National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Safety and efficacy of extended thrombophilia screening directed venous thromboembolic events (VTE) prophylaxis in live liver donors: do we really need extended thrombophilia screening routinely?

Background and aims: The study aimed to determine the prevalence of hereditary thrombophilia, and stratify its severity among live liver donors in Pakistan. Also, the authors evaluated the safety and efficacy of thrombophilia profile testing directed venous thromboembolic events (VTE) prophylaxis while balancing bleeding risk and the need for routine thrombophilia testing before live liver donation among living donor candidates. Materials and methods: Protein S (PS), protein C (PC), anti-thrombin (AT) III, and anti-phospholipid antibody panel (APLA) levels were measured in 567 potential donor candidates. Donors were divided into normal, borderline and high-risk groups based on Caprini score. The safety endpoints were VTE occurrence, bleeding complications or mortality. Results: Among 567 donors, 21 (3.7%) were deficient in protein C, and 14 (2.5%) were deficient in anti-thrombin-III. IgM and IgG. Anti-phospholipids antibodies were positive in 2/567 (0.4%) and 2/567 (0.4%), respectively. IgM and IgG lupus anticoagulant antibodies were positive in 3/567 (0.5%) and 3/567 (0.5%), respectively. VTE events, bleeding complications and postoperative living donors liver transplantation-related complications were comparable among the three donor groups (P>0.05). One donor in the normal donor group developed pulmonary embolism, but none of the donors in either borderline or high-risk group developed VTE. The mean length of ICU and total hospital stay were comparable. No donor mortality was observed in all donor groups. Conclusions: Due to thrombophilia testing directed VTE prophylaxis, VTE events were comparable in normal, borderline and high-risk thrombophilia donor groups, but more evaluations are required to determine the lower safe levels for various thrombophilia parameters including PC, PS and AT-III before surgery among living donor candidates.

Obstacles to the deceased donor transplantation in Pakistan.

INTRODUCTION: Transplantation in many Asian countries is moulded by socioeconomic, religious, cultural and health indicators. In most Asian countries, the living-related donation is the common most organ donation. Due to the limited deceased organ donation, live donor programmes flourished in many Asian countries. Another apparent reason for this tremendous growth of living-related programmes in Asian countries is their larger serving population. Several centres from Asia, including Pakistan and India from Southeast Asia and Egypt in Middle East Asia, on the one hand, have recently emerged as leading living donor transplant programmes. On the other hand, a few Asian countries, including Iran and China, have established some of the world's largest deceased donor programmes. DISCUSSION: In Pakistan, thousands of patients die from end-stage organ failure annually, seeking organ transplants for survival. The exact statics are not available, but over 50 000 people are estimated to die each year as a result of end-stage organ failure without getting a transplant, about 15 000-18 000 from kidney failure, and 10 000 from liver failure and the National Centre for Health Statistics labelled organ failure as a leading cause of death. Despite all these efforts, the knowledge of organ donation among Pakistani people was determined to be around 60%. In Pakistan, the lack of deceased organ donation programmes and the unwillingness of people to deceased organ donation contributes to an increased demand for living organ donation and patients continue to rely on living donors. We discuss various obstacles to deceased organ donation comprising various challenges that form a unique combination, including religious, economic, social, demographic and political factors.Conclusion: Every single effort should be made to initiate and establish multiple deceased donor programmes in Pakistan. Developing the deceased donor programmes in the country will be vital to counter the countrywide increasing organ shortage. The mainstay transplant activities like organ procurement and distribution systems need to be adequately developed. It will help achieve national self-sufficiency and decrease living donors' burden. With education, the behaviour of healthcare professionals and common people can be changed and a positive attitude toward deceased organ donation can be obtained. As healthcare professionals, we should come forward and take responsibility by enrolling ourselves in deceased donors' registration. Public awareness, medical community interest and government support are essential in initiating and establishing deceased donor programmes in Pakistan.

Is a Preservation Solution for Living Donor Liver Transplantation Needed? Adding a New Chapter in LDLT!

Preservation solutions are required for organ viability in deceased donor liver transplantation (LT). However, their role in live donor LT (LDLT) has not been standardized. Methods: Eighty adult recipients who underwent right lobe LDLT at the Department of Liver Transplantation Surgery, Gambat, Pakistan, were studied. Based on shorter cold ischemia time and no back table reconstruction work, recipients were assigned to receive "no preservation solution" (cases/non-histidine-tryptophan-ketoglutarate group; n = 40) or "HTK group" (controls; n = 40). Early allograft dysfunction (bilirubin, transaminases, and international normalized ratio), postoperative complications (biliary and vascular), hospital stay, and 1-y survival were reported. The direct cost was also reported. Results: Demographics and clinical characteristics were comparable in the 2 groups. Comparing cases versus controls, mean bilirubin, alanine aminotransferase, aspartate aminotransferase, and international normalized ratio on postoperative day 7 were similar in the 2 groups. Five (12.5%) cases and 4 (10%) controls developed early allograft dysfunction (P = 0.72). Post-LT complications (biliary leak 2.5% in cases versus 0 in control), strictures (15% in cases versus 17.5% in controls), hepatic artery thrombosis (2.5% versus 00%)' and portal vein thrombosis (0 versus 2.5%) were comparable. Mean hospital stay (10.80 + 2.36 and 11.78 + 2.91 d) and 30 d mortality (2.5% versus 5%) were also comparable. Finally, 1-y survival based on Kaplan-Meier analysis was comparable in both groups (ie, 92.5%; non-HTK group versus 90%; HTK group) (P = 0.71). The direct cost of using a non-HTK-based approach was less than the HTK solution. Conclusion: In a selected cohort of right lobe LDLT recipients, preservation solutions can be avoided safely with comparable outcomes.

Evolving liver transplantation in Pakistan: Future challenges.

Liver transplantation is a life-saving procedure that started in the early 60s. Initially, it struggled with multiple failed attempts but later it progressed and emerged as a gold standard procedure for liver failure secondary to various etiologies. In the first two decades, it faced various challenges like peri and post-operative care management, the quality of graft, optimal immunosuppressant use, and recipient selection criteria. Because of these challenges, the 1-year survival remained below 30% initially. Liver transplantation flourished tremendously over time due to advancements in organ preservation techniques, immunosuppressive therapies, and a better understanding of immunology. The invention of calcineurin inhibitors changed the dynamics of immunosuppressive therapies altogether. The donor organ shortage remains the leading challenge, Deceased donor transplantation activities have not yet started here due to various socio-cultural, and religious resistance. The majority population of the country is underprivileged and faces financial issues to afford the costly liver transplant procedure. The other challenges include the emerging NASH and obesity epidemics. The prevalence of viral hepatitis has not decreased in the country despite advancements in antiviral therapies and vaccine availability against hepatitis B. The local transplant community needs to overcome the limitation of organ supply through various donor expansion approaches. Although it may seem difficult to address all these challenges, still, the transplant community and health authorities need to find an effective way to sort out all these challenges.

ABO incompatible living donor liver transplant with antibody titer of 1:4: First case report from Pakistan.

Introduction and importance: The most common reason for live liver donor rejection is ABO incompatibility. With breaching this incompatibility barrier, probably an additional 25%-35% of liver transplantation (LT) procedures would become possible. Also, ABOi-LT can be lifesaving in acute settings. Initially, ABOi-LT reported a poor prognosis secondary to antibody-mediated rejection (AMR) which is more common in ABOi allograft recipients. AMR may be avoided by desensitization. Various desensitization protocols are practiced globally, however, there is no consensus available on the optimal desensitization protocol for the ABOi-LT. The ABO-incompatible (ABOi) can expand the liver donor pool tremendously. We report the first case of ABO incompatible-liver transplantation (ABOi-LT) from Pakistan. Case presentation: A 48 years old male, presented with decompensated liver diseaseand hepatocellular carcinoma secondary to HCV infection. LT was advised as the optimal modality of treatment. Due to the non-availability of a compatible donor, ABOi-LT was planned.His daughter agreed to donate.Pre-LT desensitization was started on the 23rd-day pre-LT with intravenous (I/V) rituximab 700 mg/body (375 mg/m2) along with I/V Bortezomib 2mg (1.3 mg/m2). Bortezomib was repeated subcutaneously (S/C) on the 20th, 16th, and 13th days pre-LT. One week before LT oral Mycophenolate mofetil 500 mg and Tacrolimus 1 mg were started twice daily. Therapeutic plasmapheresis was done on the 5th, 3rd, and 1st-day pre-LT. Per-operatively, Basiliximab was administeredI/V with a dose of 0.8 gm/kg during the anhepatic phase. Anti-A & Anti-B titer level was determined on the 5th day before plasmapheresis and repeated on the 2nd and 1st-day pre-LT. Then post-LT plasmapheresis was done onthe 15th day and at 3 months. The CD 19 activity was determined one day before LT and on the 15th-day post-LT. His LT was performed uneventfully and was discharged on the 15th postoperative day (POD). However, on the 26th POD, he was diagnosed with left subclavian vein thrombosis which was treated successfully with anticoagulation therapy for 6 months. Till the last follow up patient is doing well. Clinical discussion: Desensitization is the removal of preformed anti-ABO antibodies and depleting serum B cells production. Antibody-mediated rejection irreversibly damages the graft and predisposes it to graft failure. The prognosis of ABOi-LT has dramatically improved since the introduction of desensitization protocols. Conclusion: Antibody-mediated rejection may be avoided by desensitization. The intravascular infusion therapies and splenectomy can be omitted from the desensitization protocol. ABO-i LT can tremendously increase the liver donor pool.

Role of antibiotic prophylaxis on surgical site infection prevention in a low-risk population undergoing laparoscopic cholecystectomy: A randomized controlled study.

Objective: To compare the incidence of surgical site infections (SSIs) in low-risk patients undergoing laparoscopic cholecystectomy (LC) with pre-operative antibiotics versus no pre-operative antibiotics administration. Study design: Randomized controlled study. Setting: Hepatobiliary department, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Pakistan, from Jul 1, 2018, to Jun 30, 2021. Methods: This is a prospective, open-label, randomized study. Individuals scheduled for laparoscopic cholecystectomy who met the inclusion requirements were randomly assigned to two groups. Group A patients received pre-operative antibiotics (intravenous cefazolin 2-g), and group B patients were operated on without administration of pre-operative antibiotics. Post-operatively, patients were studied for the occurrence of SSIs for 30 days. Results: The mean age of patients in group A was 40.6 + 5.2 years, while group B was 41.04 + 5.03. The male to female ratio was 1:3. Gender distribution showed female dominance in both groups, i.e., 78.74% in group A and 76.80% in group B. The incidence of SSI in group A was 3.98%, while in group B was 4.9% (p-value = 0.584). No statistical significance was found while comparing both groups' age, gender, operative duration, and hospital stay. Conclusion: This study showed comparable results between both groups, and prophylactic antibiotics have no impact in preventing SSIs. In low-risk individuals undergoing laparoscopic cholecystectomy, the incidence of SSIs is quite low, and prophylactic antibiotics can be avoided.

Median Arcuate Ligament Compression on Celiac Trunk during Liver Transplantation Procedure.

Low insertion of median arcuate ligament (MAL) can cause compression over the celiac trunk with subsequent complications. During liver transplantation procedure, the graft artery is usually anastomosed with the hepatic artery of the recipient, which arises from the celiac trunk. MAL compression might reduce hepatic arterial blood flow to the graft, which can induce postoperative hepatic arterial thrombosis, causing graft failure. Here, we report a case of liver transplant procedure, during which pulsation of hepatic artery of the recipient diminished dramatically, after ligation of gastro-duodenal artery. However, dissection and division of MAL restored excellent hepatic arterial blood flow. This case highlights the significance of prompt diagnosis and management of MAL compression syndrome in liver transplant recipients during transplant surgery. Key Words: Celiac trunk, Median arcuate ligament, Liver transplant.

Central Pancreatectomy for Solid Pseudopapillary Tumour of Pancreas in A 13-Year Girl.

Solid Pseudopapillary Tumour (SPT) is a very rare tumour of the pancreas. A 13-year girl presented to us with the complaint of upper abdominal pain and non-bilious vomiting for 15 days. Preoperative diagnosis of SPT involving the body of the pancreas was made by CT scan and ultrasound- guided Trucut biopsy. A sparingly rare procedure of central pancreatectomy with distal pancreatico-jejunostomy was performed. This procedure offers excellent results in benign and low-grade malignant pancreatic neck and body tumours. In addition, it preserves functional elements of the pancreas and also eliminates the infective and haematological effects of splenectomy. Key Words: Solid pseudopapillary tumour, Central pancreatectomy, Pancreatic tumours.

Hepatic hemangioendothelioma - A rare case report.

INTRODUCTION AND IMPORTANCE: Hepatic hemangioendothelioma (HHE) is a very rare mild-moderate malignant tumor of the hepatic vascular endothelium. The etiology is yet not fully understood. Patients can be asymptomatic or may present with non-specific symptoms or hepatic insufficiency. CT and MRI scans show various radiographic features but a definitive diagnosis can be made with histological analysis and immunohistochemistry. Here we report a case of a patient who presented with a non-resectable disease for which living donor liver transplantation was done. CASE PRESENTATION: A 19-year-old female patient presented with intermittent moderate dull pain in the right hypochondrium for 9 months. Examination revealed mild tender hepatomegaly. On abdominal ultrasound, two hypoechoic lesions were noted in both lobes of the liver that were confirmed on CT scan. Histologic examination of the ultrasound-guided fine-needle aspiration cytology of the voluminous right lobe lesion clinched the diagnosis of HHE. The patient underwent successful living donor liver transplantation due to the multifocal bi-lobar nature of the lesions. At 8 months follow up, she is fine and doing well. CONCLUSION: HHE is a very rare mild-moderate malignant tumor of hepatic vascular origin. Resection is the preferable treatment option in patients with resectable disease. However, liver transplantation has become the treatment of choice for patients with non-resectable multifocal and bi-lobar lesions. The long-term outcome of this malignancy is not fully known and there is a need for long-term follow-up studies to determine the actual recurrence rate of this disease.

Primary biliary cirrhosis in early childhood - A rare case report.

INTRODUCTION AND IMPORTANCE: Primary biliary cirrhosis (PBC) is a chronic and progressive autoimmune liver disease with no known etiology. This disease is mainly characterized by granulomatous destruction of intrahepatic biliary ducts, severe peri-portal inflammation, and ultimate progress to liver fibrosis and cirrhosis. Here, we report a five-year-old girl diagnosed with PBC, presented to us with end-stage liver disease for liver transplantation. Our patient successfully underwent liver transplantation with an uneventful recovery. This case highlights the need for awareness to report further PBC cases in the pediatric age group. CASE PRESENTATION: A five-year old female child presented with a 6 months history of progressive jaundice. She had multiple admissions for hepatic encephalopathy and this time she was admitted for hepatic transplantation. On examination, she was icteric and had hepatomegaly. After thorough workup, she underwent successful hepatic transplantation and was alright post-operatively. At 6 months follow up, she is doing well. CONCLUSION: PBC is rare in childhood. The natural history and exact incidence of PBC in childhood are not known. Hence, there is a need for awareness to report further PBC cases in the pediatric age group.

Is pancreaticodoudenectomy with vascular resection a safe procedure in developing country? Early outcomes and review of national literature.

INTRODUCTION: Safety of extended lymphadenectomy (EL) ± vascular resection in patients undergoing pancreaticoduodenectomy (PD) in resource limited settings is not well established. The objective of this study was to report outcomes of PD resection with EL ± vascular resection from Pakistan and review national literature. METHODS: Data of patients who underwent PD between 2011 and 2014 was reviewed. A total of 66 patients were included in the study. Primary outcome was 90 day morbidity and mortality. Secondary objective was 2 year overall survival. RESULTS: Median age was 57 (32-82) years. Majority patients had locally advanced (pT3/T4) tumors and nodal involvement i.e. 44 (71%) and 42 (67.8%). Mean number of excised lymph nodes and positive lymph nodes was 28.2 ± 12.8 (range 3-62) and 4.8 ± 6.9 (range 0-27) respectively. There were 13 vascular resections including 3 arterial resections. Overall 90 day morbidity was 31.8% and mortality was 3%. No difference in complication rate was observed in patients who did and did not undergo vascular resection i.e. 18% versus 34.5% (P = 0.1). Similarly, median survival was 11 (3-24) months and 11 (1-36) months and not significantly different (P = 0.5). CONCLUSION: In developing countries, extended lymphadenectomy with vascular resection can be safely performed with pancreaticoduodenectomy in specialized hepatobiliary units.