Search

Abstract Pivotal articles that had been published between 2022 and 2023 on surgical and perioperative adjuvant treatments for locally advanced colorectal cancer (CRC) were reviewed. This review focuses on new evidence in the following areas: optimization of surgical procedures for colon cancer, including the optimal length of bowel resection and use of the no‐touch isolation technique; minimally invasive surgery for rectal cancer, such as laparoscopic transanal total mesorectal excision and robotic surgery; neoadjuvant treatments for rectal cancer, including total neoadjuvant therapy; neoadjuvant chemotherapy for colon cancer; and postoperative adjuvant chemotherapy for Stage II and III colon cancer. Although the current understanding may not enable perfect decision‐making for patients and medical professionals, ongoing advancements are expected to result in more effective personalized treatment plans, ultimately improving the prognosis and quality of life of patients.

Background/Aims Advanced pancreatic and biliary tract cancers can invade the duodenum and cause duodenal hemorrhagic stenosis. This study aimed to evaluate the efficacy of covered self-expandable metal stents in the treatment of cancer-related duodenal hemorrhage with stenosis. Methods Between January 2014 and December 2016, metal stents were placed in 51 patients with duodenal stenosis. Among these patients, a self-expandable covered metal stent was endoscopically placed in 10 patients with hemorrhagic duodenal stenosis caused by pancreatobiliary cancer progression. We retrospectively analyzed the therapeutic efficacy of the stents by evaluating the technical and clinical success rates based on successful stent placement, degree of oral intake, hemostasis, stent patency, and overall survival. Results The technical and clinical success rates were 100%. All 10 patients achieved a gastric outlet obstruction scoring system score of three within two weeks after the procedure and had no recurrence of melena. The median stent patency duration and overall survival after stent placement were 52 days (range, 20–220 days) and 66.5 days (range, 31–220 days), respectively. Conclusions Endoscopic placement of a covered metal stent for hemorrhagic duodenal stenosis associated with pancreatic or biliary tract cancer resulted in duodenal hemostasis, recanalization, and improved quality of life.

Abstract Aim The coronavirus disease 2019 (COVID‐19) pandemic greatly impacted medical resources such as cancer screening, diagnosis, and treatment given to people for various diseases. We surveyed the impacts of the pandemic on the incidence of complications and mortality following pancreaticoduodenectomy for pancreatic cancer in Japan. Methods Data on patients who underwent pancreaticoduodenectomy for pancreatic cancer were extracted from the Japanese National Clinical Database (NCD) between 2018 and 2021. The number of the pancreaticoduodenectomy for pancreatic cancer were obtained and then the morbidity and mortality rates were evaluated using a standardized morbidity/mortality ratio (SMR), which is the ratio of the observed number of incidences to the expected number of incidences calculated by the risk calculator previously developed by the NCD. Results This study included 22 255 cases. The number of pancreaticoduodenectomies exhibited an increasing trend even during the COVID‐19 pandemic. The mean observed incidence rates of Grade C pancreatic fistula and Clavien–Dindo grade ≥4 complications, and the 30‐day mortality and surgical mortality rates were 0.8%, 1.8%, 0.8% and 0.9%, respectively. The standardized morbidity ratios did not increase during the COVID‐19 pandemic. The standardized mortality ratios remained within the range of variations observed before the COVID‐19 pandemic. Conclusion The increasing trend in the number of pancreaticoduodenectomies and favorable short‐term outcomes even in the COVID‐19 pandemic suggest the medical care for pancreatic cancer in Japan functioned well during the pandemic.

Abstract Aim To clarify the usefulness of intraoperative lavage cytology in patients undergoing curative resection for pStage II‐III colorectal cancer in a prospective multicenter study. Methods Patients preoperatively diagnosed with stage II‐III colorectal cancer between 2013 and 2017 from 20 hospitals were enrolled. Lavage cytology was performed twice during the surgery. The primary endpoint was the effect of lavage cytology on the 5‐year relapse‐free survival (RFS) in patients with pStage II‐III colorectal cancer. The secondary endpoint was the effect of lavage cytology on the 5‐year overall survival (OS) and peritoneal recurrence. Results A total of 1378 patients were eligible for analysis. The number of patients with pStage II‐III colorectal cancer was 670 and 708, respectively. Fifty‐four patients (3.9%) had positive cytological results. In pStage II patients, the 5‐year RFS rates with positive and negative cytology were 61.1% and 81.6%, respectively (p = 0.023). The 5‐year OS rates were 67.1% and 91.7%, respectively (p = 0.0083). However, there was no difference in RFS or OS between pStage III patients with positive and negative cytology results. The peritoneal recurrence rates were 11.8% and 1.5% in pStage II patients with positive and negative cytology results, respectively (p = 0.032). These rates were 10.5% and 2.5% in patients with stage III disease, respectively (p = 0.022). Conclusion Stage II colorectal cancer patients with negative cytology had better outcomes than those with positive cytology. Peritoneal lavage cytology is useful for predicting peritoneal recurrence after curative resection of stage II‐III colorectal cancer.

Abstract Background Due to the coronavirus disease 2019 (COVID‐19) pandemic, cancer screening, diagnosis, and treatment have changed. This study aimed to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection prior to gastroenterological cancer surgeries on postoperative complications using data from a nationwide database in Japan. Methods Data on patients who underwent surgery for cancer including esophageal, gastric, colon, rectal, liver, and pancreatic cancer between July 1, 2019, and September 300, 2022, from real‐world sources in Japan were analyzed. The association between preoperative SARS‐CoV‐2 infection and short‐term postoperative outcomes was evaluated. A similar analysis stratified according to the interval from SARS‐CoV‐2 infection to surgery (4 weeks) was conducted. Results In total, 60 604 patients were analyzed, and 227 (0.4%) patients were diagnosed with SARS‐CoV‐2 infection preoperatively. The median interval from SARS‐CoV‐2 infection to surgery was 25 days. Patients diagnosed with SARS‐CoV‐2 infection preoperatively had a significantly higher incidence of pneumonia (odds ratio: 2.05; 95% confidence interval: 1.05–3.74; p = 0.036) than those not diagnosed with SARS‐CoV‐2 infection based on the exact logistic regression analysis adjusted for the characteristics of the patients. A similar finding was observed in patients who had SARS‐CoV‐2 infection

Abstract Aim To examine the potential negative effects of the COVID‐19 pandemic on short‐term postoperative outcomes of emergency surgery for gastroduodenal perforation in Japan. Methods A total of 7973 cases of gastroduodenal perforation from 2019 to 2021 were retrieved from the National Clinical Database (NCD), which includes >95% of surgical cases in Japan. Data were analyzed nationally and in subgroups for subjects in areas with high infection levels (HILs). Postoperative 30‐d mortality, surgical mortality, and complications (Clavien–Dindo (CD) grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. Results Nationally, data from 2019 vs 2020 and 2021 showed 30‐d mortality of 175 (6.7%) vs 398 (7.4%), surgical mortality of 250 (9.5%) vs 537 (10.1%), and complications (CD ≥3) of 558 (21.2%) vs 1163 (21.8%). Among these data, the only significantly high SMR was found for complications in July 2020 (1.36 [95% CI: 1.001–1.80]). In areas with HILs, data from 2019 vs 2020 and 2021 indicated 30‐d mortality of 91 (6.3%) vs 215 (7.3%), surgical mortality of 135 (9.4%) vs 294 (10.0%), and complications (CD ≥3) of 304 (21.1%) vs (23.1%). In these data, no month had a significantly high SMR. Conclusion The COVID‐19 pandemic had few negative effects on outcomes after surgery for gastroduodenal perforation. These findings suggest that the emergency system for gastroduodenal perforation in Japan was generally maintained during the pandemic.

Abstract Background This study aimed to evaluate the efficacy of lateral lymph node dissection (LLND) for rectal cancer by comparing the local control in patients with and without pathological lateral lymph node metastasis (LLNM). Methods We included 189 patients with rectal cancer who underwent total mesorectal excision and LLND at 13 institutions between 2017 and 2019. Patients with and without pathological LLNM were defined as the pLLNM (+) and (−) groups, respectively. Propensity score‐matching helped to balance the basic characteristics of both groups. The incidences of local recurrence (LR) and lateral lymph node recurrence (LLNR) were compared between the groups. Results In the entire cohort, 39 of the 189 patients had pathological LLNM. The 3‐year LR and LLNR rates were 18.3% and 4.0% (p = 0.01) and 7.7% and 3.3% (p = 0.22) in the pLLNM (+) and (−) groups, respectively. After propensity score matching, the data from 62 patients were analyzed. No significant differences in LR or LLNR were observed between both groups. The 3‐year LR and LLNR rates were 16.4% and 9.8% (p = 0.46) and 9.7% and 9.8% (p = 0.99) in the pLLNM (+) and (−) groups, respectively. Conclusion LLND would lead to comparable local control in the pLLNM (+) and (−) groups if the clinicopathological characteristics except for LLNM are similar.

Abstract Aim Possible negative effects of the COVID‐19 pandemic on short‐term postoperative outcomes for colorectal perforation in Japan were examined in this study. Methods The National Clinical Database (NCD) is a large‐scale database including more than 95% of surgical cases in Japan. We analyzed 13 107 cases of colorectal perforation from 2019 to 2021. National data were analyzed, and subgroup analyses were conducted for subjects in prefectures with high infection levels (HILs) and metropolitan areas (Tokyo Met. and Osaka Pref.). Postoperative 30‐day mortality, surgical mortality, and postoperative complications (Clavien–Dindo grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. Results In the NCD, postoperative 30‐day mortality occurred in 1371 subjects (10.5%), surgical mortality in 1805 (13.8%), and postoperative complications in 3950 (30.1%). Significantly higher SMRs were found for 30‐day mortality in November 2020 (14.6%, 1.39 [95% CI: 1.04–1.83]) and February 2021 (14.6%, 1.48 [95% CI: 1.10–1.96]), and for postoperative complications in June 2020 (37.3%, 1.28 [95% CI: 1.08–1.52]) and November 2020 (36.4%, 1.21 [95% CI: 1.01–1.44]). The SMRs for surgical mortality were not significantly high in any month. In prefectures with HILs and large metropolitan areas, there were few months with significantly higher SMRs. Conclusions The COVID‐19 pandemic had limited negative effects on postoperative outcomes in patients with colorectal perforation. These findings suggest that the emergency system for colorectal perforation in Japan was generally maintained during the pandemic.

Abstract Aim The Coronavirus Disease 2019 (COVID‐19) pandemic affected the allocation of various medical resources to several areas, including intensive care units (ICUs). However, currently, its impact on the short‐term postoperative outcomes of gastrointestinal cancer surgeries remains unclear. We aimed to evaluate the impact of the pandemic on the incidence of complications occurring after low anterior resection in patients with rectal cancer in Japan. Methods Data from the Japanese National Clinical Database between 2018 and 2021 were retrospectively examined. The primary outcome of the study was the postoperative morbidity and mortality rates before and after COVID‐19 pandemic. Moreover, the postoperative ICU admission rate was assessed. Morbidity and mortality rates were also assessed using a standardized morbidity/mortality ratio (SMR, the ratio of the actual number of incidences to the expected number of incidences calculated by the risk calculator). Results This study included 74 181 patients, including 43 663 (58.9%) from COVID‐19 epidemic areas. The mean actual incidences of anastomotic leakage (AL) and pneumonia during the study period were 9.2% and 0.9%, respectively. The SMRs of these complications did not increase during the pandemic but those of AL declined gradually. The mean 30‐day mortality and operative mortality rates were 0.3% and 0.5%, respectively. Moreover, SMRs did not change significantly in the pandemic or regional epidemic status. The ICU admission rate temporarily decreased, especially in the epidemic areas. Conclusion Although the pandemic temporarily decreased the ICU admission rate, its impact on short‐term outcomes following low anterior resection in patients with rectal cancer was insignificant in Japan.

Abstract Background The coronavirus disease 2019 (COVID‐19) pandemic had resulted in either failure to provide required medical resources or delayed treatment for gastric cancer patients. This study aimed to investigate the impact of COVID‐19 on the incidence of postoperative complications using a nationwide Japanese database of patients undergoing distal gastrectomy for gastric cancer. Methods We collected the data of patients who underwent distal gastrectomy from January 2018 to December 2021 from the National Clinical Database (NCD), a web‐based surgical registration system in Japan. The number of surgical cases, the use of intensive care units, and the incidence of morbidity per month were analyzed. We also calculated the standardized mortality ratio (SMR), defined as the ratio of the number of observed patients to the expected number of patients calculated using the risk calculator established in the NCD, for several morbidities, including pneumonia, sepsis, 30‐day mortality, and surgical mortality. Results A decrease of 568 gastrectomies was observed from April 2020 to May 2020. Although the absolute number of patients admitted to intensive care units had declined since 2020, the proportion of patients admitted to the ICU did not change before and after the pandemic. Mortality and critical morbidity (such as pneumonia and sepsis) rates were not worse during the pandemic compared to pre‐pandemic periods per the SMR. Conclusions Surgical management was conducted adequately through the organized efforts of the entire surgery department in our country even in a pandemic during which medical resources and staff may have been limited.

Abstract Aim To establish a new Japanese classification of synchronous peritoneal metastases from colorectal cancer. Methods This multi‐institutional, prospective, observational study enrolled patients who underwent surgery for colorectal cancer with synchronous peritoneal metastases. Overall survival rates were compared according to the various models using objective indicators. Each model was evaluated by Akaike's information criterion (AIC). The region of peritoneal metastases was evaluated by the peritoneal cancer index (PCI). Results Between October 2012 and December 2016, 150 patients were enrolled. The AIC of the present Japanese classification was 1020.7. P1 metastasis was defined as confined to two regions. The minimum AIC was obtained with the cutoff number of 10 or less for P2 metastasis and 11 or more for P3 metastasis. As for size, the best discrimination ability between P2 and P3 metastasis was obtained with a cutoff value of 3 cm. The AIC of the proposed classification was 1014.7. The classification was as follows: P0, no peritoneal metastases; P1, metastases localized to adjacent peritoneum (within two regions of PCI); P2, metastases to distant peritoneum, number ≤10 and size ≤3 cm; P3, metastases to distant peritoneum, number ≥11 or size >3 cm; P3a, metastases to distant peritoneum, number ≥11 and size ≤3 cm, or number ≤10 and size >3 cm; P3b, metastases to distant peritoneum, number ≥11 and size >3 cm. Conclusion This objective classification could improve the ability to discriminate prognosis in patients with synchronous peritoneal metastases from colorectal cancer.

EUS–TA in unresectable pancreatic cancer requires not only a tissue diagnosis but also tissue collection in anticipation of comprehensive genomic profiling. However, the optimal puncture target remains controversial. Therefore, the Primary and Metastatic Lesions in Pancreatic Cancer (PRIMATE) study was designed to clarify the optimal target by comparing the success rates for meeting OncoGuide NCC Oncopanel (NOP) analysis criteria on pre-check primary and metastatic lesion specimens obtained during the same EUS–TA session in patients with invasive pancreatic ductal adenocarcinoma. In this ongoing prospective study, two specimens, each from primary and metastatic lesions, are obtained by EUS–TA (typically using a 19G fine-needle biopsy needle) in patients with invasive pancreatic ductal adenocarcinoma. The primary endpoint is the proportion of EUS–TA specimens that meet NOP analysis criteria during pre-check (i.e., tumor cellularity of ≥20% and a tissue area of ≥4 mm2), which are then compared between primary and metastatic lesions. This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2022-168). The results of this study will be reported at an international conference and published in an international peer-reviewed journal. The trial registration number is UMIN 000048966.

Abstract Background In this study, we investigated infection‐related tumor growth, focusing on myeloid‐derived suppressor cells (MDSCs) in clinical and experimental settings. Patients and Methods In the clinical study, a total 109 patients who underwent gastrectomy or esophagectomy were included. Blood samples were collected from a preoperative time point through 3 months after surgery, and MDSCs were analyzed using flow cytometry. In animal experiments, peritonitis model mice were created by CLP method. We investigated the number of splenic MDSCs in these mice using flow cytometry. Malignant melanoma cells (B16F10) were inoculated on the back of the mice, and tumor growth was monitored. We compared the level of MDSC infiltration around the tumor and the migration ability between CLP and sham‐operated mice‐derived MDSCs. Finally, we focused on PD‐L1+MDSCs to examine the effectiveness of anti‐PD‐L1 antibodies on tumor growth in CLP mice. Results In patients with postoperative infectious complication, MDSC number was found to remain elevated 3 months after surgery, when the inflammatory responses were normalized. CLP mice showed increased numbers of MDSCs, and following inoculation with B16F10 cells, this higher number of MDSCs was associated with significant tumor growth. CLP‐mice‐derived MDSCs had higher levels of accumulation around the tumor and had more enhanced migration ability. Finally, CLP mice had increased numbers of PD‐L1+MDSCs and showed more effective inhibition of tumor growth by anti‐PD‐L1 antibodies compared to sham‐operated mice. Conclusion Long‐lasting enhanced MDSCs associated with infection may contribute to infection‐related tumor progression.

Introduction The current endoscopic treatment for postoperative benign hepaticojejunostomy anastomotic stricture (HJAS) has a high technical success rate and is highly effective in the short term. However, long-term results have shown a high rate of stenosis recurrence, which indicates an insufficient response to treatment. Three prospective studies on fully covered self-expandable metallic stent (FC-SEMS) treatment for benign HJAS used the stenosis resolution rate as the primary endpoint, and no study has yet used the long-term non-stenosis rate (at 12 months) as the primary endpoint.Methods and analysis We launched the ‘saddle-cross study’, which will be conducted as a multicentre, prospective intervention of endoscopic treatment using two modified FC-SEMSs (BONASTENT️ M-Intraductal) that have been improved for benign stenosis in patients with benign HJAS, with the long-term non-restenosis rate (at 12 months) as the primary endpoint. This study aims to evaluate the long-term non-restenosis rate (at 12 months) and safety of the saddle-cross technique for benign HJAS. We plan to enrol 50 participants.Ethics and dissemination This study has been approved by the Certified Review Board of the National Cancer Center, Japan (CRB3180009). The results will be reported at various conferences and published in international peer-reviewed journals.

Abstract Aim The National Clinical Database (NCD) of Japan is a nationwide data entry system for surgery, and it marked its 10th anniversary in 2020. The aim was to present the 2020 annual report of gastroenterological surgery of the NCD. Methods The data of the surgical procedures stipulated by the training curriculum for board‐certified surgeons of the Japanese Society of Gastroenterological Surgery in the NCD from 2011 to 2020 were summarized. Results In total, 5 622 845 cases, including 593 088 cases in 2020, were extracted from the NCD. The total number of gastroenterological surgeries increased gradually in these 10 years, except for the year 2020 due to the COVID‐19 pandemic. The annual number of surgeries of each organ, except the pancreas and liver, decreased by 0.4%–13.1% in 2020 compared to 2019. The surgical patients were consistently aging, with more than 20% of all gastroenterological surgeries in 2020 involving patients aged 80 years or older. The participation of board‐certified surgeons increased for each organ (75.9%–95.7% in 2020). The rates of endoscopic surgery also increased constantly. Although the incidences of postoperative complications of each organ increased by 0.7%–7.9% in these 10 years, postoperative mortality rates decreased by 0.2%–1.5%. Conclusions We present here the short‐term outcomes of each gastroenterological operative procedure in 2020. This review of the 10‐years of NCD data of gastroenterological surgery revealed a consistent increase of the number of surgeries (except for in 2020), especially endoscopic procedures, and aging of the Japanese population. The good safety of Japanese gastroenterological surgeries was also indicated.

Abstract Tumor deposits (TDs) are discontinuous tumor spread in the mesocolon/mesorectum which is found in approximately 20% of colorectal cancer (CRC) and negatively affects survival. We have a history of repeated revisions on TD definition and categorization in the tumor‐node‐metastasis (TNM) system leading to stage migration. Since 1997, TDs have been categorized as T or N factors depending on their size (TNM5) or contour (TNM6). In 2009, TNM7 provided the category of N1c for TDs in a case without positive lymph nodes (LNs), which is also used in TNM8. However, increasing evidence suggests that these revisions are suboptimal and only “partially” successful. Specifically, the N1c rule is certainly useful for oncologists who are having difficulty with TDs in a case with no positive LNs. However, it has failed to maximize the value of the TNM system because of the underused prognostic information of individual TDs. Recently, the potential value of an alternative staging method has been highlighted in several studies using the “counting method.” For this method, all nodular type TDs are individually counted together with positive LNs to derive the final pN, yielding a prognostic and diagnostic value that is superior to existing TNM systems. The TNM system has long stuck to the origin of TDs in providing its categorization, but it is time to make way for alternative options and initiate an international discussion on optimal treatment of TDs in tumor staging; otherwise, a proportion of patients end up missing an opportunity to receive the optimal adjuvant treatment.

A 54-year-old male patient presented with pneumaturia. Right scrotal swelling was observed. CT showed an intrascrotal abscess with gas formation. MRI showed a fistula extending from the sigmoid colon to the seminal vesicles. Since there are many diverticula in the sigmoid colon, an abscess caused by diverticulitis may have formed a fistula. The scrotal abscess was drained; however, the pus discharge did not decrease. A colostomy was then performed, and the scrotal infection rapidly improved. Sigmoidectomy and fistula transection were performed 11 months after the colostomy. Prompt diagnosis of a sigmoid coloseminal fistula using imaging has led to optimal treatment.

Abstract Introduction In Japanese patients with familial adenomatous polyposis (FAP), colectomy tends to be postponed or avoided. Aim This study aimed to clarify the current clinical practice from a Japanese multicenter cohort study database. Methods We analyzed the records of 250 patients with non‐dense FAP who did not require colorectal cancer removal. The clinical outcomes were compared between patients who received colectomy (n = 142) (Group A) and those who did not receive colectomy (n = 108) (Group B). Results The colectomy rate based on the age at the final follow‐up examination was 46%, 60%, 54%, 65%, at ≤29, 30–39, 40–49, and ≥ 50 years, respectively (P = .11). The development of colorectal cancer did not differ between Groups A and B (25% vs 22% P = .67); however, colorectal cancer was diagnosed at the Tis stage in 88% of the patients with colorectal cancer in Group B, and 34% of the patients with colorectal cancer in Group A (P 30 years of age, and patients who managed without colectomy showed acceptable survival with the early diagnosis of colorectal cancer, and a very low incidence of desmoid tumor development, indicating that this approach represents a potential option for the management of selected non‐dense FAP patients.

Abstract Laser thermal therapy is one of the treatments for malignant tumors. We developed a thermal endoscope using an ultra-compact thermo-sensor and established a new laparoscopic laser thermal therapy system to heat cancer tissue at an appropriate temperature, focusing on the fact that thermographic cameras are capable of two-dimensional temperature mapping. Hepatocellular carcinoma (N1S1) cells were implanted into the livers of Sprague–Dawley rats (n = 13) to create orthotopic hepatocellular carcinoma. Six of the rats underwent laparoscopic laser thermotherapy (70 °C, 5 min) using the newly developed system, and the others underwent laparoscopic insertion only. Lesion volume measurement and histological evaluation were performed in all of the rats. The laparoscopic laser thermal therapy system provided stable temperature control. When a temperature of 70 °C was used for the set temperature, the temperature of the target cancer was maintained within the range of 68–72 °C for 93.2% of the irradiation time (5 min). The median volume of the tumors that were thermally treated was significantly smaller than that of the untreated tumors. The newly developed laparoscopic laser thermal therapy system was capable of maintaining the temperature of the tumor surface at any desired temperature and was proven to be effective in treatment of the rat hepatocellular carcinoma model.

Abstract Background S-1 adjuvant chemotherapy is the standard treatment in Asia for resectable pancreatic ductal adenocarcinoma. The relative dose intensity of adjuvant chemotherapy influences survival in pancreatic cancer but does not precisely reflect treatment schedule modifications. We investigated the effects of total dose intensity of S-1 adjuvant chemotherapy on the survival of patients with pancreatic cancer and the permissible dose reduction. Methods Patients who underwent surgical resection during 2011–2019 for pancreatic cancer were selected. We determined the total dose intensity cut-off value that predicted tumor recurrence within 2 years postoperatively using receiver operating characteristic curves and compared the outcomes between the high and low total dose intensity groups. Results Patients with total dose intensity ≥ 62.5% (n = 53) showed significantly better overall survival than those with total dose intensity

Abstract Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi‐institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above‐mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b.

Background and study aims For distal malignant biliary obstruction, self-expandable metallic stents (SEMSs) have a larger inner diameter compared to plastic stents, which prolongs time to recurrent biliary obstruction (TRBO), although stent-related complications are still a problem. This study aimed to compare the outcomes between using 10– and 6-mm-diameter fully-covered SEMS (FCSEMS) for distal malignant biliary obstruction. Patients and methods This single-center, retrospective study included patients with 10-mm or 6-mm-diameter FCSEMS to treat distal malignant biliary obstruction. Clinical success, stent-related adverse events (AEs), cumulative incidence of RBO, factors involved in stent-related AEs, and factors involved in RBO were evaluated. Results There were 243 eligible cases between October 2017 and December 2021. The cumulative incidence of RBO did not differ significantly between the 10-mm and 6-mm groups. Stent-related AEs occurred in 31.6 % and 11.4 % of patients between the 10-mm and 6-mm groups, respectively (P

Upon contact with laid eggs, avians initiate incubation behavior and stop laying additional eggs. This phenomenon suggests that the productivity of laying hens in free-range facilities may decrease because of frequent contact with laid eggs. Here, we examined whether hens of a commercial breed exhibit incubation behavior in a free-range facility and whether egg productivity subsequently decreases. One-hour observations were performed twice weekly for 3 weeks, during which 9 of 129 hens (7.0%) exhibited incubation behavior (i.e., sitting on eggs) in the free-range facility and were defined as incubating hens. During 4 d of continuous behavioral observation, incubating and non-incubating hens laid the same number of eggs statistically (4.6 and 3.6, on average, respectively); however, incubating hens spent significantly more time on average incubating the eggs (2071.9 min) than did the non-incubating hens (20.9 min; P

Objectives: This retrospective study was conducted to clarify the morphological characteristics of colorectal cancer (CRC) in Japanese familial adenomatous polyposis (FAP) patients. Methods: This study was carried out by the study group for FAP of the Japanese Society for Cancer of the Colon and Rectum. FAP patients who underwent surgical resection between 2000 and 2012 were included in the study. Results: Of the 303 patients enrolled, 119 patients without CRC were excluded. Of 523 lesions, 49 lesions with missing morphological information were excluded; hence, only 474 CRC lesions in 178 patients (328 superficial lesions in 122 patients and 146 non-superficial lesions in 92 patients) were included in the study. Depressed lesions accounted for 3.0% of superficial lesions and ulcerated lesions accounted for 84.9% of non-superficial lesions. The depressed superficial lesions were observed only in patients with sparse and attenuated FAP (P = 0.003). The age of the patients at surgery differed between the two groups, with patients with depressed superficial lesions being significantly older than those with non-depressed superficial lesions (P = 0.009). Moreover, the age of the patients at FAP diagnosis differed between the two groups, with patients with ulcerated non-superficial lesions being significantly older than those with protruded non-superficial lesions (P = 0.006). Conclusions: In patients with FAP, depressed superficial CRC lesions rarely developed but were detected in our study group, and ulcerated non-superficial CRC lesions were also present with similar ratios. Clinicians should pay attention to depressed superficial lesions during endoscopic surveillance of FAP patients.

Abstract The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong the overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 1:1 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles. Japan Registry of Clinical Trials jRCTs051180199 ( https://jrct.niph.go.jp/ ).

Background and study aims Recently, the utility of endoscopic ultrasound-guided intervention without fistula dilation (EUS-IV WoD) has been reported to prevent adverse events. We clinically evaluated cases in which EUS-IV WoD was attempted using a novel self-expandable metallic stent (SEMS); this is a fully covered, laser-cut SEMS that has a tapered and stiff tip specifically designed for a 0.025-inch guidewire and a relatively thin, 7F delivery system. Patients and methods We retrospectively evaluated cases wherein EUS-IV WoD was attempted using the novel SEMS between March and December 2021. Results Treatment of 11 patients by EUS-IV WoD with the novel SEMS was attempted. The technical success rate for EUS-IV was 100 % and the clinical success rate was 100 %; the success rate for EUS-IV WoD was 72.8 %. Of these, the procedural success rate for EUS-IV WoD was 100 % in EUS-biliary drainage (BD) and 57.1 % in non-EUS-BD. Early adverse events were observed in 27.3 % of patients (3/11): mild abdominal pain in two patients and moderate bleeding in one patient. The abdominal pain cases were both cases of EUS-IV WoD failure and required fistula dilation. Conclusions The novel stent may be useful for EUS-IV WoD, especially in EUS-BD.

Abstract The expression of mesothelin correlates with a poor prognosis in patients with breast cancer. Since mesothelin plays a role in cancer metastasis in association with CA125, we herein examined the expression of mesothelin and CA125, and the clinicopathological meaning and prognosis of the co-expression of mesothelin and CA125 in breast cancer. Our results showed that among 478 patients, mesothelin and CA125 were co-expressed in 48 (10 %), mesothelin only in 75 (16 %), CA125 only in 217 (45 %), and neither in 234 (49 %). A high correlation was observed between the expression of mesothelin and CA125 (P =0.0004). The co-expression of mesothelin and CA125 correlated with poor patient relapse-free survival (RFS) (P = 0.0001) and was identified as an independent predictor of RFS by Cox’s multivariate analysis. In conclusion, this is the first to report the prognostic significance of the co-expression of mesothelin and CA125 in breast cancer. The co-expression of mesothelin and CA125 may be clinically useful for prognostication after surgical therapy in patients with breast cancer.

Abstract Background We aimed to present the 2019 annual report of the gastroenterological section of the National Clinical Database (NCD). Methods We reviewed 609,589 cases recorded in 2019 and 5,029,764 cases registered from 2011 to 2019 for the 115 selected gastroenterological surgical procedures. Results The main features of gastroenterological surgery in Japan were similar to those described in the 2018 annual report, namely, that 1) operative numbers gradually increased in all procedures, except gastrectomy and hepatectomy, which decreased in these years; 2) in all eight major gastroenterological surgeries, the age distribution tended toward older patients; 3) the morbidity of esophagectomy, hepatectomy, and pancreaticoduodenectomy increased, but mortality was minimized in all procedures; 4) all eight major gastroenterological procedures have increasingly been performed under laparoscopy; and 5) board‐certified surgeons were increasingly involved. These trends in recent years were more prominent in 2019. Conclusions Thanks to the continuous cooperation and dedication of the surgeons, medical staff, and surgical clinical reviewers who registered the clinical data into the NCD, it is possible to understand the comprehensive landscape of surgery in Japan and to disclose new evidence in this field. The Japanese Society of Gastroenterological Surgery will continue to promote the value of this database and encourage the use of feedback and clinical studies using the NCD, now and in the future. Generating further approaches to surgical quality improvement are important directions for future research.

Tertiary lymphoid structures (TLS) are transient ectopic lymphoid aggregates whose formation might be caused by chronic inflammation states, such as cancer. However, how TLS are induced in the tumor microenvironment (TME) and how they affect patient survival are not well understood. We investigated TLS distribution in relation to tumor infiltrating lymphocytes (TILs) and related gene expression in high-grade serous ovarian cancer (HGSC) specimens. CXCL13 gene expression correlated with TLS presence and the infiltration of T cells and B cells, and it was a favorable prognostic factor for patients with HGSC. Coexistence of CD8+ T cells and B cell lineages in the TME significantly improved the prognosis of HGSC and was correlated with the presence of TLS. CXCL13 expression was predominantly coincident with CD4+ T cells in TLS and CD8+ T cells in TILs, and it shifted from CD4+ T cells to CD21+ follicular DCs as TLS matured. In a mouse ovarian cancer model, recombinant CXCL13 induced TLS and enhanced survival by the infiltration of CD8+ T cells. These results suggest that TLS formation was associated with CXCL13-producing CD4+ T cells and that TLS facilitated the coordinated antitumor response of cellular and humoral immunity in ovarian cancer.

Abstract Background The prognosis of recurrent and unresectable gastric cancer remains poor despite the development of multidisciplinary treatments. Ramucirumab (RAM) has been proven effective against unresectable or recurrent gastric cancer. However, its administration is often discontinued because of adverse events, including hypertension and proteinuria. We report a patient with recurrent gastric cancer involving the paraaortic lymph node (PALN), who achieved long-term survival after repeated RAM administration following long-term drug holidays due to proteinuria. Case presentation A 79-year-old woman was diagnosed with advanced gastric cancer (cT4aN2) with PALN metastasis. Seven courses of S-1 plus cisplatin (SP) achieved downstaging. A distal gastrectomy with D2 lymphadenectomy was performed as a conversion surgery. The pathological diagnosis was ypT3N2M0. The dissected PALN did not contain viable cancer cells. CT and positron emission tomography/CT scans revealed PALN recurrence 1 year after the surgery. S-1 plus oxaliplatin (SOX) therapy was initiated. The recurrent PALN enlarged after seven courses of SOX therapy. Paclitaxel (PTX) plus ramucirumab (RAM) therapy was initiated as second-line chemotherapy. After three courses of PTX plus RAM therapy, a partial response was observed. PTX was discontinued because of a hematological adverse event 3.5 months after PALN recurrence. Disease progression was not observed after six courses of RAM monotherapy. However, RAM caused proteinuria and was withdrawn for 7 weeks. The recurrent PALN was enlarged on CT, and RAM monotherapy was resumed at a reduced dose of 6 mg/kg. The lesion subsequently shrank, but 4 + proteinuria occurred after three courses of RAM monotherapy. Thus, RAM was discontinued. The patient had chemotherapy-free days for 14 months until the PALN was re-enlarged to 13 mm in size. The three administrations of RAM successfully controlled PALN metastasis and proteinuria for 3 years. Conclusion In conclusion, even if RAM withdrawal led to disease progression, re-administration of RAM monotherapy while considering its side effects reduced the tumor size and provided long-term survival benefits.

Abstract Aim Neuroendocrine tumors (NETs) are one of the subtypes of neuroendocrine neoplasms and are defined as epithelial neoplasms with predominant neuroendocrine differentiation. The aim of this study was to clarify the clinicopathological characteristics of colorectal NETs through a nationwide retrospective study in Japan. Methods This multicenter retrospective cohort study of NETs in Japan was conducted by the study group of the Japanese Society for Cancer of the Colon and Rectum. In this study, we aimed to clarify the characteristics of Japanese patients with colorectal NETs. This cohort study included patients with colorectal NETs who were treated from January 2011 to December 2015. Results Most NETs developed in the lower rectum. Predictive factors of lymph node metastasis included size (>10 mm), depth of invasion (muscular propria or greater), NET grade (NET G2), depressed lesion of the tumor, and lymphovascular infiltration. In particular, depressed lesion of the tumor and lymphovascular infiltration were independent predictive factors of lymph node metastasis. The presence of an increased number of these predictive factors increased the lymph node metastasis rate. Conclusion Surgical resection with lymph node dissection is considered in the colorectal NETs patients with predictive factors of lymph node metastasis, the number of which is correlated with incidence of lymph node metastasis.

Abstract Objectives To evaluate the feasibility and safety of endoscopic ultrasound‐guided choledochoduodenostomy (EUS‐CDS) without fistula dilation using a novel self‐expandable metal stent (SEMS). Methods This retrospective study examined patients who underwent EUS‐CDS for malignant distal biliary obstruction between October 2017 and May 2021 at the National Cancer Center, Japan. The primary outcome was a technical success without fistula dilation. Secondary outcomes were the overall technical success, clinical success, adverse events (AEs), procedure time, recurrent biliary obstruction (RBO), and time to RBO (TRBO). Results Forty‐one patients were enrolled; 31 patients underwent EUS‐CDS with fistula dilation using a conventional SEMS with 7.5–8.5‐Fr delivery system (conventional SEMS group), and 10 patients underwent EUS‐CDS without fistula dilation using the novel SEMS with a 5.9‐Fr delivery system (novel SEMS group). In the novel SEMS group, the rate of technical success without fistula dilation was 90%. There were no differences in overall technical success (100% vs. 97%, p = 1.00), clinical success (80% vs. 90%, p = 0.58), and overall AEs (10% vs. 23%, p = 0.65) rates between the novel and conventional SEMS groups. In the novel SEMS group, no early AEs were observed and no bile leakage into the abdominal cavity was observed on the computed tomography scan after the procedure. The median procedure time was significantly shorter in the novel SEMS group (17 min vs. 24 min, p = 0.03). RBO and median TRBO did not differ between the 2 groups. Conclusions EUS‐CDS without fistula dilation using the novel SEMS with a 5.9‐Fr delivery system is technically feasible, straightforward, quick, and safe.

Abstract Aim The prognostic value of the stage III subclassification system based on the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma has not yet been clarified. This study aimed to develop a modified system with optimal risk stratification and compare its performance with the current staging systems. Methods Clinicopathological data from 6855 patients with stage III colorectal cancers who underwent D3 dissection were collected from a nationwide multicenter database. After determining patient survival rates across 13 divisions based on pathological N stage (N1, N2a, and N2b/N3) and tumor depth (T1, T2, T3, T4a, and T4b), except for T1N2a and T1N2b/N3 due to the small number, we categorized patients into three groups and developed a trisection staging system according to the Akaike information criterion. We then compared the Akaike information criterion of the developed system with those of the current staging systems. Results The T1N1[rank, 1] division (98.5%) had the most favorable prognosis in terms of 5‐year cancer‐specific survival, followed by T2N1[2] (93.9%), T2N2a[3] (92.0%), T3N1[4] (87.0%), T3N2a[5] (78.8%), T4aN1[6] (78.7%), T2N2b/N3[7] (77.8%), T4aN2a[8] (75.2%), T4bN1[9] (73.5%), T3N2b/N3[10] (64.7%), T4aN2b/N3[11] (61.5%), T4bN2b/N3[12] (43.0%), and T4bN2a[13] (42.5%). Compared to the categorizations of the Japanese and tumor‐node‐metastasis systems (Akaike information criterion, 22 684.6 and 22 727.1, respectively), the following stage categorizations were proven to be the most clinically efficacious: T1N1[1]‐T3N1[4], T3N2a[5]‐T4bN1[9], and T3N2b/N3[10]‐T4bN2a[13] (Akaike information criterion, 22 649.2). Conclusion The proposed modified system may be useful in the risk stratification of patients with stage III colorectal cancer who had undergone D3 dissection.

Abstract Aim This study aimed to evaluate the association between surgeons certified via the Endoscopic Surgical Skill Qualification System (ESSQS) of the Japan Society for Endoscopic Surgery (JSES) and surgical outcomes of laparoscopic distal gastrectomy (LDG) and laparoscopic low anterior resection (LLAR). Methods Japanese National Clinical Database data on the patients undergoing LDG and LLAR between 2014‐2016 were analyzed retrospectively. The proportion of cases performed by ESSQS‐certified surgeons was calculated for each procedure, and clinicopathological factors with or without participation of ESSQS‐certified surgeons as an operator were assessed. Then, effects of operations performed by ESSQS‐certified surgeons on short‐term patient outcomes were analyzed using generalized estimating equations logistic regression analysis. Results There were 110 610 and 65 717 patients who underwent LDG and LLAR, respectively. The operations performed by ESSQS‐certified surgeons in each procedure totaled 28 467 (35.3%) and 12 866 (31.2%), respectively. A multivariable logistic regression model showed that odds ratios of mortality for LDG and LLAR performed by ESSQS‐certified surgeons were 0.774 (95% CI, 0.566‐1.060, P = 0.108) and 0.977 (0.591‐1.301, P = 0.514), respectively. Odds ratios for secondary endpoints of anastomotic leakage in LDG and LLAR performed by ESSQS‐certified surgeons were 0.835 (95% CI, 0.723‐0.964, P = 0.014) and 0.929 (0.860‐1.003, P = 0.059), respectively, whereas that of ileus/bowel obstruction for LLAR performed by ESSQS‐certified surgeons was 1.265 (1.132‐1.415, P

Abstract Background Pancreaticobiliary maljunction (PBM) is a congenital abnormality in which the pancreatic and biliary ducts join anatomically outside the duodenal wall resulting in the regurgitation of pancreatic juice into the biliary tract (pancreatobiliary reflux). Persistent pancreatobiliary reflux causes injury to the epithelium of the biliary tract and promotes the risk of biliary cancer. Intracholecyctic papillary neoplasm (ICPN) has been highlighted in the context of a cholecystic counterpart of intraductal papillary mucinous neoplasm of the pancreas and the bile duct, but the tumorigenesis of ICPNs remains unclear. Case presentation A 52-year-old Japanese woman was referred for the assessment of dilation of the bile duct. Computed tomography which revealed an enhanced mass in the gallbladder and endoscopic retrograde cholangiopancreatography confirmed that the confluence of the main pancreatic duct and extrahepatic bile duct (EHBD) was located outside the duodenal wall. Under the diagnosis of gallbladder cancer with PBM, cholecystectomy with full thickness dissection, EHBD resection, lymph node dissection, and hepaticojejunostomy were performed. Macroscopic examination of the resected specimen showed that the cystic duct was dilated and joined into the EHBD just above its confluence with the pancreatic duct, and the inflamed change of non-tumorous mucosa of gallbladder indicating that there was considerable mucosal injury due to pancreatobiliary reflux to the gallbladder. Histopathological examination revealed that the gallbladder tumor was a gastric-type ICPN with non-invasive component. Either KRAS gene mutation or p53 protein expression that were known to be associated with the carcinogenesis of biliary cancer under the condition of pancreatobiliary reflux was not detected in the tumor cells of ICPN. Conclusion The present case might suggest that there was no association between PBM and ICPN. To reveal the tumorigenesis of ICPN and its attribution to pancreatobiliary reflux, however, further study is warranted.

Abstract The National Clinical Database (NCD) of Japan grew rapidly, harvesting over 11 million cases of data between 2011 and 2018 from more than 5000 facilities. This is the Report of the NCD based upon gastrointestinal surgery information in 4 420 175 cases from 2011 to 2018. More than 70% of all gastrointestinal surgeries were performed at certified institutions, and the percentage of surgeries performed at certified institutions was particularly high for the esophagus (93.8% in 2018), liver (89.4%), pancreas (91.3%), and spleen (86.9%). Also, more than 70% of the surgeries were performed with the participation of the board‐certified surgeon. As the patients have been getting older, the morbidities have been increasing. However, the mortalities have been kept at a low level. The rates of endoscopic surgery have been increasing year by year, especially high in low anterior resection (67.0%) and esophagectomy (61.0%). Nationwide, this database is surely expecting to ensure the quality of board certification system and surgical outcomes in gastroenterological surgery.

Abstract Cellular subpopulations within the colorectal tumor microenvironment (TME) include CD3+ and CD8+ lymphocytes, CD68+ and CD163+ macrophages, and tumor buds (TBs), all of which have known prognostic significance in stage II colorectal cancer. However, the prognostic relevance of their spatial interactions remains unknown. Here, by applying automated image analysis and machine learning approaches, we evaluate the prognostic significance of these cellular subpopulations and their spatial interactions. Resultant data, from a training cohort retrospectively collated from Edinburgh, UK hospitals (n = 113), were used to create a combinatorial prognostic model, which identified a subpopulation of patients who exhibit 100% survival over a 5-year follow-up period. The combinatorial model integrated lymphocytic infiltration, the number of lymphocytes within 50-μm proximity to TBs, and the CD68+/CD163+ macrophage ratio. This finding was confirmed on an independent validation cohort, which included patients treated in Japan and Scotland (n = 117). This work shows that by analyzing multiple cellular subpopulations from the complex TME, it is possible to identify patients for whom surgical resection alone may be curative.

Abstract Background Metronidazole (MNZ) has been clearly established as a medication for amebic liver abscess. In uncomplicated cases, surgical drainage should be avoided. We report a case of amebic liver abscess refractory to MNZ that was successfully treated using preoperative computed tomography (CT) and percutaneous and surgical drainage with intraoperative ultrasonography (IOUS). Case presentation A 53-year-old man with high-grade fever was diagnosed with a cystic lesion on his right hepatic lobe using CT. Percutaneous drainage was performed, and antibacterial drugs were administered. However, the infection and condition of the patient worsened. Entamoeba histolytica was detected from pus within the mediastinal cavity. Hence, the patient was diagnosed with amebic liver abscess. After the diagnosis was established, we administered MNZ for 10 days. Despite this, the patient’s physical condition did not improve. Blood tests suggested impending disseminated intravascular coagulation (DIC). We performed surgical intervention to drain the amebic liver abscess refractory to conservative treatment. During surgery, imaging information from preoperative CT and IOUS enabled us to recognize the anatomical structures and determine the incision lines of the hepatic capsule and hepatic tissue. The patient’s DIC immediately regressed after surgery. Unfortunately, malnutrition and disuse syndrome contributed to the patient’s long recovery period. He was discharged 137 days post-surgery. Conclusions We reported a case of amebic liver abscess refractory to conservative treatment. Surgical drainage with preoperative CT and IOUS allowed us to safely and effectively perform complex abscess decompression.

Abstract Background Trastuzumab (T-mab)-based chemotherapy is a standard regimen for human epithelial growth factor 2 (HER2)-positive gastric cancer. However, some patients have demonstrated a change in HER2 status after T-mab-based treatment of breast cancer. We report a rare case of mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after T-mab-based chemotherapy for HER2-positive gastric cancer. Case presentation A 60-year-old man presented with a mass of the upper abdomen, which was diagnosed as adenocarcinoma with a HER2 score of 3+ by endoscopic biopsy. He received seven cycles of combination chemotherapy with capecitabine, cisplatin, and T-mab. Subsequently, he underwent open total gastrectomy, distal pancreatosplenectomy, and extended left hepatic lobectomy as a conversion surgery. The surgically resected specimen demonstrated both adenocarcinoma and neuroendocrine components; therefore, it was diagnosed as HER2-negative mixed adenoneuroendocrine carcinoma. Although the patient received additional chemotherapy, multiple liver metastases appeared at 3 months postoperatively and he died at 6 months postoperatively because of the rapidly progressing metastatic tumor. Conclusions We encountered a rare case of rapidly progressive mixed adenoneuroendocrine carcinoma that was negative for HER2 expression after T-mab treatment combined with chemotherapy.

Abstract Aim Impact of several immune‐inflammatory markers on long‐term outcome has been reported in various malignancies. The aim of the present study was to evaluate through a meta‐analysis the oncological outcome of immune‐inflammatory markers, such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C‐reactive protein to albumin ratio (CAR) in esophageal cancer. Methods A systematic electronic search for relevant studies was carried out in PubMed, Cochrane library, Embase, and Google scholar. Meta‐analysis was done using hazard ratio (HR) and 95% confidence interval (CI) as effect measures. A systematic review and meta‐analysis were undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses protocol. P‐values

Costimulation pathways play an essential role in T cell activation, differentiation, and regulation. CD155 expressed on antigen-presenting cells (APCs) interacts with TIGIT, an inhibitory costimulatory molecule, and CD226, an activating costimulatory molecule, on T cells. TIGIT and CD226 are expressed at varying levels depending on the T cell subset and activation state. T follicular helper cells in germinal centers (GC-Tfh) in human tonsils express high TIGIT and low CD226. However, the biological role of the CD155/TIGIT/CD226 axis in human Tfh cell biology has not been elucidated. To address this, we analyzed tonsillar CD4+ T cell subsets cultured with artificial APCs constitutively expressing CD155. Here we show that CD226 signals promote the early phase of Tfh cell differentiation in humans. CD155 signals promoted the proliferation of naïve CD4+ T cells and Tfh precursors (pre-Tfh) isolated from human tonsils and upregulated multiple Tfh molecules and decreased IL-2, a cytokine detrimental for Tfh cell differentiation. Blocking CD226 potently inhibited their proliferation and expression of Tfh markers. By contrast, while CD155 signals promoted the proliferation of tonsillar GC-Tfh cells, their proliferation required only weak CD226 signals. Furthermore, attenuating CD226 signals rather increased the expression of CXCR5, ICOS, and IL-21 by CD155-stimulated GC-Tfh cells. Thus, the importance of CD226 signals changes according to the differentiation stage of human Tfh cells and wanes in mature GC-Tfh cells. High TIGIT expression on GC-Tfh may play a role in attenuating the detrimental CD226 signals post GC-Tfh cell maturation.

Attempts at performing endoscopic ultrasound-guided tissue acquisition (EUS-TA) with a 19G needle are increasing because histological diagnosis and comprehensive genomic profiling are a necessity. However, the diagnostic ability of the 19G fine-needle biopsy (FNB) needle, especially the third-generation FNB needle, is unclear and has been retrospectively reviewed. The 19G TopGain needle was used in 147 patients and 160 lesions between September 2020 and December 2021. The technical success rate of the biopsies was 99.4% (159/160). The early adverse event rate was 4.1% (6/147), and moderate or severe adverse event rate occurrence was 2.0% (3/147). The sensitivity, specificity, and accuracy of the 19G TopGain needle for 157 lesions with a confirmed diagnosis were 96.7%, 100%, and 96.8%, respectively. Rescue EUS-TA using the 19G TopGain needle was performed for nine lesions, and a successful diagnosis was made in six of these lesions (66.7%). The diagnostic ability of EUS-TA using the third-generation 19G TopGain needle was favorable. However, the use of 19G FNB needles may increase adverse events. Therefore, EUS-TA with a 19G FNB needle is mainly indicated in lesions where comprehensive genomic profiling may be necessary or the diagnosis could not be determined via EUS-TA using the 22G needle.

Age is a major risk factor for COVID-19 severity, and T cells play a central role in anti-SARS-CoV-2 immunity. Because SARS-CoV-2-cross-reactive T cells have been detected in unexposed individuals, we investigated the age-related differences in pre-existing SARS-CoV-2-reactive T cells. SARS-CoV-2-reactive CD4+ T cells from young and elderly individuals were mainly detected in the central memory fraction and exhibited similar functionalities and numbers. Naïve-phenotype SARS-CoV-2-reactive CD8+ T cell populations decreased markedly in the elderly, while those with terminally differentiated and senescent phenotypes increased. Furthermore, senescent SARS-CoV-2-reactive CD8+ T cell populations were higher in cytomegalovirus seropositive young individuals compared to seronegative ones. Our findings suggest that age-related differences in pre-existing SARS-CoV-2-reactive CD8+ T cells may explain the poor outcomes in elderly patients and that cytomegalovirus infection is a potential factor affecting CD8+ T cell immunity against SARS-CoV-2. Thus, this study provides insights for developing effective therapeutic and vaccination strategies for the elderly.

BackgroundBiological markers expressed in cancer cells and the surrounding cancer-associated fibroblasts (CAF) can be used for prediction of patient prognosis in colorectal cancer (CRC). Here, we used immunohistochemical techniques to evaluate cancer cells’ expression of specific biomarkers that are closely associated with neoplastic progression.MethodsImmunohistochemical markers included Ki-67, p53, β-catenin, MMP7, E-cadherin and HIF1-α. We also characterized microenvironmental markers expressed by CAF, including expression of α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, platelet derived growth factor β, fibroblast association protein, tenascin-C (TNC), ZEB1 and TWIST1. The study population consisted of 286 CRC patients with stage II and III disease. Stage II and III CRC were divided into a first and a second cohort (for validation). The CRCs were stratified using cluster analysis. To identify the utility of prognostic markers in stage II and III CRC, univariate and multivariate analyses were performed in both cohorts.ResultsStage II and III CRCs were stratified into 3 subgroups. Specific subgroups were significantly correlated to disease-free survival using univariate and multivariate analyses in the first cohort. High expression of TNC was identified as a single prognostic marker in both cohorts by univariate and multivariate analyses.ConclusionsWe suggest that the presence of a specific subgroup defined by multiple markers can be used for prediction of CRC outcome in stages II and III. In addition, we showed that high expression of TNC was correlated with a poorer prognosis in stages II and III of CRC.

Abstract Background To evaluate the clinicopathological and prognostic significance of the percentage change between maximum standardized uptake value (SUVmax) at 60 min (SUVmax1) and SUVmax at 120 min (SUVmax2) (ΔSUVmax%) using dual time point 18F-fluorodeoxyglucose emission tomography/computed tomography (18F-FDG PET/CT) in breast cancer. Methods Four hundred and sixty-four patients with primary breast cancer underwent 18F-FDG PET/CT for preoperative staging. ΔSUVmax% was defined as (SUVmax2 − SUVmax1) / SUVmax1 × 100. We explored the optimal cutoff value of SUVmax parameters (SUVmax1 and ΔSUVmax%) referring to the event of relapse by using receiver operator characteristic curves. The clinicopathological and prognostic significances of the SUVmax1 and ΔSUVmax% were analyzed by Cox’s univariate and multivariate analyses. Results The optimal cutoff values of SUVmax1 and ΔSUVmax% were 3.4 and 12.5, respectively. Relapse-free survival (RFS) curves were significantly different between high and low SUVmax1 groups (P = 0.0003) and also between high and low ΔSUVmax% groups (P = 0.0151). In Cox multivariate analysis for RFS, SUVmax1 was an independent prognostic factor (P = 0.0267) but ΔSUVmax% was not (P = 0.152). There was a weak correlation between SUVmax1 and ΔSUVmax% (P