Simple severity scale for perforated peptic ulcer with generalized peritonitis: A derivation and internal validation study.

BACKGROUND: Perforated peptic ulcer (PPU) causes peritonitis and requires surgery based on disease severity. This study aimed to develop and validate a severity scale for PPU with generalized peritonitis. MATERIALS AND METHODS: This retrospective cohort study used a nationwide multi-center surgical database (2013-2020). Patients aged >15 years who underwent surgery for PPU with generalized peritonitis were included and categorized into the derivation (2013-2018) and two validation (2019 and 2020) cohorts. Possible severity predictors were selected via a literature review, and Lasso models were developed to predict severe postoperative adverse events with 2000 bootstrapping. Final variables for the scoring system were determined based on inclusion frequency (≥90%) in the Lasso models. Discrimination and accuracy were evaluated using c-statistics and calibration plots. Cutoff values for minimal postoperative adverse events were examined using negative predictive values. RESULTS: Among 12,513 patients included (1,202 underwent laparoscopic surgery), 533 (5.9%), 138 (7.6%), and 117 (6.9%) in the derivation and two validation cohorts experienced postoperative adverse events. Age, dyspnea at rest, preoperative sepsis, III/IV/V of American Society of Anesthesiologists physical status, and albumin and creatinine were selected for the final model. A 0-11 scoring system was developed with c-statistics of 0.812-0.819. Cutoff value was determined as 5, which predicted <3% probability of postoperative adverse events regardless of type of surgery. CONCLUSIONS: A score of <5 predicts minimal risks for postoperative adverse events and therefore would be clinically useful to determine type of surgery. Further studies are needed to validate the score.

Esophagectomy for esophageal cancer in patients with a history of total pharyngolaryngectomy: a Japanese nationwide retrospective cohort study.

BACKGROUND: Second primary esophageal cancer often develops in patients with head and neck cancer, and esophagectomy in patients with a history of total pharyngolaryngectomy (TPL) is challenging. However, the clinical outcomes of these patients have yet to be examined in a multicenter setting. METHODS: We evaluated the surgical outcomes of a nationwide cohort of 62 patients who underwent esophagectomy for esophageal cancer with a history of TPL. RESULTS: Ivor-Lewis and McKeown esophagectomies were performed in 32 (51.6%) and 30 (48.4%) patients, respectively. Postoperatively, 23 patients (37.1%) developed severe complications, and 7 patients (11.3%) required reoperation within 30 days. Pneumonia and anastomotic leakage occurred in 13 (21.0%) and 16 (25.8%) patients, respectively. Anastomotic leakage occurred more frequently in the McKeown group than in the Ivor-Lewis group (46.7% vs. 6.2%, P < 0.001). The adjusted odds ratio for anastomotic leakage in the McKeown group was 9.64 (95% confidence intervals (CI), 2.11-70.82, P = 0.008). Meanwhile, the 5-year overall survival rates were comparable between the groups (41.8% for Ivor-Lewis and 42.7% for McKeown), and the adjusted hazard ratio of overall survival was 1.44 (95% CI, 0.64-3.29; P = 0.381; Ivor-Lewis as the reference). CONCLUSIONS: In our cohort, anastomotic leakage occurred more frequently after McKeown than Ivor-Lewis esophagectomy, and almost half of patients in the McKeown group experienced leakage. Ivor-Lewis esophagectomy is preferred for decreasing anastomotic leakage when oncologically and technically feasible.

Predicting surgical outcomes of acute diffuse peritonitis: Updated risk models based on real-world clinical data.

Aim: The existing predictive risk models for the surgical outcome of acute diffused peritonitis (ADP) need renovation by adding relevant variables such as ADP's definition or causative etiology to pursue outstanding data collection reflecting the real world. We aimed to revise the risk models predicting mortality and morbidities of ADP using the latest Japanese Nationwide Clinical Database (NCD) variable set. Methods: Clinical dataset of ADP patients who underwent surgery, and registered in the NCD between 2016 and 2019, were used to develop a risk model for surgical outcomes. The primary outcome was perioperative mortality. Results: After data cleanup, 45 379 surgical cases for ADP were derived for analysis. The perioperative and 30-day mortality were 10.6% and 7.2%, respectively. The prediction models have been created for the mortality and 10 morbidities associated with the mortality. The top five relevant predictors for perioperative mortality were age >80, advanced cancer with multiple metastases, platelet count of <50 000/mL, serum albumin of <2.0 g/dL, and unknown ADP site. The C-indices of perioperative and 30-day mortality were 0.859 and 0.857, respectively. The predicted value calculated with the risk models for mortality was highly fitted with the actual probability from the lower to the higher risk groups. Conclusions: Risk models for postoperative mortality and morbidities with good predictive performance and reliability were revised and validated using the recent real-world clinical dataset. These models help to predict ADP surgical outcomes accurately and are available for clinical settings.

Long-term Outcome After Surgical Resection of Paraaortic Lymph Node Metastasis of Colorectal Cancer: A Multicenter Retrospective Study.

BACKGROUND: The significance of resection of paraaortic lymph node metastasis in colorectal cancer is controversial. OBJECTIVE: To clarify the prognosis of colorectal cancer after paraaortic lymph node metastasis resection. DESIGN: Multicenter retrospective study. SETTINGS: Thirty-six institutions in Japan participated in this study. PATIENTS: Patients with resected and pathologically proven paraaortic lymph node metastasis of CRC between 2010 and 2015. DATA SOURCES: Database and medical records at each institution. MAIN OUTCOME MEASURES: Overall survival after paraaortic lymph node metastasis resection, recurrence-free survival, and recurrence patterns after R0 resection of paraaortic lymph node metastasis. RESULTS: A total of 133 patients were included in the primary analysis population in this study. The 5-year overall survival rate (95% confidence interval [CI]) was 41.0% (32.0, 49.8), and the median survival (95% CI) was 4.1 (3.4, 4.7) years. Independent prognostic factors for overall survival were the pathological T stage (pT4 vs. pT1- 3, adjusted hazard ratio [aHR]: 1.91, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.98, p = 0.005), time to metastases (synchronous vs. metachronous, aHR: 2.02, p = 0.02), and number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.13, p = 0.001). The 5-year recurrence-free survival rate (95% CI) was 21.1% (13.5, 29.7), with a median (95% CI) of 1.2 (0.9, 1.4) years. The primary tumor location (left- vs. right-sided colon, aHR: 4.77, p = 0.01; rectum vs. right-sided colon, aHR: 5.27, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.90, p = 0.03), number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.20, p = 0.001), and hospital volume (<10 vs. ≥10, aHR: 2.18, p = 0.02) were identified as independent prognostic factors for recurrence-free survival. Paraaortic lymph node recurrence was the most common at 33.3%. LIMITATIONS: Selection bias cannot be ruled out because of the retrospective nature of the study. CONCLUSIONS: Less than three paraaortic lymph node metastasis was a favorable prognostic factor for both overall survival and recurrence-free survival. However, paraaortic lymph node metastases were considered to be a systemic disease and the significance of resection was limited. See Video Abstract.

Knockdown of CDX2 Induces microRNA-221 Up-regulation in Human Colon Cancer Cells.

BACKGROUND/AIM: Caudal-type homeobox transcription factor 2 (CDX2) is a master regulator of intestinal development and maintenance of the intestinal epithelium. We previously revealed that CDX2Low colorectal cancers (CRCs) were associated with poor survival and differential response to adjuvant chemotherapy. MicroRNAs (miRNAs), a class of non-coding RNAs typically composed of fewer than 25 nucleotides, are known to regulate gene expression and signaling pathways. This study aimed to identify oncogenic miRNAs induced by CDX2 in CRC. MATERIALS AND METHODS: HCT116 cells were cultured and transfected with CDX2 siRNA. The expression levels of four oncogenic miRNAs (miR-9, miR-25, miR-106b and miR-221) were quantified by RT-qPCR. To understand whether CDX2 represented a key regulator of miR-221 expression in vivo, we analyzed the relationship between CDX2 and miR-221expression levels in the TCGA COAD database (n=454). RESULTS: The expression level of miR-221 was significantly up-regulated in CDX2 knockdown cells (n=2, p<0.05). In the TCGA database, we observed an inverse correlation between CDX2 and miR-221 expression levels, consistent with our in vitro data (r=-0.114, p=0.0149). Furthermore, the expression level of miR-221 was significantly elevated in patients with CDX2Low CRC (p<0.05). CONCLUSION: Knockdown of CDX2 induces microRNA-221 up-regulation in human CRC. Further research is warranted to elucidate the molecular mechanisms underlying miR-221 up-regulation in CDX2Low CRCs.

Local Recurrence of Rectal Cancer After Transanal Total Mesorectal Excision and Risk Factors: A Nationwide Multicenter Cohort Study in Japan.

Objective: To investigate the oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer and risk factors for local recurrence (LR). Background: A high LR rate with a multifocal pattern early after TaTME has been reported in Norway and the Netherlands, causing controversy over the oncological safety of this technique. Methods: Twenty-six member institutions of the Japan Society of Laparoscopic Colorectal Surgery participated in this retrospective cohort study. A total of 706 patients with primary rectal cancer who underwent TaTME between January 2012 and December 2019 were included for analysis. The primary endpoint was the cumulative 3-year LR rate. Results: A total of 253 patients had clinical stage III disease (35.8%) and 91 (12.9%) had stage IV. Intersphincteric resection was performed in 318 patients (45.0%) and abdominoperineal resection in 193 (27.3%). There was 1 urethral injury (0.1%). A positive resection margin (R1) was seen in 42 patients (5.9%). Median follow-up was 3.42 years, and the 2- and 3-year cumulative LR rates were 4.95% (95% confidence interval: 3.50-6.75) and 6.82% (95% confidence interval: 5.08-8.89), respectively. A multifocal pattern was observed in 14 (25%) of 56 patients with LR. Tumor height from the anal verge, pathological T4 disease, pathological stage III/IV, positive perineural invasion, and R1 resection were significant risk factors for LR in multivariable analysis. Conclusions: In this selected cohort in which intersphincteric resection or abdominoperineal resection was performed in more than half of cases, oncological outcomes were acceptable during a median follow-up of more than 3 years.

Open left diaphragm method enables safe surgery with a good visual field in a laparoscopic transhiatal approach for esophagogastric junction adenocarcinoma laparoscopic transhiatal reconstruction via an open left diaphragm method.

BACKGROUND: Despite being oncologically acceptable for esophagogastric junction adenocarcinoma with an esophageal invasion length of 3-4 cm, the transhiatal approach has not yet become a standard method given the difficulty of reconstruction in a narrow space and the risk of severe anastomotic leakage. This study aimed to clarify the safety and feasibility of the open left diaphragm method during the transhiatal approach for esophagogastric junction adenocarcinoma. METHODS: This retrospective study compared the clinical outcomes of patients who underwent proximal or total gastrectomy with lower esophagectomy for Siewert type II/III adenocarcinomas with esophageal invasion via the laparoscopic transhiatal approach with or without the open left diaphragm method from April 2013 to December 2021. RESULTS: Overall, 42 and 13 patients did and did not undergo surgery with the open left diaphragm method, respectively. The median operative time was only slightly shorter in the open left diaphragm group than in the non-open left diaphragm group (369 vs. 482 min; P = 0.07). Grade ≥ II postoperative respiratory complications were significantly less common in the open left diaphragm group than in the non-open left diaphragm group (17% vs. 46%, P = 0.03). Neither group had grade ≥ IV anastomotic leakage, and two cases of anastomotic leakage requiring reoperation were drained using the left diaphragmatic release technique. CONCLUSIONS: Transhiatal lower esophagectomy with gastrectomy using the open left diaphragm method is safe, highlighting its advantages for Siewert type II/III esophagogastric junction adenocarcinoma with an esophageal invasion length of ≤ 4 cm.

Minimally invasive elective gastrectomy after preoperative chemotherapy in a patient with frailty who presented with locally far advanced-stage gastric cancer: a case report.

BACKGROUND: Herein, we report a case of gastric antrum cancer with multiple invasions to other organs that was completely cured with laparoscopic distal gastrectomy after preoperative chemotherapy in a patient with poor general condition. CASE PRESENTATION: An 80-year-old male patient was diagnosed with anemia during follow-up for cerebral lacunar infarction at another hospital. He was diagnosed with advanced-stage gastric antrum cancer and was referred to our hospital. On esophagogastroduodenoscopy, type 2 advanced-stage gastric cancer was detected at the greater curvature of the antrum, and the biopsy results revealed tubular adenocarcinoma. Contrast-enhanced computed tomography scan revealed multiple invasions to other organs, thick gastric wall with contrast effect, and superior mesenteric vein tumor thrombus. However, there was no evidence of distant metastasis on positron emission tomography/computed tomography scan. The clinical diagnosis was stage IVA gastric cancer. Pancreatoduodenectomy with portal vein resection could be important at this point. However, preoperative chemotherapy with S-1 and oxaliplatin was administered instead of performing extended surgery because the patient had poor general condition (performance status score of 3). The patient received three cycles of preoperative chemotherapy at the hospital along with rehabilitation and nutritional management with oral nutritional supplements. After treatment, the performance status score of the patient improved from 3 to 1. Furthermore, in terms of clinical therapeutic effect, the patient achieved partial response. Hence, laparoscopic distal gastrectomy with D2 lymph node dissection and partial transverse colectomy was performed. After surgery, the patient was admitted for oral intake on postoperative day 6 and was discharged on postoperative day 21. Based on the histopathological examination, gastric cancer had disappeared, and there were no evident malignant findings. Therefore, gastric cancer was classified as grade 3 according to the histological treatment efficacy criteria. The patient did not present with recurrence at 2 years after surgery. CONCLUSIONS: By actively administering preoperative chemotherapy, minimally invasive radical surgery with maximum preservation of the surrounding organs can be performed for locally far advanced-stage gastric cancer in older patients with poor general condition.

Clinical significance of the maximum standardized uptake value on positron emission tomography to predict treatment response and outcomes in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy.

PURPOSES: The association between the reduction rate of the maximum standardized uptake value (SUVmax) on positron emission tomography (PET) during neoadjuvant chemoradiotherapy (NACRT) and the prognosis in patients with locally advanced rectal cancer is unknown. METHODS: We retrospectively analyzed 62 patients with locally advanced rectal cancer who underwent curative surgery after NACRT at Kobe University between 2008 and 2021. The SUVmax reduction rate was calculated from preoperative and postoperative PET scans, and its association with the prognosis was investigated. RESULTS: The cutoff value for SUVmax reduction rate was 61.5%. Twenty patients had an SUVmax reduction rate > 61.5% (SUV responder group) and 38 patients had an SUVmax reduction rate ≤ 61.5% (SUV nonresponder group). Regarding pathological outcomes, the rate of a good histological response was significantly higher in the SUV responder group than in the SUV nonresponder group (80.0% vs. 21.1%, p < 0.001). Both the overall (OS) and relapse-free survival (RFS) rates were significantly better in the SUV responder group than in the SUV nonresponder group (OS, p = 0.035; RFS, p = 0.019). In the SUV responder group, only 1 case of recurrence was observed, with a median follow-up period of 56 months. CONCLUSION: The rate of SUVmax reduction during NACRT might predict the long-term prognosis of patients with locally advanced rectal cancer.

Effects of the COVID-19 pandemic on short-term postoperative outcomes for colorectal perforation: A nationwide study in Japan based on the National Clinical Database.

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.

Presurgical mild anemia is a risk factor for severe postoperative complications of rectal cancer surgery: A Japanese nationwide retrospective cohort study.

Background: Anemia has negative effects on long-term outcomes of rectal cancer patients; however, its status as a risk factor for severe complications is disputed. Perioperative risks may differ based on the severity of pre-surgical anemia; nonetheless, no previous study has investigated these differences. This study identified risks of severe postoperative complications in rectal cancer patients based on severity of their pre-surgical anemia. Materials and Methods: This study enrolled patients who underwent low anterior resection for rectal cancer and were registered in the Japanese National Clinical Database (NCD) between 2017 and 2019. Anemia severity was categorized into three levels: mild, moderate, and severe. A logistic regression model was applied to calculate the risk-adjusted odds ratio (OR) of severe complications after surgery. Results: This study analyzed a cohort of 51 765 rectal cancer patients who underwent low anterior resection. Results showed that severe complications occurred in 10.9% of patients and were significantly more frequent in patients with anemia (13.6%) than those with normal hemoglobin levels (9.2%). Risk-adjusted ORs of severe complications in the severe, moderate, and mild anemia groups versus the normal group for males were 1.19 (95% confidence interval [CI]: 0.89-1.58), 1.47 (1.34-1.62), and 1.21 (1.12-1.31), respectively. Those for females were 1.39 (0.90-2.15), 1.64 (1.37-1.97), and 1.36 (1.16-1.58), respectively. Conclusions: According to this large cohort study, pre-surgical anemia significantly increases the risk of severe postoperative complications in rectal cancer patients. Even mild anemia presents a significant risk.

Investigation of the impact of COVID-19 on postoperative outcomes using a nationwide Japanese database of patients undergoing laparoscopic distal gastrectomy and low anterior resection for gastric cancer and rectal cancer.

Background: The COVID-19 outbreak made conventional medical care impossible, forcing changes in both healthcare providers and patients. In Japan, COVID-19 infection began spreading in earnest in 2020 and exploded in 2021. There was concern that the medical impact of COVID-19 in 2021 would differ from that in 2020. We aimed to clarify the impact of COVID-19 on mortality and anastomotic leakage in laparoscopic surgery for gastric cancer and rectal cancer in Japan using the National Clinical Database (NCD). Methods: We collected data from patients who underwent laparoscopic distal gastrectomy (LDG) and laparoscopic low anterior resection (LLAR) from January 2018 to December 2021 from the NCD, a web-based surgical registration system in Japan. The number of surgical cases, monthly incidence of mortality and morbidity (anastomotic leakage), standardized mortality ratio (SMR), and standardized morbidity-leakage ratio (SMLR [ratio of observed patients to expected patients calculated using the risk calculator established in the NCD]) were evaluated. Results: The numbers of LDG and LLAR cases continued to decline in the first year of the pandemic in 2020 and were as low in 2021 as in 2020. Although the numbers of robot-assisted LDG and LLAR cases increased, the growth rate was lower than the rate of increase prior to the pandemic. Mortality and anastomotic leakage, two of the most important complications, as assessed by SMR and SMLR, did not worsen during the pandemic in comparison to the pre-pandemic period. Conclusions: Laparoscopic surgeries were performed safely in Japan and were not affected by the COVID-19 pandemic.

The number of resected lymph nodes from the upper mediastinal area predicts long-term outcomes of esophageal squamous cell carcinoma after minimally invasive esophagectomy.

BACKGROUND: The total number of resected lymph nodes (LNs) is an important determinant of longer survival after esophagectomy for esophageal squamous cell carcinoma (ESCC). However, the resected LN counts from areas that affect long-term outcomes remain unclear. METHODS: This study included 406 patients who underwent minimally invasive esophagectomies (MIEs) at Kobe University Hospital. Resected LN counts were evaluated in the following areas: upper mediastinal (UM), middle mediastinal (MM), lower mediastinal (LM), and abdominal (Abd). Cut-off values for LN counts from each area were determined using receiver operating characteristics analysis of the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. RESULTS: The cut-off values for large or small numbers of resected LN counts in the UM, MM, LM, and Abd areas were 4, 8, 5, and 18, respectively, in patients with upper and middle thoracic (Ut/Mt) ESCC and 7, 6, 5, and 24, respectively, in patients with lower thoracic (Lt) ESCC. Multivariate analysis in patients with Ut/Mt ESCC revealed that tumor invasion depth, LN metastasis, and the resected LN count from the UM area were independent risk factors for overall survival [hazard ratio (HR), 7.04; 95% confidence interval (CI) 4.47-11.1; HR, 4.01; 95% CI 1.96-8.21; HR, 2.18; 95% CI 1.24-3.82, respectively]. In patients with Lt ESCC, tumor invasion depth, LN metastasis, and pulmonary complications were independent risk factors for overall survival (HR, 4.23; 95% CI 2.14-8.35; HR, 3.83; 95% CI 1.75-8.38; HR, 2.80; 95% CI 1.38-5.65, respectively). Resected LN counts from no areas were prognostic factors. CONCLUSION: The number of resected LNs from the UM area influenced the survival outcomes of patients with Ut/Mt ESCC after MIE.

Protocol for a phase II study to evaluate the efficacy and safety of nivolumab as a postoperative adjuvant therapy for patients with esophageal cancer treated with preoperative docetaxel, cisplatin plus 5-fluorouracil treatment (PENTAGON trial).

BACKGROUND: In Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. METHODS: This study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4-16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events. DISCUSSION: To our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes.

Short-term outcomes after liver resection with vascular reconstruction: Results from a study with the National Clinical Database of Japan.

BACKGROUND: Although curative resection with vascular reconstruction improves the prognosis of blood-invading locally advanced hepatobiliary tumors, the mortality and morbidity of the procedure remains unclear. This study aimed to clarify the risk factors associated with mortality and morbidity in patients undergoing liver resection with vascular reconstruction. METHODS: This retrospective observational study included 1215 patients undergoing hepatectomy of more than one section with vascular reconstruction, except for left lateral sectionectomy registered in the National Clinical Database (NCD) between 2015 and 2019. The rates of surgical mortality and relevant clinical factors were evaluated. RESULTS: Among the four types of vascular reconstruction, portal venous reconstruction was frequently performed in 724 patients (59.6% of the enrolled patients). Surgical mortality was 8.1%. Patients with hepatic artery reconstruction had the highest surgical mortality rate of 15.8%. In other types of reconstruction, surgical mortality was 9.1% in the portal vein, 5.2% in inferior vena cava, and 4.9% in hepatic vein. Factors significantly associated with surgical mortality include age, sex (male), preoperative comorbidity (American Society of Anesthesiologists grade >3, respiratory distress, diabetes, preoperative pneumonia, weight loss, and obstructive jaundice), poorer liver functional reserve (indocyanine green retention rate at 15 min and prothrombin time/international normalized ratio >1.1) and accompanying biliary reconstruction. CONCLUSIONS: The NCD revealed the detailed status of liver resection combined with vascular reconstruction in Japan. Based on the results of this analysis, understanding the factors that influence the outcome and postoperative course of each procedure will provide patients with accurate information and opportunities to improve future outcomes.

Requirements for hospitals in Japan to have low operative mortality and failure-to-rescue rates.

Aim: We explored institutional factors in Japan associated with lower operative mortality and failure-to-rescue (FTR) rates for eight major gastrointestinal procedures. Methods: A 22-item online questionnaire was sent to 2119 institutional departments (IDs) to examine the association between institutional factors and operative mortality and FTR rates. IDs were classified according to the number of annual surgeries, board certification status, and locality. In addition, the top 20% and bottom 20% of IDs were identified based on FTR rates and matched with the results of the questionnaire survey. Factors associated with operative mortality were selected by multivariate analysis. Results: Of the 1083 IDs that responded to the questionnaire, 568 (213 382 patients) were included in the analysis. Operative morbidity, operative mortality, and FTR rates in the top 20% and bottom 20% of IDs were 13.1% and 8.4% (p < 0.001), 0.52% and 4.3% (p < 0.001), and 4.0% and 51.2% (p < 0.001), respectively. Based on the patients' background characteristics, the top 20% of IDs handled more advanced cases. No significant difference in locality was seen between better or worse hospital FTR rates, but fewer esophagectomies, hepatectomies, and pancreatoduodenectomies were performed in depopulated areas. Six items were found to be associated with operative mortality by multivariate logistic analysis. Only 50 (8.8%) IDs met all five factors related to better FTR rates. Conclusions: The present findings indicate that several hospital factors surrounding surgical treatment, characterized by abundant human resources, are closely related to better postoperative recovery from severe complications.

Role of Wnt5b-Ror1 signaling in the proliferation of pancreatic ductal adenocarcinoma cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory cancers with the worst prognosis. Although several molecules are known to be associated with the progression of PDAC, the molecular mechanisms underlying the progression of PDAC remain largely elusive. The Ror-family receptors, Ror1 and Ror2, which act as a receptor(s) for Wnt-family ligands, particularly Wnt5a, are involved in the progression of various types of cancers. Here, we show that higher expression of Ror1 and Wnt5b, but not Ror2, are associated with poorer prognosis of PDAC patients, and that Ror1 and Wnt5b are expressed highly in a type of PDAC cell lines, PANC-1 cells. Knockdown of either Ror1 or Wnt5b in PANC-1 cells inhibited their proliferation significantly in vitro, and knockout of Ror1 in PANC-1 cells resulted in a significant inhibition of tumor growth in vivo. Furthermore, we show that Wnt5b-Ror1 signaling in PANC-1 cells promotes their proliferation in a cell-autonomous manner by modulating our experimental setting in vitro. Collectively, these findings indicate that Wnt5b-Ror1 signaling might play an important role in the progression of some if not all of PDAC by promoting proliferation.

Recurrence-free survival as a surrogate endpoint for overall survival after neoadjuvant chemotherapy and surgery for oesophageal squamous cell carcinoma.

BACKGROUND: Overall survival is considered as one of the most important endpoints of treatment efficacy but often requires long follow-up. This study aimed to determine the validity of recurrence-free survival as a surrogate endpoint for overall survival in patients with surgically resectable advanced oesophageal squamous cell carcinoma (OSCC). METHODS: Patients with OSCC who received neoadjuvant cisplatin and 5-fluorouracil, or docetaxel, cisplatin and 5-fluorouracil, at 58 Japanese oesophageal centres certified by the Japan Esophageal Society were reviewed retrospectively. The correlation between recurrence-free and overall survival was assessed using Kendall's τ. RESULTS: The study included 3154 patients. The 5-year overall and recurrence-free survival rates were 56.6 and 47.7% respectively. The primary analysis revealed a strong correlation between recurrence-free and overall survival (Kendall's τ 0.797, 95% c.i. 0.782 to 0.812) at the individual level. Subgroup analysis showed a positive relationship between a more favourable pathological response to neoadjuvant chemotherapy and a higher τ value. In the meta-regression model, the adjusted R2 value at the institutional level was 100 (95% c.i. 40.2 to 100)%. The surrogate threshold effect was 0.703. CONCLUSION: There was a strong correlation between recurrence-free and overall survival in patients with surgically resectable OSCC who underwent neoadjuvant chemotherapy, and this was more pronounced in patients with a better response to neoadjuvant chemotherapy.

Impact of treatment guidelines and pivotal clinical trial results on a surgeon's decision regarding treatment for gastric cancer: a retrospective cohort study using the National Clinical Database.

PURPOSES: The present study evaluated the impact of clinical guidelines for gastric cancer surgery on surgeons' choice of procedure in real-world practice. We focused on the 2014 guideline revision recommending laparoscopic surgery and the evidence concerning splenectomy for prophylactic lymphadenectomy reported in 2015 using the National Clinical Database, which is the most comprehensive database in Japan. METHODS: We investigated the monthly percentages of laparoscopic distal gastrectomies performed for stage I gastric cancer (LDG%) and splenectomies performed during total gastrectomy for advanced cancer (TGS%) between 2014 and 2017. We evaluated the descriptive statistics of the time-series changes in the LDG%, TGS%, and annual trends of outcomes. RESULTS: In total, 124,787 patients were enrolled. The mean LDG% and TGS% were 69.8% and 9.2%, respectively. The LDG% and TGS% were 66.4% and 16.7%, respectively, in January 2014 and 73.1% and 5.9%, respectively, in December 2017. LDG% consistently increased, and TGS% showed a consistent downward trend throughout the observation period. There was no significant change in this trend after the publication of the guideline recommendations or clinical trial results. CONCLUSION: No significant changes in surgical procedures were observed after publication of the guidelines or results of clinical trials.