Laparoscopic Extended Segmentectomy VIII Guided by Three-Dimensional Reconstruction and Hepatic Veins with a Cranio-Caudal Approach.

INTRODUCTION: Minimally invasive resection of segment VIII is a technically challenging procedure, made even more challenging when the resection is extended to segment IV and/or segment VII. Parenchymal-sparing resections are frequently used in the management of liver metastases but expose to the risk of R1 resection, especially with a minimally invasive approach. Preoperative surgical planning with 3D reconstruction and intraoperative guidance with hepatic vein is helpful for laparoscopic oncological liver resection.1-3 PATIENT AND METHODS: We present the case of a 58-year-old female with three metachronous liver metastases from epidermoid anal cancer. The disease was stable 6 months after cessation of chemotherapy. Metastases were mainly located in segment VIII (with a large segment VIII dorsal) but also in the territory of glissonian pedicles from segments IV and VII. Prior to surgery, three-dimensional (3D) reconstruction showed that a segmentectomy VIII would not be sufficient to have a safety margin and showed the relation between metastases and hepatic veins. Transection of the liver was performed with an ultrasonic dissector. Exposure of the hepatic veins was performed by gently pulling of the hepatic tissue from the vein, using the nonactive blade of the ultrasonic device. Activation of ultrasonic energy was performed only for sealing and dividing small collateral veins. Three transection lines were necessary. The posterior transection line, in segment VII, was determined with intraoperative ultrasound (IOUS), at 1 cm below the metastasis. The liver was transected superficially only. The medial transection line, in segment IV, was determined with IOUS, at 1 cm on the left of the metastasis, parallel to the middle hepatic vein. Finally, the inferior transection line, between segment V and segment VIII, was approximately determined with IOUS, vertically aligned with the hepatic vein of segment V. The transection line was further corrected after clamping the glissonian pedicle of segment VIII, according to fluorescence. The surgical procedure began with the mobilization of the right liver, including division of the hepato-caval ligament, followed by the superficial transection of the posterior margin in segment VII. Then, transection of segment IV was performed near the termination of the middle hepatic vein, which was further exposed with a cranio-caudal approach to minimize the risk of vein injury. The hepatic vein of segment V was then used as a landmark for the identification of the Glissonian pedicle of segment VIII, which was transected.4 Termination of the right hepatic vein (RHV) was then identified, and the ventral branch of the RHV was transected. The dorsal branch of the RHV was exposed with a cranio-caudal approach. Finally, transection of segment VII was performed toward the transection line made initially. RESULTS: Operative time was 360 min with 450 mL blood loss. The Pringle maneuver was used during 148 min. The patient was discharged on the seventh postoperative day. Pathological examination confirmed R0 resection, with 20-60% necrosis of the three liver metastases. The resected liver weight was 225 g. Six months after liver resection, the patient had a recurrence in a celiac lymph node, which was treated by radiotherapy. Fifteen months after liver resection, the patient is free of disease without active treatment. CONCLUSION: Preoperative virtual hepatectomy facilitates surgical planning by increasing the understanding of the tumors-vessels relationship. Intraoperative hepatic vein guidance with a cranio-caudal approach enables to follow preoperative surgical planning and to perform safe complex laparoscopic liver resection.

Gemcitabine and Paclitaxel Versus Gemcitabine Alone After 5-Fluorouracil, Oxaliplatin, and Irinotecan in Metastatic Pancreatic Adenocarcinoma: A Randomized Phase III PRODIGE 65-UCGI 36-GEMPAX UNICANCER Study.

PURPOSE: GEMPAX was an open-label, randomized phase III clinical trial designed to assess the efficacy and tolerability of gemcitabine plus paclitaxel versus gemcitabine alone as second-line treatment for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who previously received 5-fluorouracil, oxaliplatin, and irinotecan. METHODS: Patients with histologically or cytologically confirmed mPDAC were randomly assigned (2:1) to receive GEMPAX (paclitaxel 80 mg/m2 + gemcitabine 1,000 mg/m2; IV; once at day (D) 1, D8, and D15/arm A) or gemcitabine (arm B) alone once at D1, D8, and D15 every 28 days until progression, toxicity, or patient's decision. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), quality of life, and safety. RESULTS: Overall, 211 patients (median age, 64 [30-86] years; 62% male) were included. After a median study follow-up for alive patients of 13.4 versus 13.8 months in arm A versus arm B, the median OS (95% CI) was 6.4 (5.2 to 7.4) versus 5.9 months (4.6 to 6.9; hazard ratio [HR], 0.87 [0.63 to 1.20]; P = 0.4095), the median PFS was 3.1 (2.2 to 4.3) versus 2.0 months (1.9 to 2.3; HR, 0.64 [0.47 to 0.89]; P = 0.0067), and the ORR was 17.1% (11.3 to 24.4) versus 4.2% (0.9 to 11.9; P = 0.008) in arm A versus arm B, respectively. Overall, 16.7% of patients in arm A and 2.9% in arm B discontinued their treatment because of adverse events (AEs). One grade 5 AE associated with both gemcitabine and paclitaxel was reported in arm A (acute respiratory distress), and 58.0% versus 27.1% of patients experienced grade ≥3 treatment-related AEs in arm A versus arm B, among which 15.2% versus 4.3% had anemia, 15.9% versus 15.7% had neutropenia, 19.6% versus 4.3% had thrombocytopenia, 10.1% versus 2.9% had asthenia and 12.3% versus 0.0% had neuropathy. CONCLUSION: While GEMPAX did not meet the primary end point of OS versus gemcitabine alone in patients with mPDAC in the second-line setting, both PFS and ORR were significantly improved.

Trifluridine/tipiracil + oxaliplatin ± nivolumab vs FOLFOX ± nivolumab in HER2 negative advanced oesogastric adenocarcinoma: The PRODIGE73-UCGI40-LOGICAN trial.

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) is approved in third-line treatment of patients with advanced/metastatic gastric and gastroesophageal junction adenocarcinomas (aGA/GEJA). The association of oxaliplatin with FTD/TPI is promising and the combination of FTD/TPI + oxaliplatin + nivolumab has shown a predictable and manageable safety profile. AIMS: The aim is to evaluate the efficacy and safety of FTD/TPI plus oxaliplatin with or without nivolumab in patients, with HER2 negative aGA/GEJA, unfit for triplet chemotherapy (TFOX/mFLOT regimen), in the first-line metastatic setting in comparison with the standard of care FOLFOX with or without nivolumab. METHODS: This study is a prospective randomised, open label, comparative, multicentre, phase II trial designed to include 118 patients. The primary objective is to evaluate the superiority of FTD/TPI plus oxaliplatin with or without nivolumab over FOLFOX regimen with or without nivolumab in terms of PFS in a population of patients non candidate for triplet chemotherapy. Nivolumab will be used for patients whose tumour express PD-L1 with a CPS score ≥5. DISCUSSION: PRODIGE73-UCGI40-LOGICAN study will provide efficacy and safety data on the association of FTD/TPI plus oxaliplatin with or without nivolumab versus FOLFOX regimen with or without nivolumab in first-line palliative setting, in patients with aGA/GEJA (NCT05476796).