Complexity and Experience Grading to Guide Patient Selection for Minimally-invasive Pancreatoduodenectomy: An ISGPS Consensus.

OBJECTIVE: The ISGPS aims to develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally-invasive pancreatoduodenectomy (MIPD). BACKGROUND: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis towards appropriate patient selection according to adequate surgeon and center experience. METHODS: The ISGPS developed a complexity and experience grading system to guide patient selection for MIPD based on an evidence-based review and a series of discussions. RESULTS: The ISGPS complexity and experience grading system for MIPD is subclassified into patient-related risk factors and provider experience-related variables. The patient-related risk factors include anatomical (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors, all incorporated in an A-B-C classification, graded as no, a single, and multiple risk factors. The surgeon and center experience-related variables include surgeon total MIPD experience (cut-offs 40 and 80) and center annual MIPD volume (cut-offs 10 and 30), all also incorporated in an A-B-C classification. CONCLUSION: This ISGPS complexity and experience grading system for robotic and laparoscopic MIPD may enable surgeons to optimally select patients after duly considering specific risk factors known to influence the complexity of the procedure. This grading system will likely allow for a thoughtful and stepwise implementation of MIPD and facilitate a fair comparison of outcome between centers and countries.

Three Molecular Developmental Pathways of Remnant Pancreatic Cancer after Resection: A Nationwide Project Study of Japan Pancreas Society.

OBJECTIVE: This study aimed to clarify the molecular mechanism of remnant pancreatic cancer (PC) development after primary PC resection. SUMMARY BACKGROUND DATA: Molecular mechanisms of the development of remnant PCs following primary PC resection are largely unknown. METHODS: Forty-three patients undergoing remnant PC resection after primary PC resection between 2001 and 2017 at 26 institutes were retrospectively analyzed. Clinicopathological features and molecular alterations detected by targeted amplicon sequencing of 36 PC-associated genes were evaluated. RESULTS: These patients showed significantly lower body mass indices and higher hemoglobin A1c values at remnant PC resection than at primary PC resection. A comparison of the molecular features between primary and remnant PCs indicated that remnant PCs were likely to develop via three different molecular pathways: successional, showing identical and accumulated alterations (n=14); phylogenic, showing identical and distinct alterations (n=26); and distinct, showing independent distinctive alterations (n=3). The similarity of gene alterations was associated with time to the remnant PC development (r=－0.384, P=0.0173). Phylogenic pathways were significantly associated with the intraductal spread of carcinoma (P=0.007). Patient survival did not differ significantly depending on these molecular pathways. CONCLUSION: Molecular profiling uncovered three pathways for the development of remnant PCs, namely, successional, phylogenic, and distinct pathways. The vast majority of remnant PCs are likely to be molecularly associated with primary PCs either in the successional or phylogenic way. This information could impact the design of a strategy for monitoring and treating remnant PCs.

Impact of endoscopic ultrasound-guided tissue acquisition on prognosis and peritoneal lavage cytology in resectable or borderline resectable pancreatic ductal adenocarcinoma.

OBJECTIVES: This study aimed to evaluate the clinical impact of preoperative endoscopic ultrasound-guided tissue acquisition (EUS-TA) on the prognosis and incidence of positive peritoneal lavage cytology (PLC) during laparotomy or staging laparoscopy in patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively collected data from patients diagnosed with body and tail PDAC with/without EUS-TA at our hospital from January 2006 to December 2021. RESULTS: To examine the effect of EUS-TA on prognosis, 153 patients (122 in the EUS-TA group, 31 in the non-EUS-TA group) were analyzed. There was no significant difference in overall survival between the EUS-TA and non-EUS-TA groups after PDAC resection (P = 0.777). In univariate and multivariate analysis, preoperative EUS-TA was not identified as an independent factor related to overall survival after pancreatectomy [hazard ratio 0.96, 95 % confidence interval (CI) 0.54-1.70, P = 0.897]. Next, to examine the direct influence of EUS-TA on the results of PLC, 114 patients (83 in the EUS-TA group and 31 in the non-EUS-TA group) were analyzed. Preoperative EUS-TA was not statistically associated with positive PLC (odds ratio 0.73, 95 % CI 0.25-2.20, P = 0.583). After propensity score matching, overall survival and positive PLC were the same in both groups. CONCLUSIONS: EUS-TA had no negative impact on postoperative survival and PLC-positive rates in R/BR PDAC.

Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy.

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

Current status of the cost burden of first-line systemic treatment for patients with advanced hepatocellular carcinoma in Japan, 2021-22.

BACKGROUND: Although recent advances in systemic therapies for hepatocellular carcinoma (HCC) have led to prolonged patient survival, the high costs of the drugs place a heavy burden on both patients and society. The objectives of this study were to examine the treatment regimens used as first-line systemic treatment for patients with advanced HCC in Japan and to estimate the treatment costs per regimen. METHODS: For this study, we aggregated the data of patients who had received first-line systemic treatment for advanced HCC between July 2021 and June 2022. The treatment cost per month of each regimen was estimated based on standard usage, assuming an average weight of 60 kg for male patients. The data were categorized by the treatment regimen, and the treatments were categorized based on the cost into very high-cost (≥1 000 000 Japanese yen [JPY]/month), high-cost (≥500 000 JPY/month) and other (<500 000 JPY/month) treatments. RESULTS: Of the total of 552 patients from 24 institutions whose data were analyzed in this study, 439 (79.5%) received atezolizumab plus bevacizumab, 98 (17.8%) received lenvatinib and 15 (2.7%) received sorafenib as the first-line treatment. The treatment cost per month for each of the above regimens was as follows: atezolizumab plus bevacizumab, 1 176 284 JPY; lenvatinib, 362 295 JPY and sorafenib, 571 644 JPY. In total, 82.2% of patients received high-cost regimens, and the majority of these patients received a very high-cost regimen of atezolizumab plus bevacizumab. CONCLUSIONS: Advances in systemic therapies for HCC have led to prolonged patient survival. However, the treatment costs are also increasing, imposing a burden on both the patients and society.

Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Reconsideration of the clinical impact of neoadjuvant therapy in resectable and borderline resectable pancreatic cancer: A dual-institution collaborative clinical study.

PURPOSE: We investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer. METHODS: A total of 687 patients with resectable or borderline resectable pancreatic cancer were enrolled. Survival analysis was performed by intention-to-treat analysis and propensity score matching (PSM) was conducted. RESULTS: In resectable disease, the NAT group showed better overall survival (OS) compared with the upfront group. Multivariate analysis identified CA19-9 level (≥100 U/mL) and lymph node metastasis to be prognostic factors, and a tumor size of 25 mm was the optimal cut-off value to predict lymph node metastasis. There was no significant survival difference between patients with a tumor size ≤25 mm and CA19-9 < 100 U/mL and those in the NAT group. In borderline resectable disease, OS in the NAT group was significantly better than that in the upfront group. CEA (≥5 ng/mL) and CA19-9 (≥100 U/mL) were identified as prognostic factors; however, the OS of patients fulfilling these factors was worse than that of the NAT group. CONCLUSIONS: NAT could be unnecessary in patients with tumor size ≤25 mm and CA19-9 < 100 U/mL in resectable disease. In borderline resectable disease, surgery should be delayed until tumor marker levels are well controlled.

Development of a nomogram to predict survival in advanced biliary tract cancer.

The prognosis of advanced biliary tract cancer (BTC) patients remains poor due to limited efficacy of chemotherapy and difficulties in management. Thus, prediction of survival is crucial for the clinical management of advanced BTC. The aim was to develop and validate a nomogram to predict 6-month and 12-month survival in advanced BTC patients treated with chemotherapy. A multivariable Cox regression model was used to construct a nomogram in a training set (JCOG1113, a phase III trial comparing gemcitabine plus S-1 [GS] and gemcitabine plus cisplatin, n = 351). External validity of the nomogram was assessed using a test set (JCOG0805, a randomized, phase II trial comparing GS and S-1 alone, n = 100). Predictive performance was assessed in terms of discrimination and calibration. The constructed nomogram included lymph node metastasis, liver metastasis, carbohydrate antigen 19-9, carcinoembryonic antigen, albumin, and C-reactive protein. Uno's concordance index was 0.661 (95% confidence interval [CI] 0.629-0.696) in the training set and 0.640 (95% CI 0.566-0.715) in the test set. The calibration plots for 6-month and 12-month survival showed good agreement in the two analysis sets. The present nomogram can facilitate prediction of the prognosis of advanced BTC patients treated with chemotherapy and help clinicians' prognosis-based decision-making.

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial).

Background: Nab-paclitaxel plus gemcitabine is a standard treatment for metastatic/locally advanced pancreatic cancer. The effectiveness of neoadjuvant therapy with nab-paclitaxel plus gemcitabine (GnP-NAT) in patients with borderline resectable pancreatic cancer (BRPC) remains unclear. Patients and Methods: This single-arm phase II trial included 61 patients with BRPC that were treated with two cycles of GnP-NAT, (nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2), on days 1, 8, and 15 over a 4-week period, which comprised one cycle. The primary endpoint was overall survival time. In the absence of disease progression, patients underwent planned pancreatectomy. Results: Median overall survival, the primary endpoint, was 25.2 months, and the median recurrence-free survival was 12.3 months. The overall rate of grade 3/4 events was 73.8%. One patient, who had a history of radiation therapy for past esophageal cancer, died from exacerbation via pneumonia. The overall resection rate was 73.8% (n = 45), and the R0 resection rate was 63.9% (n = 39). Overall, postoperative complications were found in 19 patients (42%) with 24 events, and nine patients (20%) with nine events ≥ grade IIIa, based on Dindo's classification. Conclusions: This protocol treatment is thought to be a feasible, safe, and promising treatment regimen, but we caution against its use in patients with a history of interstitial lung disease and/or prior pulmonary irradiation. The survival data from this study suggest the need for further investigations of GnP-NAT efficacy in patients with BRPC, as well as prospective evaluation of adverse events. Clinical Trial Registration: UMIN Clinical Trials Registry, UMIN000024154 and ClinicalTrials.gov, NCT02926183.

Central pancreatectomy might be an acceptable surgical procedure for clinical T1 pancreatic body ductal adenocarcinoma: A multicenter retrospective analysis.

BACKGROUND: Central pancreatectomy (CP) is accepted as a function-preserving procedure for benign tumors. However, the indication of CP for pancreatic cancers is limited. This multicenter study aimed to clarify the indications of CP for clinical T1 pancreatic body cancer. METHODS: This multicenter study analyzed patients who underwent CP or distal pancreatectomy (DP) for clinical T1 pancreatic body cancer between 2013 and 2020 at three high-volume centers. RESULTS: A total of 50 patients were enrolled: nine patients, who underwent CP, were classified into the CP group, while 38 patients, who underwent DP, served as controls. Three patients converted CP to DP during operation were excluded. Five patients in the CP group and 15 patients in the control group underwent preoperative treatment. The 5-year survival rate was 100% in the CP group, and 42% (p = .040) in the control group. Recurrence was found in three patients in the CP group. Importantly, insulin was not required after surgery in patients in the CP group. CONCLUSION: The clinical outcomes of CP were comparable to or even better than that of conventional pancreatectomy. Our collaborative study suggests that CP may be an acceptable therapeutic option for selected patients with clinical T1 pancreatic body cancer.

Preoperative CA19.9 level predicts lymph node metastasis in resectable adenocarcinoma of the head of the pancreas: A further plea for biological resectability criteria.

INTRODUCTION: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative CA19.9 in predicting the N+ stage in resectable-PDAC (R-PDAC). METHODS: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analyzed. A preoperative laboratory value of CA19.9 >37 U/L was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+. RESULTS: A total of 2034 PDs from thirteen centers were included in the study. CA19.9>37 U/L was significantly associated with higher N+ at univariate and multivariate analysis (P<0.001). CA19.9 levels >37 U/L were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumors and with higher cut-off values for all cT stages. CONCLUSION: Lymph nodal involvement is strongly related to preoperative CA19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA19.9 values should be considered in a more biologically advanced stage.

Impact of antithrombotic therapy on postpancreatectomy hemorrhage in 7116 patients: A project study by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

BACKGROUND: We previously reported an association between antithrombotic therapy and an increased risk of postpancreatectomy hemorrhage (PPH). To validate our findings, we conducted a large-scale multicenter retrospective study from 63 high-volume centers in Japan. METHODS: Between 2015 and 2018, 7116 patients who underwent pancreatectomy were enrolled. The antithrombotic group consisted of 920 patients (12.9%) who received preoperative antithrombotic agents including aspirin, clopidogrel, ticlopidine, prasugrel, warfarin, and direct oral anticoagulants. RESULTS: PPH occurred in 235 (3.3%) of the patients. The incidence of PPH and mortality were significantly higher in the antithrombotic group than in the control group (5.7 vs. 3.0% and 2.2 vs. 0.9%, respectively; both p < .001). In multivariate analysis, a history of antithrombotic use was an independent risk factor for grade C PPH (p = .036). In the antithrombotic group, PPH tended to be delayed in the patients with restarting antithrombotic therapy. Notably, the occurrence of delayed PPH after restarting antithrombotic therapy was observed only when antithrombotic therapy was restarted within 10 days after pancreatectomy. CONCLUSIONS: This multicenter study demonstrated that a history of antithrombotic use was a significant risk factor for PPH and mortality. In particular, the resumption of antithrombotic therapy in the early postoperative period should be done with caution.

Randomized phase II trial of chemoradiotherapy with S-1 versus combination chemotherapy with gemcitabine and S-1 as neoadjuvant treatment for resectable pancreatic cancer (JASPAC 04).

OBJECTIVE: The aim of the present study was to investigate which treatment, neoadjuvant chemoradiotherapy (NAC-RT) with S-1 or combination neoadjuvant chemotherapy with gemcitabine and S-1 (NAC-GS), is more promising as neoadjuvant treatment (NAT) for resectable pancreatic cancer in terms of effectiveness and safety. METHODS: In the NAC-RT with S-1 group, the patients received a total radiation dose of 50.4 Gy in 28 fractions with oral S-1. In the NAC-GS group, the patients received intravenous gemcitabine at a dose of 1000 mg/m2 with oral S-1 for two cycles. The primary endpoint was the 2-year progression-free survival (PFS) rate. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894. RESULTS: From April 2014 to April 2017, a total of 103 patients were enrolled. After exclusion of one patient because of ineligibility, 51 patients were included in the NAC-RT with S-1 group, and 51 patients were included in the NAC-GS group in the intention-to-treat analysis. The 2-year PFS rate was 45.0% (90% confidence interval [CI]: 33.3%-56.0%) in the NAC-RT with S-1 group and 54.9% (42.8%-65.5%) in the NAC-GS group (p = .350). The 2-year overall survival rate was 66.7% in the NAC-RT with S-1 group and 72.4% in the NAC-GS group (p = .300). Although leukopenia and neutropenia rates were significantly higher in the NAC-GS group than in the NAC-RT with S-1 group (p = .023 and p < .001), other adverse events of NAT and postoperative complications were comparable between the two groups. CONCLUSION: Both NAC-RT with S-1 and NAC-GS are considered promising treatments for resectable pancreatic cancer.

Insights from managing clinical issues in distal pancreatectomy with en bloc coeliac axis resection: experiences from 626 patients.

BACKGROUND: Distal pancreatectomy with en bloc coeliac axis resection (DP-CAR) for pancreatic body cancer has been reported increasingly. However, its large-scale outcomes remain undocumented. This study aimed to evaluate DP-CAR volume and mortality, preoperative arterial embolization for ischaemic gastropathy, the oncological benefit for resectable tumours close to the bifurcation of the splenic artery and coeliac artery using propensity score matching, and prognostic factors in DP-CAR. METHODS: In a multi-institutional analysis, 626 DP-CARs were analysed retrospectively and compared with 1325 distal pancreatectomies undertaken in the same interval. RESULTS: Ninety-day mortality was observed in 7 of 21 high-volume centres (1 or more DP-CARs per year) and 1 of 41 low-volume centres (OR 20.00, 95 per cent c.i. 2.26 to 177.26). The incidence of ischaemic gastropathy was 19.2 per cent in the embolization group and 7.9 per cent in the no-embolization group (OR 2.77, 1.48 to 5.19). Propensity score matching analysis showed that median overall survival was 33.5 (95 per cent c.i. 27.4 to 42.0) months in the DP-CAR and 37.9 (32.8 to 53.3) months in the DP group. Multivariable analysis identified age at least 67 years (HR 1.40, 95 per cent c.i. 1.12 to 1.75), preoperative tumour size 30 mm or more (HR 1.42, 1.12 to 1.80), and preoperative carbohydrate antigen 19-9 level over 37 units/ml (HR 1.43, 1.11 to 1.83) as adverse prognostic factors. CONCLUSION: DP-CAR can be performed safely in centres for general pancreatic surgery regardless of DP-CAR volume, and preoperative embolization may not be required. This procedure has no oncological advantage for resectable tumour close to the bifurcation of the splenic artery, and should be performed after appropriate patient selection.

Autophagy Inhibition Increased Sensitivity of Pancreatic Cancer Cells to Carbon Ion Radiotherapy.

BACKGROUND/AIMS: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer. METHODS: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone. RESULTS: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining. CONCLUSION: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.

A Multicenter Survey on Eligibility for a Randomized Phase III Trial of Adjuvant Chemotherapy for Resected Biliary Tract Cancer (JCOG1202, ASCOT).

BACKGROUND: The Adjuvant S-1 for Cholangiocarcinoma Trial (JCOG1202, [ASCOT]) was a multicenter, randomized controlled trial aimed at investigating the efficacy and safety of adjuvant chemotherapy (AC) with S-1 for resected biliary tract cancer (BTC). This trial reported that overall survival was prolonged with AC compared with observation. METHODS: With the aim of increasing enrollment, the present survey biannually recorded the number of patients eligible for enrollment into ASCOT and reasons for ineligibility among patients who had undergone surgery for BTC from April 2015 to September 2017 at 36 institutions participating in ASCOT. RESULTS: Of 2039 patients who underwent surgery for BTC, 211 (10.3%) were already enrolled, 166 (8.1%) were eligible but had not been enrolled, and 1662 (81.5%) were ineligible. Among ineligible patients, the predominant reasons for ineligibility were patient refusal (n = 332, 20.0%), pathologic stage (pT1N0; n = 248, 14.9%), age (≥ 81 years; n = 196, 11.8%), and prolonged postoperative complications (n = 176, 10.6%). CONCLUSIONS: Patients undergoing surgery for BTC are a heterogeneous cohort comprising patients with earlier pathologic stage, advanced age, and prolonged postoperative complications. These factors should be considered during the design of future clinical trials of perioperative treatments for resectable BTC.

Is surgical resection justified for pancreatic ductal adenocarcinoma with distant abdominal organ metastasis? A position paper by experts in pancreatic surgery at the Joint Meeting of the International Association of Pancreatology (IAP) & the Japan Pancreas Society (JPS) 2022 in Kyoto.

Pancreatic ductal adenocarcinoma (PDAC) is a typical refractory malignancy, and many patients have distant organ metastases at diagnosis, such as liver metastasis and peritoneal dissemination. The standard treatment for unresectable PDAC with distant organ metastasis (UR-M) is chemotherapy, but the prognosis remained poor. However, with recent dramatic developments in chemotherapy, the prognosis has gradually improved, and some patients have experienced marked shrinkage or disappearance of their metastatic lesions. With this trend, attempts have been made to resect a small number of metastases (so-called oligometastases) in combination with the primary tumor or to resect the primary and metastatic tumor in patients with a favorable response to anti-cancer treatment after a certain period of time (so-called conversion surgery). An international consensus meeting on surgical treatment for UR-M PDAC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of the Japan Pancreas Society (JPS) in Kyoto in July 2022. The presenters showed their indications for and results of surgical treatment for UR-M PDAC and discussed their advantages and disadvantages with the experts. Although these reports were limited to a small number of patients, findings suggest that these surgical treatments for patients with UR-M PDAC who have had a significant response to chemotherapy may contribute to a prognosis of prolonged survival. We hope that this article summarizing the discussion and agreements at the meeting will serve as the basis for future trials and guidelines.

"Conversion surgery" for locally advanced pancreatic cancer: A position paper by the study group at the joint meeting of the International Association of Pancreatology (IAP) & Japan Pancreas Society (JPS) 2022.

Locally advanced pancreatic cancer (LAPC), which progresses locally and surrounds major vessels, has historically been deemed unresectable. Surgery alone failed to provide curative resection and improve overall survival. With the advancements in treatment, reports have shown favorable results in LAPC after undergoing successful chemotherapy therapy or chemoradiation therapy followed by surgical resection, so-called "conversion surgery", at experienced high-volume centers. However, recognizing significant regional and institutional disparities in the management of LAPC, an international consensus meeting on conversion surgery for LAPC was held during the Joint Congress of the 26th Meeting of the International Association of Pancreatology (IAP) and the 53rd Annual Meeting of Japan Pancreas Society (JPS) in Kyoto in July 2022. During the meeting, presenters reported the current best multidisciplinary practices for LAPC, including preoperative modalities, best systemic treatment regimens and durations, procedures of conversion surgery with or without vascular resections, biomarkers, and genetic studies. It was unanimously agreed among the experts in this meeting that "cancer biology is surpassing locoregional anatomical resectability" in the era of effective multiagent treatment. The biology of pancreatic cancer has yet to be further elucidated, and we believe it is essential to improve the treatment outcomes of LAPC patients through continued efforts from each institution and more international collaboration. This article summarizes the agreement during the discussion amongst the experts in the meeting. We hope that this will serve as a foundation for future international collaboration and recommendations for future guidelines.