 ]

Tab Liv 52 DS is one of the formulations that has been frequently utilized to strengthen the liver. It contains Himsra ( Capparis spinosa ), Kasani ( Cichorium intybus ), Mandur Bhasma , Kakamachi ( Solanum nigrum ), Arjuna ( Terminalia arjuna ), Kasamarda ( Cassia occidentalis ), Biranjasipha ( Achillea millefolium ), Jhavuka ( Tamarix gallica ). It has digestive, liver-stimulating, anti-hepatotoxic, and antioxidant properties. [ 11-14 ] Tab Nirocil contains Bhumyamalaki ( Phyllanthus niruri ), which also has purgative, appetizer, liver stimulating, blood purifying, hepatoprotective, and Balya (provide strength) action [ 15-17 ] [ Table 4 ].

The preferred treatment principle was improving digestive metabolism and mild therapeutic purgation. At first instance, the child was planned with alleviation of vitiated Pitta , anti-inflammatory, clearing obstruction, and increased digestive fire treatment. Virechana was difficult considering Amavastha of disease and the reduced strength of the child. So, the first 3 days of treatment resulted in the relief of acute pain in the abdomen and improved digestive fire, which was indicated by reduced abdominal pain, increased hunger, easy evacuation of bowels, and considerable relief from the initial complaints. Further effectiveness of this step was supported by a reduction in bilirubin level and liver enzyme level (SGOT, SGPT, Alkaline phosphatase) observed in liver function test. Tablet Liv 52 DS and Tablet Nirocil were beneficial for reducing the liver enzyme level. The child’s general health was gradually improved. The clinical absence of jaundice symptoms was observed during a follow-up evaluation. The absence of pigment and bile salts in urine tests further supported this assertion. 1 kg weight gain and decreased yellowishness of the body were also noted during the treatment.

Along with hepatoprotective medicines, Virechana plays a vital role in treating jaundice. This case report reveals that Ayurveda medications are beneficial for managing jaundice in children.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. The consent for publication of picture and clinical information was obtained from the patient and the parents. The patient and parents understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Conflicts of interest.

There are no conflicts of interest.

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Obstructive Jaundice Mimicking Pancreatic Cancer: An Unusual Presentation of Autoimmune Pancreatitis

Affiliations.

• 1 General Surgery, Peoples Friendship University of Russia, Moscow, RUS.
• 2 Internal Medicine, American University of Antigua, Osbourn, ATG.
• 3 Medicine and Surgery, University of Benin, Benin, NGA.
• 4 Medicine, Shadan Institute of Medical Sciences, Hyderabad, IND.
• 5 General Surgery, Jimma University, Jimma, ETH.
• 6 Internal Medicine, University of Ghana Medical Centre, Accra, GHA.
• PMID: 37900366
• PMCID: PMC10600591
• DOI: 10.7759/cureus.45970

Autoimmune pancreatitis (AIP) is an uncommon variant of chronic pancreatitis characterized by inflammatory changes within the pancreatic tissue triggered by autoimmune mechanisms. It is known to mimic pancreatic cancer due to its similar clinical and radiological presentations. We underline a case of a 55-year-old male who presented with weight loss, jaundice, and pruritus. Radiological imaging suggested a pancreatic mass, raising suspicion of malignancy. However, subsequent evaluation, absence of parenchymal tissue and lymphoplasmacytic cells on endoscopic ultrasound-guided biopsy, and elevated serum immunoglobulin G4 level resulted in the diagnosis of AIP. Our case emphasizes that AIP should be included in the differential diagnosis of obstructive jaundice, especially when clinical and radiological findings are inconclusive for pancreatic cancer.

Keywords: autoimmune pancreatitis; endoscopic ultrasound; immunosuppressive therapy; obstructive jaundice; pancreatic cancer.

Copyright © 2023, Ogunlaja et al.

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The authors have declared that no competing interests exist.

Figure 1. Abdominal ultrasonography reveals a dilated…

Figure 1. Abdominal ultrasonography reveals a dilated pancreatic duct wall (a), and CT abdomen reveals…

Figure 2. A tissue biopsy shows fibrocollagenous…

Figure 2. A tissue biopsy shows fibrocollagenous tissue with scattered lymphoplasmacytic infiltrates containing neutrophils and…

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The constellation of risk factors and paraneoplastic syndromes in cholangiocarcinoma: integrating the endocrine panel amid tumour-related biology (a narrative review).

Simple Summary

1. introduction, 2. cca-associated risk factors and potential contributors, 2.1. chronic biliary diseases, 2.2. chronic liver conditions, 2.3. digestive ailments, 2.4. parasitic infections, 2.5. lifestyle influence, 2.6. environmental exposure, 2.7. genetic and epigenetic (potential) interplay, 3. metabolic and endocrine interferences in cca development, 3.1. non-alcoholic fatty liver disease (nafld), 3.2. obesity, 3.3. type 2 diabetes mellitus, 3.4. vitamin d status, 3.5. glucagon-like peptide 1 receptor (glp-1r), 3.6. galanin system, 3.7. sex hormone therapy, 4. paraneoplastic syndrome in ccas, 4.1. dermatological features have been found as followings, 4.1.1. acanthosis, 4.1.2. alopecia, 4.1.3. dermatomyositis, 4.1.4. porokeratosis, 4.1.5. necrotic migratory erythema, 4.1.6. persistent erythema multiform, 4.1.7. sweet syndrome, 4.1.8. bazex syndrome, 4.1.9. erythema, 4.1.10. pityriasis, 4.1.11. lupus, 4.1.12. leser–trelat sign, 4.1.13. porphyria, 4.2. neurological paraneoplastic elements, 4.3. renal findings, 4.4. haematological manifestations, 4.5. humoral manifestations, 5. discussion, 5.1. imagery tools to help the clinical assessment, 5.2. is there a place for endocrine considerations in ccas, 5.3. current limits and further expansion, 6. conclusions, author contributions, institutional review board statement, informed consent statement, data availability statement, conflicts of interest, abbreviations.

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Ciobica, M.-L.; Sandulescu, B.-A.; Chicea, L.-M.; Iordache, M.; Groseanu, M.-L.; Carsote, M.; Nistor, C.; Radu, A.-M. The Constellation of Risk Factors and Paraneoplastic Syndromes in Cholangiocarcinoma: Integrating the Endocrine Panel Amid Tumour-Related Biology (A Narrative Review). Biology 2024 , 13 , 662. https://doi.org/10.3390/biology13090662

Ciobica M-L, Sandulescu B-A, Chicea L-M, Iordache M, Groseanu M-L, Carsote M, Nistor C, Radu A-M. The Constellation of Risk Factors and Paraneoplastic Syndromes in Cholangiocarcinoma: Integrating the Endocrine Panel Amid Tumour-Related Biology (A Narrative Review). Biology . 2024; 13(9):662. https://doi.org/10.3390/biology13090662

Ciobica, Mihai-Lucian, Bianca-Andreea Sandulescu, Liana-Maria Chicea, Mihaela Iordache, Maria-Laura Groseanu, Mara Carsote, Claudiu Nistor, and Ana-Maria Radu. 2024. "The Constellation of Risk Factors and Paraneoplastic Syndromes in Cholangiocarcinoma: Integrating the Endocrine Panel Amid Tumour-Related Biology (A Narrative Review)" Biology 13, no. 9: 662. https://doi.org/10.3390/biology13090662

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• Open access
• Published: 24 August 2024

Total laparoscopic radical resection of hilar cholangiocarcinoma: preliminary experience of a single center

• Yusheng Du 1 ,
• Ji Wang 1 ,
• Hongqin Ma 1 ,
• Wenxing Zhao 1 &
• Ying Li 1  

BMC Surgery volume  24 , Article number:  241 ( 2024 ) Cite this article

48 Accesses

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The aim of this study was to describe our preliminary experience in the procedure of laparoscopic radical resection of hilar cholangiocarcinoma and to evaluate its feasibility, safety, and clinical efficacy.

A retrospective analysis was conducted on 44 patients with hilar cholangiocarcinoma who underwent laparoscopic surgery at our hospital from August 2019 to September 2023. Clinical data were collected from these patients, including 13 cases of Bismuth type I, 17 cases of Bismuth type II, 5 cases of Bismuth type IIIa, and 9 cases of Bismuth type IIIb.

Laparoscopic radical resection of hilar cholangiocarcinoma was successfully performed in 38 patients (86.3%). Among the remaining patients, 3 required vascular reconstruction to complete radical surgery and were converted to laparotomies, while 3 others underwent T-tube drainage only due to unresectable metastases. The median operation time was 285 min (range, 190–450), and the median estimated blood loss was 360 mL (range, 260–1200). The postoperative hospital stay duration was 14.3 ± 3.6 days. No perioperative mortality was observed. Postoperative pathological examination revealed negative microscopic margins (R0) in 39 cases and positive microscopic margins (R1) in 2 cases. Postoperative complications occurred in 8 patients (18.1%), with 4 cases (9.0%) of Grade I, 3 cases (6.8%) of Grade II, 1 case (2.2%) of Grade IIIa, and no Grade IIIb or IV complications. The median overall survival for patients who underwent radical R0 resection was 30.4 months (range, 5.3–43.6). The Disease-free survival rates were 73.6% at 1 year, 61.2% at 2 years, and 40.1% at 3 years.

Total laparoscopic radical resection of hilar cholangiocarcinoma can be performed safely, feasibly, and effectively by experienced surgeons after an accurate preoperative evaluation.

Peer Review reports

Introduction

Hilar cholangiocarcinoma, a malignant biliary epithelial tumor originating from the common hepatic duct, left and right hepatic ducts, and their junctions, accounts for approximately 40–60% of all cholangiocarcinomas [ 1 ]. This tumor is characterized by a low early diagnosis rate and a poor prognosis. Radical resection remains the only effective treatment for hilar cholangiocarcinoma, with a 5-year survival rate ranging from 20 to 40% following radical surgery [ 2 , 3 , 4 ]. However, traditional open surgery is highly invasive and poses greater risks for elderly patients with comorbid underlying diseases and poor cardiopulmonary function, resulting in many patients being deemed unsuitable for surgery. Therefore, it is imperative to explore a less invasive radical surgical approach that has a reduced impact on cardiopulmonary function in clinical practice to improve this situation. This paper aims to analyze a case series and summarize the surgical experience of total laparoscopic radical resection for hilar cholangiocarcinoma, with the goal of providing surgeons with a better understanding of this novel technique.

Materials and methods

A retrospective study was conducted, approved and adopted by the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University (Ethics No.XYFY2019-KL051-01). Informed consent was obtained from all patients. Clinical data were collected from 44 patients who underwent laparoscopic surgery for hilar cholangiocarcinoma at the Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, from August 2019 to September 2023. The study population consisted of 29 males and 15 females, with a mean age of 69.3 ± 7.8 years and a mean BMI of 24.5 ± 2.8 kg/m 2 . Among the patients4 had diabetes, 3 had coronary artery disease, 6 had hypertension, and one had previously undergone laparoscopic cholecystectomy. The median preoperative total bilirubin level was 189.7 µmol/L (range: 91.9-347.9 µmol/L), and the median preoperative direct bilirubin level was 164.3 µmol/L (range: 75.8-208.5 µmol/L). All patients were diagnosed with hilar cholangiocarcinoma combined with obstructive jaundice by color Doppler ultrasound, computed tomography (CT), and magnetic resonance cholangiopancreatography (MRCP) before surgery. For patients considered preoperatively for possible combined extensive hepatectomy, 3D image reconstruction imaging was performed, and the residual liver volume was assessed. Endoscopic nasobiliary drainage (ENBD) was performed in one patient to attenuate jaundice due to severe jaundice (347.9 µmol/L) and cholangitis. Two patients with severe jaundice required a period of preoperative nutritional support due to poor nutrition and underwent percutaneous transhepatic cholangial drainage (PTCD). The American Society of Anesthesiologists (ASA) classification was as follows: 15 cases were Grade I, 27 cases were Grade II, and 2 cases were Grade III. According to the Bismuth classification, there were 13 cases of Bismuth type I, 17 cases of Bismuth type II, 5 cases of Bismuth type IIIa, and 9 cases of Bismuth type IIIb. No obvious operative contraindications or distant metastases were found on preoperative examination (details in Table  1 ).

Surgical procedures

Surgical position and exploration.

The patient was placed in the supine and Trendelenburg positions. A 5-port laparoscopic approach was employed, with the primary operator positioned on the patient’s left side. An observation port was established using a 10-mm trocar placed under the umbilicus, while a 12-mm trocar, serving as the main operation port, was inserted under the left anterior axillary costal margin. Two 5-mm trocars were placed in the midclavicular line of the middle abdomen and the symmetrical position of the right abdomen as auxiliary operation ports, and an additional 12-mm trocar was positioned in the right abdomen. Upon entering the abdominal cavity, a thorough exploration was conducted to confirm the absence of implantation metastasis. Subsequently, the hilar plate was exposed and meticulously dissected to assess the tumor’s location, size, texture, and the presence of enlarged surrounding lymph nodes, facilitating an initial evaluation of the feasibility of radical surgery.

Resection of cholangiocarcinoma

The gastrocolic ligament was opened to clear the Group 8 lymph nodes of the common hepatic artery (CHA) along the upper edge of the pancreas. The anterior wall fascia of the hepatoduodenal ligament was incised to strip the proper hepatic artery (PHA) and remove the Group 12 lymph nodes on the left portal vein (PV). The right gastric artery was then resected by dissociating towards the porta hepatis and the stripped PHA, followed by the stripping of the left hepatic artery (LHA) and right hepatic artery (RHA). By lifting the PHA and dissecting the right wall of the PV, the posterior wall of the PV was stripped. The lymphatic adipose tissue on the left side of the hepatoduodenal ligament was pulled from behind the PV to the right side, ensuring complete removal of the lymphatic adipose tissue along with the tumor. The common bile duct was resected along the upper edge of the duodenum and pancreas until the pancreatic segment, and the lymph nodes behind the pancreatic head (Group 13) were cleared using a Kocher incision. An anastomosis stapler was used to resect the common bile duct along the upper edge of the pancreas, and the margin was subjected to fast-frozen pathology. The gallbladder was retrogradely stripped from the gallbladder bed and resected towards the hilar region along the bile duct. The left and right hepatic gallbladder and caudate bile duct were separated at least 1 cm above the tumor, with the margin undergoing fast-frozen pathology. Additionally, the liver tissue surrounding the bile duct was removed to achieve radical resection of hilar cholangiocarcinoma (Fig. 1 A). In cases with multiple bile duct openings at the upper cutting edge of the bile duct stump, rapid freezing pathology was mandatory. Following confirmation of negative pathological reports, the anastomosis operation was performed.

Hepatectomy

In instances where intraoperative exploration or rapid pathology suggested tumor invasion of one side of the intrahepatic bile duct, a combined hepatectomy was necessary to achieve radical surgery. The specific method, using combined left hepatectomy as an example, involved dissecting the portal blood vessels and branches, followed by the disconnection of the LHA (Fig.  2 A) and the left branch of the PV (Fig.  2 B).

Surgical field of view after hilar cholangiocarcinoma (Bismuth type I) A Hepatoduodenal ligament after lymph node dissection. B Portal vein naked 360°

Surgical field of view during radical operation of hilar cholangiocarcinoma combined with left hepatectomy (Bismuth type IIIb) A The left hepatic artery is being cutting and closing. B The Left portal vein is being cutting and closing. C The left liver is being cutting and closing

The perihepatic ligament of the left liver was dissected, exposing the hepatic vein at the second hepatic hilar. The peritoneum was dissected anterior to the inferior hepatic vena cava, and the short hepatic veins were gradually dissected from the bottom up, clipped, and dissected, separating the liver from the posterior hepatic vena cava. The liver parenchyma was transected using an ultrasonic knife combined with an electric hook along the left hepatic ischemic zone, and the intrahepatic vessels were sequentially ligated. The left hepatic vein was dissected using an anastomosis stapler (Fig.  2 C), completing the left hepatectomy and caudate lobectomy. Throughout the procedure, meticulous hemostasis was ensured, and the remaining liver section was carefully examined, with any missing vessel or bile duct sections being sutured.

Gastrointestinal reconstruction

Roux-en-Y hepaticojejunostomy was performed for gastrointestinal reconstruction. Approximately 15–20 cm away from the Treitz ligament, the jejunum was dissected using an anastomosis stapler. Following closure of the distal jejunum, the hepatic duct-jejunum anastomosis was carried out after lifting the jejunum to the hilar region over the back of the colon. In cases where the tumor location was high, multiple lumens would be present in the broken end of the hepatic duct after cutting off the left and right hepatic ducts. In such instances, hilar cholangioplasty was performed prior to bilioenteric anastomosis (Fig.  3 A). The size of the anastomosis was determined by the cross-sectional diameter of the bile duct after shaping. An incision was made in the distal jejunum, matching the size of the mesangial limbus. Using 4 − 0 VOL-C, a continuous full-thickness suture of the hepatic duct and jejunum was performed in the order from left to right, starting with the first wall and then the front wall (Fig.  3 B-C). In cases where the opening of the hepatic duct was too far apart, multiple hepatic duct jejunostomies were required (Fig.  3 D).

Roux-en-Y anastomosis of hepatic duct and jejunum A Left and right hepatic duct reshaping. B Hepatic jejunostomy after perihepatic resection. C Hepatic jejunostomy after combined left hepatectomy. D Two hepatic duct jejunostomy

Postoperative management

Postoperative management was conducted in accordance with the principles of Enhanced Recovery After Surgery (ERAS) [ 5 ]. Briefly, the patients were encouraged to engage in off-bed activities on the first postoperative day and were allowed to consume an appropriate amount of water. The liquid diet was reintroduced as soon as possible, guided by the individualized target-oriented fluid infusion principle. Additionally, conventional anti-infection measures, somatostatin, acid suppression, and nutritional support therapy were implemented. Albumin and plasma were supplemented as necessary. Abdominal CT scans were performed 3 to 5 days following surgery, and drainage tubes were removed in patients with no significant surgical area effusion or bile leakage. For patients with distinct peritoneal effusions, ultrasound-guided puncture drainage was employed.

Data collection and statistical analysis

The following data were collected and analyzed: average operation time, intraoperative blood loss, intraoperative transfusion requirement, time to first postoperative bowel movement, average postoperative hospitalization duration, postoperative pathological grading and staging, number of dissected lymph nodes, negative margin rate (including the radial margin, hepatic and duodenal margin of the resected bile duct, and cut surface of the liver), and postoperative complications (assessed using the Clavien–Dindo classification [ 6 ].

Follow-up was not preplanned but was generally conducted at intervals of 3–6 months. It included comprehensive physical examinations, laboratory testing, and computed tomography when necessary. If patient survival status was unknown at the time of data collection, it was verified through telephone communication.

Statistical analysis was performed using SPSS 23.0 software. Measurement data with a normal distribution are presented as mean ± standard deviation (x ± s), while measurement data with a skewed distribution are presented as median (range). Count data are expressed as absolute numbers.

Laparoscopic radical resection of hilar cholangiocarcinoma was ultimately performed in 38 (86.3%) patients. The remaining patients included 3 who required vascular reconstruction to complete radical surgery and thus converted to laparotomy, and 3 who underwent T-tube drainage only due to unresectable metastases. Among the patients who underwent laparoscopic radical resection, 13 underwent perihilar resection, 11 underwent perihilar resection combined with caudate lobectomy, 11 underwent left hemi hepatectomy combined with caudate lobectomy, and 6 underwent right hemi hepatectomy combined with caudate lobectomy. Among the 17 patients who underwent combined hemihepatectomy, the transected ends of the right or left hepatic ducts were reshaped and subsequently anastomosed with the jejunum. Similarly, for the 22 patients who underwent perihilar hepatectomy or perihilar hepatectomy combined with caudate lobe resection, the bile ducts at the hepatic hilum required reshaping prior to the anastomosis with the jejunum.The median operation time was 285 min (range, 190–450), and the median estimated blood loss was 360 mL (range, 260–1200). Postoperative pathological examination revealed negative microscopic margins (R0) in 39 cases and positive microscopic margins (R1) in 2 cases. The number of lymph nodes harvested ranged from 6 to 17 per case, with a median of 8. According to the American Joint Committee on Cancer (AJCC) eighth edition staging system for hilar cholangiocarcinoma, 14 cases were classified as stage I, 17 as stage II, 10 as stage III, and 3 as stage IV (Table  2 ). The mean time to the first postoperative flatus was 2.7 ± 0.3 days, and the average postoperative hospital stay was 14.3 ± 3.6 days. Postoperative complications occurred in 8 patients (18.1%), with 4 cases (9.0%) classified as Grade I, 3 cases (6.8%) as Grade II, and 1 case (2.2%) as Grade IIIa according to the Clavien–Dindo complication grading system. No Grade IIIb or IV complications were observed. The main complications included pulmonary infection (1 case), postoperative abdominal infections (3 cases), postoperative hepatic insufficiency (1 case), and Grade A biliary fistulas (3 cases). The patient with a Grade IIIa complication had preoperative diabetes mellitus and hypoalbuminemia and developed persistent hyperthermia on the sixth postoperative day. Abdominal culture showed multidrug-resistant bacterial infection with a positive fungal culture. The patient was discharged on the 23rd postoperative day with a normal white blood cell count and no significant effusion on repeat CT. All other patients with complications were cured after symptomatic treatment and discharged from the hospital. No perioperative deaths or severe postoperative complications, such as bleeding, liver failure, or cardiovascular or cerebrovascular events, were observed (Table  3 ).

As of December 10, 2023, 35 of 44 patients (79.5%) were followed up.The median overall survival for patients who underwent radical R0 resection was 30.4 months (range, 5.3–43.6). The Disease-free survival rates were 73.6% at 1 year, 61.2% at 2 years, and 40.1% at 3 years.

Laparoscopic hepatectomy (LH) has gradually expanded in hepatobiliary surgery since Reich’s first successful LH in 1991 [ 7 ]. However, laparoscopy is more often used for exploratory assessment of surgical feasibility in managing hilar cholangiocarcinoma, avoiding unnecessary open surgery [ 8 ]. The porta hepatis’s special location and the region’s complex structures make tumor resection difficult and complex, requiring extensive experience in open surgery and laparoscopic techniques. Consequently, only a few larger hepatobiliary and pancreatic centers in China and abroad have performed experimental procedures for this purpose [ 9 , 10 , 11 ]. It is worth investigating the availability of minimally invasive surgery for patients with hilar cholangiocarcinoma. Our institute has explored laparoscopic radical resection of hilar cholangiocarcinoma based on numerous laparoscopic resections of the digestive tract and pancreatic tumors, with satisfactory clinical efficacy [ 12 , 13 ].

Feasibility of laparoscopic radical resection of hilar cholangiocarcinoma

The surgeon and team’s laparoscopic experience play a crucial role.

Laparoscopic surgery differs from open surgery due to the lack of longitudinal depth and tactile sensation. Simultaneously, the difficult and complex anatomical relationships of the surgery itself for hilar cholangiocarcinoma make this procedure highly demanding for the surgeon and team. Our team can now routinely perform laparoscopic radical gastric cancer surgery, laparoscopic pancreaticoduodenectomy, and laparoscopic hemihepatectomy. Through these procedures, we have mastered the critical techniques required in radical laparoscopic surgery for hilar cholangiocarcinomas, such as “naked vascularization of the hilum,” “laparoscopic biliary-enteric anastomosis,” and laparoscopic hemihepatectomy, which has significantly accelerated our learning curve for this procedure. The surgeon’s extensive laparoscopic experience plays a vital role in managing intraoperative bleeding and accidental injury, reducing the rate of conversion from laparoscopy to open surgery, and ensuring the operation’s safety.

We believe that for a highly challenging operation such as laparoscopic hilar cholangiocarcinoma, a smooth and safe learning curve requires the above-mentioned laparoscopic technical reserve, as well as the close cooperation of anesthesiologists and nursing teams. It is recommended to select suitable type 1 or partial type 2 cases in the initial stage, because these patients are relatively less difficult to operate. Because if serious complications occur early in the development of a new technology, it is a fatal blow to the confidence of the surgeon.

Evaluation of the assistance of preoperative imaging

Advanced imaging techniques can accurately determine tumor staging, classification, and resectability preoperatively, which is crucial for surgical success. MRCP displays the complete hepatic hilum mass, intrahepatic bile duct distribution, and invasion extent of the left and right hepatic ducts [ 14 ]. Three-dimensional CT reconstruction is essential for assessing vascular variation and the relationship between tumors and blood vessels. For patients potentially undergoing extensive hepatectomy, the residual liver volume should be evaluated before surgery. These factors guide surgical planning. All patients underwent enhanced CT and MRCP, followed by careful assessment to determine the preset upper edge. Additionally, the feasibility of safely performing R0 resection laparoscopically was judged, ensuring a safe and thorough operation while saving time.

Understanding and development of the scope of surgery

Radical R0 resection of hilar cholangiocarcinoma requires complete mass resection, negative margins, and clearance of potentially invaded surrounding tissues [ 15 ]. The previously prevalent theory of enlarged hepatectomy positively impacts tumor radical resection. However, it increases the risk of liver failure due to insufficient postoperative residual liver function, failing to improve prognosis and increasing risk [ 16 ]. Recently, many scholars have proposed ‘perihepatic resection’ under the guidance of precision hepatic surgery, which retains functional liver tissue while radically resecting tumor lesions [ 17 ]. This view aligns with our goal of radical laparoscopic surgery. We routinely handle the hepatoduodenal ligament during surgery to expose the hepatic artery, portal vein, and extrahepatic bile ducts, accurately localizing the tumor and its relationship with arterial and portal vein branches. Intraoperative fast frozen pathological examination confirms resection margins, including secondary bile ducts, caudate lobe bile ducts, and liver tissues.

For Bismuth type I and some type II cases, R0 resection is achievable after the above procedure. However, if preoperative examination or intraoperative exploration detects tumor invasion of the left (right) hepatic duct or caudate lobe hepatic duct, combined or extended hepatectomy is performed strictly according to standardized consensus [ 1 ].

Safety and clinical effect of this surgery

In this study, 39 out of 44 patients (88.6%) successfully underwent radical R0 resection, with most procedures (37/39) performed laparoscopically. The operation time and intraoperative blood loss were comparable to, or slightly better than, data from open surgery in most local and international centers in recent years [ 7 , 8 , 9 , 10 , 11 ]. Regarding postoperative complications, no cases of postoperative bleeding, perioperative death, or severe cardiopulmonary complications were observed. According to the Clavien–Dindo postoperative complication grading system, only one patient had a grade of 3 or higher, and this patient was successfully discharged after aggressive nutritional support, anti-infection, and other nonsurgical treatments.

The median age of the 44 patients in this study was 69.3 years, with the oldest patient being 80 years old, which is higher than previously reported in China [ 8 , 9 ]. All patients recovered well after surgery, suggesting that the upper age limit for inclusion in this procedure can be relaxed. The minimally invasive nature of laparoscopic surgery may provide an opportunity for patients of advanced age and poor cardiopulmonary function to experience better postoperative recovery and a reduced incidence of postoperative cardiopulmonary-related complications.

Experiences and problems

Preoperative biliary drainage (pbd) strategy.

Undoubtedly, PBD can significantly reduce the risk of liver resection in patients with hyperbilirubinemia. However, there remains ongoing debate about the benefits and drawbacks of PBD for perioperative and long-term survival in patients with hilar cholangiocarcinoma (HCCA) [ 18 ]. Guidelines from Europe and the United States recommend PBD before HCCA surgery, but there are no clear recommendations on the specific drainage route or protocol [ 19 ]. Our approach is to advocate for PBD in patients with cholangitis, prolonged biliary obstruction, poor nutritional status, serum total bilirubin > 200 µmol/L, and when extensive liver resection is needed with a residual liver volume of less than 40%. Currently, there is no uniform standard for the duration of preoperative biliary drainage. It is generally believed that the duration of drainage should be preferably more than 3 weeks, with a serum total bilirubin level below 50 µmol/L, and the liver function should be basically restored to normal.

Lymph node clearance

As shown by data, lymph node metastasis is a significant indicator of poor prognosis in hilar cholangiocarcinoma. The eighth edition of AJCC recommends routine dissection of lymph nodes located in the hilar, cystic duct, common bile duct, hepatic artery, pancreaticoduodenum, and near the portal vein [ 20 ]. Lymph node dissection in the hepatoduodenal ligament is a challenging and critical aspect of radical resection due to the presence of important blood vessels and the risk of uncontrollable bleeding during the dissection process.

Incomplete clearance of the site can lead to the remaining cancer cells in the hepatoduodenal ligament tissue becoming a high-risk factor for the recurrence of cholangiocarcinoma after resection19 [ 21 ]. Laparoscopy offers advantages in this regard, as it can be performed perpendicular to the visceral surface of the liver. The 30-degree lens provides a wide and deep field of vision, allowing for flexible rotation in the hilar region. The ultrasonic knife can be operated in close proximity to the blood vessel wall under close-sight operation. Additionally, laparoscopy facilitates the identification and clipping of small blood vessels supplying the tumor during lymph node dissection in the hilar area, minimizing unnecessary bleeding and ensuring a clear operation field and smooth progress of the operation. These advantages enable a more detailed and secure’skeletonization’ operation of the hepatoduodenal ligament, which is associated with a high risk of haemorrhage. Although lymph node dissection behind the pancreatic head was previously considered to pose a risk of postoperative pancreatic leakage, our experience in laparoscopic pancreaticoduodenectomy suggests that a ‘Kocher incision’ can be utilized to expose the posterior segment of the common bile duct, allowing for the clearance of posterior pancreatic lymph nodes [ 13 ]. If the tumor is closely related to the blood vessels and the preoperative assessment indicates possible resection, a complete dissection and subsequent nondestructive blocking clip are recommended before proceeding with other relevant interventions.

Hepaticojejunostomy anastomosis

Hepaticojejunostomy anastomosis is another critical step in this operation, as the quality of the anastomosis is generally associated with the risk of postoperative biliary fistula. The fundamental principle of hepatic duct reconstruction is the mucosa-to-mucosa anastomosis of the hepatic duct to the jejunum [ 11 , 22 ]. The main challenge arises from the deep location of the high bile duct and its proximity to the main branches of the portal vein, necessitating extra caution during the procedure. The magnification provided by laparoscopic surgery enables the operator to better control suture spacing, avoiding issues such as missed stitches and inadvertent injury to surrounding vessels, ultimately enhancing the quality of the anastomosis. It is recommended that the residual bile duct should not be excessively stripped, with 3–5 mm being an appropriate length. For patients undergoing PTCD before surgery, the catheter is generally visible after biliary duct incision, and the drainage tube is slightly retracted visually to avoid suture of the catheter during anastomosis, and then pulled out about 4 weeks after surgery. Dilated bile duct can be an advantage when constructing the anastomosis, in cases of significantly dilated and flexible bile ducts, a single layer of continuous epithelialization using a 4 − 0 or 5 − 0 barbed suture can be employed. However, if the bile duct is edematous and fragile, a 5 − 0 PDS II suture is preferable to prevent tissue tearing. When addressing bile duct severed ends, type III bile duct confluence is low, and adjacent bile ducts can be assembled and shaped into a single duct, reducing both the complexity of the anastomosis and the likelihood of biliary fistula formation. If the opening distance remains too excessive after rectification, separate anastomoses may be necessary. In situations where the bile duct openings are large and difficult to reshape, where excessive tension is present after reshaping, or where the bile duct wall is weak and prone to tearing during suturing, a pelvic anastomosis utilizing the Glisson sheath or the tough tissue of the porta hepatis is recommended.

Determination of negative hepatic duct margins

The “skeletonization” of the hepatoduodenal ligament, high-quality bile-intestinal anastomosis, and even combined hemihepatectomy no longer pose insurmountable technical barriers for surgeons with extensive laparoscopic experience. However, ensuring negative hepatic duct margins remains a challenge. Negative hepatic duct margins are of paramount importance for achieving R0 resection [ 23 ].

In open surgery, the texture of the bile duct and surrounding tissues can be visualized to provide a comprehensive view of the incisional margin. Even so, accurate determination by palpation can be difficult, relying on preoperative imaging and intraoperative frozen section pathology. Laparoscopic surgery, on the other hand, relies more heavily on intraoperative frozen section pathology to determine margins, requiring a higher level of pathology expertise in the hospital and greater demands on the surgeon to remove the bile duct stump during surgery. Ensuring the integrity of the anterior and posterior walls of the bile ducts and marking the upper and lower ends before sending the specimen for pathological examination, with a margin of at least 3 mm, is crucial. The magnification provided by the laparoscope can help distinguish small bile ducts and the specific location of tumor invasion, offering certain advantages. Future technological advances (e.g., 3D printing) may better address this issue [ 24 ].

Limitations of this study

This study is a single-center retrospective analysis with a small sample size, so the conclusions drawn are one-sided to a certain extent. Therefore, prospective studies with large sample size and long follow-up time are still needed in the later stage to further verify the findings. Additionally, the role of neoadjuvant chemotherapy, targeted therapy, and immunotherapy for patients with resectable hilar cholangiocarcinoma was not addressed. Despite these shortcomings, this minimally invasive surgery is friendly for elderly patients with liver insufficiency, and laparoscopic surgery also has advantages in amplification for lymph node dissection and high bilioenteric anastomosis. The most important thing is that none of the patients in this study had serious complications or died after surgery, and the safety of this operation can be preliminarily confirmed.

Laparoscopic hilar cholangiocarcinoma is a challenging procedure, and our limited experience suggests that it can be performed safely by selecting the appropriate cases for surgeons with extensive laparoscopic experience, which warrants further exploration to confirm its clinical efficacy.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

Endoscopic nasobiliary drainage

Ercutaneous transhepatic cholangial drainage

Computed tomography

Magnetic resonance cholangiopancreatography

The American Society of Anaesthesiologists classification

Common hepatic artery

Proper hepatic artery

Hepatic artery

American Joint Committee on Cancer

Laparoscopic hepatectomy

Total bilirubin

Direct bilirubin

Body mass index

Interquartile range

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W.X.Z and Y.L proposed the study. Y.S.D designed and wrote the article. All authors contributed to literature searching, data collecting and interpretation of the study. Y.L and W.X.Z supervised the study and revised the article. All authors have reviewed and approved the final article.

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Du, Y., Wang, J., Liu, L. et al. Total laparoscopic radical resection of hilar cholangiocarcinoma: preliminary experience of a single center. BMC Surg 24 , 241 (2024). https://doi.org/10.1186/s12893-024-02533-w

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Introduction, case report, conflict of interest statement, type i choledochal cyst. total laparoscopic resection and roux-en-y reconstruction to two separated ducts.

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Natalia Reyes, Camila Sotomayor, Martín Inzunza, Eduardo Briceño, Eduardo Viñuela, Jorge Martínez, Nicolás Jarufe, Type I choledochal cyst. Total laparoscopic resection and Roux-en-Y reconstruction to two separated ducts, Journal of Surgical Case Reports , Volume 2024, Issue 8, August 2024, rjae543, https://doi.org/10.1093/jscr/rjae543

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A choledochal cyst is a rare condition that requires surgical treatment to prevent complications, such as obstructive jaundice, cyst rupture, cholangitis, and the risk of malignancy. Complete cyst excision is considered the best option, as it reduces the risk of inflammation and the development of cholangiocarcinoma. Therefore, cholecystectomy and complete cyst resection followed by reconstruction with a Roux-en-Y hepaticojejunostomy is the treatment of choice. We present a case (with video) that shows the complete resection of a type I choledochal cyst with Roux-en-Y reconstruction of two separate ducts since the right posterior duct reached the cyst independently. The laparoscopic approach offers all the advantages of mini-invasive surgery and better visualization of the structures; however, biliary reconstruction to fine ducts implies a surgical challenge that requires high training in mini-invasive surgery.

Choledochal cyst (CC) is a rare congenital pathology that causes dilation of the extrahepatic, intrahepatic biliary tree, or both. Its incidence varies between 1 in every 13 000 and 2 000 000 live births [ 1 ], with type I CC representing 80%–90% of these cases [ 2 ]. Symptoms appear in 84.5% of patients, with abdominal pain and jaundice being the most prevalent. Complications include cholelithiasis, cholangitis, spontaneous rupture, pancreatitis, and cholangiocarcinoma [ 3 ].

Complete resection of type I CC involves removing the entire dilated extrahepatic biliary tree from the confluence to the intrapancreatic common bile duct to eliminate the risk of malignant transformation. Reconstruction is generally performed using Roux-en-Y hepaticojejunostomy (RYHJ). The association between an anatomical variant of the right posterior hepatic duct (RPHD) and CC is rare, with few documented cases in the medical literature [ 4 ].

We present the case of a patient with a type I CC resolved by laparoscopic surgery, with complete resection of the cyst and Roux-en-Y reconstruction of two separate ducts since the right posterior duct reached the cyst independently. Our goal is to contribute to the limited evidence regarding this rare case, as a few published cases in the medical literature have undergone this surgical technique treatment.

The present case corresponds to a 45-year-old woman with a history of recurrent episodes of recurrent abdominal pain and jaundice, which has required sporadic hospitalizations, during which she underwent endoscopic retrograde cholangiopancreatography with a bile duct stent placed.

A magnetic resonance cholangiopancreatography revealed the presence of a large 5 cm CC, classified as type I according to the Todani classification, accompanied by significant lithiasis of up to 3 cm inside and cholelithiasis. An anatomical variant was identified in which the RPHD drained directly into the CC.

The surgical team performed a complete resection of the CC, accompanied by reconstruction using two independent enterotomies and anastomoses, given the considerable distance between the right anterior and posterior bile ducts. The common hepatic duct (CHD) was dissected distally until the intrapancreatic bile duct of normal caliber was reached. Proximally, dissection continued to the confluence of the right anterior and left ducts. Two separate hepaticojejunostomy were performed, first to the right posterior duct and then to the CHD (see Video 1 ).

The patient showed a favorable recovery with no signs of biliary fistula, allowing the drain to be removed, and the patient to be discharged 5 days postoperatively. Follow-up revealed no stenosis of the hepaticojejunostomy, and the patient reported no significant discomfort.

CC is a rare pathology in adults. Although mainly diagnosed during childhood, 20%–25% of patients are diagnosed in adulthood. It affects 0.1% of the population and is four times more common in women [ 5 ]. The incidence of malignant transformation to cholangiocarcinoma is 3%–5%, increasing from 0.7% in the first decade to over 14% after 20 years [ 1 ]. Therefore, early diagnosis and cyst resection surgery are essential.

The evolution of surgical treatment has progressed from cyst-enteral anastomosis, associated with symptom recurrence and malignancy risk, to complete cyst resection with biliodigestive reconstruction via open or laparoscopic approaches [ 6 ].

Currently, minimally invasive approaches are used to treat CC, as laparoscopy provides better visualization and more precise manipulation. Zhen et al. compared the open and laparoscopic techniques, finding that laparoscopy resulted in a shorter hospital stays (MD = −1.93; 95%CI = −2.51 to −1.36; P  < .00001) and faster recovery of intestinal function (MD = −0.94; 95%CI = −1.33 to −0.55; P  < .00001), with no significant differences in postoperative complications (RR = 1.04; 95%CI = 0.66–1.62; P  = .88). Although the laparoscopic group had longer operative times (MD = 56.57; 95%CI = 32.20–80.93; P  < .00001), it had lower rates of red blood cell transfusion (RR = 0.20; 95%CI = 0.11–0.38; P  < .00001) and intestinal obstruction (RR = 0.17, 95%CI = 0.04–0.77; P  = .02) [ 7 ].

The laparoscopic technique represents a surgical challenge that requires advanced experience and skills from the surgical team.

The standard biliodigestive reconstruction technique is RYHJ. However, studies have defended hepaticoduodenostomy as a more physiological tension-free technique, faster to perform, and with potential for future endoscopic interventions. Ai et al. identified that patients undergoing biliodigestive reconstruction with hepaticoduodenostomy had a shorter hospital stay (MD = −0.40; P  = .02), a shorter operative time (MD = −59.54; P  < .00001), and a lower incidence of adhesive intestinal obstruction (OR = 0.20; P  = .02) than those undergoing hepaticojejunostomy. However, it was associated with a higher incidence of gastritis (OR = 6.24; P  = .002) [ 8 ]. Howell et al. [ 9 ] reported that patients undergoing hepaticojejunostomy had a lower readmission rate compared to those undergoing hepaticoduodenostomy (4.0% vs. 10.5%, OR = 0.34, CI [0.12, 0.79], P  = .02), the causes of readmission being pancreatitis, surgical site infection, abdominal pain, and cholangitis.

Regarding the reconstruction technique of the anatomical variant of the RPHD, there are two approaches depending on the distance between the CHD and the RPHD: ductoplasty and double hepaticojejunostomy [ 4 ]. Ligation or failure to identify the RPHD during surgery can lead to complications such as cholangitis, liver abscess, liver atrophy, cirrhosis, biliary fistula, or biliary peritonitis [ 10 ].

There is little evidence comparing both techniques, the majority being in the pediatric population. Diao et al. [ 11 ] evaluated laparoscopic treatment for aberrant hepatic duct (AHD) in children with CC, identifying that the AHD was frequently confused with adhesions, causing bile leaks in the postoperative period. Xie et al. [ 12 ], when comparing robotic versus laparoscopic surgery for CC in children with AHDs, found that of a total of 22 patients, the majority required ductoplasty and only two required double hepaticojejunostomy in both groups, with no significant differences in postoperative complications. Bile leak is one of the most worrying complications associated with this procedure [ 4 ].

In this case, the technique of choice was separate hepaticojejunostomy, given the distance between both ducts, as the evidence suggests. It is essential to mention that to perform this procedure, a specialized team with the experience and skills necessary to perform fine anastomoses laparoscopically was required, and adequate training was necessary to achieve good results.

It is important to note that little additional published evidence resembles this case. We hope to contribute to medical knowledge to manage these challenging cases effectively.

None declared.

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Ai C , Wu Y , Xie X , et al.    Roux-en-Y hepaticojejunostomy or hepaticoduodenostomy for biliary reconstruction after resection of congenital biliary dilatation: a systematic review and meta-analysis . Surg Today   2023 ; 53 : 1 – 11 . https://doi.org/10.1007/s00595-021-02425-z .

Howell TC , Beckhorn CB , Antiel RM , et al.    Contemporary trends in choledochal cyst excision: an analysis of the pediatric national surgical quality improvement program . World J Surg   2024 ; 48 : 967 – 77 . https://doi.org/10.1002/wjs.12128 .

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Etiology of obstructive jaundice and its correlation with the ethnic population of Sikkim

Karma d. bhutia.

1 Department of Intermediate Reference Laboratory, S.T.N.M. Hospital, Gangtok, Sikkim, India

Tsella Lachungpa

2 Department of Radiology, S.T.N.M. Hospital, Gangtok, Sikkim, India

Sangey C. Lamtha

3 Department of Gastroenterology, S.T.N.M. Hospital, Gangtok, Sikkim, India

The aim of the study was to find out the etiology of obstructive jaundice and its correlation with the ethnic population of Sikkim.

Material and Method:

The data of patients with obstructive jaundice admitted under the Department of Gastroenterology was collected retrospectively from March 2019 till February 2020. There were a total of 73 patients of obstructive jaundice patients, the benign etiology was found to be more common than malignant etiology.

The male-to-female ratio in our study was 0.35:1. The most common etiology of benign cause of obstructive jaundice was choledocholithiasis (95.83%) followed by common bile duct stricture (3.07%), Mirizzi syndrome (1.53%). The most common causes of malignant obstructive jaundice were carcinoma of gall bladder (62.5%) followed by carcinoma of periampullary region (12.5%), cholangiocarcinoma (12.5%), carcinoma of head of pancreas (12.5%).

Conclusions:

The most common etiology of obstructive jaundice in this study was choledocholithiasis. There was no any correlation of obstructive jaundice with ethnic population of Sikkim.

Introduction

Obstructive Jaundice is a common problem that occurs when there is an obstruction to the passage of conjugated bile from liver cells to intestine.[ 1 ] Endoscopic retrograde cholangiopancreatography (ERCP) has become the one of treatment modality for patients with obstructive jaundice because of its therapeutic capabilities. The success rate of ERCP for treatment is highly variable ranging from 50% to 96% depending on the operator, endoscopic aspect, disease severity, and anatomical abnormality.[ 2 , 3 ] Jaundice due to biliary obstruction may be caused by a heterogeneous group of diseases that include both benign and malignant conditions.[ 4 ] The common etiologies of obstructive jaundice have been reported to vary from one center to another and from one individual to another.[ 4 , 5 ] The morbidity and mortality related to obstructive jaundice depends upon the causes of obstruction.[ 6 ] There are some studies on the etiology of obstructive jaundice but none from the state of Sikkim. Lack of literature lead to this study. This study was done to find out the etiologies of obstructive jaundice among the ethnic population of Sikkim, India.

As per first colonial census of Sikkim 1891, there were thirteen ethnic races in the Kingdom of Sikkim groups namely Chettri, Subba, Bhutia, Tamang, Gurung, Biswakarma (BK) and others.[ 7 ]

Material and Method

The data of the admitted patients of obstructive jaundice was collected retrospectively from the department of gastroenterology, Sir Thutop Namgyal Memorial Hospital (S.T.N.M.), Socheygang a tertiary care referral center from March 2019 till February 2020. There were a total of 73 patients of obstructive jaundice during that period. Patients of hepatocellular jaundice, prehepatic jaundice and young patients with age less than 15 years were excluded. All patients have undergone complete blood counts, liver function tests, kidney function test, prothrombin time with internationalized ratio, hepatitis B surface antigen, anti-HCV antibody test, retrovirus test. Diagnosis of obstructive jaundice etiology was made with ultrasound of whole abdomen, magnetic resonance cholangiography (MRCP) and contrast-enhanced computed tomography (CECT) whole abdomen. ERCP was done in these patients only as therapeutic procedure.

Of 73 cases, 2 patients of advanced malignancy refused further interventions (one patient of gall bladder malignancy and other of carcinoma of head of pancreas), 3 cases of large common bile duct stone about 2 cm in size on MRCP, underwent open laparotomy and common bile duct exploration and therapeutic ERCP procedures was done in only 69 cases. 8 cases of ERCP developed mild to moderate post ERCP pancreatitis despite using rectal diclofenac 100 mg suppository and they were managed conservatively. Pancreatic plastic stent was placed in 11 cases due to repeated pancreatic duct cannulation, while biliary plastic stent was placed in 63 cases. Self-expanding biliary metal stent was placed in 6 patients, four patients of gall bladder malignancy, one each of periampullary carcinoma and cholangiocarcinoma [ Table 1 ].

Details of therapeutic procedures

In our study, the male-to-female ratio was 0.35:1 [ Table 2 ]. The female patients were more in number as compared to male patients. The age group of the patients ranged from 23 years to 80 years with benign disease while age group from 40 years old to 73 years old patients were found with malignant disease. The most common etiology among benign causes was Choledocholithiasis (95.83%) followed by common bile duct stricture (3.07%), mirrizzi syndrome type 1 (1.53%). The most common malignant causes was carcinoma of gall bladder (62.50%) followed by periampullary cancer (12.5%), cholangiocarcinoma (12.5%), carcinoma of head of pancreas (12.5%). Among the ethnic group, the obstructive jaundice was common among Chettri ethnic group in both benign as well as malignant cause compared with the rest of other ethnic groups. But this difference with other ethnic groups was not found to be statistically significant [ Table 3 ].

Etiology of obstructive jaundice and its correlation with ethnic population of Sikkim

Obstructive jaundice is characterized by presence of jaundice, itching, pain abdomen, vomiting, fever or cholangitis, in some cases depending upon the etiology, weight loss, clay color stool. The treatment and prognosis depends upon the etiology and level of biliary obstruction. The occurrence of the most frequent cholesterol stones is connected with the manner and place of living, nourishment, and sex.[ 8 ] The benign etiology of obstructive jaundice are choledocholithiasis, common bile duct strictures, mirrizzi syndrome, impacted parasites in common bile duct, chronic pancreatitis while the malignant causes are carcinoma gall bladder, carcionoma of pancreas, hilar metastasis, periampullary carcinoma, cholangiocarcionoma.[ 9 ]

This study was done to find out the most common etiology of obstructive jaundice both benign and malignant cause prevalent in the state of Sikkim. This study was also done to guide the primary care physicians to know the commonest etiology of obstructive jaundice in their day-to-day practice and also for early referral to tertiary care center for treatment and management of such patients.

Mangam et al .[ 10 ] concluded in their study that males (54.71%) had more obstructive jaundice compare to females (45.28%). Gill HS et al .[ 11 ] in their study, they found that the incidence of gall stones was more common in female than male. Kotwal et al .[ 12 ] in their study concluded gallstones are common in Sikkim and North Bengal among dyspeptics and majority of these stones were cholesterol stones. The gallstones was more common in females and in patients with normal weight. In our study also female had more common bile duct stones than males. Ahsan Ali Laghari et al .[ 13 ] in their study among 50 patients of Obstructive jaundice, males (62%) were more common than females (38%). Jaundice was the most common presentation and majority of patients had benign etiology 31 patients and 19 patients had malignant etiology of obstructive jaundice.

Björnsson et al .[ 14 ] in their study, they found pancreatic cancer and cholangiocarcinoma were the most common cause of obstructive jaundice. The age group among the malignant obstruction was ranging 61 years to 81 years. Shalini et al .[ 15 ] also found in their study carcinoma of head of pancreas (66.7%) was the most common cause of overall obstructive jaundice and choledocholithiasis (33.3%) was the common cause among benign disease. Lindberg et al .[ 16 ] studied 64 cases of bile duct obstruction and observed gallstones disease in 29 patients, pancreatitis in 1 patient, sclerosing cholangitisin 2 patients, pancreatic carcinoma in 18 patients, bile duct carcinoma in nine patients, and gall bladder carcinoma in five patients. Kajal Kumar Patra et al .[ 17 ] found that the most common age group among obstructive jaundice was between 31 years to 70 years and the most common etiology was choledocholithiasis followed by carcinoma of head of pancreas. However, in our study, the most common etiology was choledocholithiasis while the most common malignant etiology was carcinoma of gall bladder in association with gallstones.

Few studies related to ethnicity and gallbladder disease were done. Comparisons across studies suggest that the highest risk of gallstones occurs among American Indians with progressively lower risk among whites, blacks, and some Asian groups.[ 18 ] Mexican American women also have a higher prevalence of gallstones than U.S. Hispanic women.[ 19 ] In this study, there was no any correlation of ethnicity with obstructive jaundice.

In India, gallbladder carcinoma (GBC) is most prevalent in northern and northeastern states of Uttar Pradesh, Bihar, Orissa, West Bengal, and Assam.[ 20 ] GBC is two times higher in women than men and is the leading digestive cancer in women in northern Indian cities.[ 21 ] Six Cancer registries of the Indian Council of Medical Research (1990–96) show a 10 times lower incidence of GBC per 100 000 in South India compared with the North, the age-adjusted incidence rate for females being 0.8 in Chennai in the south and 8.9 in Delhi in the north.[ 22 ] Gallstones were said to play a major role.[ 23 ] Other risk factors are obesity, multiparity, and chronic infections.[ 24 ]

In this study, the key points to highlight were that the benign cause was more common than malignant cause among obstructive jaundice prevalent in the state of Sikkim. Choledocholithiaisis was the most common etiology among benign etiology and while gall bladder carcinoma was the commonest malignant etiology. Both the conditions require early diagnosis and management of such cases.

Overall the most common etiology of obstructive jaundice was choledocholithiasis while gall bladder carcinoma was the most common malignant cause in Sikkim which lies in the eastern Himalayan region of India. Our study also concluded that there was no any association of ethnicity with obstructive jaundice in the state of Sikkim.

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Carcinoma esophagus with small bowel metastasis: a case report with review of literature

• Case report - Complication
• Published: 27 August 2024

Cite this article

• Vigneshwaran Chandran 1 ,
• Kannan Periasamy   ORCID: orcid.org/0000-0001-7440-0996 1   nAff4 ,
• Lileswar Kaman 2 ,
• Kirti Gupta 3 &
• Uma Nahar 3  

Small intestinal metastasis is extremely rare and only 13 cases have been reported till date and almost all such patients have presented with intestinal obstruction. The 5-year overall survival for metastatic esophageal cancer is as low as 5% while the patients with small intestinal metastasis have a median survival of only 3 months (range 1–12 months) despite undergoing radical resection of the small bowel. We present a case of a male in his 50’s who presented with difficulty in swallowing for 4 months. On evaluation, he was found to have squamous cell carcinoma in the mid thoracic esophagus. He underwent radical chemo-radiation up to 60 Gy in 25 fractions over 5 weeks. One week after completion of treatment he presented with ileal obstruction and omental nodules and surgical resection and evaluation of the respective ileal segment and omental biopsy revealed a metastatic squamous cell carcinoma. The patient expired 3 months post-surgery. Carcinoma esophagus with small bowel metastasis has a very grave prognosis that patients rarely survive beyond 1 year despite undergoing resection. Hence it is imperative to consider a small bowel metastasis when such patients present with clinical features of intestinal obstruction for early diagnosis and aggressive management.

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The patient’s medical file is available in PGIMER, Chandigarh. Dr. Kannan Periasamy has got full access to the medical records of the patient and can be made available on request.

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Kannan Periasamy

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Department of Radiotherapy and Oncology, PGIMER, Chandigarh, India

Vigneshwaran Chandran & Kannan Periasamy

Department of General Surgery, PGIMER, Chandigarh, India

Lileswar Kaman

Department of Histopathology, PGIMER, Chandigarh, India

Kirti Gupta & Uma Nahar

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Chandran, V., Periasamy, K., Kaman, L. et al. Carcinoma esophagus with small bowel metastasis: a case report with review of literature. Int Canc Conf J (2024). https://doi.org/10.1007/s13691-024-00717-y

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• Published: 28 August 2024

Effect of Tiotropium on eye findings in the treatment of chronic obstructive pulmonary disease

• Hayriye Bektaş Aksoy   ORCID: orcid.org/0000-0002-4390-5198 1 &
• Hakan Koç   ORCID: orcid.org/0000-0003-1241-1686 2  

BMC Pulmonary Medicine volume  24 , Article number:  418 ( 2024 ) Cite this article

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Chronic obstructive pulmonary disease (COPD) is a persistent, chronic inflammatory disease of the lungs. Tiotropium, used in the treatment of COPD, is a muscarinic receptor antagonist that provides long-acting bronchodilation. Our study aimed to investigate the effects of Tiotropium on anterior chamber parameters.

The study was conducted as an observational cross-sectional and prospectively between October 2023 and April 2024. Patients were examined in three groups: Group 1 consisted of untreated COPD patients; Group 2 consisted of healthy volunteers similar age and gender, and Group 3 included COPD patients receiving Tiotropium 18 mcg via HandiHaler. Anterior chamber parameters, intraocular pressure values, and photopic-mesopic pupil diameters were measured at the initial visit for Group 1 and Group 2 patients, and at the third month of treatment for Group 3 patients.

Thirty-six patients were included in each group in the study. No significant differences were observed in ocular findings between the patient and control groups. In COPD patients receiving Tiotropium, narrowing of angle parameters, an increase in photopic-mesopic pupil diameters, and intraocular pressure were observed at the third month of treatment.

This study is the first research that investigate the effects of Tiotropium on anterior chamber parameters, pupil diameters, and intraocular pressure in COPD treatment. In conclusion, patients with COPD receiving Tiotropium therapy for three months showed narrowing in angle parameters, an increase in intraocular pressure, and photopic-mesopic pupil diameter; however, no patients developed drug-induced acute angle closure glaucoma.

Trial registration

An independent ethics committee approved the study (Giresun EAH KEAK 2023/180 and 9.10.2023/02) which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice. The study was conducted as prospectively, observational case–control. The Clinical Trial Number obtained for the study is NCT06525051 and was taken on 2024–07-29.

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Introduction

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by persistent obstruction of the airways and chronic respiratory symptoms, often with progressive features [ 1 ]. The basic pathophysiological events in the course of COPD can be defined as airflow limitation, air trapping, changes in lung parenchyma, gas exchange abnormalities, excessive mucus secretion, and vascular changes [ 2 ].

There are five types of muscarinic receptors in the airways (M1-M5). M3 receptors mediate the bronchoconstrictor effect of acetylcholine in the airways. Therefore, antimuscarinic drugs that selectively block M3 receptors are considered ideal agents in the treatment of chronic airway disorders [ 3 ].

Bronchodilator drugs are used initially for pharmacotherapy in COPD. Short-acting bronchodilators are used for rapid symptom relief, while long-acting bronchodilators provide more prolonged symptom control. One of the long-acting bronchodilator drugs is inhaled antimuscarinics and the first member of this drug class is Tiotropium. Inhaled antimuscarinic drugs have been used in the treatment of COPD for many years and have a bronchodilator effect lasting more than 24 h [ 4 ]. Tiotropium reduces exacerbations of the disease and related hospitalizations and improves quality of life by providing effective symptom control.

Inhaled antimuscarinic agents have a broad therapeutic range and are well tolerated [ 5 ]. The most common side effects of Tiotropium include dry mouth, metallic taste in the mouth, and ocular side effects such as visual disturbances, mydriasis, increased intraocular pressure, narrow-angle glaucoma, and cataracts [ 6 ].

This study aims to investigate the effects of Tiotropium, a long-acting bronchodilator used in the treatment of COPD, on anterior chamber parameters.

Materials and methods

The study was conducted as prospectively, observational case–control at the Chest Diseases and Ophthalmology Clinic of Giresun Training and Research Hospital between October 2023 and April 2024 after obtaining local Ethics Committee approval (Giresun EAH KEAK 2023/180 and 9.10.2023/02). The Clinical Trial Number obtained for the study is NCT06525051 and was taken on 2024–07-29. Patients diagnosed with COPD and included in Group A according to the GOLD 2024 guidelines, along with healthy volunteers, were enrolled. Patients diagnosed with COPD, with mMRC scale 0–1, CAT score < 10, who had never experienced an exacerbation before or had a mild severity exacerbation once that not required hospitalization were considered as Group A [ 1 ].

Three groups were formed for the study. Group 1 consisted of COPD patients not receiving treatment, Group 2 consisted of healthy volunteers for similar age and gender, and Group 3 consisted of COPD patients of the same age and gender with receiving Tiotropium 18 mcg Handihaler. Anterior chamber parameters, intraocular pressure values and photopic-mesopic pupil diameters were measured at the initial visit for Group 1 and Group 2 patients, and at the third month of treatment for Group 3 patients.

Patients under 18 years of age, pregnant women, those who did not provide written consent, patients diagnosed with COPD who were using inhaled and/or systemic steroids, those using long-acting inhaled beta-2 agonists alone, and those using combined long-acting beta-2 agonists and long-acting anticholinergics, patients with comorbidities receiving medication (e.g., diabetes mellitus, hypertension), those diagnosed with or suspected of glaucoma, those using topical medication, those with shallow anterior chambers, those had previously undergone eyelid, refractive, or intraocular surgery, those with corneal diseases altering the corneal surface, those using contact lenses, and those with chronic eye diseases were excluded from the study.

Anterior segment optical coherence tomography (AS-OCT) was used to measure anterior chamber and angle parameters, corneal topography was utilized to assess anterior chamber depth, pupil diameter measurements in mesopic and photopic conditions, and intraocular pressure (IOP) was calculated using Goldmann applanation tonometry. Each patient underwent a comprehensive ophthalmic evaluation, including testing of best-corrected visual acuity, slit-lamp biomicroscopy, and fundoscopic examination.

Anterior segment optical coherence tomography (AS-OCT)

Ocular measurements were performed using the AS-OCT device (NIDEK RS-3000, NIDEK Co. Ltd, Japan). All measurements were conducted by the same AS-OCT operator, who was blinded to the treatment. Measurements were obtained for nasal and temporal quadrants (180° and 0° meridians) using the ACA line until adequate centering and quality were achieved.

The width of anterior chamber angle (ACA) was measured by calculating the angle between the posterior corneal angle and the tangent iris line. After manually identifying the apex of the iris recess and scleral protrusion, the width of ACA was analyzed using standard parameters. Angle opening distances (AOD), measured at 750 mm (AOD 750) and 500 mm (AOD 500), were measured as the perpendicular distances from the anterior surface of the iris to the scleral spur at 750 mm and 500 mm, respectively. Trabecular iris space area (TISA) was defined as the trapezoidal area (TISA 750 or 500) limited by the vertical distance between the anterior iris surface, the inner corneo-scleral wall, and the scleral spur, for either AOD 750 or 500 (Fig.  1 ). Intraocular pressure measurements were performed around 10:00 a.m. by the same researcher using the same Goldmann applanation tonometer, without any manipulation of the eyelids or with negligible manipulation. Angle parameters measured with anterior segment OCT were obtained by the same researcher, using the same device, at the same times of day and under similar lighting conditions.

Anterior segment OCT image of angle parameters. ACA Anterior Chamber Angle, TISA Trabecular Iris Space Area, AOD Angle Opening Distance

Corneal topography

Corneal topography (Topcon Aladdin Corneal Topography, Japan) was used to evaluate anterior chamber depth and pupil diameter in mesopic and photopic conditions. Pupil diameters measured with corneal topography were obtained by the same researcher, using the same device, at the same times of day and under similar lighting conditions.

Goldmann applanation tonometry

In addition, intraocular pressure was measured using Goldman Applanation tonometry. All measurements were conducted by the same researcher around 10 a.m., using the same tonometer device, without any manipulation or negligible manipulation of the eyelids. Applanation was performed by rotating the dial on the Goldman tonometer previously set to 10 mm Hg. The procedure was repeated after one minute. If the difference between the first and second readings was greater than 2 mm Hg, a third reading was performed. The average of the data obtained from two readings was taken, and if a third reading was needed, the median was used instead.

Statistical analysis

Statistical analysis was performed using IBM SPSS v23. The normality distribution of quantitative data was assessed using the Shapiro–Wilk test. Independent samples t-test was used for normally distributed quantitative data comparison. The Pearson Chi-square test was used for qualitative data comparison. Data were presented as mean ± SD, minimum—maximum, and n (%). A p -value of < 0.05 was considered statistically significant.

Thirty-six patients were included in each group in the study. Healthy volunteers matched for similar age and gender were included as the control group. There were no significant differences in age and gender between all three groups. The demographic characteristics, smoking status, mMRC score, CAT score, exacerbation history in the last year and spirometry results of COPD patients not using any bronchodilator (Group 1) and those using only Tiotropium (Group 3) are presented in Table  1 . Group 1 consisted of 58.3% ( n  = 21) active smokers, while 52.8% ( n  = 19) of group 3 were ex-smokers. All patients in group 3 had an mMRC score of 1. %47.2 ( n  = 17) of group 1 did not experience any exacerbations of COPD in the last year, whereas all of group 3 experienced one exacerbation in the last year. There were no statistically significant differences observed between group 1 and group 3 in terms of smoking status, CAT score and spirometry findings. In group 3, parameters of mMRC score and COPD exacerbation in the last year were found to be statistically significant (p < 0.001).

No significant differences were observed in ocular findings between COPD patient group and healthy volunteers matched for age and gender (Table  2 ). According to the ocular measurements at the third month, a decrease was observed in ACD, ACA T, ACA N, AOD 500 T, AOD 500 N, AOD 750 T, AOD 750 N, TISA 500 T, TISA 500 N, TISA 750 T and TISA 750 N values, while an increase was observed in photopic diameter, mesopic diameter, and IOP values. Statistically significant differences were observed in ocular measurements between patients receiving Tiotropium therapy (Group-3) and those not receiving any bronchodilator therapy (Group-1) (Table  2 ).

After three months of Tiotropium therapy in patients diagnosed with COPD; narrowing in angle parameters, an increase in photopic-mesopic pupil diameters and intraocular pressure were observed.

Chronic inflammation and hypoxia seen in COPD can lead to ocular changes such as choroidal thinning, thinning of the retinal nerve fiber layer, retinal arterial hypoxia, increased retinal vein diameter, and subfoveal choroidal thickening [ 7 ].

In a study evaluating the effects of anticholinergic drugs in stable COPD, it was reported that accidental application of any anticholinergic drug directly to the eye during inhalation could cause pupil dilation and blurred vision, potentially exacerbating acute glaucoma [ 8 ]. These effects may occur when the drug is administered using a metered-dose inhaler (MDI) with eyes open, a poorly fitting mask with a nebulizer inhaler, or when inhaled in HandiHaler form [ 8 ]. Francis et al. reported a statistically significant increase in intraocular pressure in COPD patients following inhaler Tiotropium therapy [ 9 ]. Similarly, Verma et al. reported an increase in intraocular pressure after inhaled Tiotropium therapy [ 10 ]. In our study, we included healthy volunteers to investigate if HandiHaler Tiotropium has a more pronounced effect on the anterior chamber without influencing anterior chamber parameters, pupil diameter, and IOP in COPD. Tasli et al. reported no statistically significant difference in anterior chamber depth between COPD patients and healthy volunteers in their study comparing anterior segment parameters between the two groups [ 11 ]. In this study, we evaluated not only anterior chamber depth but also all angle parameters (AOD500, AOD750, TISA500, TISA750), anterior chamber angle (ACA N, ACA T), pupil diameters (mesopic, photopic), and intraocular pressure (IOP) between COPD patients not using any bronchodilator (Group 1) and healthy volunteers (Group 2). We found no statistically significant differences in any of these parameters between the two groups. The lack of significant differences in anterior chamber and angle parameters between Group 1 and Group 2 may be attributed to several factors. Patients in Group 1 did not use medications (such as steroids) that could potentially affect eye parameters. Additionally, both groups of patients did not have comorbidities (such as hypertension, diabetes mellitus, or glaucoma) that could lead to pathological findings in the eyes, as per exclusion criteria. These factors likely contributed to the absence of significant differences observed in the eye parameters between the two groups.

A case of unilateral angle closure glaucoma in the right eye of a patient using Tiotropium for COPD was reported by Oksuz et al. They speculated that the shorter axial length and narrower anterior chamber angle in the patient's right eye, as well as the dilation of the pupil caused by the Tiotropium treatment, contributed to the development of angle closure glaucoma. They hypothesized that the reason for the absence of angle closure glaucoma in the left eye was likely due to the wider anterior chamber angle resulting from the patient's previous cataract surgery in the left eye. They also suggested that patients receiving Tiotropium therapy should be warned about the inadvertent exposure of the eyes to Tiotropium dry powder with compromised capsule integrity, which could potentially lead to acute angle closure glaucoma, especially in high-risk individuals [ 12 ].

An analysis of Tiotropium found that neither the HandiHaler nor nebulized forms caused glaucoma development or worsening of preexisting glaucoma when compared to the placebo group [ 13 ]. Another study found that short- and long-acting antimuscarinic drugs (Ipratropium and Tiotropium) in MDI form did not cause a significant increase in intraocular pressure in COPD patients [ 14 ].

In our study, although narrowing in angle parameters, an increase in photopic-mesopic pupil diameter, and intraocular pressure values were observed in COPD patients receiving Tiotropium therapy via HandiHaler, none of the patients developed acute angle closure glaucoma due to the treatment. There were no ocular or systemic side effects potentially leading to discontinuation of the medication were observed in patients receiving Tiotropium therapy. We hypothesize that the increase in both mesopic and photopic pupil diameters could be attributed to anticholinergic effects of Tiotropium. The resulting partial mydriasis may cause peripheral iris crowding into the iridocorneal angle. This tissue crowding could partially obstruct aqueous humor outflow through the trabecular meshwork, leading to angle narrowing and a potential increase in intraocular pressure.

Since patients identified with narrow angles during anterior segment examinations were excluded from our study, the results allow for certain conjectures to be made regarding individuals with narrow angles. The findings suggest that reductions in angle parameters observed in patients using HandiHaler Tiotropium could be particularly clinically significant for those with narrow angles. In patients with narrow angles, HandiHaler Tiotropium may potentially lead to angle closure glaucoma. In patients with glaucoma, HandiHaler Tiotropium should be used cautiously due to its potential to increase intraocular pressure by causing pupil dilation, which can reduce the passage of aqueous humor through the iridocorneal angle. Similarly, when planning intraocular anterior segment surgery, potential changes in angle parameters, intraocular pressure, and pupil diameter due to HandiHaler Tiotropium should be considered.

This study is the first research that investigate the effects of HandiHaler Tiotropium on anterior chamber parameters, pupil diameters, and intraocular pressure in the treatment of COPD. It suggests that prior to commencing Tiotropium treatment for stable COPD, patients should undergo a detailed ophthalmological examination, and particular caution should be exercised in receiving of Tiotropium therapy in patients with narrow anterior chamber angles. Furthermore, due to the risk of exposure to the powdered form of Tiotropium when the capsule integrity is compromised, it should be specifically emphasized to patients that the medication should be used without compromising the capsule integrity.

Limitations of our study include the relatively small sample size, short-term follow-up, and the use of only the HandiHaler form of the drug.

In conclusion, patients receiving Tiotropium therapy via HandiHaler for three months showed narrowing in angle parameters, an increase in intraocular pressure, and photopic-mesopic pupil diameter; however, no patients developed drug-induced acute angle closure glaucoma.

Although acute angle closure glaucoma was not observed in patients using Tiotropium for three months, the changes in angle parameters raise concerns about the careful use of Tiotropium therapy, especially in patients with narrow angles. The reliability of our study could be further supported by larger patient cohorts and more comprehensive studies with longer follow-up periods.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Hayriye Bektaş Aksoy

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HBA: Study concept design, data acquisition/ analysis, manuscript drafting/revision/editing, literature review, statistics. HK: Study concept design, data acquisition/analysis, literature review. All authors have read and agreed to the published version of the manuscript.

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Aksoy, H.B., Koç, H. Effect of Tiotropium on eye findings in the treatment of chronic obstructive pulmonary disease. BMC Pulm Med 24 , 418 (2024). https://doi.org/10.1186/s12890-024-03240-1

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DOI : https://doi.org/10.1186/s12890-024-03240-1

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