The landscape of etiological patterns of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in Thailand.

Thailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER-LC consortium-based population study covering all high-incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011-2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history. Multivariate logistic regression and Cox proportional hazards analyses were used to evaluate risk factors and associated survival patterns. Our models identified shared risk factors between HCC and iCCA, such as viral hepatitis infection, liver fluke infection, and diabetes, including novel and shared associations of agricultural pesticide exposure (OR range of 1.50; 95% CI: 1.06-2.11 to 2.91; 95% CI: 1.82-4.63) along with vulnerable sources of drinking water. Most patients had multiple risk factors, magnifying their risk considerably. Patients with lower risk levels had better survival in both HCC (HR 0.78; 95% CI: 0.64-0.96) and iCCA (HR 0.84; 95% CI: 0.70-0.99). Risk factor co-exposures and their common associations with HCC and iCCA in Thailand emphasize the importance for future prevention and control measures, especially in its large agricultural sector. The observed mortality patterns suggest ways to stratify patients for anticipated survivorship and develop plans to support medical care of longer-term survivors, including behavioral changes to reduce exposures.

Pan-viral serology uncovers distinct virome patterns as risk predictors of hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

This study evaluates the pan-serological profiles of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) compared to several diseased and non-diseased control populations to identify risk factors and biomarkers of liver cancer. We used phage immunoprecipitation sequencing, an anti-viral antibody screening method using a synthetic-phage-displayed human virome epitope library, to screen patient serum samples for exposure to over 1,280 strains of pathogenic and non-pathogenic viruses. Using machine learning methods to develop an HCC or iCCA viral score, we discovered that both viral scores were positively associated with several liver function markers in two separate at-risk populations independent of viral hepatitis status. The HCC score predicted all-cause mortality over 8 years in patients with chronic liver disease at risk of HCC, while the viral hepatitis status was not predictive of survival. These results suggest that non-hepatitis viral infections may contribute to HCC and iCCA development and could be biomarkers in at-risk populations.

Gut dysbiosis in Thai intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

Primary liver cancer (PLC), which includes intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC), has the highest incidence of all cancer types in Thailand. Known etiological factors, such as viral hepatitis and chronic liver disease do not fully account for the country's unusually high incidence. However, the gut-liver axis, which contributes to carcinogenesis and disease progression, is influenced by the gut microbiome. To investigate this relationship, fecal matter from 44 Thai PLC patients and 76 healthy controls were subjected to whole-genome metagenomic shotgun sequencing and then analyzed by marker gene-based and assembly based methods. Results revealed greater gut microbiome heterogeneity in iCCA compared to HCC and healthy controls. Two Veillonella species were found to be more abundant in iCCA samples and could distinguish iCCA from HCC and healthy controls. Conversely, Ruminococcus gnavus was depleted in iCCA patients and could distinguish HCC from iCCA samples. High Veillonella genus counts in the iCCA group were associated with enriched amino acid biosynthesis and glycolysis pathways, while enriched phospholipid and thiamine metabolism pathways characterized the HCC group with high Blautia genus counts. These findings reveal distinct landscapes of gut dysbiosis among Thai iCCA and HCC patients and warrant further investigation as potential biomarkers.

Outcomes of the Initial Phase of an Adult Living vs Deceased Donor Liver Transplantation Program in a Low-Volume Transplant Center: Integration of Hepatobiliary and Transplant Surgery.

BACKGROUND: The development of living donor liver transplantation (LDLT) is clinically challenging, especially in a low-volume transplant program. We evaluated the short-term outcomes of LDLT and deceased donor liver transplantation (DDLT) to demonstrate the feasibility of performing LDLT in a low-volume transplant and/or high-volume complex hepatobiliary surgery program during the initial phase. MATERIAL AND METHODS: We conducted a retrospective study of LDLT and DDLT in Chiang Mai University Hospital from October 2014 to April 2020. Postoperative complications and 1-year survival were compared between the 2 groups. RESULTS: Forty patients who underwent LT in our hospital were analyzed. There were 20 LDLT patients and 20 DDLT patients. The operative time and hospital stay were significantly longer in the LDLT group than in the DDLT group. The incidence of complications in both groups was comparable, except for biliary complications, which were higher in the LDLT group. Bile leakage, found in 3 patients (15%), is the most common complication in a donor. The 1-year survival rates of both groups were also comparable. CONCLUSION: Even during the initial phase of the low-volume transplant program, LDLT and DDLT had comparable perioperative outcomes. Surgical expertise in complex hepatobiliary surgery is necessary to facilitate effective LDLT, potentially increasing case volumes and promoting program sustainability.

Efficacy of intravenous versus intraperitoneal lidocaine for postoperative analgesia in laparoscopic cholecystectomy: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Laparoscopic cholecystectomy (LC) has become the gold standard for gallbladder removal due to the low degree of invasiveness. However, postoperative pain still persists. Local anesthetics provide analgesia, reduce opioid consumption, and accelerate the return of bowel activity with a rare incidence of toxicity. However, it is still inconclusive to verify the more superior route of administration. This study aimed to compare the efficacy of intravenous lidocaine infusion, intraperitoneal lidocaine instillation, and placebo in reducing postoperative analgesia. METHODS: In this prospective, randomized, double-blind, placebo-controlled trial, the participants were randomized into three groups; intravenous lidocaine infusion (IV group), intraperitoneal lidocaine instillation (IP group), and control. The primary outcome was opioid consumption and secondary outcomes were side effects and recovery profiles. RESULTS: Opioid consumption at 2, 4, and 6 postoperative hours was statistically lower in IV group compared to the IP and control group (P<0.05). VAS for abdominal pain (VAS(abd) at 6, 12, and 24 hours were reduced in both IV and IP groups compared to the control group. However, VAS at incision site (VAS(inc) were not different amongst all three groups. Number of patients who met the discharge criteria within six hours after surgery was significantly higher in the IV group (P=0.028). CONCLUSIONS: Intravenous lidocaine is superior to intraperitoneal lidocaine instillation and placebo in reducing postoperative analgesic requirement and visceral pain within the first six hours. Intravenous infusion is a simple and reliable method for reducing abdominal pain following laparoscopic cholecystectomy.

Comparative outcomes of pure laparoscopic and open donor right hepatectomy: the first report from a Southeast Asian transplant center.

BACKGROUND: Pure laparoscopic donor right hepatectomy (PLDRH) can provide better operative outcomes for the donor than conventional open donor right hepatectomy (CODRH). However, the complexity of the procedure typically makes transplant teams reluctant to perform it, especially in low-volume transplant centers. We compared the outcomes of PLDRH and CODRH to demonstrate the feasibility of PLDRH in a low-volume transplant program. METHODS: We carried out a retrospective study of adult living donor liver transplantation in Chiang Mai University Hospital from January 2015 to March 2021. The patients were divided into a PLDRH group and a CODRH group. Baseline characteristics, operative parameters, and postoperative complications of donors and recipients were compared between the two groups. RESULTS: Thirty patients underwent donor hepatectomy between the dates selected (9 PLDRH patients and 21 CODRH patients). The baseline characteristics of the 2 groups were not significantly different. The median graft volume of the PLDRH group was 693.8 mL, which was not significantly different from that of the CODRH group (726.5 mL) The PLDRH group had a longer operative time than the CODRH group, but the difference was not statistically significant (487.5 min vs 425.0 min, p = 0.197). The overall complication rate was not significantly different between the two groups (33.3% vs 22.2%, p = 0.555). Additionally, for the recipients, the incidence of major complications was not significantly different between the groups (71.3 vs 55.6%, p = 0.792). CONCLUSION: Even in the context of this low-volume transplant program, whose staff have a high level of experience in minimally invasive hepatobiliary surgery, PLDRH showed similar results to CODRH in terms of perioperative outcomes for donors and recipients.

Efficacy and safety of infrahepatic inferior vena cava clamping under controlled central venous pressure for reducing blood loss during hepatectomy: A randomized controlled trial.

BACKGROUND: The purpose of this study was to evaluate the effectiveness and safety of inferior vena cava (IVC) clamping for reducing blood loss during hepatectomy. METHODS: In total, 120 elective hepatectomy patients who underwent surgery from May 2016 to October 2017 were enrolled and randomized into the IVC clamping group or nonclamping group. Both groups were managed by anesthesiological techniques for CVP reduction. Blood loss and clinical parameters were analyzed for 30 days after surgery. RESULTS: Fifty-nine patients were assigned to the IVC clamping group and 61 to the non-IVC clamping group. There was a significant difference in the total blood loss between both groups, with less blood loss observed in the IVC clamping group [500 vs 600 mL, P = .006]. The transection blood loss in the IVC clamping group was also significantly lower than that in the non-IVC clamping group [300 vs 500 mL, P < .001]. However, CVP was not associated with blood loss volume. Postoperative outcomes were not significant in either group. CONCLUSIONS: IVC clamping is beneficial for reducing blood loss during hepatectomy and is safe when combined with anesthesiological techniques. If feasible, this technique should be used regardless of the CVP value.

The benefit of curative liver resection with a selective bile duct preserving approach for hepatocellular carcinoma with macroscopic bile duct tumor thrombus.

BACKGROUND: Hepatocellular carcinoma (HCC) presenting with macroscopic bile duct tumor thrombus (BDTT) is an uncommon event. The role of a curative hepatic resection and associated long-term outcomes remain controversial. In addition the necessity for bile duct resection is still unclear. The aim of this study was to evaluate outcomes of hepatectomy with a selective bile duct preservation approach for HCC with BDTT in comparison to outcomes without BDTT. METHODS: A total of 22 HCC with BDTT patients who had undergone curative hepatic resection with a selective bile duct preservation approach at our institute were retrospectively reviewed. These were compared to group of 145 HCC without BDTT patients. The impact of curative surgical resection and BDTT on clinical outcomes and survival after surgical resection were analyzed. RESULTS: All HCC with BDTT cases underwent major hepatectomy vs. 32.4% in the comparative group. Bile duct preservation rate was 56.5%. The 1-, 3- and 5-year survival rates of HCC with BDTT patients in comparison to the HCC without BDTT group were 81.8%, 52.8% and 52.8% vs. 73.6%, 55.6% and 40.7% (P=0.804) respectively. Positive resection margin, tumor size ≥5 cm and AFP ≥200 IU/mL were significant risk factors regarding overall survival. However, it is unclear whether presence of a bile duct tumor thrombus has an adverse impact on either recurrence free survival or overall survival. CONCLUSIONS: Bile duct obstruction from tumor thrombus did not necessarily indicate an advanced form of disease. Tumor size and AFP had greater impact on long-term outcomes than bile duct tumor thrombus. Major liver resection with a selective bile duct preserving approach in HCC with BDTT can achieve favorable outcomes comparable to those of HCC without BDTT in selected patients.

Adult-to-Adult Living Donor Liver Transplantation: Postoperative Outcomes and Quality of Life in Liver Donors: First Report in Thailand.

BACKGROUND: Deceased donor liver transplantation is a rare procedure in Northern Thailand because of cultural issues. Living donor liver transplantation (LDLT) can decrease waiting list mortality for the patients who have end-stage liver disease. In Thailand, our center is the only active adult-to-adult LDLT program. This study is the first report of outcomes and health-related quality of life in liver donors. OBJECTIVES: The aim of this study was to evaluate the postoperative outcomes and health related quality of life in living liver transplant donors at the Transplant Center in Thailand. MATERIALS AND METHODS: All patients undergoing liver resection for adult-to-adult LDLT at our center between March 2010 and July 2018 were evaluated in a cross-sectional study. The effect of donor demographics, operative details, postoperative complications (Clavien-Dindo classification), hospitalization, and health related quality of life was evaluated through health-related quality of life questionnaires (short-form survey, SF-36) RESULTS: A total of 14 donor patients were included in this study with an age range from 26 to 51 years (mean 39.86 years, standard deviation [SD] = 8.59 years). The patients were 71.43% female and 28.57% male. The majority of patients had primary and secondary education (57.14%) and were married (64.29%). After hepatectomy, there was no mortality in the evaluated donors. The Clavien-Dindo classification of postoperative complications were as follows: Grade I (none), Grade II (50%), Grade IIIa (7.14%), and Grade IIIb (7.14%). The serum levels of total protein and albumin were decreased on postoperative day 5. The hospital stays averaged 11.5 days (SD = 4.9 days) and ranged from 5 to 22 days. After considering each aspect of the donors' postoperative quality of life, the highest mean score was related to physical composite scores in physical roles with a mean of 96.42 (SD = 13.36) and physical function with a mean of 95.35 (SD = 13.36). Moreover, the mental composite scores in social function was the highest mean of 91.96 (SD = 12.60) and role emotion was a mean of 90.47 (SD = 27.51). CONCLUSIONS: Living donor hepatectomy was safe, with an acceptable morbidity, and recognized as a safe procedure with an excellent long-term health quality of life.

Price to pay; Portal vein arterialization for hepatic artery thrombosis after living donor liver transplantation; A case report.

OBJECTIVE: Hepatic artery thrombosis (HAT) is one of the most serious complications of liver transplantation that can potentially lead to loss of the allograft. Retransplantation is the only option when revascularization can't be performed but the donor may be not available in the short period of time. We report the technique of using portal vein arterialization (PVA) for bridging before retransplantation. There are few reports in living donor setting. CASE DESCRIPTION: The recipient of the liver was a 59 year old male who received an extended right lobe graft from his son. Post operative day 41, HAT was diagnosed from angiogram and liver function got rapidly worse. We decided to re-anastomose the hepatic artery but this was not possible due to a thrombosis in the distal right hepatic artery. So PVA by anastomosis of the common hepatic artery to splenic vein was performed. During the early postoperative period liver function gradually improved. Unfortunately, he died from massive GI hemorrhage one month later. DISCUSSION: PVA has previously been reported as being useful when revascularization was not successful. The surgical technique is not complicated and can be performed in sick patient. Liver graft may be salvaged with oxygenated portal flow and recover afterwards. However, portal hypertension after PVA seem to be an inevitable complication. CONCLUSIONS: PVA may be a bridging treatment for retransplantation in patients whom hepatic artery reconstruction is impossible after HAT. Regards to the high morbidity after procedure, retransplantation should be performed as definite treatment as soon as possible.

Lacerated Liver Graft in an Open Abdomen Setting: A Case Report.

Donor scarcity is a primary problem in the development of a transplant program. The imbalance between an extremely increasing demand and the number of organs in the supply has led to an extended criteria donor approach. The successful use of donors with infectious diseases and septic shock has been reported. However, organs from deceased donors with traumatic abdominal injury and open abdomen are usually discarded due to risks of severe infections. Thus far, only 1 such case, in which a liver graft from an open abdomen was used successfully, has been reported. Herein, we report of a case of liver transplant using a traumatized liver allograft procured from a deceased donor with an open abdomen. The donor was a 16-year-old patient who had blunt abdominal trauma and severe head injury from a car accident, resulting in emergency laparotomy with suturing of the lacerated wound at the liver and abdominal packing. The donor was subsequently pronounced brain dead, and the family consented to organ donation. A multiorgan procurement was performed, and the liver was transplanted to 52-year-old patient who had multiple hepatocellular carcinomas. The postoperative course was without any infection or rejection. In conclusion, the use of donor livers with preexisting trauma in open abdomen settings can be used as alternative to expand the organ donor pool.

Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integration of genomics, transcriptomics, and metabolomics. While ICC and HCC share recurrently mutated genes, including TP53, ARID1A, and ARID2, mitotic checkpoint anomalies distinguish the C1 subtype with key drivers PLK1 and ECT2, whereas the C2 subtype is linked to obesity, T cell infiltration, and bile acid metabolism. These molecular subtypes are found in 582 Asian, but less so in 265 Caucasian patients. Thus, Asian ICC and HCC, while clinically treated as separate entities, share common molecular subtypes with similar actionable drivers to improve precision therapy.

A single institution report of 19 hepatocellular carcinoma patients with bile duct tumor thrombus.

BACKGROUND: Obstructive jaundice caused due to bile duct tumor thrombus (BDTT) in a hepatocellular carcinoma (HCC) patient is an uncommon event. This study reports our clinical experiences and evaluates the outcomes of HCC patients with BDTT in a single institution. METHODS: A retrospective review of 19 HCC patients with secondary obstructive jaundice caused due to BDTT during a 15-year period was conducted. RESULTS: At the time of diagnosis, 14 (73.7%) patients had obstructive jaundice. Eighteen (94.7%) patients were preoperatively suspected of "obstruction of the bile duct". Sixteen patients (84.2%) underwent a hepatectomy with curative intent, while two patients underwent removal of BDTT combined with biliary decompression and another patient received only palliative care as his liver reserve and general condition could not tolerate the primary tumor resection. The overall early recurrence (within 1 year) after hepatectomy occurred in more than half (9/16, 56.3%) of our patients. The 1-year survival rate of patients was 75% (12/16). The longest disease-free survival time was >11 years. CONCLUSION: Identification of HCC patients with obstructive jaundice is clinically important because proper treatment can offer an opportunity for a cure and favorable long-term survival.

Prognostic Factors and Survival of Patients with Carcinoma of the Ampulla of Vater after Pancreaticoduodenectomy

Background: Although carcinoma of the ampulla of Vater (CAV) is a rare tumor, accounting for just 0.2% of gastrointestinal cancers, the survival of CAV patients is unfavorable. The five-year rates have ranged from 36.8-75.2% in previous reports but there is a lack of data relating to Thai people. Also prognostic factors are controversial. Objectives: This study aimed to determine survival outcomes and to identify prognostic factors for a positive outcome for CAV patients after surgery. Methods: In this retrospective cohort study, data were collected from CAV patients who underwent surgery in Chiang Mai University Hospital from 2005 to 2012 for time to event analysis, the log rank test and univariate and multivariate Cox's regression analysis. Results: There were 72 CAV patients recruited, 45.8% being male. The mean age was 65.1 ± 10.5 years and the median waiting time for surgery was 56.5 days (24.5-91.5). The 30 day mortality rate was 5.6%., while 5-yr survival was 33.3%. The average disease free survival was 14.6 months. Prognostic factors relating to recurrence were positive lymph nodes (50% VS 19.6% p = 0.015) and advanced stage (44.1% VS 18.4% p = 0.023). Multivariate analysis showed that the potential prognostic factors for CAV patients included recurrence, moderate and poor differentiation, comorbidities and a tumor size > 2.0 cm. Conclusions: The findings of the study indicate that the overall survival of CAV patients after surgery is quite fair, with a tendency for better outcome with early as compared to advanced lesions. The key prognostic factors were recurrence, moderate and poor differentiation, comorbidity and tumor size > 2.0 cm.

Predictive Factors for a Long Hospital Stay in Patients Undergoing Laparoscopic Cholecystectomy.

Background. Although the advantages of laparoscopic cholecystectomy (LC) over open cholecystectomy are immediately obvious and appreciated, several patients need a postoperative hospital stay of more than 24 hours. Thus, the predictive factors for this longer stay need to be investigated. The aim of this study was to identify the causes of a long hospital stay after LC. Methods. This is a retrospective cohort study with 500 successful elective LC patients being included in the analysis. Short hospital stay was defined as being discharged within 24 hours after the operation, whereas long hospital stay was defined as the need for a stay of more than 24 hours after the operation. Results. Using multivariable analysis, ten independent predictive factors were identified for a long hospital stay. These included patients with cirrhosis, patients with a history of previous acute cholecystitis, cholangitis, or pancreatitis, patients on anticoagulation with warfarin, patients with standard-pressure pneumoperitoneum, patients who had been given metoclopramide as an intraoperative antiemetic drug, patients who had been using abdominal drain, patients who had numeric rating scale for pain > 3, patients with an oral analgesia requirement > 2 doses, complications, and private ward admission. Conclusions. LC difficulties were important predictive factors for a long hospital stay, as well as medication and operative factors.

Metoclopramide, versus its combination with dexamethasone in the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy: a double-blind randomized controlled trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) are significant problems in laparoscopic surgery. OBJECTIVE: Compare the prophylactic use of metoclopramide and its combination with dexamethasone in the prevention of PONV in patients undergoing laparoscopic cholecystectomy (LC). MATERIAL AND METHOD: One hundred patients aged 18 to 75 with American Society of Anesthesiologists (ASA) class 1-2 who candidates for elective LC at Chiang Mai University Hospital, were included in this double-blind, randomized controlled trial (parallel design). Patients were randomly divided into two groups, by 'Block offour 'randomization. Treatment group received 8 mg dexamethasone and 10 mg metoclopramide, and control group received 10 mg metoclopramide and normal saline solution 1.6 ml. These medications were administered intravenously when the gallbladder was removedfrom gallbladder bed. All of investigators, anesthetists, patients, care providers, and outcome assessor were blinded. Patients were asked to assess their nausea and vomiting at 2, 6, 12, and 24 hours postoperatively, and at discharge. The overall score of PONV in each patient based on afour-point whole number of nausea and vomiting by verbal rating scale 0-3 (0 = no nausea and vomiting, 1 = nausea, 2 = nausea with vomiting, and 3 = repeated vomiting >2 times). RESULTS: Fifty eligible patients were randomized to each group, and all were analyzed. There were no significant differences between baseline characteristics of patients in the two groups. The combination of dexamethasone and metoclopramide indicated a greater antiemetic effect with significant statistical analysis, odds ratio = 0.25 (95% confidence interval O. 11-0.55, p = 0.001). Thepostoperative hospital stay in the combined group and metoclopramide group were, 1 day = 47 (94%) and 37 (74%), >1 day = 3 (6%) and 13 (26%), respectively (p = 0.012). There were no postoperative complications occurred in both groups. CONCLUSION: Intravenous administration of dexamethasone combined with metoclopramide had significant effects in prophylaxis of nausea and vomiting after LC and shorten the hospital stay. Clinical trials registration number: TCTR20140128001