Vena cava replacement and major hepatectomy for liver tumors: international multicenter retrospective cohort study.

INTRODUCTION: Involvement of the inferior vena cava (IVC) and hepatic veins (HV) has been considered a relative contraindication to hepatic resection for primary and metastatic liver tumors. However, patients affected by tumors extending to the IVC have limited therapeutic options and suffer worsening of quality of life due to IVC compression. METHODS: Cases of primary and metastatic liver tumors with vena cava infiltration from 10 international centers were collected (7 European, 1 US, 2 Brazilian, 1 Indian) were collected. Inclusion criteria for the study were major liver resection with concomitant vena cava replacement. Clinical data and short-term outcomes were analyzed. RESULTS: 36 cases were finally included in the study. Median tumor max size was 98 mm (range: 25-250). A biliary reconstruction was necessary in 28% of cases, while a vascular reconstruction other than vena cava in 34% of cases. Median operative time was 462 min (range: 230-750), with 750 median ml of estimated blood loss and a median of one pRBC transfused intraoperatively (range: 0-27). Median ICU stay was 4 days (range: 1-30) with overall in-hospital stay of 15 days (range: 3-46), post-operative CCI score of 20.9 (range: 0-100), 12% incidence of PHLF grade B-C. Five patients died in a 90-days interval from surgery, 1 due to heart failure, 1 due to septic shock and 3 due to multiorgan failure. With a median follow-up of 17 months (interquartile range: 11-37), the estimated five-years overall survival was 48% (95% CI: 27%-66%), and five-year cumulative incidence of tumor recurrence was 55% (95% CI: 33%-73%). CONCLUSIONS: Major liver resections with vena cava replacement can be performed with satisfactory results in expert HPB centers. This surgical strategy represents a feasible alternative for otherwise unresectable lesions and is associated with favorable prognosis compared to non-operative management, especially in patients affected by intrahepatic cholangiocarcinoma.

Size Matching Deceased Donor Livers: The Tampa General Measurement System.

BACKGROUND: No reliable or standardized system exists for measuring the size of deceased donor livers to determine whether they will fit appropriately into intended recipients. METHODS: This retrospective, single-center study evaluated the efficacy of Tampa General Hospital's size-matching protocol for consecutive, deceased donor liver transplantations between October 2021 and November 2022. Our protocol uses cross-sectional imaging at the time of organ offer to compare the donor's right hepatic lobe size with the recipient's right hepatic fossa. Outcomes were analyzed, including large-for-size syndrome, small-for-size syndrome, early allograft dysfunction, primary nonfunction, graft survival, and patient survival. RESULTS: We included 171 patients in the study. The donor liver physically fit in all the patients except one whose pretransplant imaging was outdated. One patient (0.6%) had large-for-size syndrome, none had small-for-size syndrome, 15 (10%) had early allograft dysfunction, and none had primary nonfunction. There were 11 (7%) patient deaths and 11 (7%) graft failures. CONCLUSION: Our measurement system is fast and effective. It reliably predicts whether the donor liver will fit in the intended recipient and is associated with low rates of early allograft dysfunction.

Treatment Pattern and Outcomes in Verrucous Carcinoma of Oral Cavity: A Single Institutional Retrospective Analysis from a Tertiary Cancer Center and Review of Literature.

Verrucous carcinoma (VC) is a locally invasive uncommon histopathological variant of oral squamous cell cancer. There is paucity of literature regarding control rates in these cases. We intend to report the outcomes in terms of administered treatment and control rates. 28 patients of oral cavity verrucous carcinomas treated at our institute from March 2014 to December 2018 were reviewed retrospectively. Demographic profile, histopathological features and clinical outcomes were analyzed. Statistical analysis was performed with SPSS for Mac (version 23.0). Median age was 54 years (range 31-75) with M:F ratio of 25:3. Buccal mucosa was the most common site. All patients underwent surgical resection except one. Of these, 24 had neck dissection; 12 had supra-omohyoid neck dissection, eleven had modified neck dissection and one patient underwent radical neck dissection. Three patients had their histology upgraded to squamous cell carcinomas in the post-operative histopathology. The post-operative staging was as follows: 21% stage I and 35% stage II. One patient opted for non-surgical approach and received radical concurrent chemoradiotherapy. Median follow up was 12 months (range 6-36). Two patients had local failures and one had a regional failure. No distant metastasis was found. There was one death. 14-Months survival rate was 92%. Estimated 18 month loco-regional control rate was 92%. Curative surgical resection remains the cornerstone for VC of oral cavity. Any change of histopathology post-operatively to squamous cell carcinoma is a poor prognostic sign and needs appropriate adjuvant treatment.

Correlation between Programmed Death Ligand-1(PD-L1) Expression and Driver Gene Mutations in Non-Small Cell Lung Carcinoma- Adenocarcinoma Phenotype.

BACKGROUND: Targeted therapy in adenocarcinoma is recommended. The use of immune check point inhibitors for the treatment of Non-small cell lung carcinoma (NSCLC) is used as both first-line and the second-line treatment strategy. The current study was undertaken to assess the frequency of programmed cell death ligand-1 (PD-L1) expression with anaplastic lymphoma kinase (ALK), proto-oncogene 1, receptor tyrosine kinase (ROS), epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (KRAS), and v-Raf murine sarcoma viral oncogene homolog B (BRAF)V600E driver gene mutations in NSCLC adenocarcinoma phenotype. It assesses the frequencies of all markers in the cases where both treatment strategies can be implemented. Expression of the all markers was further compared with demographic, clinical parameters, and overall survival rate. MATERIALS AND METHODS: The formalin-fixed paraffin-embedded (FFPE) tissue blocks were used in immunohistochemistry (IHC) staining and real-time polymerase chain reaction (RT-PCR) for determining the driver genes and PD-L1 expression in the 100 NSCLC-Adenocarcinoma cases. RESULTS: PD-L1 positivity was observed in 26.36% (n=29/110) cases in adenocarcinoma. No significant differences in PD-L1 expression were observed among patients harboring ALK, ROS1, EGFR, KRAS, and BRAF mutations EGFR mutations had significant association with smoking status. (p= 0.008), Thyroid transcription factor 1 (TTF1) (p=0.0005) and Napsin (p=0.002) expression. ALK gene re-arrangement was significantly related to age (p= 0.001), gender (p= 0.009) and smoking status (p= 0.043). The single versus multiple driver mutations were significantly correlated with smoking status (p=0.005). In the survival rate analysis, EGFR (p=0.058), KRAS (p=0.021), and PD-L1 (p=0.039) were significantly high with the positive versus negative group. CONCLUSIONS: The current study is a novel attempt to document the co-expression of multiple driver mutations in the NSCLC-adenocarcinoma phenotype. PD-L1 immunopositivity in NSCLC-adenocarcinoma was higher with EGFR mutation as compared to those of KRAS, ALK, ROS, and BRAF driver genes.

Assessment of Speech and Deglutition in Patients with Carcinoma Tongue Post Radial Forearm Free Flap Cover.

Over the past 30 years, the introduction of reconstructive techniques incorporating microvascular free tissue transfer has transformed the quality of life of patients undergoing head and neck surgery.The free forearm flap was first described for head and neck reconstruction by Yang in 1981 when he used this flap to reconstruct a neck defect secondary to a burn scar contracture.In this retrospective cohort study, we have evaluated patients who underwent reconstruction of hemiglossectomy defect with radial forearm free flap for malignancy of tongue, from year 2018 to 2020, with reference to deglutition and speech.As per the data obtained, 41.7% and 50% of the patients had achieved excellently intelligible speech and moderately intelligible speech respectively whereas only 8.3% had poorly intelligible speech. On evaluation of post operative swallowing, 83.4% of the patients had excellent swallowing score and the remaining 16.6% had moderate and poor swallowing score.Hence, reconstruction of hemiglossectomy defects with radial forearm free flap is an excellent method to restore the functional outcomes in speech and deglutition.

Venous outflow reconstruction using a polytetrafluoroethylene (PTFE) graft in right lobe living donor liver transplantation: A single center study.

BACKGROUND: Venous outflow reconstruction is very important especially in right lobe living donor liver transplantation without middle hepatic vein. Various interposition (venous or synthetic) grafts have been recommended for reconstruction of anterior sector tributaries. METHODS: We aimed to describe our surgical technique and analyze anterior sector venous reconstruction using expanded polytetrafluroethylene graft. Retrospective analysis of prospectively collected data for 760 primary right lobe living donor liver transplantations performed at our institute between December 2011 and June 2018. Reconstruction of anterior sector: expanded polytetrafluroethylene (group A, n = 705) and autologous vein (group B, n = 55). RESULTS: Pretransplant characteristics were comparable among both groups. Group A has significantly lower cold ischemia time (68.7 ± .3.5 minutes vs 127.8 ± 7.2 minutes; P < .001) and anhepatic time (116.3 ± 5.5 minutes vs 190.81 ± 9.35 minutes; P < .001) compared with group B. There was no difference in recovery pattern of liver functions, morbidity, and mortality between the 2 groups. One- and 6-month patency rates of interposition grafts were 97.6% and 84.4% (group A) and 96.4% and 78.1% (group B), respectively. CONCLUSION: In centers with limited access to homologous or autologous vascular grafts, use of expanded polytetrafluroethylene graft for anterior sector venous outflow reconstruction in right lobe living donor liver transplantation is a viable option with excellent patency and patient outcomes.

Living-donor liver transplantation: Right versus left.

A dilemma of graft selection between right or left livers occurs during the planning of living-donor liver transplantation (LDLT) as well as splitting a whole liver graft into full right/full left grafts in deceased-donor liver transplantation. The right liver's relation to the whole liver could be considered as the trunk of a tree; it has a larger volume, the main axis of bile ducts, and the inferior vena cava mainly belongs to the right liver. Therefore, it was considered as the standard graft in LDLTs. Whether to procure the middle hepatic vein (MHV) with a right liver graft or to leave it attached to the left-liver remnant largely depends on the transplant institute. Recently, most transplant institutes tend to leave the MHV with the left liver for the sake of donor safety. Unlike hepatectomy for liver tumors, it is vital to preserve inflow and outflow for both the resected as well as the remaining livers. While procuring any graft type, the most important is to procure a liver graft with reconstructable portal veins, hepatic arteries, hepatic veins, and bile ducts, which should be well preoperatively planned using 3D-computed tomography with considerations given to graft volume and potential congestion areas.

The role of living donor liver transplantation for acute liver failure.

Acute liver failure (ALF) is a life-threatening illness that occurs in the absence of pre-existing liver disease. When symptoms seriously progress under continuous supportive medical care, liver transplantation becomes the only therapeutic strategy. However, the available sources of organs for liver transplantation differ worldwide. In regions in which organs from cadaveric donors are more common, deceased donor liver transplantation (DDLT) is performed in this urgent situation. Conversely, in countries where cadaveric donors are scarce, living donor liver transplantation (LDLT) is the only choice. Special considerations must be made for urgent LDLT for ALF, including the expedited evaluation of living donors, technical issues, and the limitations of ABO blood type combinations between recipients and donor candidates. In this review, we highlight the role of LDLT for ALF and the considerations that distinguish it from DDLT. LDLT is well-established as a life-saving procedure for ALF patients and there is often no alternative to LDLT, especially in countries where DDLT is not feasible. However, from a global perspective, an increase in the deceased donor pool might be an urgent and important necessity.

Kirsten rat sarcoma virus protein overexpression in adenocarcinoma lung: Association with clinicopathological and histomorphological features.

CONTEXT: Lung cancer is the leading cause of cancer-related deaths worldwide. The constitutive activation of multiple signaling pathways is the major cause of carcinogenesis. AIMS: The study evaluates the frequency of Kirsten rat sarcoma virus (KRAS) protein overexpression and correlates with clinicopathological and histomorphological features in non-small cell lung carcinoma (NSCLC)-adenocarcinoma. SETTINGS AND DESIGN: Tertiary hospital-based retrospective and prospective case series included 100 cases of NSCLC-adenocarcinoma. MATERIALS AND METHODS: The basic panel of Immunohistochemistry including Napsin-A, thyroid transcription factor-1 (TTF-1), and markers for squamous differentiation, p-40 was used in formalin-fixed paraffin-embedded tissue blocks. The KRAS monoclonal antibody (9.13, Thermo Fisher Scientific, USA) was used. STATISTICAL ANALYSIS USED: The IBM-Statistical Package for the Social Sciences (SPSS) (SPSS, International Business Machines Corporation, New York, NY, USA) analysis software, version 16 was used for all statistical calculations. RESULTS: KRAS protein expressed in 28.0% (28/100) cases. Cases were grouped as KRAS positive and negative. TTF-1 and Napsin-A were expressed in 89.25% (n = 25) and 92.86% (n = 26) cases, respectively. Stage IV clinical disease was identified in 55% of cases, and 36.84% of cases had a mean survival between 6 and 12 months. In KRAS positive group, the most common pattern of cellular arrangement was acinar/loose clusters pattern present in 64.29% (n = 21) and 75.0% (n = 18) cases followed by the solid pattern present in 42.86% of cases (n = 12), respectively. Necrosis was identified in 57.14% (n = 16) cases. Mucin pattern was present in 32.14% of cases (n = 9), which was significantly different when compared with the KRAS negative group (P = 0.036). CONCLUSIONS: This finding may imply that KRAS mutations may not be entirely triggered by alterations induced by carcinogens in smoke. KRAS gene is frequently mutated in pulmonary tumors. It should be tested in NSCLC owing to its predictive and prognostic effects.

Utility of prothrombin complex concentrate as first-line treatment modality of coagulopathy in patients undergoing liver transplantation: A propensity score-matched study.

BACKGROUND: Transfusion management during liver transplantation (LT) is aimed at reducing blood loss and allogeneic transfusion requirements. Although prothrombin complex concentrate (PCC) has been used satisfactorily in various bleeding disorders, studies on its safety, and efficacy during LT are limited. METHODS: A retrospective chart review of adult patients who underwent living donor LT at a single institute between October 2016 and January 2018 was carried out. The safety and efficacy of PCC in reducing transfusion requirements intraoperatively in patients who received PCC were compared with patients who did not receive PCC. A propensity score-matching technique was used, at a 1:1 ratio, to remove selection bias. RESULTS: After completing the 1:1 propensity score-matched analysis, 60 pairs of patients were identified. The use of PCC was associated with significantly decreased red blood cell transfusion requirements (6.2 ± 4.1 vs 8.23 ± 5.18, P < 0.001) and fresh frozen plasma transfusion requirements (2.6 ± 2 vs 6.18 ± 4.1, P < 0.001). The number of patients developing postoperative hemorrhagic complications was higher in the non-PCC group. CONCLUSIONS: During LT, the use of PCC led to decreased transfusion requirements. No thromboembolic complications related to PCC were noted in this series.

Analysis of caudate lobe biliary anatomy and its implications in living donor liver transplantation - a single centre prospective study.

Biliary complications are a significant cause of morbidity after living donor liver transplant (LDLT). Bile leak may occur from bile duct (anastomotic site in recipient and repaired bile duct stump in donor), cystic duct stump, cut surface pedicles or from divided caudate ducts. The first three sites are amenable to post-operative endoscopic stenting as they are in continuation with biliary ductal system. However, leaks from divided isolated caudate ducts can be stubborn. To minimize caudate duct bile leaks, it is important to understand the anatomy of hilum with attention to the caudate lobe biliary drainage. This single-centre prospective study of 500 consecutive LDLTs between December 2011 and December 2016 aims to define the biliary anatomy of the caudate lobe in liver donors based on intraoperative cholangiograms (IOCs) with special attention to crossover caudate ducts and to study their implications in LDLT. Caudate ducts were identified in 468 of the 500 IOCs. Incidence of left-to-right crossover drainage was 61.37% and right to left was 21.45%. Incidence of bile leak in donors was 0.8% and in recipients was 2.2%. Proper intraoperative identification and closure of divided isolated caudate ducts can prevent bile leak in donors as well as recipients.

EpCAM-based Flow Cytometric Detection of Circulating Tumor Cells in Gallbladder Carcinoma Cases

Purpose: Liquid biopsy has entered the arena of cancer diagnostics in the past decade and detection of circulating tumor cells (CTC) is one diagnostic component. CTCs in gallbladder cancer (GBC) have hitherto not been comprehensively analysed. Methods and Results: The current study focused on the diagnostic role of CTCs in 27 cases of treatment-naive GBC and 6 normal controls as well as 6 cases of cholecystitis. An EasySep kit featuring negative immunomagnetic bead separation and flow cytometric detection of EpCAM positive and CD45 negative cells revealed CTCs in 25 of the 27 cases. At a cut-off point of ≥1, the CTC count discriminated GBC from controls with a sensitivity, specificity and diagnostic accuracy of 92.6%, 91.7% and 92.3%, respectively. CTC levels in turn correlated significantly with clinico-pathological parameters of cases in terms of known prognostic indicators, with significant diagnostic potential at a cut-off point of >4, to discriminate disease stage I and II vs. III and IV GBC. With a cut-off of >3, the CTC count discriminated tumor stages I and II vs. III and IV and at >6 CTCs could discriminate metastatic vs. non metastatic GBCs with a sensitivity, specificity and diagnostic accuracy of 55. 6%, 100.0% and 85.2, respectively. A review of CTC in pancreatico-biliary malignancies is included. Conclusion: Detection and quantification of CTCs may serve as a non-invasive biomarker for GBC diagnosis in correlation with radiological studies.

Paraneoplastic Hypoglycaemia: A Rare Manifestation of Pelvic Gastrointestinal Stromal Tumour.

Non-Islet Cell Tumour Induced Hypoglycaemia (NICTH), presenting with recurrent fasting hypoglycaemia is a very rare paraneoplastic syndrome. It usually presents with large metastatic mesenchymal tumours. NICTH secondary to Gastrointestinal Stromal Tumour (GIST) is even rarer. Diagnosis of NICTH is based on the low serum insulin level, low serum concentrations of Insulin Like Growth Factor (IGF-I) and IGF binding protein- III (IGFBP-III) in combination with elevated concentrations of pro-IGF-II. Various Immunohistochemical (IHC) markers are integral to diagnosis of GIST namely 2-deoxyglucose-6-phosphate phosphatase -1(DOG-1), Cluster Differentiation 34 (CD 34), Cluster Differentiation 117 (CD117). The management requires prompt intravenous hydration and glucose infusions followed by surgical resection. We hereby, report a rare case of a 65-year-old female with intractable fasting hypoglycaemia due to overproduction of "big" insulin-like growth factor II diagnosed to have pelvic GIST and managed by Steroids and Imatinib.

Report of the 22nd Annual Congress of the International Liver Transplantation Society.

The 2016 Annual Congress of the International Liver Transplantation Society was held in Seoul, South Korea in May. The 22nd Congress marked the largest multidisciplinary liver transplantation meeting in Asia since 2010. The principal themes were living donation, allocation, immunosuppression, machine preservation, novel treatment of hepatitis C, and expansion of the deceased-donor allograft pool. This report presents select abstracts from the scientific sessions within the context of the published literature to serve as a quick reference.

Quantification of Circulating Free DNA as a Diagnostic Marker in Gall Bladder Cancer.

Gall bladder Carcinoma (GBC) is the fifth most common cancer of the digestive tract and frequently diagnosed in late stage of disease. Estimation of circulating free DNA (cfDNA) in serum has been applied as a "liquid biopsy" in several deep seated malignancies. Its value in diagnosis of gall bladder carcinoma has not been studied. The present study was designed to assess the role of cfDNA in the diagnosis of GBC and correlate levels with the TNM stage. Serum was collected from 34 patients with GBC and 39 age and sex matched controls including 22 cholecystitis and 17 healthy individuals. Serum cfDNA levels were measured through quantitative polymerase chain reaction (qPCR) by amplification of ß-globin gene. Performance of the assay was calculated through the receiver operating characteristic (ROC) curve. The cfDNA level was significantly lower in healthy controls and cholecystitis (89.32 ± 59.76 ng/ml, 174.21 ± 99.93 ng/ml) compared to GBC (1245.91 ± 892.46 ng/ml, p = <0.001). The cfDNA level was significantly associated with TNM stage, lymph node involvement and jaundice (0.002, 0.027, and 0.041, respectively). Area under curve of ROC analysis for cancer group versus healthy and cholecystitis group was 1.00 and 0.983 with sensitivity of 100 %, 88.24 % and specificity of 100 % respectively. Quantitative analysis of cfDNA may distinguish cholecystitis and gall bladder carcinoma and may serve as new diagnostic, noninvasive marker adjunct to imaging for the diagnosis of GBC.