Japanese Classification Research Articles

Occupational physical activity differentially affects the risk for developing later-onset Crohn’s disease and ulcerative colitis among middle-aged and older populations

Background A person’s occupation may increase his/her risk for developing inflammatory bowel disease (IBD). This study investigated the association between risk for later-onset of IBD and both specific occupations and occupational physical activity (OPA) levels. Materials and methods A multicenter hospital-based matched case-control study was conducted using the Inpatient Clinico-Occupational Survey database. Cases were patients with Crohn’s disease (CD) and ulcerative colitis (UC) patients admitted for the first time between 2005 and 2015. Four controls matched by age, sex, admission year and hospital were selected for each case. Cases and controls were grouped into the longest-held occupations as classified by the Japanese Standard Occupational Classification and OPA levels. We conducted conditional logistic regressions to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for IBD, CD and UC adjusted for alcohol consumption and smoking status. Results There were 564 cases (172 CD, 392 UC) and 2086 controls. The risk for UC was higher among sales workers and carrying, cleaning and packing workers (ORs 2.62 [95%CIs 1.18–5.82], 2.52 [1.04–6.09]). There was no association between occupation type and CD risk. Higher OPA level decreased CD risk (OR 0.51 [95%CIs 0.26–1.00]) and increased UC risk (OR 1.53 [95%CIs 1.02–2.30]). Conclusions Our study revealed that the risk for later-onset of UC, but not CD, was associated with longest-held 'service' and 'manufacture' work. The risk by OPA levels was inversely associated between CD and UC. Further studies are needed by follow-up method for long-term effects of physical activity.

History of the lymph node numbering system in the Japanese Classification of Gastric Carcinoma since 1962.

The Japanese Classification of Gastric Carcinoma was established by the Japanese Research Society for Gastric Cancer in 1962. The latest 15th edition was published in 2017. One of its main features is that lymph nodes are numbered as stations. The number of groups has increased from 16 to 36 in 55years. Seven groups (nos. 1, 2, 5, 7, 9, 10, and 15) were retained from the original classification. Nine groups (nos. 3, 4, 6, 8, 11, 12, 13, 14, and 16) were sub-divided into two or more groups. Furthermore, seven groups (nos. 17, 18, 19, 20, 110, 111, and 112) were added in the 6th, 11th, and 12th editions. This numbering system helps surgeons recognize the exact lymph nodes that need to be dissected. However, the numbering system has become extremely complicated. It is necessary to organize the historical background of each lymph node station and share the definitions clearly. This review focuses on nine anatomical zones around the stomach and summarizes the history of lymph node stations in the Japanese Classification of Gastric Carcinoma. Lymph node stations will continue to be modified in the future, and the historical background may be useful in future revisions.

Comparison of Two Major Staging Systems in Predicting Survival and Recommendation of Postoperative Radiotherapy Based on the 11th Japanese Classification for Esophageal Carcinoma After Curative Resection

To compare the prognostic predictive power of the 11th Japan Esophageal Society (JES) system with the 8th American Joint Committee on Cancer (AJCC) system in patients with thoracic esophageal squamous cell carcinoma (TESCC), and to estimate the survival benefits of postoperative radiotherapy (PORT) based on substage of the JES system.Area under the curve (AUC) values of receiver operating characteristic curve were calculated to evaluate prognostic efficacy. Propensity score matching (PSM) analysis was conducted to balance the two groups (surgery only [S group] or surgery plus postoperative radiotherapy [S+RT group]) across substages of the 11th JES system according to independent prognostic factors for overall survival (OS) identified using the Cox proportional hazards regression.A total of 2960 patients were eligible. The 5-year OS AUC for the 8th AJCC system was significantly higher than that for the 11th JES system (0.701 vs. 0.675, P < 0.001). Before PSM, PORT significantly improved 5-year OS rates for patients in stage III and IVA by 9.1% (P < 0.001) and 21.1% (P < 0.001), respectively. After PSM, the 5-year OS rates in stage II, III, and IVA of the S+RT group were significantly higher than those in the S group (70.9%, 39.7%, and 35.1% vs. 57.8%, 27.2%, and 10.3%, respectively; P < 0.001).The 11th JES system was less capable of predicting prognosis than the 8th AJCC system and patients in stage III of the JES system were highly recommended to undergo PORT.

Comprehensive registry of esophageal cancer in Japan, 2014

BackgroundThe registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes annually.MethodsWe analyzed the data of patients who had visited the participating hospitals in 2014. We collected the data with a web-based data collection system using the National Clinical Database. We used the Japanese Classification of Esophageal Cancer 10th edition by JES and the TNM classification 7th edition by the Union of International Cancer Control (UICC) for cancer staging.ResultsA total of 9026 cases were registered from 344 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.9% and 7.1%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.1%, 33.7%, 25.3%, and 59.3%, respectively. Esophagectomy was performed in 5204 cases. Concerning the approach used for esophagectomy, 48.1% of the cases were treated thoracoscopically. The operative mortality (within 30 days after surgery) was 0.75%, and the hospital mortality was 2.0%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system, because pStage IV included the patients with supraclavicular lymph-node metastasis (M1 LYM).ConclusionWe hope that this report contributes to improving all aspects of diagnosing and treating esophageal cancer in Japan.

A Multicenter Retrospective Study Comparing Surgical Outcomes Between the Overlap Method and Functional Method for Esophagojejunostomy in Laparoscopic Total Gastrectomy: Analysis Using Propensity Score Matching.

This study aimed to compare the postoperative outcomes after laparoscopic total gastrectomy (LTG) with esophagojejunostomy (EJS) performed using the overlap method or the functional method in a multicenter retrospective study with propensity score matching. We retrospectively enrolled all patients who underwent curative LTG for gastric cancer at 6 institutions between January 2004 and December 2018. Patients were categorized into the overlap group (OG) or functional group (FG) based on the type of anastomosis used in EJS. Patients in the groups were matched using the following propensity score covariates: age, sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, and Japanese Classification of Gastric Carcinoma stage. The surgical results and postoperative outcomes were compared. We identified 69 propensity score-matched pairs among 440 patients who underwent LTG. There was no significant between-group difference in the median operative time, intraoperative blood, or number of lymph nodes resected. In terms of postoperative outcomes, the rates of all complications [Clavien-Dindo (CD) classification ≥II; OG 13.0 vs. FG 24.6%, respectively; P=0.082], complications more severe than CD grade III (OG 8.7 vs. FG 18.8%, respectively; P=0.084), and the occurrence of EJS leakage and stenosis more severe than CD grade III (OG 7.3% vs. FG 2.9%, P=0.245; OG 1.5 vs. FG 8.7%, P=0.115, respectively) were comparable. The median follow-up period was 830 days (range, 18 to 3376 d), and there were no differences in overall survival between the 2 groups. There was no difference in surgical outcomes and overall survival based on the type of anastomosis used for EJS after LTG. Therefore, selection of anastomosis in EJS should be based on each surgeon's preference and experience.

54 CLINICOPATHOLOGICAL FEATURES AND TREATMENT OUTCOMES OF ESOPHAGOGASTRIC JUNCTIONAL CARCINOMA TREATED WITH CURATIVE SURGERY

Abstract Compared to Western countries, Japanese esophagogastric junctional carcinoma (JC) demonstrates different epidemiologic backgrounds; squamous cell carcinoma is dominant over Barrett adenocarcinoma, and there is no consensus on surgical approach or dissection range of lymph node. JC is defined as the cancer, that is the center of the tumor is within 2 cm from the esophagogastric junction to the esophagus and stomach respectively by the Japanese Classification of Esophageal Cancer, 11th edition. Methods According to the definition, we examined the clinicopathological features and treatment outcomes of patients who underwent curative resection and pathologically defined as JC. From 2012 to 2019, 23 consecutive patients with JC who received with curative surgery in Shiga University of Medical Science Hospital were included. Clinicopathological classification was based on Japanese Classification of Esophageal Cancer, 11th edition. The patients consisted of 18 males and 5 females, median age was 68 (43–91) years old. Results Pathological diagnoses were 19 adenocarcinoma, 1 squamous cell carcinoma, 2 mixed adenoneuroendocrine carcinoma (MANEC) and 1 malignant melanoma. Patients with Barrett’s esophagus were 7 cases (30.4%). Surgical procedure was esophagectomy via right thoracotomy 9 cases, esophagectomy via left thoracotomy 2 case and laparotomy 12 cases. Tumor invasion was pT1:6 (26.1%), pT2:3 (13.0%), pT3:5 (21.7%) and pT4:9 (39.1%). Lymph node metastases were observed in 16 cases (69.6%) and #1,2,3:15 cases (93.8%), #4,5: 3 cases (18.8%), #7,8a,9: 6 cases (37.5%), #19,20: 3 cases (18.8%) and #105–110: 5 cases (31.3%). Among 7 recurrence patients, peritonitis carcinomatosa was 4 cases. Conclusion In most positive lymph node metastasis cases, metastasis was observed in #1, 2 and 3 lymph nodes, but metastasis to the cervical lymph node was not observed. In the G, GE cases, right thoracotomy was not performed because there were no metastases to the upper mediastinal lymph nodes. These results suggested that surgical operation could be reduced to proximal gastrectomy for early G, GE cases. Future studies are necessary to further evaluate this result.

Efficacy of neoadjuvant chemotherapy in patients with high-risk resectable colorectal liver metastases.

The role of preoperative neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastases (CRLM) remains undetermined. This study aimed to assess the efficacy of NAC in patients with resectable CRLM, especially in high-risk subgroups for recurrence, with special reference to synchronicity and the CRLM grade in the Japanese classification system. A retrospective analysis of a multi-institutional cohort who was diagnosed with resectable CRLM was performed. CRLM was classified into three grades (A, B, and C) according to the combination of H stage (H1: ≤ 4 lesions and ≤ 5cm, H2: ≥ 5 lesions or > 5cm, H3: ≥ 5 lesions and > 5cm), nodal status of the primary tumor (pN0/1: ≤ 3 metastases, pN2: ≥ 4 metastases), and the presence of resectable extrahepatic metastases. Among 222 patients with resectable CRLM, 97 (43.7%) had synchronous CRLM. The surgical failure-free survival (SF-FS) of patients with synchronous CRLM (without NAC) was significantly worse than that of patients with metachronous CRLM (P = 0.0264). The SF-FS of patients with Grade B/C was also significantly worse than that of Grade A (P = 0.0058). Among the 53 patients with synchronous and Grade B/C CRLM, 31 were assigned to NAC, and all of them underwent liver surgery. In this high-risk subgroup, the SF-FS and OS in the NAC group were significantly better than those in the upfront surgery group (P < 0.0001 and P = 0.0004, respectively). Patients with synchronous and Grade B/C CRLM could be good candidates for indication of NAC.

Short-term outcomes of robotic distal gastrectomy with the "preemptive retropancreatic approach": a propensity score matching analysis.

We report the usefulness of the preemptive retropancreatic approach (PRA) in robotic distal gastrectomy (RDG) using multi-jointed forceps. Therefore, this study aimed to compare the short-term outcomes of RDG with PRA and conventional laparoscopic distal gastrectomy using the propensity score matching method. A total of 126 patients [RDG = 55; laparoscopic distal gastrectomy (LDG) = 71] were retrospectively enrolled. Patients were matched using the following propensity score covariates: age, sex, body mass index, American Society of Anesthesiologists physical status, the extent of lymph node dissection, and Japanese Classification of Gastric Carcinoma stage. Surgical results and postoperative outcomes were compared. We identified 28 propensity score-matched pairs. The median operative time and blood loss were comparable (P = 0.272 and P = 0.933, respectively). Regarding postoperative outcomes, the incidence of postoperative complications [Clavien-Dindo classification II (CD ≥ II)] was lower in the RDG group than in the LDG group (P = 0.020). No significant differences in the peak C-reactive protein value and length of hospital stay were observed between the two groups (P = 0.391 and P = 0.057, respectively). In addition, no patients had postoperative pancreas-related complications (≥ CD II) in the RDG group. RDG using PRA seems to be a safe and feasible procedure for gastric cancer because of short-term outcomes and reduction of postoperative complications (especially postoperative pancreas-related complications) as compared to conventional LDG.

1519TiP Japanese Society of Medical Oncology/Health Authority of the Japanese Government Cooperative Virtual Educational Program for Improving the Clinical Annotation for Cancer Genomic Medicine

Comprehensive genomic profiling tests are approved for refractory cancer patients in Japan with the condition that all tests be annotated by a molecular tumor board (MTB), at 12 core and 33 hub government-designated hospitals. Our study assessing the MTB performance of all core hospitals using 50 simulated cases indicated that sharing information on available matched therapies, particularly for genomic alterations with low evidence levels by the Japanese classification (PMID: 33249514), is needed to improve the quality of recommendations by MTBs (Kage H, et al #1097 ESMO 2021).

Dialyzer Classification and Mortality in Hemodialysis Patients: A 3-Year Nationwide Cohort Study.

Background: Dialyzers are classified as low-flux, high-flux, and protein-leaking membrane dialyzers internationally and as types I, II, III, IV, and V based on β2-microglobulin clearance rate in Japan. Type I dialyzers correspond to low-flux membrane dialyzers, types II and III to high-flux membrane dialyzers, and types IV and V to protein-leaking membrane dialyzers. Here we aimed to clarify the association of dialyzer type with mortality.Methods: This nationwide retrospective cohort study analyzed data from the Japanese Society for Dialysis Therapy Renal Data Registry from 2010 to 2013. We enrolled 238,321 patients on hemodialysis who were divided into low-flux, high-flux, and protein-leaking groups in the international classification and into type I to V groups in the Japanese classification. We assessed the associations of each group with 3-year all-cause mortality using Cox proportional hazards models and performed propensity score matching analysis.Results: By the end of 2013, 55,308 prevalent dialysis patients (23.2%) had died. In the international classification subgroup analysis, the hazard ratio (95% confidence interval) was significantly higher in the low-flux group [1.12 (1.03–1.22), P = 0.009] and significantly lower in the protein-leaking group [0.95 (0.92–0.98), P = 0.006] compared with the high-flux group after adjustment for all confounders. In the Japanese classification subgroup analysis, the hazard ratios were significantly higher for types I [1.10 (1.02–1.19), P = 0.015] and II [1.10 (1.02–1.39), P = 0.014] but significantly lower for type V [0.91 (0.88–0.94), P < 0.0001] compared with type IV after adjustment for all confounders. These significant findings persisted after propensity score matching under both classifications.Conclusions: Hemodialysis using protein-leaking dialyzers might reduce mortality rates. Furthermore, type V dialyzers are superior to type IV dialyzers in hemodialysis patients.

Development and Validation of a Computed Tomography–Based Radiomics Signature to Predict Response to Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer

Neoadjuvant therapies have been shown to decrease tumor burden, increase resection rate, and improve the outcomes among patients with locally advanced gastric cancer (GC). However, not all patients are equally responsive; therefore, differentiating potential respondents from nonrespondents is clinically important. To use pretreatment computed tomography (CT)-pixelated feature-difference extraction techniques to identify diagnostically relevant features that could predict patients' response to neoadjuvant chemotherapy at diagnosis. This multicenter cohort study included patients with locally advanced GC who were treated from January 2010 to July 2017 at 2 hospitals in southern China (training cohort) and 1 hospital in northern China (external validation cohort). Their clinicopathological data, pretreatment CT images, and pathological reports were retrieved and analyzed. Data analysis was conducted from December 2017 to May 2021. All patients underwent 2 to 4 cycles of fluorouracil in combination with a platinum-based neoadjuvant chemotherapy regimen. All gastrectomies were performed according to the Japanese Classification of Gastric Carcinoma (14th edition) guidelines. Reliability of clinicopathological and radiomics-based features were assessed with area under receiver operating characteristic curve (AUC) and Mann-Whitney U test. A total of 323 patients (242 [74.9%] men; median [range] age, 58 [24-82] years) were included in the study, with 250 patients (77.4%) in the training cohort and 73 (22.6%) in the validation cohort. The baseline pretreatment characteristics of the training and validation cohorts were well-balanced. The number of respondents in the training and validation cohort was 122 (48.8%) and 40 (54.8%), respectively, and the number of nonrespondents was 128 (51.2%) and 33 (45.2%), respectively. No clinicopathological variables were significantly associated with treatment response. Using radiomics, 20 low-intercorrelated features from a total of 7477 features were used to construct a radiomics signature that demonstrated significant association with treatment response. Good discrimination performance of the radiomics signature for predicting treatment response in the training (AUC, 0.736; 95% CI, 0.675-0.798) and external validation (AUC, 0.679; 95% CI, 0.554-0.803) cohorts was observed. Decision curve analysis confirmed the clinical utility of the radiomics signature. In this study, the proposed radiomics signature showed potential as a clinical aid for predicting the response of patients with locally advanced GC before treatment, thereby allowing timely planning for effective treatments for potential nonrespondents.

Reconsideration of the Appropriate Dissection Range Based on Japanese Anatomical Classification for Resectable Pancreatic Head Cancer in the Era of Multimodal Treatment.

Simple SummaryAlthough the survival benefit of “regional lymph node dissection” for pancreatic head cancer remains unclear, the R0 resection rate is reportedly associated with prognosis. We reviewed the literature that could be helpful in determining the appropriate resection range. The recent development of high-quality computed tomography has made it possible to evaluate the extent of cancer infiltration. Even if the “dissection to achieve R0 resection” range is simulated based on the computed tomography evaluation, it is difficult to identify the range intraoperatively. It is necessary to be aware of the anatomical landmarks to determine the appropriate dissection range intraoperatively.Patients with resectable pancreatic cancer are considered to already have micro-distant metastasis, because most of the recurrence patterns postoperatively are distant metastases. Multimodal treatment dramatically improves prognosis; thus, micro-distant metastasis is considered to be controlled by chemotherapy. The survival benefit of “regional lymph node dissection” for pancreatic head cancer remains unclear. We reviewed the literature that could be helpful in determining the appropriate resection range. Regional lymph nodes with no suspected metastases on preoperative imaging may become areas treated with preoperative and postoperative adjuvant chemotherapy. Many studies have reported that the R0 resection rate is associated with prognosis. Thus, “dissection to achieve R0 resection” is required. The recent development of high-quality computed tomography has made it possible to evaluate the extent of cancer infiltration. Therefore, it is possible to simulate the dissection range to achieve R0 resection preoperatively. However, it is often difficult to distinguish between areas of inflammatory changes and cancer infiltration during resection. Even if the “dissection to achieve R0 resection” range is simulated based on the computed tomography evaluation, it is difficult to identify the range intraoperatively. It is necessary to be aware of anatomical landmarks to determine the appropriate dissection range during surgery.

Pathological complete response at the para-aortic nodes as a possible surrogate endpoint in gastric cancer surgery with para-aortic node dissection after neoadjuvant chemotherapy

PurposeGastric cancer with para-aortic node (PAN) metastasis has a chance to be cured with multidisciplinary treatment of D2 and PAN dissection (PAND) following neoadjuvant chemotherapy (NAC), but its prognosis remains unsatisfactory. To establish a better multidisciplinary treatment, a better surrogate endpoint is needed. The present study focused on a pathological complete response at the PANs alone as a new surrogate endpoint and evaluated its prognostic value. MethodsThe study examined patients who received radical gastrectomy with D2 and PAND after NAC for gastric cancer with PAN metastasis from 2004 to 2015. The study compared five methods of evaluating the response to NAC: RECIST, clinical disappearance of PANs (cPAN), histological response of the primary tumor defined by Japanese Classification of Gastric Carcinoma (JCGC histological criteria) and Becker's criteria, and pathological disappearance of PANs (pPAN). The efficacy of these methods was compared using the hazard ratio (HR) for death between responders and non-responders. ResultsThirty-two patients were analyzed. The respective HR and 5-year overall survival rates of responders and non-responders were 1.316 and 49.1% vs. 60.0% by RECIST, 1.106 and 52.9% vs. 52.5% by cPAN, 0.246 and 71.3% vs. 28.6% by JCGC histological criteria, 0.239 and 76.2% vs. 36.8% by Becker's criteria, and 0.074 and 81.0% vs. 0.0% by pPAN. ConclusionsA pathological complete response at the PANs had the lowest HR and clearly differentiated the survival, suggesting it might be a good surrogate endpoint for identifying future candidates for NAC in multidisciplinary treatment for gastric cancer with PAN metastasis.

Comparison of model fit and discriminatory ability of the 8th edition of the tumor-node-metastasis classification and the 9th edition of the Japanese classification to identify stage III colorectal cancer.

The most widely accepted staging system for colorectal cancer (CRC) is the tumor-node-metastasis (TNM) classification. In Japan, the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (JCCRC) system is used. The two systems differ mainly in relation to tumor deposits (TD) and metastasis in the regional lymph nodes along the main feeding arteries and lateral pelvic lymph nodes (N3). Here, we investigated the prognostic ability of the two systems for stage III CRC. We reviewed 696 consecutive patients who underwent curative resection of stage III CRC at the National Cancer Center Hospital between May 2007 and April 2014. We examined the clinicopathological features of CRC and predicted overall survival (OS) and relapse-free survival (RFS) according to the 8th TNM and 9th JCCRC systems. The systems were compared using Akaike's information criterion (AIC), Harrell's concordance index (C-index), and time-dependent receiver-operating characteristic (ROC) curves. The 9th JCCRC system was more clinically effective according to AIC (OS, 1199 vs. 1206; RFS, 2047 vs. 2057), showed better discriminatory ability according to the C-index (OS, 0.65 vs. 0.62; RFS, 0.62 vs. 0.58), and its time-dependent ROC curve was superior compared with the 8th TNM system. These results suggest that the 9th JCCRC system has superior discriminative ability to the 8th TNM system, because the 9th JCCRC accounts for the presence of TD and N3 disease, which were both significant predictors of poor prognosis. Reconsidering the clinical value of these two factors in the TNM system could improve its clinical significance.

Femoral head collapse rate among Japanese patients with pre-collapse osteonecrosis of the femoral head.

ObjectiveIn this study, we aimed to elucidate the relationship between the duration from diagnosis to femoral head collapse and the collapse rate among patients with pre-collapse osteonecrosis of the femoral head (ONFH).MethodsIn this retrospective, observational, multicenter study, we analyzed 268 patients diagnosed with ONFH and classified them using the Japanese Investigation Committee classification. The primary endpoint was duration from the time of diagnosis to femoral head collapse for each type of ONFH.ResultsThe 12-, 24-, and 36-month collapse rates among participants were 0%, 0%, and 0% for type A, respectively; 0%, 2.0%, and 10.8% for type B, respectively; 25.5%, 40.8%, and 48.5% for type C-1, respectively; and 57.4%, 70.3%, and 76.7% for type C-2 ONFH, respectively. A comparison of unilateral and bilateral ONFH, using Kaplan–Meier survival curves demonstrated similar collapse rates.ConclusionsThe lowest collapse rate was observed for ONFH type A, followed by types B, C-1, and C-2. Additionally, a direct association was observed between the collapse rate and location of the osteonecrotic lesion on the weight-bearing surface.

Efficacy and safety of nintedanib in Japanese patients with early-stage idiopathic pulmonary fibrosis: a study protocol for an observational study

IntroductionIdiopathic pulmonary fibrosis (IPF) is a fibrotic disease of unknown aetiology with a poor prognosis. Several clinical trials of nintedanib in patients with IPF have reported its inhibitory effect on...

A STUDY ON TECHNOLOGY TREND OF CAMERA BY USING FI CODE IN JAPANESE PATENT

In development of technology and product, it’s important to make decisions based on technology trend. Some previous studies obtained technology trend based on patent information. In our previous study, we tried to investigate the state of innovation and the emergence of dominant design by using patent information. We analyzed inkjet printers and NC machines with theme codes and F term codes in Japanese patent classification codes. In this study, we tried to know the change of technology of other products other than inkjet printers or NC machines by using patent information. The target product of this study is camera. Camera products changed its key technology of imaging and recording from analogue film to digital imaging sensor and semiconductor memories. We attempted to obtain this change by using patent information.

Risk factors for recurrence in each pattern after curative gastrectomy for pStage II/III gastric cancer: An exploratory analysis of a randomized controlled trial (JCOG1001).

4052 Background: Peritoneal, lymph node, and hematogenous recurrence are frequently observed as patterns of recurrence after surgery for gastric cancer. However, the clinicopathological characteristics associated with each recurrence have rarely been comprehensively reported in a multicenter study. Understanding the risk factors for each pattern of recurrence would be helpful for the early detection of recurrence and the initiation of optimal treatment. This study investigated the risk factors for the first recurrence in each pattern after curative gastrectomy, using data from a multicenter randomized controlled trial (JCOG1001) that was designed to investigate the efficacy of bursectomy. Methods: Patients of 20-80 years of age, with cT3(SS)-T4a(SE) gastric carcinoma according to the 14th Japanese Classification of Gastric Carcinoma, with an ECOG PS of 0-1, and a body mass index of &lt; 30 kg/m2, and without bulky lymph nodes, Borrmann type 4 or large type 3 carcinoma were eligible for inclusion in JCOG1001. Of the 1204 patients who were enrolled in JCOG1001, 932 pStage II/III patients with a common histological type were included in this study. Risk factors for hematogenous, lymph node, and peritoneal patterns of recurrence were estimated by a multivariable Fine and Grey model considering death or site of recurrence other than the first site of recurrence as competing risks. Results: The overall rate of recurrence was 27.1%. Hematogenous recurrence was the most frequent pattern (12.3%), followed by peritoneal (11.2%) and lymph node (7.5%) recurrence. Differentiated type (HR, 1.818; 1.237-2.674; p = 0.0024), pT4 (in comparison to pT1-3, HR, 1.511; 95% CI, 1.011-2.257; p = 0.0440), and pN3 (in comparison to pN0-2, HR, 2.431; 95% CI, 1.635-3.616; p &lt; 0.0001) were associated with an increased incidence of hematogenous recurrence. Conversely, more than D2 lymphadenectomy reduced this pattern of recurrence (in comparison to D1+or D2 lymphadenectomy, HR, 0.575; 95% CI, 0.364-0.907; p = 0.0174). Peritoneal recurrence was significantly associated with large (≥5 cm) tumor (HR, 1.649; 95% CI, 1.034-2.629; p = 0.0356), pT4 (in comparison to pT1-3, HR, 3.222; 95% CI, 2.086-4.976; p &lt; 0.0001), pN3 (in comparison to pN0-2, HR, 1.865; 95% CI, 1.275-2.727; p = 0.0013), and undifferentiated type (HR, 2.674; 95% CI, 1.628-4.394; p = 0.0001). Extended lymph node metastasis (pN3) was the only risk factor (in comparison to pN0-2, HR, 8.030; 95% CI, 4.605-14.002; p &lt; 0.0001) for lymph node recurrence. Conclusions: The risk factors for recurrence differed according to the patterns of recurrence. Vigilant follow-up with an understanding of patterns of recurrence is required, especially for high-risk patients.

Safety and tolerability of combination therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis: A multicenter retrospective observational study in Japan.

Phase IV clinical trials in Western countries have reported that combined therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) has a manageable safety profile. However, data on the long-term safety and tolerability of this combination treatment in the real-world setting in Japan are limited. The retrospective data of 46 patients with IPF who received combination therapy with pirfenidone and nintedanib were obtained from 16 institutes in Japan. Adverse events and adverse drug reactions (ADRs) were reported through a retrospective review of medical records. Nintedanib and pirfenidone were added to preceding treatment with antifibrotic drugs in 32 (69.6%) and 13 (28.3%) patients, respectively. In one patient (2.1%), the two drugs were concurrently initiated. The mean duration of monotherapy before initiating the combination was 26.3 months. In 26 of 38 patients (68.4%), the Gender-Age-Physiology index stage was II or III. Thirty-three patients (71.7%) had some ADRs, and 14 patients (30.4%) permanently discontinued either drug or both drugs owing to the development of ADRs during the observation period (mean: 59 weeks). The percentage of grade III or IV IPF according to the Japanese Respiratory Society severity classification was higher in patients who permanently discontinued either drug or both drugs than in those who continued both drugs (90.9% [10/11; 3 undetermined grade] vs. 61.1% [11/18; 1 undetermined grade]). Decreased appetite (18/46, 39.1%) and diarrhea (16/46, 34.8%) were frequently observed ADRs. Two patients (4.3%) had serious ADRs (liver toxicity and pneumothorax). Real-world data imply that combination therapy with pirfenidone and nintedanib for IPF has a manageable safety/tolerability profile.

Comparison of Two Major Staging Systems in Predicting Survival and Recommendation of Postoperative Radiotherapy Based on the 11th Japanese Classification for Esophageal Carcinoma After Curative Resection: A Propensity Score-Matched Analysis.

The aim of this study was to compare the prognostic predictive power of the 11th Japan Esophageal Society (JES) staging system with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system in patients with thoracic esophageal squamous cell carcinoma (TESCC), and to estimate the survival benefits of postoperative radiotherapy (PORT) based on a substage of the JES staging system. Area under the curve (AUC) values of the receiver operating characteristic curve were calculated to evaluate prognostic efficacy. Propensity score matching (PSM) analysis was conducted to balance the two groups (surgery only [S group] or surgery plus PORT [S+RT group]) across substages of the 11th JES staging system according to independent prognostic factors for overall survival (OS) identified using Cox proportional hazards regression. A total of 2960 patients were eligible. The 5-year OS AUC for the 8th AJCC staging system was significantly higher than that for the 11th JES staging system (0.701 vs. 0.675, p<0.001). Before PSM, PORT significantly improved 5-year OS rates for patients in stage III and IVA by 9.1% (p<0.001) and 21.1% (p<0.001), respectively. After PSM, the 5-year OS rates in stage II, III, and IVA of the S+RT group were significantly higher than those in the S group (70.9%, 39.7%, and 35.1% vs. 57.8%, 27.2%, and 10.3%, respectively; p<0.001). The 11th JES staging system was less capable of predicting prognosis than the 8th AJCC staging system and patients in stage III of the JES staging system were highly recommended to undergo PORT.