Anon Chotirosniramit

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.

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.

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.

Abstract LB-173: The Thailand initiative in genomics and expression research for liver cancer (TIGER-LC): Defining novel subtypes of hepatocellular carcinoma and cholangiocarcinoma

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent two major histological cancer subtypes confined within the liver. They are clinically and biologically heterogeneous, and are highly resistant to treatment, which makes them the second most lethal cancer for men in the world. In Thailand, liver cancer represents the primary cause of cancer-related death and is a major health problem, especially in north-eastern area of Thailand where liver fluke (O. viverrini) is endemic and approximately 70% of liver cancers are CCA. While HBV and HCV are major etiological factors for HCC globally, liver fluke infection is a major etiological factor for CCA in Thailand. These unique risk factor patterns provide an opportunity to study cancer heterogeneity and its unique tumor biology. The Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC) consortium was established to identify genomic and expression factors that may modify HCC and CCA susceptibility and progression. In a Phase I study, we determined molecular subtypes of HCC and CCA. We performed genomic profiling of 398 surgical specimens derived from 199 liver cancer patients. We employed the Affymetrix Human Transcriptome Array 2.0 to examine transcriptome profiles. Unsupervised Consensus Clustering (cCluster), Subclass Mapping (SM) and Gene Set Enrichment Analysis (GSEA) algorithms were used to analyze transcriptome data. The results were validated in 247 Asian HCC cases and 104 Caucasian CCA cases. We found that the Thai HCC cases consisted of 3 stable subgroups (C1-C3), while the Thai CCA cases contained 4 stable subgroups (C1-C4) based on gene expression patterns determined by cCluster. SM analysis revealed that CCA-C1 and HCC-C1 subtypes shared a similar gene expression matrix, as did CCA-C2 and HCC-C2 for a separate pattern. Interestingly, patients in both CCA-C1 and HCC-C1 had a poor prognosis, while those in CCA-C2 and HCC-C2 had a good prognosis. These prognostic subtypes were validated in an independent Asian HCC cohort but not in a Caucasian CCA cohort. GSEA revealed that among 17 significantly altered canonical pathways in the C1 subtype, 8 are related to mitotic checkpoint signaling. In contrast, the main signaling pathways associated with the C2 subtype were related to cytokine and chemokine signaling. We found that certain mitotic checkpoint genes are highly activated only in C1, but not in the C2 subtype. These results are consistent with the hypothesis that CCA and HCC from Asian populations consist of molecularly-similar tumor subgroups with similar prognostic impacts and unique tumor biology and that the C1 subtype may be sensitive to mitotic checkpoint blockage. Our ability to rigorously classify and validate both HCC and CCA using these tools may represent a new avenue for the development of targeted therapeutic interventions. Citation Format: The TIGER-LC Consortium, Jittiporn Chaisaingmongkol, Anuradha Budhu, Hien Dang, Siritida Rabibhadana, Benjarath Pupacdi, Marshonna Forgues, Vajarabhongsa Bhudhisawasdi, Nirush Lertprasertsuke, Anon Chotirosniramit, Chawalit Pairojkul, Chirayu U. Auewarakul, Thaniya Sricharunrat, Kannika Phornphutkul, Suleeporn Sangrajrang, Maggie Cam, Ping He, Stephen M. Hewitt, Xiaolin Wu, Snorri S. Thorgeirsson, Paul S. Meltzer, Christopher A. Loffredo, Robert H. Wiltrout, Curtis C. Harris, Chulabhorn Mahidol, Mathuros Ruchirawat, Xin W. Wang. The Thailand initiative in genomics and expression research for liver cancer (TIGER-LC): Defining novel subtypes of hepatocellular carcinoma and cholangiocarcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-173. doi:10.1158/1538-7445.AM2015-LB-173

How to Reconstruct Middle Hepatic Vein Branches With Explanted Portal Vein and Inferior Mesenteric Vein Graft: A Case Report

OBJECTIVE The middle hepatic vein reconstruction is one of the crucial parts in adult living donor liver transplantation. Numerous techniques had been reported by using cadaveric iliac vessel or synthetic graft. The limitations of reported techniques are availability of the vessel and complication of synthetic graft. We report the technique of using explanted portal vein and inferior mesenteric vein graft in sequential fashion. PATIENTS AND METHODS The recipient was a 54-year-old man with chronic hepatitis B cirrhosis and multiple hepatocellular carcinomas. He underwent living donor liver transplantation with modified right lobe graft from spouse. The venous drainages of segments 5 and 8 were reconstructed by explanted left portal vein and inferior mesenteric vein from the donor. The operative time was 9 hours 30 minutes. RESULTS The postoperative course was uneventful. The recipient did not show any signs of small-for-size syndrome such as ascites or hyperbilirubinemia. He recovered well and showed no signs of recurrent disease 1 year after his transplantation. CONCLUSION The explanted portal vein graft can be used with another autogenous vein graft such as inferior mesenteric vein for reconstruction of all middle hepatic vein branches.

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

Highlights • Portal vein arterialization may be a bridging treatment for retransplantation.• This case demonstrates feasible of portal vein arterialization in sick patient.• Portal hypertension usually occurs after portal vein arterialization.• Calibration of fistula after recovery of liver allograft should be considered.

Abstract 4390: The Thailand initiative in genomics and expression research in liver cancer: Race related common molecular subtypes among Asian hepatocellular carcinoma and cholangiocarcinoma identified by integrated genomics

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two distinct histological liver cancers. They are clinically and biologically heterogeneous and highly resistant to treatment, making liver cancer the second most lethal malignancy in the world. In Thailand, liver cancer represents the primary cause of cancer-related death and is a major health problem. While HBV and HCV are major etiological factors for HCC globally, liver fluke infection (O. viverrini) is a major etiological factor for ICC in Thailand, especially in north-eastern Thailand where O. viverrini is endemic and approximately 70% of liver cancers are ICC. These unique risk factor patterns provide an opportunity to study cancer heterogeneity and unique liver tumor biology. The Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC) consortium was established to identify genomic and expression factors that may modify HCC and ICC susceptibility and progression. Here, we determined molecular subtypes and features of HCC and ICC through systems integration of genomic, transcriptomic and metabolic profiles. We performed genome wide profiling of 398 surgical specimens derived from 199 Thai liver cancer patients. We employed the Affymetrix Human Transcriptome Array 2.0, the Affymetrix Genome-Wide Human SNP Array 6.0, Metabolon9s DiscoveryHD4 platform and Exome Sequencing to examine transcriptome profiles, somatic copy number alterations (SCNA), cancer metabolic profiles and mutation patterns, respectively. The results were validated in 847 independent Asian or Caucasian HCC or ICC cases. Transcriptomic analyses revealed that Thai HCC consisted of 3 stable subgroups (C1-C3), while Thai ICC contained 4 stable subgroups (C1-C4). Interestingly, HCC-C1 and ICC-C1 subtypes shared a similar gene expression matrix, as did HCC-C2 and ICC-C2, which correlated with patient survival. These prognostic subtypes were validated in independent Asian HCC and ICC cohorts, but not in Caucasian patients, and were associated with tumor biology rather than etiology. GSEA revealed that the C1 subtype is enriched for mitotic checkpoint anomalies, while the C2 subtype is related to cytokine and chemokine signaling. We found that the C1 subtype encompassed a higher degree of SCNA when compared to the C2 subtype, suggesting an association with a genomic instability phenotype. Further analysis showed that the C2 subtype is linked to an increased body mass index, inflammatory responses and unique tumor metabolic activities. HCC and ICC from Asian populations, while clinically treated as separate entities, share common subtypes with similar actionable drivers which can be targeted to improve precision therapy. Citation Format: Anuradha Budhu, Jittiporn Chaisaingmongkol, Hien Dang, Siritida Rabibhadana, Benjarath Pupacdi, So Mee Kwon, Marshonna Forgues, Yotsawat Pomyen, Vajarabhongsa Bhudhisawasdi, Nirush Lertprasertsuke, Anon Chotirosniramit, Chawalit Pairojkul, Chirayu U. Auewarakul, Thaniya Sricharunrat, Kannika Phornphutkul, Suleeporn Sangrajrang, Maggie Cam, Ping He, Stephen M. Hewitt, Xiaolin Wu, Snorri S. Thorgeirsson, Joshua J. Waterfall, Yuelin J. Zhu, Jennifer Walling, Holly S. Stevenson, Daniel Edelman, Paul S. Meltzer, Christopher A. Loffredo, Robert H. Wiltrout, Curtis C. Harris, Chulabhorn Mahidol, Mathuros Ruchirawat, Xin W. Wang. The Thailand initiative in genomics and expression research in liver cancer: Race related common molecular subtypes among Asian hepatocellular carcinoma and cholangiocarcinoma identified by integrated genomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4390. doi:10.1158/1538-7445.AM2017-4390

Intraductal papillary neoplasm of the bile duct: clinicopathological study of 10 cases

Background and aims: Intraductal papillary neoplasm of the bile duct (IPNB) is a new entity of biliary neoplasm that is characterized by predominant intraductal papillary growth with various degrees of malignant transformation. It has better prognosis compared with conventional cholangiocarcinoma. Although IPNB has been recently added to the WHO classification, preoperative diagnosis is still challenging and the classification system might need refinements. Methods: We retrospectively reviewed clinicopathological features of 10 surgically resected cases of IPNB, which were previously diagnosed as intraductal cholangiocarcinoma or papillary adenocarcinoma of the bile duct from 2008 to 2014. Histologic features are classified into intestinal, gastric, pancreaticobiliary, and oncocytic types as described in the literature, together with invasive growth pattern and immunohistochemistry. Results: Eight tumors (80%) were invasive IPNB and two (20%) were non-invasive. All of the non-invasive cases are IPNB with high-grade dysplasia. Three cases (30%) were cystic type which having a communication to the bile duct lumen. Discussion: Intraductal growth type cholangiocarcinoma (invasive IPNB) showed a worse prognosis than IPNB with high-grade dysplasia. Curative resection is the major treatment and an important favorable factor for long-term survival, especially in patients with early-stage. Due to its rarity, a mechanism of histopathogenesis remains to be studied.