Adjuvant Gemcitabine Plus Cisplatin and Chemoradiation in Patients With Gallbladder Cancer: A Randomized Clinical Trial.

Importance: There is limited evidence with regard to the benefit of adjuvant chemotherapy chemoradiotherapy in resected gallbladder cancers (GBCs). Objective: To establish a baseline survival rate for operated GBCs in patients receiving either gemcitabine plus cisplatin (GC) or capecitabine and capecitabine concurrent with chemoradiation (CCRT). Design, Setting, and Participants: The GECCOR-GB study was a multicenter, open-label, randomized phase 2 noncomparator "pick the winner" design trial of adjuvant GC and CCRT in patients with resected histologically confirmed adenocarcinoma or adenosquamous carcinoma of the gallbladder, (stage II/III) with no local residual tumor (R0) or microscopic residual tumor (R1). The study was carried out in 3 tertiary cancer institutions in India. Patients 18 years or older with adequate end-organ functions, and Eastern Cooperative Oncology Group Performance Status of 1 or lower between May 2019 and February 2022 were enrolled. The cutoff date for data analysis was February 28, 2023. Interventions: Patients were randomized 1:1 to receive either GC every 3 weeks (maximum of 6 cycles) or CCRT comprising capecitabine with concurrent chemoradiation (capecitabine concurrent with radiotherapy) sandwiched between capecitabine chemotherapy. Main Outcomes and Measures: The primary outcome was disease-free survival (DFS) at 1 year in randomized patients. This study was conducted as 2 parallel, single-stage phase 2 clinical trials. Within each treatment arm, a 1-year DFS rate of less than 59% was considered as insufficient activity, whereas a 1-year DFS rate of 77% or higher would be considered as sufficient activity. Results: With a median follow-up of 23 months, 90 patients were randomized, 45 in each arm. Overall, there were 31 women (69%) and 14 men (31%) in the GC arm with a mean (range) age of 56 (33-72) years and 34 women (76%) and 11 men (24%) in the CCRT group with a mean (range) age of 55 (26-69) years. In the GC and CCRT arms, 1-year DFS and estimated 2-year DFS was 88.9% (95% CI, 79.5-98.3) and 74.8% (95% CI, 60.4-89.2), and 77.8% (95% CI, 65.4-90.2) and 74.8% (95% CI, 59.9-86.3), respectively. Completion rates for planned treatment was 82% in the GC arm and 62% in the CCRT arm. Conclusions and Relevance: In this randomized clinical trial, GC and CCRT crossed the prespecified trial end points of 1-year DFS in patients with resected stage II/III GBCs. The results set a baseline for a larger phase 3 trial evaluating both regimens in operated GBCs. Trial Registration: ClinicalTrials.gov Identifier: CTRI/2019/05/019323I.

Preventing futile surgery in Intrahepatic and Perihilar cholangiocarcinomas: Can we identify preoperative factors to improve patient selection and optimize outcomes?

BACKGROUND: Intraoperative unresectability, postoperative deaths and early recurrences remain devastating futile events in the surgical management of Intrahepatic cholangiocarcinomas (iCCA) and Perihilar cholangiocarcinomas (pCCA). The present study aims to determine the preoperative predictors of futile surgery in cholangiocarcinomas. METHODS: Consecutive hepatectomies for iCCA and pCCA, between September 2010 and June 2022 were included. Futility of surgery was defined as either intraoperative unresectability, postoperative 30-day mortality or recurrence within six months of surgery. Multivariable logistic regression was used to identify predictors of futility. RESULTS: One hundred and fifty patients of iCCA and pCCA underwent surgery during the time period. Thirty-seven (38.1 %) out of 97 patients of iCCA and 25(47.16 %) out of 53 patients of pCCA underwent futile resection. The predictive factors of futile surgery for iCCA were tumour number (≥2) (OR, 9.705; 95%CI, 2.378-39.614; p = 0.002), serum aspartate transaminase (OR, 8.31; 95%CI, 2.796-24.703; p < 0.001) and serum CA-19.9 (>37 U/ml) (OR, 2.95; 95%CI, 1.051-8.283; p = 0.04). The predictive factors of futility for pCCA were lymph node involvement (OR, 7.636; 95%CI, 1.824-31.979; p = 0.005) and serum alkaline phosphatase (>562.5 U/L) (OR, 11.211; 95%CI, 1.752-71.750; p = 0.011). CONCLUSION: Futile surgery was observed in over one third of our patients. Five strong preoperative predictors of futility were identified. Careful analysis of these factors may reduce futile surgical explorations.

Investigating the Influence of Preoperative Trans Arterial Embolization (TAE) and Predictive Potential of Circulating Tumor Cells (CTCs) in Prognosis of Hepatocellular Carcinoma.

Introduction: Circulating tumor cells are a promising biomarker in many malignancies. CTC dissemination during the operative procedure can lead to disease recurrence. The effect of preoperative transarterial embolization on the release of CTCs and miRNA panels and oncological outcomes in large hepatocellular carcinomas has been evaluated. Materials and methods: The study included non-metastatic HCC >5 cm in size, that were completely resected after TAE (n = 10). Blood was collected pre-TAE, post-TAE, postoperative (day 2,30 and 180) and analyzed for the presence of CTC and miRNA (miR-885-5p, miR-22-3p, miR-642b-5p). The samples were subjected to CTC enrichment, isolation and staining using the markers CD45, EpCAM, and cytokeratin (CK). The data was analyzed using Gene Expression Suite software. Results: The CTC enumeration resulted in three groups: Group 1- CTC present at both pre-TAE and postoperative day 30 (n = 4), Group 2- CTC present at pre-TAE and clearing at postoperative day 30 (n = 2), Group 3- No CTC detected at any stages (n = 3). Group 2 patients had better survival compared with the other groups. Downregulation of miRNA 22-3p also had favorable prognostic implications. Conclusion: Although preoperative TAE does not seem to impact CTC shedding, CTC clearance may prove to be a valuable biomarker in prognosticating HCC. A larger study to evaluate the significance of CTCs as a prognostic marker is warranted to further evaluate these findings.

Tumor burden score as a prognostic factor in patients with intermediate and locally advanced hepatocellular carcinoma undergoing liver resection: an attempt to extend resectability criteria.

BACKGROUND: Surgery is currently recommended as a curative treatment option for hepatocellular carcinomas (HCC) belonging to Barcelona Clinic Liver Cancer (BCLC) stage A only. This study aims to classify various BCLC groups as per Tumor Burden Score (TBS) in an attempt to identify patients who could benefit from resection. MATERIALS AND METHODS: A retrospective analysis of a prospectively maintained database of all patients operated for HCC between January 2010 and July 2022 was performed. TBS was defined as, TBS2 = (maximum tumor diameter)2 + (number of tumors)2. RESULTS: Two hundred and ninety-one patients who underwent resection were staged as per the latest BCLC (A = 219, B = 45, C = 27) staging. Patients were segregated into low (<7.3) and high (>7.3) TBS. With a median follow-up of 36.2 months, the median OS for stages, A and B in the low TBS group was 107.4 and 42.7 months respectively. Median OS was not reached for patients in the BCLC C stage. In patients with high TBS, the median OS for BCLC A, B and C was 42.3, 25.72, and 16.9 months respectively. CONCLUSION: TBS is a significant factor influencing survival in patients of HCC. TBS can be used to stratify patients in BCLC B and C stages and help select patients who would benefit from surgical resection to achieve good long-term survival with acceptable morbidity.

Comparison of age-stratified survival outcomes of gallbladder cancers in an Indian population.

BACKGROUND: Gallbladder cancers (GBCs) occur a decade earlier in India in comparison to the global occurrence, limiting the applicability of existing literature on age adjusted outcomes. METHODS: Patients who underwent surgery between 01.01.2010 and 31.12.2020 for GBC were analyzed. Patients were divided into three age groups: group 1(≤40 years), group 2(41-60 years), group 3(>60 years) and their outcomes were compared. RESULTS: Total of 6190 patients were treated for suspected or diagnosed GBC with a median age of 57 years. Curative resection was performed in 749 (67.9%) patients, of whom 114 (16.2%), 471 (62.9%), and 164 (21.9%) patients were in groups 1, 2, and 3, respectively. 5-year disease-free survival (DFS) [46.8% vs. 58.5%, p = 0.031] and overall survival (OS)[53.5% vs. 66.6%, p = 0.05] of group 3 were significantly lower than group 1. Patient age (HR 1.021), AJCC stage (HR 6.413), pathologic residual disease in the gallbladder fossa (HR 2.44), and extranodal tumor deposits (HR 1.762) were identified as independent predictors of poor OS. CONCLUSIONS: Gallbladder cancers in the Indian population show poorer outcomes with advancing age. Higher proportion of males in the elderly group with a more advanced stage at presentation are plausible reasons for poorer outcomes.

Standardizing Surgical Management of Retroperitoneal Sarcomas: Dawn of a New Surgical Subspeciality in India.

BACKGROUND: Retroperitoneal sarcomas are a complex and heterogenous group of tumors. An approach to these tumors should be guided by a clear understanding of the disease biology and anatomical principles, which mandates a dedicated multidisciplinary team approach at all steps of management. We present our experience of evolution as a high-volume sarcoma center with a dedicated multidisciplinary tumor board (the RP clinic) with consequent standardization of surgeries and management protocols. METHODS: A retrospective analysis of a prospectively maintained database for patients undergoing surgery from January 2011 to June 2023 was performed. Data were divided into the pre-clinic era (2011-2017) and post-clinic era (2018-2023). Survival curves were obtained using the Kaplan-Meier method, and the Chi-square test was used to test significance for categorical variables. Time trends were analyzed using the one-way analysis of variance (ANOVA) test. A p value ≤ 0.05 was considered significant. RESULTS: Overall, 254 patients were operated during this period; 36.6% of patients underwent surgeries in the pre-RP clinic era (6 years) and 63.3% in the post-RP clinic era (4.5 years). There was a statistically significant increase in the number of cases being operated per year, from an average of 16.3 in the pre-clinic era to 42.4 in the post-RP clinic era (p = 0.001). The post-RP clinic era also showed a significant increase in compartment and multivisceral resections (49% vs. 18.2%; p = 0.0001). CONCLUSIONS: Establishment of a dedicated multidisciplinary tumor board (RP clinic) resulted in standardization of management protocols, resulting in optimal oncological and surgical outcomes.

Minimally Invasive Simultaneous Colorectal and Liver Resection for Synchronous Colorectal Liver Metastasis-Short-Term Outcomes.

Surgical management of colorectal disease and liver metastatectomy can be staged or synchronous. A minimally invasive approach in synchronous resection in the selected group of patients may improve postoperative outcomes. The present study aimed to explore the safety and feasibility of simultaneous liver and colorectal resection for synchronous metastasis by a minimally invasive approach in terms of major morbidity and R0 resection rates. The present study is a retrospective review of a prospectively maintained database. All patients who underwent minimally invasive simultaneous resection of colorectal malignancy and liver metastases between January 2020 and April 2023 were included. A total of 39 patients were included in the study. The median age was 54 (23-79) years with 28 male (72%) and 11 female (28%) patients. Rectum (n = 21, 54%) was the most common primary location. The most commonly performed procedures were low anterior resection (n = 12) and parenchymal sparing non-anatomical resection (n = 23, 59%). The median surgery duration was 280 (150-520) min, and the median blood loss was 400 (50-2100) ml. The median hospital stay was 7 (5-18) days. Five (12.6%) patients had major complications. With a median follow-up of 12 months, the 2-year overall survival (OS) and disease-free survival (DFS) were 84.6% and 37%, respectively. Simultaneous liver and colorectal resection by minimal access approach is feasible in selected groups of patients depending on the extent of hepatectomy, the patient's general condition, and surgical team experience. A minimal access approach leads to faster recovery without compromising on the oncological radicality.

Predictive Value of Preoperative ICG-R15 Testing in Post-hepatectomy Liver Failure Following Major Liver Resection: Indian Experience.

Surgical resection stands as the preeminent therapeutic approach for both primary hepatocellular carcinoma and metastatic liver malignancies. Its efficacy is contingent upon the attainment of a comprehensive excision while ensuring a sufficient future liver remnant (FLR). However, post-hepatectomy liver failure (PHLF) remains a significant challenge, particularly in patients with preexisting liver disease. The present study aims to investigate the predictive value of the preoperative indocyanine green retention test at 15 min (ICG-R15) in identifying patients at risk of PHLF following major liver resection. This retrospective review focused on patients who underwent the ICG-R15 test before major liver resection between August 2021 and January 2023. All patients underwent standard preoperative evaluation and staging. Patients with primary or metastatic liver cancer planned for major resection and undergoing ICG-R15 were included in the study. Patients with elevated serum bilirubin (> 3 mg/dl) and those not undergoing liver resection or minor liver resection (< 3 segments) were excluded from the study. PHLF was defined by the International Study Group of Liver Surgery (ISGLS) criteria. Follow-up was performed to identify 90-day morbidity. Using univariate and multivariate logistic regression analyses, we confirmed independent risk parameters that predicted postoperative major complications and severe PHLF. The study included 72 patients who underwent preoperative ICG-R15 testing prior to major liver resection. PHLF occurred in 28 patients (38.9%), with 24 patients (33.3%) classified as severity score B and 3 patients (4.16%) had severity score C. Univariate analysis revealed future liver remnant (FLR), ICG-R15, and blood transfusion as predictors of PHLF. Multivariate analysis confirmed FLR (p = 0.019) and ICG-R15 (p = 0.032) as significant predictors. Receiver operating characteristic curve analysis yielded an area under the curve of 0.642 for ICG-R15 in predicting PHLF. An optimal cut-point of 7.5 was determined. Our study highlights the importance of preoperative risk assessment of liver function evaluation using the ICG-R15 test, to predict the risk of PHLF following liver resection. Implementing appropriate interventions, especially in patients with borderline FLR, can improve surgical outcomes and enhance patient safety. Further research and prospective studies are essential to refine risk prediction models and improve rates of PHLF after liver resections.

Feasibility of Hepatic Artery Infusion Chemotherapy for Colorectal Liver Metastasis in an Indian Setting.

Hepatic artery infusion chemotherapy (HAIC) is a popular treatment modality for the treatment of colorectal liver metastasis (CRLM). The aim of this study was to determine the feasibility of HAIC for high-risk resected CRLM delivered using repeated femoral puncture and delivering 5-fluorouracil infusional chemotherapy along with systemic adjuvant chemotherapy. The present study is a retrospective review of a prospectively maintained database. All patients who underwent HAIC for colorectal liver metastases between July 2022 and July 2023 were included. A total of 12 patients were included in the study of which 11 completed four sessions as planned. The median age was 47 (29-73) years with nine male (81%) and two female (18%) patients. Rectum (n = 7, 63%) was the most common primary location. All patients received systemic chemotherapy with 5-fluorouracil-based regimens prior to HAIC (median 12 cycles). The median number of metastasis was 2 (1-8). Eight patients had metastasis in unilobar distribution (73%). On completion of HAIC treatment, nine patients (64%) were completely disease free with a median follow-up of 8 months. None of the patients experienced any immediate adverse events during or after completion of the procedure. Conventional HAIC comes with various challenges such as unavailability of the agent floxuridine and the specialized HAIC pump. Percutaneous HAIC has a lower chance of infection. The delivery of HAIC using repeated femoral punctures and 5FU chemotherapy was successful in over 90% of the patients making it a feasible option in the treatment of CRLM.

Outcomes of Robotic Surgery in a Single-institution, High-volume Hepatobiliary Oncology Unit.

Hepatobiliary surgery has traditionally been performed via an open approach. With the advent of robotic surgery, the minimal access approach in hepatobiliary oncology has gained impetus due to its technical superiority and favorable learning curve over laparoscopy. We present our experience with the Da Vinci Xi system in hepatobiliary oncology. This is a retrospective study from a prospectively maintained database. All patients who underwent surgery between June 2015 and July 2023 for suspected gallbladder cancer and primary or metastatic liver tumors were included. After excluding all inoperables and conversions, a total of 92 patients were included for analysis. There was a conversion rate of 15.6% (17 of 109 patients). Sixty-four (69.6%) patients underwent surgery for gallbladder-related pathologies that included 39 (60.9%) radical cholecystectomies, 24 (37.5%) simple cholecystectomies, and 1 (0.01%) revision cholecystectomy. Twenty-eight patients underwent surgeries for primary or metastatic liver tumors, which included 25 (92.9%) minor and 2 (7.1%) major hepatectomies. Significant morbidity (Clavien-Dindo grade III or more) was seen in 8 (8.6%). There was no postoperative mortality. In the group with gallbladder cancer, the median lymph nodal yield was 7 (2-22) in patients who underwent lymph nodal dissection. The median follow-up was 63.9 (0.49-100.67) (IQR = 37.76) months. The 5-year OS and DFS were 76.4 and 71.3%, respectively. Robotic hepatobiliary surgery is feasible and can be performed safely after adequate training. Patient selection is of utmost importance and is the key to establishing a robust robotic hepatobiliary oncosurgery program.

Neuroendocrine Tumours of Extrahepatic Biliary Tract: Report of Four Cases with Literature Review.

Neuroendocrine tumours (NETs) originating from extrahepatic bile duct are an extremely rare entity. They are typically slow growing tumours with malignant potential. Commonly presenting as obstructive jaundice, preoperative clinico-radiologic differentiation between extrahepatic biliary tract neuroendocrine tumours and cholangiocarcinoma is difficult and the final diagnosis is usually established after surgical histopathology and immunohistochemistry examination. R0 resection offers the only curative option with good long-term outcomes for well-differentiated NETs (grade1, grade2, and grade3) while the aggressive poorly differentiated neuroendocrine carcinoma (NEC) needs multimodality approach. We present our experience of management of four cases including three cases of grade II NET and one case of NEC undergoing surgical resection at a single centre with a short review of available literature.

Artificial Intelligence in Perioperative Planning and Management of Liver Resection.

Artificial intelligence (AI) is a speciality within computer science that deals with creating systems that can replicate the intelligence of a human mind and has problem-solving abilities. AI includes a diverse array of techniques and approaches such as machine learning, neural networks, natural language processing, robotics, and expert systems. An electronic literature search was conducted using the databases of "PubMed" and "Google Scholar". The period for the search was from 2000 to June 2023. The search terms included "artificial intelligence", "machine learning", "liver cancers", "liver tumors", "hepatectomy", "perioperative" and their synonyms in various combinations. The search also included all MeSH terms. The extracted articles were further reviewed in a step-wise manner for identification of relevant studies. A total of 148 articles were identified after the initial literature search. Initial review included screening of article titles for relevance and identifying duplicates. Finally, 65 articles were reviewed for this review article. The future of AI in liver cancer planning and management holds immense promise. AI-driven advancements will increasingly enable precise tumour detection, location, and characterisation through enhanced image analysis. ML algorithms will predict patient-specific treatment responses and complications, allowing for tailored therapies. Surgical robots and AI-guided procedures will enhance the precision of liver resections, reducing risks and improving outcomes. AI will also streamline patient monitoring, better hemodynamic management, enabling early detection of recurrence or complications. Moreover, AI will facilitate data-driven research, accelerating the development of novel treatments and therapies. Ultimately, AI's integration will revolutionise liver cancer care, offering personalised, efficient and effective solutions, improving patients' quality of life and survival rates.

Role of Intraoperative Frozen Section Assessment of Proximal Bile Duct Margins and the Impact of Additional Re-Resection in Perihilar Cholangiocarcinomas.

Intraoperative frozen section (FS) analysis to assess the bile duct margin status is commonly used to assess the completeness of resection during surgery for perihilar cholangiocarcinoma (pCCA) resection. However, the impact of additional re-section on the long-term outcome after obtaining an initial positive margin remains unclear. Patients diagnosed as pCCA on preoperative imaging and subjected to curative intent surgery from May 2013 to June 2021 with a minimum follow-up of 2 years were included. Intraoperative FS analysis of the proximal bile duct margin was performed in all patients. A positive margin was defined by the presence of invasive cancer. Out of the 62 patients with a preoperative diagnosis of pCCA on imaging, 35 patients were included for final analyses after excluding patients with inoperable disease (on staging laparoscopy or local exploration) and other/benign pathology on the final histopathology report. Out of the 35 patients, patients with postoperative 90-day mortality were excluded from the final survival analysis. FS analysis revealed an initial positive margin in 10 (28.5%) patients. Among 10 patients who underwent re-resection to achieve negative proximal margins, only 5 patients achieved a negative margin (secondary R0). An initial positive margin was associated with poor long-term outcomes. Median disease-free survival (DFS) and overall survival (OS) were 16 and 19.6 months for patients with an initial positive margin, but 36 and 58.2 months for patients with an initial negative margin, respectively (p = 0.012). The median DFS and OS were significantly lower for those with secondary R0 as compared to primary R0 (16 vs. 36 months for DFS, p = 0.117 and 19.6 vs. 58.2 months for OS, p = 0.027, respectively). An intraoperative FS positive proximal hepatic duct margin dictates poor long-term outcomes for patients with resectable pCCA. Additional resection has a questionable benefit on survival, when a secondary negative margin is achieved.

En Bloc Inferior Vena Cava (IVC) Resection Without Reconstruction With Right Hepatectomy and Right Nephrectomy for a Large IVC Leiomyosarcoma.

BACKGROUND: Radical resection remains the only potential cure in the management of inferior vena cava (IVC) leiomyosarcomas with multivisceral resections often needed (Borghi et al. in J Cardiovasc Surg (Torino) 63:649-663, 2022). This video describes the technical nuances of surgical resection of a large retrohepatic IVC leiomyosarcoma. PATIENT AND METHODS: Computed tomography of a 60-year-old woman revealed a 12 × 12 × 9.5 cm mass in the right suprarenal region infiltrating the IVC with intraluminal extension up to the hepatic venous confluence. The mass involved the right hepatic vein with infiltration of segment 7 of the liver and splaying of the right portal vein. Robust lumbar venous drainage from the infratumoral IVC was seen. En bloc IVC resection without reconstruction along with a right hepatectomy and right nephrectomy was performed via a right thoracoabdominal approach. RESULTS: After a Catell-Braasch maneuver, the surgery can be broadly divided into four major steps: (1) Right retroperitoneal mobilization of the tumor and right kidney with infratumoral IVC control, (2) mobilization of the right liver with suprahepatic IVC control, (3) division of the right portal structures with right hepatectomy, and (4) en bloc resection of the IVC tumor. Reconstruction of the IVC was not performed owing to the presence of venous collaterals (Langenbecks et al. in Arch Surg 407:1209-1216, 2022). Final histopathology showed a high-grade leiomyosarcoma with histologic organ invasion in the liver and right kidney with resected margins free of the tumor (R0). CONCLUSIONS: Meticulous preoperative planning and expertise in liver resection and retroperitoneal surgeries facilitates such radical yet safe multivisceral resection for a large retrohepatic IVC leiomyosarcoma without the need for a cardiopulmonary bypass.

Tata Memorial Centre Evidence Based Management of Colorectal cancer.

ABSTRACT: This review article examines the evidence-based management of colorectal cancers, focusing on topics characterized by ongoing debates and evolving evidence. To contribute to the scientific discourse, we intentionally exclude subjects with established guidelines, concentrating instead on areas where the current understanding is dynamic. Our analysis encompasses a thorough exploration of critical themes, including the evidence surrounding complete mesocolic excision and D3 lymphadenectomy in colon cancers. Additionally, we delve into the evolving landscape of perioperative chemotherapy in both colon and rectal cancers, considering its nuanced role in the context of contemporary treatment strategies. Advancements in surgical techniques are a pivotal aspect of our discussion, with an emphasis on the utilization of minimally invasive approaches such as laparoscopy and robotic surgery in both colon and rectal cancers, including advanced rectal cases. Moving beyond conventional radical procedures, we scrutinize the feasibility and implications of endoscopic resections for small tumors, explore the paradigm of organ preservation in locally advanced rectal cancers, and assess the utility of total neoadjuvant therapy in the current treatment landscape. Our final segment reviews pivotal trials that have significantly influenced the management of colorectal liver and peritoneal metastasis.

Neuroendocrine differentiation in a metachronous metastatic deposit in a case of mature growing ovarian teratoma: A rare occurrence.

ABSTRACT: Growing teratoma syndrome is a rare condition seen in non seminomatous germ cell tumor after completion of chemotherapy. Ectodermal, mesodermal and endodermal differentiation is commonly seen in mature teratoma. neuroendocrine differentiation in a metastatic deposit of mature teratoma is rarely reported. We are presenting a case of neuroendocrine differentiation in a long standing metastatic deposit of a mature teratoma.