New criteria of resectability for pancreatic cancer: A position paper by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS).

The symposium "New criteria of resectability for pancreatic cancer" was held during the 33nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) in 2021 to discuss the potential modifications that could be made in the current resectability classification. The meeting focused on setting the foundation for developing a new prognosis-based resectability classification that is based on the tumor biology and the response to neoadjuvant treatment (NAT). The symposium included selected experts from Western and Eastern high-volume centers who have discussed their concept of resectability status through published literature. During the symposium, presenters reported new resectability classifications from their respective institutions based on tumor biology, conditional status, pathology, and genetics, in addition to anatomical tumor involvement. Interestingly, experts from all the centers reached the agreement that anatomy alone is insufficient to define resectability in the current era of effective NAT. On behalf of the JSHBPS, we would like to summarize the content of the conference in this position paper. We also invite global experts as internal reviewers of this paper for intercontinental cooperation in creating an up-to-date, prognosis-based resectability classification that reflects the trends of contemporary clinical practice.

Nutritional impact of active hexose-correlated compound for patients with resectable or borderline-resectable pancreatic cancer treated with neoadjuvant therapy.

Active hexose-correlated compound (AHCC) is a standardized extract from cultured Lentinula edodes mycelia, used as a potent biological response modifier in cancer treatment. We evaluated the nutritional effect of AHCC, given during neoadjuvant therapy, to patients with pancreatic ductal adenocarcinoma (PDAC). Thirty patients with resectable or borderline-resectable PDAC received neoadjuvant therapy with gemcitabine plus S-1. We compared, retrospectively, the outcomes of 15 patients who received AHCC combined with neoadjuvant therapy with those of 15 patients who did not receive AHCC combined with neoadjuvant therapy. The median changes of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) were significantly better in the AHCC group. The relative dose intensity of neoadjuvant therapy was also significantly higher in the AHCC group. Thus, AHCC may improve the nutritional status during neoadjuvant therapy of patients with pancreatic ductal adenocarcinoma. To validate these results and examine the long-term impact of AHCC, a prospective phase II study for PDAC is ongoing.

Evaluation of the efficacy of daikenchuto (TJ -100) for the prevention of paralytic ileus after pancreaticoduodenectomy: A multicenter, double-blind, randomized, placebo-controlled trial.

BACKGROUND: We assessed the efficacy of TJ-100 taken perioperatively to recovery among patients with periampullary tumor or tumor of the head of the pancreas who underwent pancreaticoduodenectomy (PD). PATIENTS AND METHODS: In this multicenter, randomized, double-blinded, placebo-controlled, phase II trial (JAPAN-PD Study), patients were assigned randomly in a 1:1 ratio to receive TJ-100 or placebo. The coprimary endpoints were (1) incidence of postoperative paralytic ileus lasting >72 hours after surgery and (2) time to occurrence of postoperative paralytic ileus. This trial is registered at the UMIN Clinical Trials Registry (000007975) and at ClinicalTrials.gov (NCT01607307). RESULTS: From August 2012 through July 2013, we assessed 273 patients for eligibility, and 224 underwent randomization; 112 patients received TJ-100, and 112 patients received placebo. The population for analysis consisted of 104 patients who received TJ-100 and 103 who received placebo. Paralytic ileus occurred 35 (33.7%) in the TJ-100 group and 38 (36.9%) in the placebo group (P = .626). Time to first flatus was 2.25 (2.00-2.50) days in the TJ-100 group and 2.50 (1.50-2.50) days in the placebo group (P = .343). Among 23 patients who underwent a pylorus ring-preserving PD, time to first flatus was lower in the TJ-100 group than in the placebo group: 0.50 (0.50-1.00) days versus 1.50 (0.50-3.00) days (P = .034). CONCLUSION: Our findings suggest that use of TJ-100 did not improve recovery from paralytic ileus after PD, and may preclude the routine use of TJ-100 in clinical practice after PD operation.

Proposed preoperative risk factors for early recurrence in patients with resectable pancreatic ductal adenocarcinoma after surgical resection: A multi-center retrospective study.

BACKGROUND/OBJECTIVE: Although surgical resection remains the only chance for cure in patients with pancreatic ductal adenocarcinoma (PDAC), postoperative early recurrence (ER) is frequently encountered. The purpose of this study is to determine the preoperative predictive factors for ER after upfront surgical resection. METHODS: Between 2001 and 2012, 968 patients who underwent upfront surgery with R0 or R1 resection for PDAC at seven high-volume centers in Japan were retrospectively reviewed. ER was defined as relapse within 6 months after surgery. Study analysis stratified by resectable (R) and borderline resectable (BR) PDACs was conducted according to the National Comprehensive Cancer Network guidelines. RESULTS: ER occurred in 239 patients (25%) with a median survival time (MST) of 8.8 months. Modified Glasgow prognostic score = 2 (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.05-3.95; P = 0.044), preoperative CA19-9 ≥300 U/ml (OR 1.94, 1.29-2.90; P = 0.003), and tumor size ≥30 mm (OR 1.72, 1.16-2.56; P = 0.006), were identified as preoperative independent predictive risk factors for ER in patients with R-PDAC. In the R-PDAC patients, MST was 35.5, 26.3, and 15.9 months in patients with 0, 1 and ≥2 risk factors, respectively. There were significant differences in overall survival between the three groups (P < 0.001). No preoperative risk factors were identified in BR-PDAC patients with a high rate of ER (39%). CONCLUSIONS: There is a high-risk subset for ER even in patients with R-PDAC and a simple risk scoring system is useful for prediction of ER.

Granulocyte-colony stimulating factor producing anaplastic carcinoma of the pancreas treated by distal pancreatectomy and chemotherapy: report of a case.

Granulocyte-colony stimulating factor (G-CSF) producing pancreatic cancers are extremely rare. These tumors have an aggressive clinical course but no established treatment. We encountered a patient with a G-CSF-induced pancreatic cancer who was treated by surgical resection, followed by steroid treatment and chemotherapy. A 68-year-old Asian male presented at a local hospital with a 3-month history of fever, loss of appetite, and 10-kg weight loss. Laboratory data showed leukocytosis and elevation of C-reactive protein. Computed tomography (CT) revealed a 50-mm mass in the tail of the pancreas, but no signs of infective foci. He was transferred to our hospital for further evaluation. Contrast-enhanced CT showed rapid growth of this tumor over 1 week, and (18) F-2-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) showed FDG accumulation in the tail of the pancreas (SUV max, 17.1) but at no other sites in his body. Magnetic resonance imaging showed a heterogeneous mass, similar to that observed by CT. Three weeks later, the patient underwent a distal pancreatectomy with splenectomy. The resected specimen was 154 mm in diameter, a threefold increase from the initial image. Histopathological examination identified the tumor as an anaplastic carcinoma of the pancreas. Following surgery, his leukocyte count and body temperature were reduced. He recovered well and was discharged from our hospital on postoperative day 18. Immunohistochemical expression of G-CSF in the resected specimen and elevated serum G-CSF concentration confirmed that the mass was a G-CSF producing anaplastic carcinoma of the pancreas. Subsequently, the patient experienced a high fever and loss of appetite. CT showed recurrence of cancer in the abdominal cavity, for which he was started immediately on tegafur-gimeracil-oteracil potassium combination S-1 and steroid. Unfortunately, he died on postoperative day 83. To our knowledge, this patient was the first with a G-CSF producing anaplastic carcinoma of the pancreas to be treated by surgical resection, steroid and adjuvant chemotherapy.

National Comprehensive Cancer Network Resectability Status for Pancreatic Carcinoma Predicts Overall Survival.

BACKGROUND: The aim of this study was to evaluate the validity of preoperative resectability status, as defined by the National Comprehensive Cancer Network (NCCN), from the viewpoint of overall survival. METHODS: A total of consecutive 704 patients with pancreatic head carcinoma who underwent pancreatoduodenectomy with upfront surgery at seven Japanese hospitals between 2001 and 2012 were evaluated retrospectively. According to the NCCN definition of preoperative resectability status, tumors were divided into resectable tumors without vascular contact (R group), resectable tumors with portal or superior mesenteric vein (PV/SMV) contact of ≦180° (R-PV group), borderline resectable(BR) tumors with PV/SMV contact of >180° (BR-PV group), and BR tumors with arterial contact (BR-A group). The relationship between the NCCN definition of preoperative resectability status and overall survival was analyzed. RESULTS: Of the 704 patients, 389, 114, 145, and 56 were classified into the R group, the R-PV group, the BR-PV group, and the BR-A group, respectively. Overall survival of the BR-PV and BR-A groups was significantly worse than that of the R group and R-PV groups (P < 0.05), although there was no significant difference in overall survival between the R group and the R-PV group (P = 0.310). Multivariate analysis revealed that PV/SMV contact of >180° (P = 0.008) and arterial contact (P < 0.001) were independent prognostic factors of overall survival. CONCLUSION: From the viewpoint of overall survival, the NCCN definition of preoperative resectability status was valid.

Surgical results after preoperative chemoradiation therapy for patients with pancreatic cancer.

OBJECTIVES: The results of surgical therapy alone for pancreatic cancer are disappointing. We explored surgical results after neoadjuvant chemoradiation therapy (NACRT) for patients with pancreatic cancer that extended beyond the pancreas. METHODS: Sixty-eight consecutive patients with pancreatic cancer who underwent pancreatic resection were included. Twenty-seven patients underwent surgical resection after NACRT (NACRT group). The other 41 patients were classified as surgery-alone group. Surgical results were compared in patients who underwent curative resection (R0/1) who were followed up for at least 25 months and underwent no adjuvant therapy. RESULTS: A lower frequency of lymph node metastasis was observed in the NACRT group (P < 0.05). The frequency of residual tumor grading in the NACRT group was significantly different from that in surgery-alone (R0/1/2%, 52/15/33 vs 22/51/27; P = 0.0040). In R0/1 cases, overall survival and disease-free survival rates in the NACRT group (n = 18) were significantly longer than in surgery-alone (n = 30, P < 0.05). The rate of local recurrence in the NACRT group was significantly less than in surgery-alone (11% vs 47%, P = 0.0024). CONCLUSIONS: This single-institution experience indicates that NACRT is able to increase the resectability rate with clear margins and to decrease the rate of metastatic lymph nodes, resulting in improved prognosis of curative cases with pancreatic cancer that extended beyond the pancreas.