Anesthesia Aspects of Multivisceral Transplantation: A Case Series Study.

Background: Multi-visceral transplantation (MvTx) usually refers to the transplantation of more than three intra-abdominal organs. A successful MvTx requires strong multidisciplinary teamwork of transplant surgeons, anesthesiologists, and intensivists. Case presentation: We present five cases of MvTx with a history of short bowel syndrome admitted to the Abu-Ali Sina Hospital, Shiraz, Iran from May 2019 to January 2020 and describe anesthetic considerations in MvTx. Subjects were identified (4F/1M) with a mean age of 43 years old (range 35-51). The most frequent cause of intestinal failure was portal vein thrombosis, followed by bowel gangrene and short bowel syndrome. The mean ±SD duration of the operation was 360±60 min. The bleeding volume was approximately 2600±1474 cc, and 4±1 bags of packed red blood cells were transfused. Sepsis was the main cause of death in our series. Conclusion: Careful preoperative planning, vigilant intraoperative anesthetic management, and prevention of postoperative infection are imperative to achieve the best outcomes.

Liver Transplantation in Hepatocellular Carcinoma: Experiences from the Shiraz Transplant Center.

BACKGROUND: Studies evaluating liver transplantation (LT) in hepatocellular carcinoma (HCC) in the Middle East have been scarce, mainly due to intricacy of this type of surgery. OBJECTIVE: In here we report our experiences with LT among patients with HCC cirrhosis.Methods: All patients who underwent LT with primary diagnosis of HCC older than 18 years old, during 2004 to 2019, were initially included in our study. RESULTS: Overall, 124 patients entered our study, among which majority were males (86.3%). Mean (SD) age of patients was 53.1±10.6 years old. Most common underlying liver diseases were HBV (55.6%) and HCV infections (12.1%). Mean MELD score of patients was 18±5.5. Child-Pugh score of most patients was class B (50%). Mean (SD) duration of hospitalization was 12.1±3.5 days. Patients were followed for a median of 32 (9, 62) months. The most common causes of death were recurrence of HCC (47.7%) and sepsis (34.1%). Median (IQR) duration to recurrence and death were 18 (4, 34) months and 17.5 (5.7, 44.5) months, respectively. One-year survival (89%, 86.4%, and 63.2%, respectively) (p=0.011) and one-year DFS (89%, 86.4%, and 57.9%, respectively) (p=0.001) was significant different between those who were selected based on the Milan, UCSF and extended criteria. CONCLUSION: Our study provides valuable experiences on LT and HCC from one of the largest LT centers in the world. Accordingly, we found that the Milan criterion provides the best survival compared to the UCSF and our extended criteria for patient selection.

Effects of Different Cold Preservation Solutions on the Functions of Cultured Isolated Human Hepatocytes.

BACKGROUND: Hepatocyte transplantation using isolated human hepatocytes is an alternative source that can be used for the treatment of metabolic diseases and acute liver failure as a time bridge to liver transplantation. These cells can also be used for bioartificial liver systems and in vitro study of drug toxicity. OBJECTIVE: To determine which cold preservation solution is better maintain the liver function. METHODS: We prepared 4 cold preservation solutions made of different combination of antioxidants, chelating, membrane protective, and anti-apoptotic agents as well as inhibitor of cyclophilin D. For hepatocyte isolation, we used livers obtained from unused deceased donor livers and the liver of patients with Crigler-Najjar syndrome who were candidates of partial liver transplantation. After culture and cold preservation, the level of albumin, and urea production were measured as indices of liver functionality. RESULTS: We found that albumin production significantly decreased after cold preservation in solution 1. There was no significant difference in urea production after cold preservation in solution 1 compared with control 24 h. No significant differences in albumin production were found after cold storage in solution 2 and solution 4 compared with control 24 h. Urea production significantly decreased after cold storage in solutions 2 and 4 compared with control 24 h. As a whole albumin and urea production were significantly decreased after cold preservation. Although albumin and urea production were decreased after cold preservation, but the results of albumin production of two solutions were not significantly different from that of the control group (p=0.109 and 0.951). CONCLUSION: Cold preservation of cultured human hepatocytes in solution 2 and solution 4 could maintain the function of albumin production better than other cold preservation solutions in our experiments; solution 1 was more effective on urea production of cultured human hepatocytes at 4 °C for 24 h. To determine if these hepatocytes are suitable candidates for transplantation, further studies should be performed.

Donors' Quality of Life after Living Donor Liver Transplantation: Shiraz Organ Transplant Center Experience.

BACKGROUND: Probable effects of living donor liver transplantation on the wellbeing of the donor and psychological difficulties are necessary to be understood. OBJECTIVE: To assess the quality of life of living donors after liver donation. METHODS: 140 living donors who underwent hepatectomy between 2012 and July 2015 were enrolled in this study. Donors were asked to complete the Short Form 36-question Health Survey (SF-36) through face to face or by telephone interview. RESULTS: The mean±SD age of donors at transplantation was 32.1±7.3 years; 83 (59.3%) of donors were female. 134 (95.7%) were married. The mean±SD BMI was 23.8±3.5 (kg/m2). "Mother-to-child" was the most frequent relationship (n=79, 56.4%). 22 (15.7%) complications were reported by participants. The mean±SD score of Physical Component Summary and Mental Component Summary were 48.8±14.6 and 50.1±6.9, respectively. CONCLUSION: Most living donors sustain a near average quality of life post-donation. It seems that living donation does not negatively affect the quality of life.

The Effects of Cold Preservation Solutions Supplemented with UDCA and α-Lipoic Acid on the Viability and Function of Isolated Human Hepatocytes.

BACKGROUND: Liver transplantation is the only treatment for end-stage and genetic liver diseases. The main burden of this treatment is the shortage of both living and cadaveric liver donors. An alternative treatment is using liver cell transplantation, which can be obtained from unused livers for transplantation. These hepatocytes should be kept ready in viable and functional situation in a frozen state to be instantly used when they would be needed. In our previous experience, we had isolated hepatocytes from unused livers. OBJECTIVE: To find a preserving solution for increasing viability and function of the isolated hepatocytes that are stored to be transplanted. METHODS: 9 cadaveric donor livers, which were not used for transplantation due to various causes such as severe steatosis, were selected to isolate hepatocytes. Various cold storage solutions were tried to find the best temperature for more viability and functionality for preservation of hepatocytes. University of Wisconsin (UW) solution and Williams E media were used as control media. 2 anti-apoptotic and anti-oxidative solutions, i.e., α-lipoic acid and ursodeoxycholic acid (UDCA), were used as cold preservatives solutions. The numbers of viable hepatocytes were estimated by trypan blue method; the functionality was assessed by the cells ability to produce urea. RESULTS: The highest number of viable and functional hepatocytes was obtained from freshly isolated cells. However, after preservation, the number of these viable hepatocytes and their functionality were not significantly different in cold storage solutions comparing to the control media used. Functionality of the isolated hepatocytes stored in UW with and without UCDA solution was similar to freshly isolated hepatocytes. CONCLUSION: Preservatives with anti-apoptotic and antioxidant activity could not increase the number of viable hepatocytes. Functionality of cold storing hepatocytes could be preserved similar to freshly isolated hepatocytes by UW solution with and without UCDA.

Ex-vivo Resection and Small-Bowel Auto-transplantation for the Treatment of Tumors at the Root of the Mesentery.

BACKGROUND: Tumors involving the root of the mesentery are generally regarded as "unresectable" with conventional surgical techniques. Resection with conventional surgery may end in life-threatening complications in these patients. Ex-vivo resection and auto-transplantation avoids excessive bleeding and prevents ischemic related damage to the small intestine and other organs. OBJECTIVE: To share our experience of ex-vivo resection of the tumors with involvement of small bowel mesentery followed by small bowel auto-transplantation. METHODS: In this study, medical records of all the patients who underwent ex-vivo resection and auto-transplantation at our center were retrospectively analyzed. RESULTS: The most common indication for the procedure in our series was locally advanced pancreatic carcinoma. Our survival rate was 50% with a mean±SD follow-up of 10.1±9.8 (range: 0-26) months. Causes of early in-hospital mortality were multi-organ failure, sepsis, and cerebrovascular accident. Recurrence of disease was noted in one patient while one patient developed hepatic metastasis after 20 months of surgery. CONCLUSION: Ex-vivo resection of the tumor and auto-transplantation is the surgical treatment of choice for the locally advanced abdominal tumors involving the root of the mesentery.

Multivisceral and small bowel transplantation at shiraz organ transplant center.

BACKGROUND: Multivisceral transplantations were initially done in animal models to understand the immunological effects. Later on, in human beings, it has been considered a salvage procedure for unresectable complex abdominal malignancies. With advancement in surgical techniques, availability of better immunosuppressive drugs, and development of better post-operative management protocols, outcomes have been improved after these complex surgical procedures. OBJECTIVE: To analyze and report results of multivisceral, modified multivisceral, and small bowel transplantations done at Shiraz Organ Transplant Center, Shiraz, southern Iran. METHODS: Medical records of all patients who underwent multivisceral, modified multivisceral, and small bowel transplants were retrospectively analyzed. RESULTS: There were 18 patients. The most common indications for the procedure in our series were unresectable carcinoma of pancreas followed by short bowel syndrome. 10 patients were alive after a median follow-up of 8.7 (range: 3-32) months. The remaining 8 patients died post-operatively, mostly from septicemia. CONCLUSION: Multivisceral and small bowel transplantations are promising treatments for complex abdominal pathologies.

Multivisceral transplantation for the treatment of intra-abdominal tumors.

BACKGROUND: Some intra-abdominal or retroperitoneal tumors such as low-grade slow-growing malignancies may seem unresectable due to major vessel encasement or presence of intra-abdominal dissemination, but the slow growth rate and to some extent long life expectancy of the patients urge us to find some strategies to cure the patients or at least achieve tumor remission or symptom palliation. En bloc resection, followed by multivisceral or liver-sparing "modified" multivisceral transplantation has recently been used for treatment of these patients. RESULTS: Between May 2010 and October 2012, 3 multivisceral and 3 modified multivisceral transplantations were performed in 6 patients (aged 14 to 55 years; mean, 32 years) with some slow growing intra-abdominal malignancies (2 neuroendocrine tumors, 2 gastrointestinal stromal tumors, 1 desmoid tumor, and 1 low-grade sarcoma). All patients survived the procedure. One patient died of pancytopenia 2 months after transplantation and another died with pulmonary emboli at 4 months. The remaining 4 patients are alive without any evidence of disease recurrence. CONCLUSIONS: Although large intra-abdominal desmoid tumors, well-differentiated neuroendocrine tumors, and gastrointestinal stromal tumors are slow growing, they tend to invade locally, especially to the mesenteric root and/or celiac axis and other abdominal viscera. Complete resection followed by multivisceral transplantation could be a therapeutic option for these advanced tumors.

Liver transplantation in the presence of old portal vein thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) has been mentioned as a potential obstacle to liver transplantation (LTx). OBJECTIVE: To review the impact of PVT on orthotopic liver transplant (OLT) outcome. METHOD: Between January 2006 and April 2009, 440 OLT were performed in Shiraz Transplant Unit of whom, 35 (7.9%) cases had old PVT with recanalization. Data were retrospectively collected regarding the demographics, indication for OLT, Child-Turgot-Pugh classification, pre-transplant diagnosis of PVT, perioperative course and managements, relapse of PVT, early post-operative mortality and morbidity. All patients received liver from deceased donors, underwent thrombendvenectomy with end-to-end anastomosis without interposition graft and evaluated daily for 5 days and thereafter, biweekly by duplex sonography during the follow-up period for 2 months. They were treated by therapeutic doses of heparin followed by warfarin to maintain an INR of 2-2.5. RESULTS: The causes of end-stage liver disease were hepatitis B in 11, cryptogenic cirrhosis in 11, primary sclerosing cholangitis in 5 and other causes in 8 recipients. Extension of thrombosis was through confluence of superior mesenteric and splenic vein in 32 and to superior mesenteric vein in 3 patients. The mean±SD operation time was 7.2±1.5 hrs. The mean±SD transfusion requirement was 5.4±2.8 units of packed cells. The mean±SD duration of hospital stay in these patients was 17.7±10.9 days. Eight patients died; 1 developed early in-hospital PVT, 1 had hepatic vein thrombosis, and 1 died of in-hospital ischemic cerebrovascular accident, despite a full anticoagulant therapy. The mean±SD follow-up period for those 28 patients discharged from hospital was 16.6±7.9 months; none of them developed relapse of PVT. The overall mortality and morbidity was 28% and 32%, respectively. There was no relapse of PVT in the other patients. CONCLUSION: The presence of PVT at the time of OLT is not a contraindication for the operation but those with PVT have a more difficult surgery, develop more postoperative complications, and experience a higher in-hospital mortality.

Transperitoneal laparoscopic living donor nephrectomy: 2 years' experience.

BACKGROUND: Due to the shortage of organ donations and the rising number of patients with terminal renal insufficiency, living donor kidney donation has become increasingly important during recent years. Hand-assisted laparoscopic living donor nephrectomy (LLDN) is an alternative to the conventional open approach and may decrease the surgical trauma to the donor. The aim of this study was to report our experience with this technique. MATERIALS AND METHODS: We reviewed demographic data, operative duration, hospital stay, and postoperative complications among 100 LLDNs performed from August 2006 to July 2008. We also performed a retrospective analysis of chemical and biochemical data of recipients. RESULTS: Thirty female and 70 male subjects of mean age of 35.88 +/- 12.21 years were operated on during this period. The mean operative time for donor nephrectomy was 138.30 +/- 31.92 minutes (range 60-205) and for recipients, 87.66 +/- 11.79 minutes (range = 75-120), with a mean warm ischemia time of 5.19 +/- 1.76 minutes (range = 2-8). The donors' mean hospital stay was 28.34 +/- 8.31 hours (range = 24-72). Five donor operations were converted to open nephrectomy because of uncontrolled bleeding or abnormal anatomy. There was no need for blood transfusions or reoperations in the donors. Mean hospital stay for the recipients was 9.44 +/- 3.61 days (range = 5-22). Creatinine and blood urea nitrogen decreased from preoperative values of 10.46 +/- 3.73 and 66.10 +/- 25.16 to 1.39 +/- 0.38 and 29.64 +/- 8.83 mg/dL at discharge. The renal graft was rejected in two cases due to immunologic causes without any response to therapy. There was no vascular thrombosis in the transplanted kidneys. CONCLUSION: LLDN is a viable alternative to the standard open nephrectomy. It may have a positive impact on the donor pool by minimizing disincentives to living donation. The results of our program were acceptable; this approach may be the procedure of choice in the future in our center.

Liver transplantation for homozygous familial hypercholesterolemia: two case reports.

Homozygous familial hypercholesterolemia (HFHC) is a rare inherited condition with an incidence of one in one million. It is associated with severe premature atherosclerosis and early death from cardiovascular complications. Mutation in the gene that encodes the synthesis of the cellular receptor for low-density lipoprotein (LDL) is responsible for this metabolic disorder. Currently, the only effective treatment for this disease is liver transplantation, which alone or in association with medications, normalizes plasma cholesterol level. The authors report the results of liver transplantation for two cases of HFHC. The first case, a 15-year-old boy received a whole liver from a deceased donor, and the second, an 11-year-old boy, received a left liver lobe transplant from his mother's sister. Their preoperative fasting lipid concentrations were grossly raised. The older boy had severe atherosclerotic heart disease and had undergone coronary artery bypass grafting 5 months before transplantation. Both had preoperative plasma cholesterol levels higher than 750 mg/dL with normal thyroid and liver function tests. After the operation, the patients received methylprednisolone as pulse therapy followed by oral prednisolone, mycophenolate mofetil, and tacrolimus for immunosuppression. Their hospital stays were 24 and 13 days, respectively. The first case needed reexploration because of bleeding on the second day after the operation. The lipid concentrations rapidly returned to the normal range in the first week after the operation, remaining in this range over the first 6 months of follow-up. Liver transplantation offers an highly effective treatment for HFHC. It is better to operate on patients before severe atherosclerotic changes in the coronary arteries. All patients must undergo a complete cardiac evaluation before surgery.