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Purpose: Comprehensive genomic profiling is useful for patients with Thyroid carcinoma (TC) for whom standard treatment has become refractory. We analyzed the clinical and genomic characteristics of patients with TC using the Japanese nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database., Methods: This retrospective observational study used the data obtained from the C-CAT database. Genomic information has been accumulated on representative gene mutations associated with TC., Results: Among the 482 patients, 212 (44%) were male and 270 (56%) were female. According to histological type, 259 (54%), 46 (10%), 16 (3%), 51 (11%), and 110 (23%) patients had papillary TC (PTC), follicular TC, medullary TC, poorly differentiated TC, and anaplastic TC (ATC), respectively. Among the genomic profiling tests, FoundationOne CDx (n = 388; 80%) was the most frequently performed. The frequencies of BRAF, NRAS, HRAS, KRAS, and RET mutations were 259 (54%), 62 (13%), 13 (3%), 16 (3%), and 12 (2%), respectively. The BRAF V600E mutation (n = 257) was the predominant BRAF mutation. TERT promoter mutations, which are associated with tumor aggressiveness, were detected in 308 patients (64%)., Conclusions: PTC was the most common histologic type of TC for which genetic profiling was performed in Japan, followed by ATC. Since the most common targetable mutation is the BRAF mutation, practical application of BRAF-targeted therapy can be an important treatment option for Japanese patients with TC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although functional end-to-end anastomosis (FEEA) using a stapler in the colorectal field has been recognised worldwide, the technique varies by surgeon, and the safety of anastomosis using different techniques is unknown., Methods: This multicentre prospective observational cohort study was conducted by the KYCC Study Group in Yokohama, Japan, and included patients who underwent colonic resection at seven centres between April 2020 and March 2022. This study compared the incidence of surgery-related abdominal complications (SAC: anastomotic leakage [AL], anastomotic bleeding, intra-abdominal abscess, enteritis, ileus, surgical site infection, and other abdominal complications) between two different methods of FEEA (one-step [OS] method: simultaneous anastomosis and bowel resection; two-step [TS] method: anastomosis after bowel resection). Complications of Clavien-Dindo classification grade 2 or higher were assessed., Results: Among 293 eligible cases, the OS and TS methods were used in 194 (66.2%) and 99 (33.8%) patients, respectively. The baseline characteristics were similar between the groups. The OS method used fewer staplers (three vs. four staplers, p < 0.00001). There were no significant differences in SAC rate between the OS (19.1%) and the TS (16.2%) groups (p = 0.44). The OS group had four cases (2.1%) of AL (two patients; grade 3, two patients; grade 2) while the TS group had one case (1.0%) of grade 2 AL (p = 0.67). Multivariate logistic regression analysis showed that male sex (odds ratio [OR] 3.95; p < 0.00001), an open surgical approach (OR 2.36; p = 0.03), and longer operative duration (OR,2.79; p = 0.002) were independent predictors of complications, whereas the OS method was not an independent predictor (OR 1.17; p = 0.66)., Conclusions: The OS and the TS technique for stapled colonic anastomosis in a FEEA had a similar postoperative complication rate., Trial Registration Number: UMIN000039902 (registration date 23 March 2020)., (© 2024. Springer Nature Switzerland AG.)

Background: This study aimed to investigate outcomes in the same cohort of patients with papillary thyroid carcinoma (PTC) risk-stratified according to the Japan Association of Endocrine Surgery (JAES) and American Thyroid Association (ATA) guidelines., Methods: A total of 1044 patients with PTC who underwent initial thyroidectomy at Yokohama City University Medical Center between January 2000 and June 2022 were included., Results: According to the JAES guidelines, 480 (46%), 386 (37%), and 178 (17%) patients were classified as low, intermediate, or high risk, respectively. Furthermore, according to the ATA guidelines, 590 (57%), 261 (25%), and 193 (18%) patients were reclassified as low, intermediate, or high risk, respectively. Among 1044 patients with PTC, the 10-year cause-specific survival (CSS) rates of patients with JAES low and intermediate risk were 99.7 and 98.6%, respectively, and there was no statistically difference (p = 0.096). However, the 10-year CSS rates of patients with ATA low and intermediate risk were 100 and 99.5%, respectively (p = 0.007). Among 1001 patients with M0 PTC, the 10-year distant metastasis-free survival (DMFS) rates of patients with JAES intermediate and high risk were 94.2, and 76.7%, respectively (p < 0.001). However, the 10-year DMFS rates of patients with ATA intermediate and high risk were 88.1 and 86.6%, respectively (p = 0.233), and there was no statistically difference., Conclusions: Both JAES and ATA risk classifications properly stratified the PTC patients. Furthermore, the ATA risk classification more precisely extracted patients with better and worse prognoses., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background/aim: This study aimed to examine the clinical significance of the protein expression of the cancer stem cell (CSC) markers ALDH1A1, CD133, CD44, and MSI-1 in primary and metastatic tissues of patients with breast cancer (BC)., Patients and Methods: ALDH1A1, CD133, CD44, and MSI-1 protein expression in pairs of primary and metastatic tissues of 55 patients with BC with metastases treated at Kanagawa Cancer Center between January 1970 and December 2016 were evaluated using immunohistochemical assay and their association with clinicopathological factors and survival was examined., Results: There were no significant differences in CSC marker expression rates between primary and metastatic tissues for any CSC markers. Regarding the relationship between CSC marker expression in primary tissues and survival, patients with high CD133 expression had significantly lower recurrence-free survival (DFS) and overall survival. On multivariate analysis, they were also a poor independent predictor of DFS (hazard ratio=4.993, 95%CI=2.189-11.394, p=0.0001). In contrast, there was no significant association between the expression of any CSC marker in metastatic tissues and survival., Conclusion: CD133 expression in the primary BC tissue may be a useful risk factor for recurrence in patients with BC., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Objectives: Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM., Methods: This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%., Results: Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%., Conclusions: The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice., (© 2021 Wiley Periodicals LLC.)

Background: This study aimed to investigate the short-term and oncological impact of the Endoscopic Surgical Skill Qualification System (ESSQS) by the Japan Society for Endoscopic Surgery on the operator performing laparoscopic surgery for colon cancer., Methods: This retrospective cohort study was based on medical records from a multicentre database. A total of 417 patients diagnosed with stage II/III colon and rectosigmoid cancer treated with curative resection were divided into two groups according to whether they were operated on by qualified surgeons (Q group, n=352) or not (NQ group, n=65). Through strict propensity score matching, 98 cases (49 in each group) were assessed., Results: Operative time was significantly longer in the NQ group than in the Q group (199 vs. 168 min, p=0.029). The amount of blood loss, post-operative complications, and duration of hospitalisation were similar between both groups. No mortality was observed. One conversion case was seen in the NQ group. The 3-year recurrence-free survival rate was 86.6% in the NQ group and 88.2% in the Q group, which was not statistically significant (log-rank p=0.966)., Conclusion: Direct operation by ESSQS-qualified surgeons contributed to a shortened operation time. Under an organised educational environment, almost equivalent safety and oncological outcomes are expected regardless of the surgeon's qualifications.

Background: Cancer cells are often found postoperatively at surgical resection margins (RM) in patients with gastric cancer because of submucosal infiltration or hesitation to secure adequate RM. This study was designed to evaluate risk factors for microscopic positive RM and to clarify which patients should undergo intraoperative frozen section diagnosis (IFSD)., Methods: Patients who underwent R0/1 gastrectomy for gastric adenocarcinoma between 2000 and 2018 in a single cancer center in Japan were studied. We divided the patients into a positive RM group and negative RM group according to the results of definitive histopathological examinations. We performed multivariate analysis to analyze risk factors for positive RM by and used the identified risk factors to risk stratify the patients., Results: A total of 2757 patients were studied, including 49 (1.8%) in the positive RM group. The risk factors significantly associated with positive RM were remnant gastric cancer (odds ratio [OR] 4.7), esophageal invasion (OR 6.3), tumor size ≥80 mm (OR 3.9), and a histopathological diagnosis of undifferentiated type (OR 3.6), macroscopic type 4 (OR 3.7), or pT4 disease (OR 4.6). On risk stratification analysis, the incidence of positive RM was 0.1% without any risk factors, increasing to 0.4% with one risk factor, 3.1% with two risk factors, 5.3% with three risk factors, 21.3% with four risk factors, and 85.7% with five risk factors., Conclusions: The risk of macroscopically positive RM increased in patients who have risk factors. IFSD should be performed in patients who have four or more risk factors.

Background: Laparoscopic gastrectomy is becoming more commonly performed, but acquisition of its technique remains challenging. We investigated whether laparoscopy-assisted distal gastrectomy (LDG) performed by trainees (TR) supervised by a technically qualified experienced surgeon (QS) is feasible and safe., Methods: The short-term outcomes of LDG were assessed in patients with gastric cancer between 2008 and 2018. We compared patients who underwent LDG performed by qualified experienced surgeons (QS group) with patients who underwent LDG performed by the trainees (TR group)., Results: The operation time was longer in the TR group than in the QS group (median time: 270 min vs. 239 min, p < 0.001). The median duration of the postoperative hospital stay was 9 days in the QS group and 8 days in the TR group (p = 0.003). The incidence of postoperative complications did not differ significantly between the two groups. Grade 2 or higher postoperative complications occurred in 18 patients (12.9%) in the QS group and 47 patients (11.7%) in the TR group (p = 0.763). Grade 3 or higher postoperative complications occurred in 9 patients (6.4%) in the QS group and 17 patients (4.2%) in the TR group (p = 0.357). Multivariate analysis showed that the American Society of Anesthesiologist Physical Status was an independent predictor of grade 2 or higher postoperative complications and that gender was an independent predictor of grade 3 or higher postoperative complications. The main operator (TR/QS) was not an independent predictor of complications., Conclusions: Laparoscopy-assisted distal gastrectomy performed by trainees supervised by an experienced surgeon is a feasible and safe procedure similar to that performed by experienced surgeons.

Purpose: Angiogenesis plays a crucial role in the development, growth, and metastasis of carcinomas, and studies have reported conflicting evidence regarding the VEGFR expression in anaplastic thyroid cancer. We investigated the expression of VEGFR2 in patients with anaplastic thyroid cancer (ATC) and analyzed the clinical response to the VEGFR inhibitor lenvatinib., Methods: This cross-sectional study included primary tumor samples obtained from 12 patients with ATC, including 5 males and 7 females (age range 63-89 years) who underwent surgery or core needle biopsy for a thyroid tumor in the Department of Breast and Endocrine Surgery at Kanagawa Cancer Center in Kanagawa, Japan. VEGFR2 protein expression in the ATC samples was analyzed by immunohistochemistry in all patients, and the therapeutic effect of lenvatinib was evaluated in seven patients who underwent tissue biopsy and lesion evaluation., Results: VEGFR expression was not detected in any of the samples from the 12 patients. Four of the 12 patients treated with lenvatinib had partial response, the three patients achieved stable disease, and the five patients were not examined., Conclusions: There was no correlation between the expression of VEGFR2 in tumor tissue and the clinical response to lenvatinib among patients with ATC. Further studies are necessary to elucidate the mechanism underlying the response to lenvatinib.

Background: Several studies from other countries have reported that patients with screen-detected breast cancer have better survival than those with symptomatic breast cancer. However, no such comparison has been performed in Japan. Therefore, we aimed to compare the clinicopathological characteristics and survival rates between symptomatic and screen-detected breast cancer in Japanese women., Methods: From January 2000 to December 2004, 977 and 182 women with symptomatic or screen-detected breast cancer, respectively, underwent surgery at a single Japanese hospital. We retrospectively reviewed these patients' clinicopathological data. Likelihood of death was estimated using the Kaplan-Meier method and the log-rank test. Multivariate analysis including mode of detection, tumor size, lymph node status, hormone receptor status, and adjuvant therapy administration was performed using the Cox proportional hazards model., Results: Screen-detected breast cancer was associated with increased rate of breast-conserving surgery, non-invasive carcinoma, smaller tumor size, decreased lymph node involvement, increased hormone receptor positivity, and decreased adjuvant chemotherapy administration. Compared to women with symptomatic tumors, those with screen-detected tumors had improved overall and breast cancer-specific survival rates. Factors associated with survival in univariate analysis were screen detection, tumor size, lymph node status, progesterone receptor status, and adjuvant chemotherapy administration., Conclusions: Breast cancer screening in Japanese women has led to increases in the rates of breast-conserving surgery, hormone receptor positivity, and survival rates along with reductions in axillary lymph node dissection and adjuvant chemotherapy administration.

Background/aims: The clinical implications of peritoneal lavage cytology (CY) status in the patients who received curative resection and adjuvant chemotherapy have not been established., Methodology: We retrospectively analyzed clinical data from 143 consecutive patients who underwent macroscopically curative resection and received adjuvant gemcitabine or S-1 chemotherapy for pancreatic cancer from 2005 to 2014 in our institution. Correlations between CY status and survival and clinicopathological features were investigated., Results: Of the 143 patients, 21 patients were peritoneal washing cytology positive (CY+) (14.7%). Although significant difference was observed in the tumor size, no other correlation between cytology status and clinicopathological parameter existed. The recurrence free survival (RFS) rates at 3 and 5 years after surgery were 5.1% and 0% in CY+ patients, respectively, and were 21.5% and 16.1% in peritoneal washing cytology negative (CY-) patients, respectively, which were significantly different (p=0.001). The OS rates at 3 and 5 years after surgery were 17.1% and 8.6% in CY+ patients, respectively, and were 26.1% and 16.1% in CY- patients, respectively, which were trend to worse in the CY+ patients (p=0.254)., Conclusion: The patients with CY+ are likely to experience recurrence, even after they received curative resection and adjuvant Gemcitabine or S-1 adjuvant chemotherapy.

Aim: To identify the subset of patients with stage IB gastric cancer with an unfavorable prognosis., Methods: Overall survival (OS) rates were examined in 103 patients with stage IB (T1N1M0 and T2N0M0) gastric cancer between January 2000 and December 2011. Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model., Results: The OS rates of patients with T1N1 and T2N0 cancer were 89.2% and 94.1% at 5-years, respectively. Both univariate and multivariate analyses demonstrated that tumor location was the only significant prognostic factor. The OS rate was 81.8% at 5-years when the tumor was located in the upper third of the stomach and was 95.5% at 5-years when the tumor was located in the middle or lower third of the stomach (P = 0.0093)., Conclusion: These data may suggest that tumor location is associated with survival in patients with stage IB gastric cancer.

Adjuvant chemotherapy aims to eradicate micrometastatic tumor cells before and after curative surgery. Many Phase III trials have been conducted to study the efficacy of postoperative adjuvant chemotherapy; however, most trials have failed to show any survival benefit because of their low statistical power and/or poor patient compliance. Since 2000, two pivotal Phase III trials, the ACTS-GC and the CLASSIC, have demonstrated the efficacy of postoperative adjuvant chemotherapy following D2 gastrectomy. Although treatment with S-1 for 1 year or combination therapy with capecitabine and oxaliplatin for 6 months is effective, more intensive chemotherapy is necessary to further improve the survival rates. In Europe, two Phase III trials, the MAGIC and the FNCLCC/FFCD, have produced results that strongly suggest that neoadjuvant chemotherapy is beneficial. The advantages of neoadjuvant chemotherapy include a high rate of R0 resection, tumor regression, high compliance and the avoidance of unnecessary surgery. The disadvantage of neoadjuvant chemotherapy is over-diagnosis. In Japan, the Japan Clinical Oncology Group has conducted several clinical trials using neoadjuvant chemotherapy to target extensive nodal disease and/or scirrhous carcinomas. The optimal courses and regimens of neoadjuvant chemotherapy should, therefore, be clarified in the future.

Background and Objectives: We clarified the impact of omentectomy for advanced gastric cancer on patient survival from the surgical results of a high-volume center in Japan., Methods: Patients who received curative gastrectomy were divided into two groups based on whether they underwent omentectomy. The propensity score-matching method was used to assemble a well-balanced cohort, and relapse-free survival and the pattern of recurrence were compared., Results: For this study, 330 patients who fulfilled the inclusion criteria participated and were divided into two groups: group R, patients who received omentectomy, and group P, patients who received omentum-preserving gastrectomy. After performing score-matching, 196 patients were selected. The 3- and 5-year relapse-free survival rates were 72.9% (95% confidence interval, 64.1-81.7) and 66.2% (56.6-75.8%) in group R, and 76.7% (67.9-81.2) and 67.3% (55.1-79.5) in group P, which were not significantly different (P = 0.750). Regarding sites of relapses, no differences were observed between the groups (P = 0.863)., Conclusions: In this series, omentum-preserving gastrectomy for advanced gastric cancer did not increase the peritoneal relapse rate or affect patient survival compared to conventional gastrectomy. The non-inferiority of the omission of omentectomy should be evaluated by a randomized controlled trial.

This randomized Phase II trial is being conducted to evaluate the impact of omentectomy for advanced gastric cancer on patient survival. The primary endpoint is the 3-year relapse-free survival rate and the secondary endpoints are 5-year overall survival, intraoperative blood loss, length of the operation and postoperative morbidity (especially postoperative ileus). The planned sample size is 250 patients (125 for complete removal of the omentum and 125 for preservation of the omentum) to determine whether omentum-preserving gastrectomy may be a candidate procedure for a Phase III trial in a randomized Phase II setting.

Background: We aimed to estimate whether the macroscopic extent of gastric mucosal atrophy is associated with a risk for esophageal squamous cell carcinoma using a case-control study in Japanese subjects, a population known to have a high prevalence of CagA-positive H. pylori infection., Methods: Two hundred and fifty-three patients who were diagnosed as having esophageal squamous cell carcinoma, and 253 sex- and age-matched controls were enrolled in the present study. The macroscopic extent of gastric mucosal atrophy was evaluated based on the Kimura and Takemoto Classification. A conditional logistic regression model with adjustment for potential confounding factors was used to assess the associations., Results: Body gastritis, defined endoscopically, was independently associated with an increased risk for esophageal squamous cell carcinoma., Conclusion: Our findings suggest that macroscopic body gastritis may be a risk factor for esophageal squamous cell carcinoma in Japan. Further studies are needed to confirm these findings.

Objective: This study aimed to analyse whether age, metastasis, extrathyroidal invasion and size (AMES) risk definition is valuable for Japanese patients with differentiated thyroid carcinoma (DTC)., Methods: Two hundred and fifteen Japanese DTC patients (43 men, 172 women; mean age, 51.0 years; mean follow-up, 102 months) treated surgically at our institutions between 1981 and 2001 were retrospectively analysed. Clinicopathological features were compared between high-risk and low-risk patients by AMES criteria. Various risk factors were also evaluated for each group of patients., Results: There were 57 high-risk and 158 low-risk patients. Recurrence and mortality rates were 43.9% and 24.6% in high-risk patients and 7.6% and 0.6% in low-risk patients, respectively (p < 0.0001). Disease-specific survival rates at 5, 10 and 15 years were 84.3%, 74.0% and 63.5% in high-risk patients and 100%, 100% and 98.3% in low-risk patients, respectively (p < 0.0001). Univariate analysis revealed that curative resection, local recurrence and distant metastasis were risk factors for mortality in the high-risk group. Multivariate analysis revealed that curative resection (hazard ratio [HR], 4.68; 95% confidence interval [CI], 1.23-17.83; p = 0.024) and distant metastasis (HR, 4.79; 95% CI, 1.24-18.40; p = 0.023) were significantly related to mortality in high-risk patients., Conclusion: AMES can identify high-risk and low-risk Japanese patients. Distant metastasis and curative resection are prognostic factors for disease-specific death.