Histology of metastatic colorectal cancer in a lymph node.

BACKGROUND: A primary colorectal cancer (CRC) tumor can contain heterogeneous cancer cells. As clones of cells with different properties metastasize to lymph nodes (LNs), they could show different morphologies. Cancer histologies in LNs of CRC remains to be described. METHODS: Our study enrolled 318 consecutive patients with CRC who underwent primary tumor resection with lymph node dissection between January 2011 and June 2016. 119 (37.4%) patients who had metastatic LNs (mLNs) were finally included in this study. Cancer histologies in LNs were classified and compared with pathologically diagnosed differentiation in the primary lesion. The association between histologies in lymph node metastasis (LNM) and prognosis in patients with CRC was investigated. RESULTS: The histologies of the cancer cells in the mLNs were classified into four types: tubular, cribriform, poorly differentiated, and mucinous. Same degree of pathologically diagnosed differentiation in the primary tumor produced various histological types in LNM. In Kaplan-Meier analysis, prognosis was worse in CRC patients with moderately differentiated adenocarcinoma who had at least some mLN also showing cribriform carcinoma than for those whose mLNs all showed tubular carcinoma. CONCLUSIONS: Histology in LNM from CRC might indicate the heterogeneity and malignant phenotype of the disease.

What is related to postoperative outcome of frail status in elective colorectal cancer surgery?

Background: The population affected by colorectal cancer is growing, and there is an increasing need for prevention of functional decline following treatment. We proposed that the Kihon Checklist published by the Japanese Ministry of Health, Labor, and Welfare would be an appropriate means of frailty assessment for prediction of postoperative complications in older patients with colorectal cancer. This prospective cohort study aims to identify the factors influencing postoperative frailty. Methods: We prospectively enrolled consecutive patients with colorectal cancer and aged ≥ 65 year (N = 500) between May 2017 and December 2018. Eligible patients were assessed with the Kihon Checklist prior to surgery and 30 days after surgery. The main measures were variables related to postoperative change in view of frail status. Results: According to the Kihon Checklist questionnaire, 164 patients were frail preoperatively and 172 patients were frail postoperatively, whereas 38 patients changed from "nonfrail" before surgery to postoperative "frail." Overall complications were counted in 97 patients (19.4%), and 5 patients died. Performance status ≥ 2, history of laparotomy, open surgery, complication, ostomy creation, and delirium were significantly associated with changing postoperative "frail" (P = .014, P = .023, P = .006, P < .001, P = .023, and P = .024, respectively). In multivariate analysis, independent related factors of changing postoperative "frail" were complication (odds ratio 2.69, 95% confidence interval 1.19-6.09, P = .018) and ostomy creation (odds ratio 2.32, 95% confidence interval 1.01-5.33, P = .047). Conclusion: The Kihon Checklist questionnaire could identify the factors related to postoperative change of frailty status in older patients with colorectal cancer. This cohort concluded that whether postoperative complication occurred or not was closely associated with perioperative change of frailty status.

Malignant potential and specific characteristics of pure main duct type intraductal papillary mucinous neoplasm.

BACKGROUND: As the malignant potential of main duct (MD-) type intraductal papillary mucinous neoplasm (IPMN) has been discussed together with Mixed-type in most previous studies, the malignant potential of pure MD-type IPMN remains unclear. This study evaluated the specific characteristics and predictors of high-grade dysplasia (HGD) and invasive intraductal papillary mucinous carcinoma (IPMC) for pure MD-type IPMN. METHODS: From 1,100 patients with IPMN, this study includes 387 patients that underwent surgery. We evaluated the specific characteristics of pure MD-type IPMN by comparing clinicopathological factors between MD-type (n = 79) and branch duct (BD-) type (n = 146) or Mixed-type IPMN (n = 162), and predictors of HGD/invasive IPMC in pure MD-type IPMN. RESULTS: The rate of HGD/invasive IPMC was significantly higher in MD-type than in BD-type (70.9 vs. 48.6%, P = 0.001), although there was no difference between MD-type and Mixed-type IPMNs (P = 0.343). Recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with MD-type were better than those of patients with Mixed-type (P = 0.008 and P = 0.009, respectively). There were no significant differences in RFS, overall survival, and DSS between patients with MD-type and patients with BD-type IPMNs. Multivariate analysis showed two independent predictors of HGD/invasive IPMC in MD-type IPMN; mural nodule height ≥5 mm (P = 0.025, odds ratio [OR]; 16.949) and carcinoembryonic antigen (CEA) level in the pancreatic juice obtained by preoperative endoscopic retrograde pancreatography ≥50 ng/ml (P = 0.039, OR; 9.091). CONCLUSIONS: Measurement of mural nodule height and CEA in the pancreatic juice might be useful in determining surgical indication for pure MD-type IPMN, although further studies for confirmation are essential.

Optimal Assessment of Frailty Predicts Postoperative Complications in Older Patients with Colorectal Cancer Surgery.

OBJECTIVES: The increasingly elderly worldwide population has affected the incidence of colorectal cancer. Establishment of reliable assessment of frailty and proposals for multi-disciplinary interventions are urgently required in oncology practices. Kihon Checklist (KCL) was published by the Japanese Ministry of Health, Labor and Welfare originally to identify individuals ≥ 65 years old at probable risk for requiring care or social support. We investigate the validity of KCL for frailty assessment to predict postoperative complication in older patients with colorectal cancer. METHODS: Consecutive colorectal cancer patients aged ≥ 65 (n = 500) were prospectively examined between May 2017 and December 2018. Preoperative frailty assessment was conducted by the G8 questionnaire and KCL. The main outcome measures were correlation between frailty, other clinical variables, and postoperative complications within 30 days after elective surgery. RESULTS: Of the 500 patients, 278 (55.6%) and 164 (32.8%) patients were classified as 'frail' by G8 and KCL, respectively. Overall complications counted among 97 patients (19.4%), and they were significantly associated with KCL ≥ 8-frail (46/164, p = 0.001), as opposed to G8 ≤ 14-frail (56/278, p = 0.531). Multivariate analysis showed that KCL ≥ 8 (hazard ratio 1.88, 95% confidence interval 1.16-3.04, p = 0.011) was an independent risk factor for these complications. CONCLUSIONS: KCL assessment can identify frail older patients likely to suffer from postoperative complications after colorectal cancer surgery. Preoperative screening of frailty, particularly by KCL, would help older patients prevent their worse outcomes in colorectal cancer. TRIAL REGISTRATION: UMIN000026689.

Effects on flowering and seed yield of dominant alleles at maturity loci E2 and E3 in a Japanese cultivar, Enrei.

'Enrei' is the second leading variety of soybean (Glycine max (L.) Merr.) in Japan. Its cultivation area is mainly restricted to the Hokuriku region. In order to expand the adaptability of 'Enrei', we developed two near-isogenic lines (NILs) of 'Enrei' for the dominant alleles controlling late flowering at the maturity loci, E2 and E3, by backcrossing with marker-assisted selection. The resultant NILs and the original variety were evaluated for flowering, maturity, seed productivity and other agronomic traits in five different locations. Expectedly, NILs with E2 or E3 alleles flowered later than the original variety in most locations. These NILs produced comparatively larger plants in all locations. Seed yields were improved by E2 and E3 in the southern location or in late-sowing conditions, whereas the NIL for E2 exhibited almost the same or lower productivity in the northern locations due to higher degrees of lodging. Seed quality-related traits, such as 100-seed weight and protein content, were not significantly different between the original variety and its NILs. These results suggest that the modification of genotypes at maturity loci provides new varieties that are adaptive to environments of different latitudes while retaining almost the same seed quality as that of the original.

Treatment strategy for intraductal papillary mucinous neoplasm of the pancreas based on malignant predictive factors.

BACKGROUND: Noninvasive intraductal papillary mucinous neoplasms (IPMNs) have a favorable prognosis; however, the prognosis of invasive intraductal papillary mucinous carcinoma (invasive IPMC) is poor. Identification of predictive factors for differentiating IPMC from benign IPMNs would assist in providing appropriate treatment. DESIGN: Retrospective study (1999-2006). SETTING: Wakayama Medical University Hospital, Wakayama, Japan. PATIENTS: Fifty-four patients with IPMN who underwent surgery; histologic examination showed benign adenomas in 29, carcinoma in situ in 14, and invasive carcinoma in 11 patients. MAIN OUTCOME MEASURES: Clinical data, preoperative imaging findings, cytologic findings, tumor markers in serum and pancreatic juice, and overall survival. RESULTS: Age of 70 years or older, presence of mural nodules, mural nodule size of 5 mm or larger, and carcinoembryonic antigen (CEA) level in pancreatic juice of 110 ng/mL or higher (as obtained by preoperative endoscopic retrograde pancreatography) were predictive of a malignant IPMN by univariate analysis, and a CEA level of 110 ng/mL or higher in pancreatic juice was identified as the only independent predictive factor for the malignant entity. The presence of jaundice or body weight loss, main pancreatic duct type, presence of mural nodules, mural nodule size of 5 mm or larger, and CEA level in the pancreatic juice of 110 ng/mL or higher were all predictive of invasive IPMCs by univariate analysis. CONCLUSION: Measurement of the CEA level in pancreatic juice should be considered in the diagnosis of IPMC.

Pylorus-preserving pancreaticoduodenectomy versus conventional pancreaticoduodenectomy for pancreatic adenocarcinoma.

PURPOSE: A few randomized controlled trials have questioned the justification of pylorus-preserving pancreaticoduodenectomy (PpPD) for pancreatic cancer and periampullary cancer. However, the characteristics of pancreatic cancer are remarkably different from those of other periampullary cancers, so the outcomes of PD and PpPD for pancreatic cancer are being re-evaluated. METHODS: We studied retrospectively, 55 patients who underwent PpPD at Wakayama Medical University Hospital between 1999 and 2005, when PpPD was available, for pancreatic head adenocarcinoma. The main outcome measures were the postoperative complications, mortality, and survival of the patients who underwent PpPD vs. those who underwent conventional pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma. RESULTS: There were no significant differences between PD and PpPD in postoperative complications; however, the incidences of delayed gastric emptying (DGE) differed significantly according to the type of reconstruction (P < 0.01). The body weight ratio and the incidence of diarrhea 6 months after PpPD and PD were similar. Patients treated with PD had a higher duodenal invasion rate than those treated with PpPD (P < 0.05); therefore, the cause-specific survival of the PpPD patients was better than that of the PD patients (P < 0.05). CONCLUSION: The surgical outcomes and incidence of postoperative complications in this series suggest that PpPD is an appropriate surgical procedure for pancreatic adenocarcinoma.

Liver metastasis as an initial recurrence has no impact on the survival of patients with resectable pancreatic adenocarcinoma.

BACKGROUND: Prognosis of the patients with pancreatic adenocarcinoma is still poor due to a recurrence, and liver metastasis is a distant metastasis that is foreboded the short survival period. METHODS: Between 1999 and 2005, 68 patients for pancreatic adenocarcinoma underwent a pancreaticoduodenectomy (n = 17), a pylorus-preserving pancreaticoduodenectomy (n = 27), distal pancreatectomy (n = 22), or total pancreatectomy (n = 2) with an extensive lymph node dissection. RESULTS: A tumor recurrence occurred to 55 patients (13 of the liver, 21 of the local recurrence, 16 of peritoneal dissemination, three of the lymph node, and two of lung). The low tumor grade and female demonstrated a risk factor for a liver metastasis (P = 0.043, P = 0.031). A logistic regression analysis demonstrated female (P = 0.02) and low tumor grade (P = 0.04) as independent risk factors for recurrence with liver metastasis. The median survival time (MST) was 13.6 months, and MST of patients with a liver metastasis as an initial recurrent site was 13.7 months; the liver metastasis as an initial recurrent site has no impact on the MST after pancreatic resection. CONCLUSIONS: We concluded potentially supporting the hypothesis that even patients thought to be at higher risk of liver metastasis may still be given the chance of resection, considering the satisfying survival.

Phase 2 trial of oral S-1 combined with low-dose cisplatin for unresectable advanced pancreatic cancer.

OBJECTIVES: A phase 2 trial of S-1 combined with cisplatin was conducted for unresectable pancreatic cancer. PATIENTS AND METHODS: S-1 was administered for 28 days followed by a rest of 14 days. Cisplatin was infused on days 1-5, 8-12, 15-19 and 22-26 of the first course. After the second course, S-1 was administered as maintenance chemotherapy. RESULTS: Thirty patients were enrolled and the responses observed were 0 complete response, 5 partial response, 22 stable disease and 3 progressive disease, with an overall response rate of 17% (95% confidence internal (CI), 6-35%). Toxicity was tolerable, with grade 3 toxicities observed for leukocytopenia (10%), neutropenia (7%), anemia (3%), thrombocytopenia (3%), anorexia (13%), and nausea and vomiting (7%). The median survival time (MST) and the 1-year survival rate were 9.0 months (95% CI, 6.0-14.5 months) and 35.7% (95% CI, 19-55%), respectively. CONCLUSION: S-1 with low-dose cisplatin is well tolerated and effective for advanced pancreatic cancer.