Patients Underwent R0 Resection Research Articles

Adjuvant 5-fluorouracil and portal vein infusion chemotherapy followed by gemcitabine for pancreatic cancer.

Although adjuvant gemcitabine (GEM) monotherapy improves the overall survival (OS) of patients with resected pancreatic cancer, its efficacy requires further improvement. This multicenter, phase II study investigated the efficacy of adjuvant portal vein infusion (PVI) chemotherapy followed by GEM therapy in patients with resected pancreatic cancer. 5-fluorouracil (250 mg/day) and heparin (2000 IU/day) PVI chemotherapy were combined with systemic administration of mitomycin C (4 mg; days 6, 13, 20, and 27) and cisplatin (10 mg; days 7, 14, 21, and 28) for 4 weeks (PI4W), followed by GEM (1000 mg/m2; days 1, 8, and 15 every 4 weeks for 6 months). The primary endpoint was relapse-free survival (RFS) and the secondary endpoints were OS and treatment completion. Between November 2010 and August 2013, 53 patients who underwent complete resection were enrolled, including 30, 20, and 3 patients who underwent pancreaticoduodenectomies and distal and total pancreatectomies, respectively. In total, 51 (96.2%) patients underwent R0 resection, of whom 3, 2, 12, 35, 0, and 1 had stages IA, IB, IIA, IIB, III, and IV cancer, respectively, and 47 (88.7%) patients completed PI4W. The median RFS was 22.0 months (1-, 3-, 5, and 10 years RFS: 64.9%, 38.1%, 38.1%, and 38.1%, respectively), whereas the median OS was 32.0 months (1-, 3-, 5, and 10 years OS:86.6%, 47.2%, 44.4%, and 44.4%, respectively). Treatment with PI4W followed by GEM for 6 months after surgery may be beneficial in patients undergoing curative resection of pancreatic cancer.

Prognostic Impact of Perioperative CA125 Status in Gastric Cancer Based on New Cutoff Values.

Objectives The current carbohydrate antigen 125 (CA125) cutoff value demonstrated high specificity but low sensitivity. Therefore, we used new cutoff values to evaluate the clinical impact of perioperative CA125 in gastric cancer. Methods This study retrospectively analyzed 525 patients with gastric cancer (349 males and 176 females), of whom 445 patients underwent R0 resection and 80 patients underwent R1/R2 resection between 2011 and 2020. The receiver operating characteristic curve indicated preoperative and postoperative cutoff CA125 values of 15.7 IU/mL and 17.3 IU/mL, respectively, to predict overall survival. Furthermore, we analyzed changes in postoperative CA125 levels and evaluated their prognostic impact using multivariate analysis. Results The preoperative CA125-positive rate was 25%. Males, advanced TNM factors, and noncurative resection cases demonstrated significantly higher positive rates than the other group. The preoperative CA125-positive group exhibited a significantly higher noncurative resection rate than the preoperative CA125-negative group (32% versus 10%, P < 0.01). Preoperatively, CA125-positive status was an independent poor prognostic factor (P < 0.01), and at three months postoperatively, it tended to be a poor prognostic factor. Conclusions High preoperative CA125 (>15.7 IU/mL) was a significant predictor for noncurative resection and poor overall prognosis in gastric cancer. Furthermore, postoperative CA125-positive status three months postoperatively was also a potential predictor of recurrence and poor prognosis.

Preoperative nivolumab plus SOX in patients with locally advanced gastric or gastro-esophageal junction cancer: A phase 2, single-arm trial.

4074 Background: Preoperative chemotherapy has been widely recommended in patients with locally advanced gastric or gastro-esophageal junction cancer (GC/GEJC), and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. We conducted a single-arm phase II trial (Stimulate-01) to evaluate the efficacy and safe of the anti-PD-1 antibody nivolumab plus SOX regimen in patients with locally advanced GC/GEJC and to explore the biomarker associated with therapy response. Methods: Patients with locally advanced GC/GEJC (cT3-4N+M0) were enrolled and received either 3 preoperative and 3 postoperative cycles of nivolumab (360 mg, IV, d1, Q21d) plus SOX regimen (oxaliplatin 130 mg/m2, IV, d1 with oral S-1 40-60mg, bid, d1-d14, Q21d) therapy, followed by 11 cycles of nivolumab monotherapy. The primary endpoint was the pathological complete response (pCR) rate, while the major pathological response rate (mPR), 3-year-DFS and 3-year-OS as the second endpoint. This clinical trial was registered at Clinicaltrial.gov (NCT05739045). In addition, tissue sample before and after treatment from patients were performed scRNA-seq. Results: Forty-six patients were enrolled from November 2022 to March 2023, with a median age of 66 years (range, 34-74), and 38 were male. The pCR rate was 28.26% [95% confidence interval (CI), 15.2%-41.3%], and the major pathologic response (mPR) [tumor regression grade (TRG)0/1] rate was 41.3% (95% CI, 27.1%-55.5%). All the patients underwent R0 resection. The mPR rate in patients with PD-L1 CPS ≥5 and patients with PD-L1 CPS&lt;5 was 42.86% vs 38.89% ( P= 0.790). In addition, This clinical study period spans from epidemic control to full liberalization in China. The mPR rate in patients infected with COVID-19 was 44.44% (12/27), while the mPR rate in patients who have not been infected with COVID-19 was 36.84% (7/19) ( P=0.146). There were no severe complications or death related to the surgery. The scRNA-seq data revealed that the composition of MHC-II (HLA-DRA, HLA-DPA1, HLA-DRB1, HLA-DPB1 and HLA-DQB1) were significantly over-expressed in cancer cell of treatment-sensitive patients (TRG0/1) compared to that of treatment-insensitive patients (TRG2/3). Then the MHC-II expression in pre-treatment biopsy samples from 240 GC patients who received preoperative immunotherapy plus chemotherapy were performed by immunohistochemistry. The results showed that the mPR rate in patients with MHC-II IHC ≥2 and patients with MHC-II IHC&lt;2 was 58.87% (83/141) vs 21.21% (21/99) ( P&lt;0.001). Conclusions: Nivolumab plus SOX as neoadjuvant therapy showed an encouraging pCR rate, mPR rate, and manageable safety. The long-term efficacy of this combination of regimens will be continued to follow up. In addition, the MHC-II expression may be a potential biomarker for predicting the effectiveness of immunotherapy combined with chemotherapy for GC/GEJC. Clinical trial information: NCT05739045 .

A retrospective study of postoperative adjuvant therapy following immunotherapy combined with targeted therapy and sequential curative surgical procedures for initially unresectable hepatocellular carcinoma

Objective: To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma. Methods: This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People's Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer(BCLC) stage C. Survival curves were made using Kaplan Meier method. Results: Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95%CI:93.4% to 100%) and 90.7%(95%CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95%CI:83.0% to 99.8%) and 71.3%(95%CI:58.7% to 86.5%). Conclusions: The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Malignancy After Living Donor Liver Transplantation

ObjectivesDe novo malignancy (DNM) is a major cause of death in long-term recipients of liver transplantation (LT). We herein report our experience with DNM after living-donor LT (LDLT). Patients and MethodsA total of 111 LDLT procedures were performed in our institute from 1999 to 2022. Among them, 70 adult (>13 years old) LDLT recipients who survived for more than 1 year were included in this study. ResultsDuring a median follow-up of 146 (range, 12-285) months, 7 out of 70 recipients developed 8 DNMs, including lung cancer in 4, post-transplant lymphoproliferative disease in 3, and skin cancer in 1. One patient developed metachronal skin cancer and post-transplant lymphoproliferative disease. The pre-LT smoking history rate in patients with DNM was higher than in patients without DNM (P = .004). The survival time after DNM was 6 (1-166) months. Only 2 patients underwent R0 resection. DNM did not recur during follow-up. Other patients who underwent R1 resection and/or chemotherapy and/or radiotherapy all died due to DNMs during the follow-up. The cumulative DNM incidence was 3.5% at 10 years and 18.4% at 20 years after LDLT. The cumulative survival rate in patients with DNM was significantly worse than that in patients without DNM after LDLT (P = .049). ConclusionThe survival rate of patients with DNM was lower than that of those without DNM. A pre-LT smoking history is a risk factor for DNM. R0 resection is effective for improving the prognosis of patients with DNM. Regular cancer screening is important for detecting DNM early after LDLT.

Neo-adjuvant tislelizumab combined with lenvatinib treatment for resectable, recurrent hepatocellular carcinoma.

517 Background: The persistent challenge of elevated re-recurrence rates following secondary hepatectomy complicates the prospects for improving survival in recurrent hepatocellular carcinoma (rHCC) patients. Immunotherapy combined with targeted drugs have been the first-line therapy for advanced HCC and shown good response rate in neoadjuvant situation. However, the effectiveness and safety of the combination treatment has not been reported in rHCC patients. To address this, we conducted the present phase 2 clinical trial of neoadjuvant treatments using tislelizumab in combination with lenvatinib for rHCC patients. Methods: Patients with resectable rHCC patients who had previously undergone curative treatment were enrolled. Enrolled patients were treated with 2 neoadjuvant cycles of a combination of tislelizumab 200mg intravenously every 3 weeks and lenvatinib 8mg every day (12mg for patients over 60kg) for 4 weeks. Hepatectomy was conducted in six weeks after enrollment. One month after surgery, adjuvant combination of tislelizumab and lenvatinib was started for at least one year or until disease progression or intolerance of adverse reactions. The primary objective of the trial is to evaluate one-year disease-free survival (DFS) rate, and secondary endpoints include objective response rate (ORR) as assessed by RECIST 1.1, major pathologic response (defined as over 90% tumor necrosis), and safety considerations. Results: Until Sep 30th, 2023, a total of 14 patients have been enrolled. All participants underwent the complete neoadjuvant therapy with a combination of tislelizumab and lenvatinib before proceeding to hepatectomy. Throughout the neoadjuvant phase, 14.3% (2/14) of patients occurred adverse events below grade 3, with no severe adverse events occurring. The most common adverse events were fatigue (in 2 patients), hypertension (in 1 patient) and reduced appetite (in 1 patient). In 14 patients, 12 patients underwent R0 resection and 2 were waiting for hepatectomy. The average time from the initiation of the neoadjuvant therapy to hepatectomy was approximately 40.42 days. On the radiological front, one patient (8.3%) exhibited a partial response, while 11/12 (91.7%) displayed stable disease with 8 patients had tumor shrinkage. In terms of pathological outcomes, 25% of patients (3/12) achieved a complete response, whereas the remaining patients showed varying degrees of pathologic response, ranging from 5% to 85%. Conclusions: In summary, the dual therapy of tislelizumab and lenvatinib demonstrates encouraging safety and effectiveness as a neoadjuvant intervention for patients with rHCC. The long-term results of this combined treatment approach are eagerly anticipated. Clinical trial information: NCT04615143 .

Malignant Chest Wall Tumors: Complex Defects and Their Management-A Review of 181 Cases.

Chest wall tumors are a heterogeneous group of tumors that are managed by surgeons from diverse specialties. Due to their rarity, there is no consensus on their diagnosis and management. This retrospective, descriptive analysis includes patients with malignant chest wall tumors undergoing chest wall resection. Tumors were classified as primary, secondary, and metastatic tumors. The analysis includes clinicopathological characteristics, resection-reconstruction profile, and relapse patterns. A total of 181 patients underwent chest wall resection between 1999 and 2020. In primary tumors (69%), the majority were soft tissue tumors (59%). In secondary tumors, the majority were from the breast (45%) and lung (42%). Twenty-five percent of patients received neoadjuvant chemotherapy, and 98% of patients underwent R0 resection. Soft tissue, skeletal + soft tissue, and extended resections were performed in 45%, 70%, and 28% of patients, respectively. The majority of patients (60%) underwent rib resections, and a median of 3.5 ribs were resected. The mean defect size was 24 cm2. Soft tissue reconstruction was performed in 40% of patients, mostly with latissimus dorsi flaps. Rigid reconstruction was performed in 57% of patients, and 18% underwent mesh-bone cement sandwich technique reconstruction. Adjuvant radiotherapy and chemotherapy were given to 29% and 39% of patients, respectively. This is one of the largest single-institutional experiences on malignant chest wall tumors. The results highlight varied tumor spectra and multimodality approaches for optimal functional and survival outcomes. In limited resource setting, surgery, including reconstructive expertise, is very crucial.

Clinical impact of skeletal muscle mass change during the neoadjuvant chemotherapy period in patients with gastric cancer: An ancillary study of JCOG1002.

Recent studies have revealed that sarcopenia is associated with postoperative complications and poor prognosis. Although neoadjuvant chemotherapy is a promising treatment for gastric cancer, its toxicity may lead to the loss of skeletal muscle mass. This study investigates the changes in skeletal muscle mass during neoadjuvant chemotherapy and its clinical impact on patients with locally advanced gastric cancer. Fifty patients who completed two courses of neoadjuvant chemotherapy followed by surgery were included. Skeletal muscle mass was measured using computed tomography images before and after chemotherapy. The proportion of skeletal muscle mass change (%SMC) during neoadjuvant chemotherapy and its cutoff value was explored using the receiver operating characteristic for the overall survival of patients undergoing R0 resection. Risk factors of skeletal muscle mass loss were also evaluated. Overall, 64% of patients had skeletal muscle mass loss during neoadjuvant chemotherapy (median %SMC -3.4%; range: -18.9% to 10.3%). Multivariable analysis identified older age (≥70years) as an independent predictor of skeletal muscle mass loss (mean [95% confidence interval]: -4.70% [-8.83 to -0.58], p=0.026). Among 43 patients undergoing R0 resection, %SMC <-6.9% was an independent poor prognostic factor for overall survival (hazard ratio, 11.53; 95% confidence interval, 2.78-47.80) and relapse-free survival (hazard ratio 4.54, 95% confidence interval 1.50-13.81). Skeletal muscle mass loss occurs frequently during neoadjuvant chemotherapy for locally advanced gastric cancer and could adversely affect survival outcomes.

Study of perioperative safety of laparoscopic pancreaticoduodenectomy in elderly patients

To investigate the safety of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients and the related risk factors admitted to the intensive care unit (ICU) after LPD. The perioperative data of patients who underwent LPD in Tianjin Medical University General Hospital from February 2017 to June 2023 were retrospectively collected, including basic data, preoperative laboratory indicators, intraoperative and postoperative indicators, pathological results (tumor size, lymph node dissection and pathological type), postoperative complications, ICU postoperative management and prognosis. The patients were divided into the elderly group (≥ 65 years) and the non-elderly group (< 65 years) according to age. Perioperative data between two groups were compared. Kaplan-Meier survival curve was drawn to analyze the survival rate of the elderly group and the non-elderly group, and the pancreatic head carcinoma group and other type of tumors group after LPD. Logistic regression was used to analyze the risk factors of ICU stay (length of ICU stay > 1 day) after LPD in elderly patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of this risk factor for ICU stay after LPD in elderly patients. A total of 160 patients were enrolled, including 57 cases in the elderly group (17 cases of vascular reconstruction) and 103 cases in the non-elderly group (40 cases of vascular reconstruction). All patients underwent R0 resection and were transferred to the comprehensive ICU for treatment. The follow-up time of patients with malignant tumors was 43 (6, 72) months. The elderly group had significantly longer surgery time, postoperative hospital stay and oral feeding time than the non-elderly group, and the incidence of delayed gastric emptying (DGE) was significantly higher than that in the non-elderly group. There were no significant differences in intraoperative blood transfusion rate, intraoperative blood loss, pathological results, short-term and severe postoperative complications, reoperation rate and 90-day mortality between the two groups. In patients with vascular resection reconstruction, the intraoperative blood loss in the elderly group was significantly higher than that in the non-elderly group, and the operation time and postoperative hospital stay were significantly longer. During ICU, the acute physiology and chronic health evaluation II [APACHE II: 12 (9, 14) vs. 8 (7, 10)], sequential organ failure assessment [SOFA: 6 (4, 8) vs. 3 (2, 5)] within 24 hours after admission to ICU were significantly increased in the elderly group (both P < 0.05), the time of mechanical ventilation [hours: 12 (10, 15) vs. 9 (5, 13)] and the length of ICU stay [days: 2 (1, 2) vs. 1 (1, 1)] were significantly increased in the elderly group (both P < 0.05), and the proportion of multi-disciplinary team (MDT) was also significantly increased in the elderly group (33.3% vs. 17.4%, P < 0.05), there were no significant differences in the levels of hemoglobin (Hb), albumin, and blood lactic acid between the two groups. Logistic regression analysis showed that the APACHE II score was an independent risk factor for ICU stay after LPD in elderly patients (β = 1.737, P = 0.028). ROC curve showed that the prediction performance was the best when the APACHE II score was 13, with the sensitivity of 72.41% and the specificity of 96.43%, and the area under the ROC curve (AUC) of 0.884. The Kaplan-Meier survival curve showed that there were no significant difference in median survival time (months: 24.1 vs. 24.7) and 5-year survival rate (19.01% vs. 19.02%) between the elderly group (52 cases) and the non-elderly group (92 cases) among the 144 patients with malignant tumors (both P > 0.05). The median survival time in the pancreatic head carcinoma group was significantly shorter than that in the other tumors group (63 cases; months: 20.2 vs. 40.1, P < 0.05), 5-year survival rate was significantly lower than that in the other tumors group (21.98% vs. 30.91%, P < 0.05). LPD is a safe and feasible treatment for elderly patients. APACHE II score has a certain predictive value for ICU stay after LPD in elderly patients.

Pembrolizumab, Radiotherapy, and Chemotherapy in Neoadjuvant Treatment of Malignant Esophago-Gastric Diseases (PROCEED): Assessment of Pathologic Response in a Prospective, Phase II Single-Arm Trial

A standard treatment paradigm for locally advanced, resectable, non-metastatic esophageal or gastric adenocarcinomas (EGA) is neoadjuvant chemoradiation (CRT) followed by surgical resection. Historical pathologic complete response (pCR) rate after CRT with carboplatin/paclitaxel per the CROSS trial was 23%. The efficacy of immune checkpoint inhibition in the adjuvant setting has since been demonstrated in this patient population. The primary objective of this trial was to investigate whether neoadjuvant CRT combined with pembrolizumab improves pCR compared to the historical control of CRT alone. Single-institution, prospective phase II trial (NCT03064490) evaluating the efficacy and safety of neoadjuvant pembrolizumab combined with CRT followed by adjuvant pembrolizumab in patients with locally advanced operable EGA. CRT (45 Gy in 25 fractions with concurrent, weekly carboplatin [AUC 2] and paclitaxel [50mg/m2 of BSA]) with three cycles of pembrolizumab were administered as neoadjuvant therapy. Patients also received three cycles of adjuvant pembrolizumab after surgical resection. Baseline characteristics were collected. Pathologic response was scored from 0-3 based on tumor regression grading (TRG), with 0 indicating a complete response, 1 indicating marked response (<10% residual disease), 2 indicating partial response, and 3 indicating poor or no response. The percentage of patients with pCR and major pathologic response (MPR, score of 0-1) are described. Accrual of this trial is now complete, with 35 patients with cT2-3N0-2M0 EGA enrolled from 10/10/2017-10/07/2022. 89% of enrolled patients are male, and 94% are white. 97% of patients have an esophageal primary. One patient withdrew from the study prior to completing neoadjuvant therapy due to a severe drug reaction. Two other patients did not undergo surgery, one due to preference and the other due to development of metastatic disease. Of 32 remaining eligible patients, 28 have completed neoadjuvant therapy and surgical resection to date. 100% of patients underwent IMRT/VMAT. 27/28 (97%) patients underwent R0 resection. 10/28 (35.7%: 95% CI: 17%, 53%) patients achieved a pCR, and 14/28 (50%: 95% CI: 31%, 68%) patients achieved an MPR. Patients undergoing neoadjuvant CRT combined with pembrolizumab for EGA experienced a higher rate of pCR/MPR compared to historical controls treated with CRT alone. This phase II trial demonstrates the efficacy of this treatment paradigm, which warrants assessment in future prospective studies.

Robotic esophagectomy with outermost layer-oriented dissection for esophageal cancer: technical aspects and a retrospective review of a single-institution database.

Systematic lymph node dissection in patients with gastric cancer could be sufficiently and reproducibly achieved along the outermost layer of the autonomic nerves and similar concept has been extensively used for robotic esophagectomy (RE) since 2018. This study aimed to determine the surgical and oncological safety of RE using the outermost layer-oriented approach for esophageal cancer (EC). Sixty-six patients who underwent RE with total mediastinal lymphadenectomy for primary EC between April 2018 and December 2021 were retrospectively reviewed. All underwent the outermost layer-oriented approach with intraoperative nerve monitoring (IONM). Postoperative complications within 30 days were analyzed. Among the patients, 51 (77.3%) were male. The median age was 64 years, and the body mass index was 21.8 kg/m2. Furthermore, 58 (87.9%) patients had squamous cell carcinoma and eight (12.1%) patients had adenocarcinoma. Clinical stages I, II, and III were seen in 23 (34.8%), 23 (34.8%), and 16 (24.2%) patients, respectively. Thirty-four (51.5%) patients received preoperative treatment. No patient shifted to conventional thoracoscopic or open procedure intraoperatively. The median operative time was 716 min with 119 mL of blood loss. Additionally, 64 (97%) patients underwent R0 resection. The morbidity rates based on Clavien-Dindo grades ≥ II and ≥ IIIa were 30.3% and 10.6%, respectively, within 30 postoperative days. None died within 90 days postoperatively. Three (4.5%) patients exhibited recurrent laryngeal nerve (RLN) palsy (CD grade ≥ II). The sensitivity and specificity of IONM for RLN palsy were 50% and 98.3% at the right RLN and 33.3% and 98.0% at the left RLN, respectively. RE with the outermost layer-oriented approach can provide safe short-term outcomes.

ALPPS technique for two-stage liver resections: immediate and long-term results

Aim. To evaluate the immediate and long-term results of two-stage liver resection performed by means of ALPPS technique.Materials and methods. The retrospective analysis involved 7 patients (mean age 62 years) with intact liver parenchyma volume (Future Liver Remnant, FLR) &lt;25%. All patients underwent ALPPS from 2014 to 2021. Both stages of ALPPS were performed in the traditional way. The increment of intact parenchyma on days 6–8 after stage I was evaluated by CT volumetry. The main operative characteristics, incidence of postoperative complications according to Clavien-Dindo and ISGLS, time without progression and life expectancy were analyzed.Results. The median duration of ALPPS stage I was 250 min, median blood loss was 600 ml, and stage II – 210 min and 300 ml, correspondingly. The median FLR before and after ALPPS stage I was 15.3% and 31.6%. The median FLR hypertrophy after ALPPS stage I accounted for 123%. The median interval between stage I and II of ALPPS was 10 days. All patients underwent R0 resection. The incidence of postoperative complications after ALPPS stage I was 14.3% (Clavien–Dindo I), after stage II – 57.1% (Clavien–Dindo III–V). The mortality rate within 90 days after ALPPS stage II accounted for 14.3%. Median follow-up was 25 months. The median time without progression in 6 patients operated for colorectal cancer metastases was 6 months, the median life expectancy was 31 months. The patient who underwent ALPPS for hepatocellular carcinoma is alive, no signs of disease progression have been detected.Conclusion. ALPPS provides a rapid and more than two-fold growth in FLR and increases the likelihood of R0 resection in patients with initially unresectable primary and secondary liver tumors. However, the immediate results of ALPPS are unsatisfactory. The indications for surgery are extremely controversial due to the development of drug therapies, ablation techniques and radiotherapy.

31. MULTICENTER RANDOMIZED CLINICAL TRIAL OF CRT VS DCF AS INITIAL TREATMENT FOR SUBSEQUENT CONVERSION SURGERY FOR CLINICAL T4B ESOPHAGEAL CANCER

Abstract Backgroud Although induction followed by conversion surgery (CS) is potentially curative for T4b esophageal cancer, the optimal initial induction treatment is unclear. We conducted a multicenter randomized prospective phase 2 trial of chemoradiotherapy (CRT) versus chemotherapy (CT) as initial induction therapy for CS in clinical T4b esophageal cancer. We compared treatment effects, adverse events and survival. Methods Ninety-nine patients with T4b esophageal cancer were randomly allocated to chemoradiotherapy (Group A, n = 49) or CT (Group B, n = 50) as initial induction treatment. CRT consisted of radiation (50.4 Gy) with cisplatin and 5-fluorouracil. CT consisted of 2 cycles of docetaxel plus cisplatin and 5-fluorouracil (DCF). CRT or CT was followed by CS if resectable. If unresectable, the patient received the other treatment as secondary treatment. CS was performed if resectable after secondary treatment. The primary end point was 2-year overall survival. The Japan Registry of Clinical Trials (s051180164). Results In Group A, CS was performed in 34 (69%) and 7 patients (14%) after initial and secondary treatment. In Group B, CS was performed in 25 (50%) and 17 patients (34%) after initial and secondary treatment. The R0 resection rate after initial and secondary treatment was similar (78% vs 76%, P = 1.000). Adverse events including leukopenia, neutropenia, febrile neutropenia, and diarrhea were significantly more frequent in Group B. Group A had better histological complete response of the primary tumor (40% vs 17%, P = 0.028) and histological nodal status (P = 0.038). The 2-year survival rate was 55.1% (95% CI 41.1–68.3%) in the CRT group and 34.7% (95% CI 22.8–48.9%) in the CT group, although the difference was not significant (p = 0.11). Local and regional lymph node recurrence in patients undergoing R0 resection was significantly higher in CT group than CRT group (30% versus 8%, p = 0.03 and 37% versus 8%, p = 0.002, respectively). Conclusions The results of the present trial showed that upfront CRT was superior to upfront CT in terms of adverse effects, pathological effects and 2 year-overall survival as initial induction therapy for CS in clinical T4b esophageal cancer.

Different Approaches of Laparoscopic Mesohepatectomy for Centrally Located Hepatocellular Carcinomas.

This study aimed to describe a simple and novel positional classification system for centrally located hepatocellular carcinoma (CL-HCC), based on which different surgical approaches for laparoscopic mesohepatectomy (LMH) were chosen. The data of patients with CL-HCC who underwent LMH between January 2017 and December 2021 were retrospectively analyzed. The positional classification method was used to locate tumors. In addition, different approaches were used during the surgery according to the classification type. All 98 patients underwent LMH, of whom 4 were converted to open surgery. Types I, Ⅱ, and Ⅲ were 24, 37, and 37, respectively. Blood transfusions were performed in only 7 patients, of which the amount was 800 (600, 900) mL. All the patients underwent R0 resection. The complication rate was 9.2% in all cases. No deaths occurred. Our proposed classification system and corresponding surgical approach in LMH is conducive to the successful completion of surgery.

Impact of Surgical Margin Width on Prognosis Following Resection of Hepatocellular Carcinoma Varies on the Basis of Preoperative Alpha-Feto Protein and Tumor Burden Score.

We sought to examine the prognosticimpact of margin width at time of hepatocellular carcinoma (HCC) resection relative to the alpha-feto protein tumor burden score (ATS). Patients who underwent curative-intent hepatectomy for HCC between 2000 and 2020 were identified from a multi-institutional database. The impact of margin width on overall survival and recurrence-free survival was examined relative to ATS using univariable and multivariable analyses. Among 782 patients with HCC who underwent resection, median ATS was 6.5 [interquartile range (IQR) 4.3-10.2]. Most patients underwent R0 resection (n = 613, 78.4%); among patients who had an R0 resection, 325 (41.6%) had a margin width > 5mm while 288 (36.8%) had a 0-5 mm margin width. Among patients with high ATS, an increasing margin width was associated with incrementally better overall and recurrence-free survival. In contrast, among patients with low ATS, margin width was not associated with long-term outcomes. On multivariable Cox regression analysis, each unit increase in ATS was independently associated with a 7% higher risk of death [hazard ratio (HR) 1.07; 95% confidence interval (CI) 1.03-1.11, p < 0.001]. While the incidence of early recurrence was not associated with margin width among patients with low ATS, wider margin width was associated with an incrementally lower incidence of early recurrence among patients with high ATS. ATS, an easy-to-use composite tumor-related metric, was able to risk stratify patients following resection of HCC relative to overall survival and recurrence-free survival. The therapeutic impact of resection margin width had a variable impact on long-term outcomes relative to ATS.

Safety and Efficacy of Neoadjuvant SABR in Pancreatic Cancer: Effect of Magnetic Resonance Imaging–Guided Respiratory-Gated Adaptive Radiation Therapy

We aimed to evaluate the safety and efficacy of neoadjuvant SABR using magnetic resonance imaging-guided respiratory-gated adaptive radiation therapy (MRgRg-ART) in pancreatic cancer. We performed a single-institution retrospective review in patients with pancreatic cancer who underwent neoadjuvant SABR followed by surgical resection. After neoadjuvant chemotherapy, those considered resectable by the multidisciplinary team received SABR over 5 consecutive days using MRgRg-ART. Factors associated with severe postoperative complications (Clavien-Dindo grade ≥III) and prognostic factors for overall survival were analyzed. Sixty-two patients were included in the analysis, with a median follow-up of 10.3 months. The median prescribed dose to the planning target volume was 50 Gy. Fifty-two (85.3%) patients underwent R0 resection, and 11 (18.0%) experienced severe postoperative complications. No factors were associated with the incidence of severe postoperative complications. There were 3 cases of locoregional recurrence, resulting in a 12-month local control rate of 93.1%. Elevated postoperative carbohydrate antigen 19-9 was significantly associated with poor overall survival in the multivariate analysis (P=.037). Neoadjuvant SABR with 50 Gy using MRgRg-ART delivered to pancreatic cancer resulted in a notable survival outcome with acceptable toxicities. Further studies are warranted to investigate the long-term effects of this method.

Efficacy and safety of preoperative immunotherapy alone followed by surgery in the treatment of advanced gastric cancer with MSI-H/dMMR or EBV-positive.

At present, there is no consensus on whether preoperative immunotherapy (PIT) without chemotherapy followed by surgery could benefit patients with advanced gastric cancer (AGC). Here, we report a six-case series study to describe the safety and efficacy of PIT plus gastrectomy in patients with AGC. This study involved six patients with AGC who received PIT and surgery at our center between January 2019 and July 2021. Demographic characteristics, preoperative gastroscope biopsy pathology, surgical tissue pathology, radicalness of tumor resection, surgical safety, and recovery parameters were reported. Six patients, including four patients with Epstein-Barr virus (EBV)-positive gastric cancer (GC) and two patients with microsatellite instability-high (MSI-H)/expression deficiency of mismatch repair (dMMR) protein GC, were enrolled in this study. Four patients experienced immunotherapy-related adverse events (irAEs), without severe adverse events (SAEs). Five patients underwent R0 resection, and one patient underwent palliative gastrectomy due to liver and hilar lymph node metastasis. Pathologic responses from the surgical tissue were observed in all patients, including two pathological complete response (pCR). No operative complications or postoperative deaths occurred. Three patients (50%) experienced mild or moderate postoperative complications without severe postoperative complications. All six patients eventually recovered and were discharged. This study indicated that PIT was effective and tolerant in some patients with MSI-H/dMMR and/or EBV-positive AGC. PIT followed by gastrectomy might be an alternative treatment option for these selected patients.

A Multidisciplinary Treatment Strategy With Conversion Surgery for Hepatocellular Carcinoma.

Sorafenib was previously the only targeted therapy for hepatocellular carcinoma (HCC). However, pharmaceutical therapy for HCC has undergone remarkable advances in recent years. Herein, we report cases of unresectable advanced HCC responding to pharmaceutical therapy resulting in improved prognosis through surgical intervention. Five patients with intermediate and advanced stage HCC treated with lenvatinib followed by hepatectomy between October 2019 and September 2022 were retrospectively reviewed. Patient characteristics, tumor factors, and treatment factors were compared. The median patient age was 66 (60-79) years, and all patients (100%) were male. The median follow-up period was 10.4 months. All five patients received lenvatinib treatment for more than 2 months before surgery. Three patients achieved partial responses and 2 patients had stable disease with modified RESIST in response to lenvatinib. Three patients had a partial pathological response (50% or more tumor necrosis). Four patients underwent R0 resection and 3 cases had no recurrence. Lenvatinib might be useful for intermediate and advanced HCC and long-term survival may be obtained by combining lenvatinib therapy with surgery.

Comparing a PD-L1 inhibitor plus chemotherapy to chemotherapy alone in neoadjuvant therapy for locally advanced ESCC: a randomized Phase II clinical trial

BackgroundA Phase II study was undertaken to evaluate the safety and efficacy of the neoadjuvant socazolimab, a novel PD-L1 inhibitor, in combination with nab-paclitaxel and cisplatin for locally advanced esophageal squamous cell carcinoma (ESCC).MethodsSixty-four patients were randomly divided between the Socazolimab + nab-paclitaxel + cisplatin (TP) arm (n = 32) and the control arm (n = 32), receiving either socazolimab (5 mg/kg intravenously (IV), day 1) or a placebo with nab-paclitaxel (125 mg/m2 IV, day 1/8) and cisplatin (75 mg/m2 IV, day 1) repeated every 21 days for four cycles before surgery. The primary endpoint was major pathological response (MPR), and the secondary endpoints were pathological complete response (pCR), R0 resection rate, event-free survival (EFS), overall survival (OS), and safety.ResultsA total of 29 (90.6%) patients in each arm underwent surgery, and 29 (100%) and 28 (98.6%) patients underwent R0 resection in the Socazolimab + TP and Placebo + TP arms, respectively. The MPR rates were 69.0 and 62.1% (95% Confidence Interval (CI): 49.1–84.0% vs. 42.4–78.7%, P = 0.509), and the pCR rates were 41.4 and 27.6% (95% CI: 24.1–60.9% vs. 13.5–47.5%, P = 0.311) in the Socazolimab + TP and Placebo + TP arms, respectively. Significantly higher incidence rates of ypT0 (37.9% vs. 3.5%; P = 0.001) and T downstaging were observed in the Socazolimab + TP arm than in the Placebo + TP arm. The EFS and OS outcomes were not mature.ConclusionsThe neoadjuvant socazolimab combined with chemotherapy demonstrated promising MPR and pCR rates and significant T downstaging in locally advanced ESCC without increasing surgical complication rates.Trial registrationRegistration name (on clinicaltrials.gov): A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma. Registration number: NCT04460066.

A phase II study of CAPOXIRI as a neoadjuvant chemotherapy in patients with locally advanced rectal cancer (Colorectal Cancer Treatment Group, MSCSGO).

109 Background: Addition of perioperative multi-agent chemotherapy to the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. We conducted a multicenter single-arm phase II study to evaluate the safety and efficacy of capecitabine combined with oxaliplatin and irinotecan (CAPOXIRI) as triplet neoadjuvant chemotherapy in patients with LARC. Methods: The key eligibility criteria were as follows: (1) age over 20 years; (2) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; (3) resectable clinical stage II (T3 or T4 with N0) or III (any T and N1–3), with the primary tumor located within 12 cm of the anal verge. Patients received intravenous oxaliplatin (85 mg/m2) and intravenous irinotecan (150 mg/m2) on day 1 and oral capecitabine (1,000 mg/m2) twice daily on days 1–7 followed by 7 days of rest, repeated every 2 weeks for six cycles. Total mesothelial resection was performed 4–8 weeks after chemotherapy ended. In addition to the treatment protocol, patients received adjuvant chemotherapy for four cycles. The primary study endpoint was the pathological complete response (pCR) rate. We based the sample size of the study described herein on an expected pCR rate of 18% and a threshold pCR rate of 5% to detect differences at a two-sided alpha error of 0.05 and a statistical power of 0.2. Results: Between June 2013 and December 2016, 55 patients were enrolled in the study. Forty-five (83.3%) of the 54 patients who underwent NAC received the full six courses. Fifty-two (94.5%) patients underwent tumor resection. Laparoscopic surgery was performed in 47 (90.4%) patients, and lateral lymph node dissection was performed in 35 (67.3%) patients. Forty-nine (94.2%) patients underwent R0 resection. The pCR rate was 7.7% (95% CI 3.0% to 18.2%). The 3-year local recurrence rate was 3.9%, the 3-year disease-free survival (DFS) rate was 77.3, and the 3-year overall survival rate was 96.0%. NAC-related grade 3/4 adverse event rates were as follows: neutropenia (25.9%), anorexia (13.0%), diarrhea (11.1%) and anemia (7.4%). Conclusions: CAPOXIRI neoadjuvant chemotherapy appears to be feasible and efficacious for patients with LARC. Although neoadjuvant XELOXIRI alone did not yield our expected pCR rate, the local recurrence rate, 3-year DFS and measures of safety met current standards. Clinical trial information: UMIN000009974 .