Surgical aspects of choledochal cyst in children and adults: an experience of 106 cases.

PURPOSE: To describe clinical features of choledochal cyst (CC) patients in terms of demographic data, clinical presentation, investigations, treatment, and outcomes among children and adults. METHODS: The medical records of patients undergoing choledochal cyst (CC) surgery from 2002 to 2021 at a university hospital were retrospectively reviewed. The patients were divided into two groups: children (< 15 years) and adults (≥ 15 years). Descriptive statistics were used. RESULTS: There were 106 cases of CC (Female/male = 88/18, children/adult = 53/53). Abdominal pain was the predominant presenting symptom, followed by jaundice in both groups. Adults were significantly more prone to present with abdominal pain compared to children (86.8% vs. 52.8%; p < 0.001), while children were more likely to experience acholic stool than adults (22.6% vs. 3.8%; p = 0.004). Ultrasound was the preferred investigation screening modality (75.5%). Most patients were presented with type I CC (71.7%). Laparoscopic-assisted approach was performed in 8.5%. CC excision with roux-en-y hepatico-jejunostomy was the main procedure (88.7%). Adults had a higher incidence of post-op complications, including stones, anastomosis stricture, abdominal collection, and cholangitis. Adults were significantly more likely to require intervention after surgery, compared to children (26.4% vs. 5.7%; p = 0.04). CONCLUSIONS: Ultrasound was the most common screening tool for diagnosis. Postoperatively, adults with CC experience more serious post-op complications compared to children. This could be attributed to long-standing cystic inflammation. Therefore, prompt definitive surgery is recommended for CC patients.

Survival outcomes of surgical resection in perihilar cholangiocarcinoma in endemic area of O. Viverrini, Northeast Thailand.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is an intractable malignancy and remains the most challenge for surgeon. This study aims to investigate survival outcomes and prognostic factors in pCCA patient. METHODS: From October 2013 to December 2018, 240 consecutive patients with pCCA underwent surgical exploration were retrospectively reviewed. The clinicopathological parameters and surgical outcomes were extracted. Patients were divided into two groups: unresectable and resectable group. The restricted mean survival time between two groups were analyzed. Factors associated with overall survival in resectable group were explored with multivariable Cox regression analysis. RESULTS: Of the 240 patients, 201 (83.75%) were received surgical resection. The survival outcomes of resectable group were better than unresectable group significantly. The restricted mean survival time difference were 0.5 (95%CI 0.22-0.82) months, 1.8 (95%CI 1.15-2.49) months, 4.7 (95%CI 3.58-5.87) months, and 9.1 (95%CI 7.40-10.78) months at four landmark time points of 3, 6, 12 and 24 months, respectively. The incidence of major complications and 90-day mortality in resectable group were 35.82% and 11.44%, respectively. Multivariable analysis revealed that Bismuth type IV (HR:4.43, 95%CI 1.85-10.59), positive resection margin (HR:4.24, 95%CI 1.74-10.34), and lymph node metastasis (HR:2.29, 95%CI 1.04-4.99) were all independent predictors of long-term survival. For pM0, R0 and pN0 patients, the median survival time was better than pM0, R1 or pN1/2 patients and pM0, R1 and pN1/2 patients (32.4, 10.4 and 4.9 months, respectively; p < 0.001) CONCLUSION: Surgical resection increased survival in pCCA. Bismuth type IV, positive resection margin and lymph node metastasis were independent factors for long-term survival.

Cirrhotic and non-cirrhotic huge hepatocellular carcinoma (≥ 10 cm): a comparative study of surgical management and follow-up treatment in a single institution.

PURPOSE: Liver resection (LR) of huge hepatocellular carcinoma (HCC) has increasingly been regarded as a viable option of enhanced efficacy for patients, but most studies have focused on comparing various tumor sizes and the outcomes of surgery. The study aim was to evaluate the clinicopathologic characteristics and surgical outcomes of huge HCC with and without cirrhosis that underwent LR, and to delineate the treatment for recurrence. METHODS: Sixty-three patients with huge HCC who underwent hepatectomy from 2010 to 2019 were enrolled and reviewed. Clinicopathological findings, surgical outcomes of the entire cohort, and differences between the cirrhotic and non-cirrhotic groups were analyzed. RESULTS: Forty patients (60.3%) had huge HCC with cirrhosis. Clinicopathological findings were not different between the two groups, except tumor size ≥ 15 cm (40% in cirrhosis vs 17.4% in non-cirrhosis, p = 0.024) and major portal vein tumor thrombus were detected only in the cirrhosis group (11 patients, p = 0.006). Extended LR was performed in 13 cirrhotic patients (32.5%) and in 1 non-cirrhotic patient (4.4%) (p = 0.010). Operative data, postoperative complications including postoperative liver failure, and pattern of recurrence were not different between the two groups. For the entire cohort, mortality rate was 1.5%. The 1-, 3-, and 5-year overall survival rates (OS) were 81%, 54%, and 39%. Multivariate analysis showed resection margin ≥ 0.1 cm was a good prognostic factor for OS (HR 0.247 (p = 0.017)). For tumor recurrence, local ablative treatment for liver recurrence and resection for lung recurrence provided good long-term outcomes. CONCLUSION: Although huge HCC with cirrhosis has been a more unfavorable tumor, LR still provided long-term survival with acceptable risk morbidity and mortality.

Comparison of Three Inferior Vena Cava Reconstruction Techniques in Adult Orthotopic Liver Transplantation: Result From King Chulalongkorn Memorial Hospital, Thailand.

BACKGROUND: In orthotopic liver transplantation (OLT), 3 caval reconstruction techniques are being performed worldwide. These are conventional, piggyback technique, and side-to-side cavocaval anastomosis (CCA). Each has its own advantages and drawbacks. Herein we report the result from our hospital comparing the 3 techniques. METHODS: We retrospectively reviewed the detail of OLT performed from January 2008 to March 2020. Data being collected included type of caval reconstruction, blood loss, operative time, ischemic time, length of stay in the intensive care unit (ICU) and total hospital stay, and several postoperative complications. RESULTS: In the given period, 11 conventional, 90 piggyback, and 113 CCA caval reconstruction were done. There were no statistically significant differences in blood loss, operative time, cold ischemic time, and length of ICU and hospital stay. The CCA group had the lowest warm ischemic time (40 minutes) followed by the piggyback technique (43 minutes) and the conventional technique (47 minutes; P < .001). Regarding postoperative complications, there were no statistically significant differences in rate of primary nonfunction, early allograft dysfunction, hepatic artery/portal vein/biliary complication, or rate of acute kidney injury. The hepatic venous outflow complication rate was indifferent between 3 groups. CONCLUSIONS: The present study showed no difference in outflow obstruction rate among the 3 techniques. The choice for reconstruction should rely on the preference of each institute and the suitability of each patient. The CCA technique may provide the lowest warm ischemic time.

Targeted Proteins Reveal Cathepsin D as a Novel Biomarker in Differentiating Hepatocellular Carcinoma from Cirrhosis and Other Liver Cancers

OBJECTIVE: Hepatocellular carcinoma (HCC) represents a global health concern, particularly in Southeast Asia where hepatitis B virus (HBV) infection is common. In this study, we applied tissue-based proteomics to identify novel serological proteins for HCC and validated their performance in serum specimens. METHODS: In a discovery set, liver tissue specimens of HBV-related HCC, intrahepatic cholangiocarcinoma (iCCA) and colorectal cancer with liver metastasis (CRLM) were analyzed using mass spectrometry (LTQ-Orbitrap-XL). A subset of proteins that showed highly expressed in HCC were then confirmed by Western blotting. Additionally, clinical significance of selected candidate proteins was tested in serum samples of 80 patients with HBV-related HCC, 50 patients with HBV-related liver cirrhosis and 30 healthy controls. RESULTS: Based on LTQ-Orbitrap-XL mass spectrometer, various differentially expressed proteins (DEPs) between tumor and adjacent non-tumor tissues were identified. These included 77 DEPs for HCC, 77 DEPs for iCCA and 55 DEPs for CRLM. Among selected candidate proteins, annexin A2 and cathepsin D were confirmed to be overexpressed in HCC tissue by Western blot analysis. In a validate cohort, serum cathepsin D level, but not annexin A2, was significantly higher in HCC compared with the non-HCC groups. Serum cathepsin D level was also positively correlated with tumor size and tumor stage. Additionally, the combined assay of serum cathepsin D and alpha-fetoprotein had a high sensitivity in detecting early HCC (83%) and intermediate/advanced HCC (96%). Moreover, patients with low serum cathepsin D (<305 ng/mL) displayed significantly better overall survival than those whose serum levels were high (≥305 ng/mL). CONCLUSIONS: Proteomics and subsequent validation revealed cathepsin D as a novel biomarker for HCC. Apart from its diagnostic role, serum cathepsin D might also serve as a prognostic biomarker of HCC. Additional large-scale studies are needed to verify our findings.

Partial segments 4/5 liver resection facilitates the repair of complicated bile duct injuries: a technical challenge and long-term outcomes.

Adequate exposure with optimal anteroposterior view of the hilar plate is challenging and crucial in a surgical repair of complicated hilar bile duct injuries. A high-quality anastomosis depends on the ability to identify non-scarred, non-inflamed, non-ischemic bile ducts. This study provides operative details of the Partial Segments 4/5 Liver Resection with a Roux-en-Y hepaticojejunostomy (PS4/5LRHJ) and presents its long-term outcomes. 36 patients with the Strasberg type E bile duct injuries (BDIs) who underwent the PS4/5LRHJ from 2003 to 2019 were retrospectively reviewed. Outcomes of the surgical treatments were analyzed. The mean age of the patients was 46.3 years. 22 patients underwent BDI repair as index operations and 14 patients as re-repair operations. Operative times between the index operation group and the re-repair group (396.6 min vs 391.3 min, respectively, p = 0.876) and blood loss (590.6 ml vs 640 ml, respectively, p = 0.587) were not statistically different. The mean length of hospital stay was 23 days. The median follow-up duration was 73 months. Major complications developed in 10 patients (27.8%), of which intra-abdominal collection was the most common (eight patients, 22.2%). Anastomotic stricture developed in one patient (2.8%). The mortality rate was zero. The overall 10-year patency rate was 95.2%. PS4/5LRHJ offered long-term patency with acceptable morbidity in the hilar bile duct injuries and re-repair operations.

Cell-Free DNA Analysis by Whole-Exome Sequencing for Hepatocellular Carcinoma: A Pilot Study in Thailand.

Cell-free DNA (cfDNA) has been used as a non-invasive biomarker for detecting cancer-specific mutations. However, the mutational profile of cfDNA in Thai patients with hepatocellular carcinoma (HCC) has not been investigated. Here, we demonstrated the utility of using whole-exome sequencing (WES) of cfDNA to define the somatic mutation profiles of HCC in Thai patients. The comprehensive profile of cfDNA was determined with WES to identify variants in matched cfDNA and germline DNA from 30 HCC patients in Thailand who underwent nonoperative therapies. The level of cfDNA was higher in HCC patients compared with chronic hepatitis patients (p-value < 0.001). Single nucleotide variants were present in somatic genes in cfDNA, including in ZNF814 (27%), HRNR (20%), ZNF492 (20%), ADAMTS12 (17%), FLG (17%), OBSCN (17%), TP53 (17%), and TTN (17%). These same mutations were matched to HCC mutation data from The Cancer Genome Atlas (TCGA) and a previous Thai HCC study. The co-occurrence of HRNR and TTN mutations in cfDNA was associated with shorter overall survival in HCC patients (hazard ratio = 1.60, p-value = 0.0196). These findings indicate that the mutational profile of cfDNA accurately reflected that of HCC tissue and suggest that cfDNA could serve as a useful biomarker for diagnosis and prognosis in Thai HCC patients. In addition, we demonstrated the use of the pocket-sized sequencer of Oxford Nanopore Technology to detect copy-number variants in HCC tissues that could be applied for onsite clinical detection/monitoring of HCC.

Identification of BHLHE40 expression in peripheral blood mononuclear cells as a novel biomarker for diagnosis and prognosis of hepatocellular carcinoma.

Novel and sensitive biomarkers is highly required for early detection and predicting prognosis of hepatocellular carcinoma (HCC). Here, we investigated transcription profiles from peripheral blood mononuclear cells (PBMCs) of 8 patients with HCC and PBMCs from co-culture model with HCC using RNA-Sequencing. These transcription profiles were cross compared with published microarray datasets of PBMCs in HCC to identify differentially expressed genes (DEGs). A total of commonly identified of 24 DEGs among these data were proposed as cancer-induced genes in PBMCs, including 18 upregulated and 6 downregulated DEGs. The KEGG pathway showed that these enriched genes were mainly associated with immune responses. Five up-regulated candidate genes including BHLHE40, AREG, SOCS1, CCL5, and DDIT4 were selected and further validated in PBMCs of 100 patients with HBV-related HCC, 100 patients with chronic HBV infection and 100 healthy controls. Based on ROC analysis, BHLHE40 and DDIT4 displayed better diagnostic performance than alpha-fetoprotein (AFP) in discriminating HCC from controls. Additionally, BHLHE40 and DDIT4 had high sensitivity for detecting AFP-negative and early-stage HCC. BHLHE40 was also emerged as an independent prognostic factor of overall survival of HCC. Together, our study indicated that BHLHE40 in PBMCs could be a promising diagnostic and prognostic biomarker for HBV-related HCC.