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Background The phase III ATTRACTION-3 study showed that second-line nivolumab monotherapy for advanced esophageal squamous cell carcinoma prolonged overall survival (OS) but did not improve progression-free survival (PFS). Subsequent systemic therapy after discontinuing nivolumab may affect these outcomes. To test this possibility, we evaluated the outcomes of treatment with taxanes after nivolumab in ATTRACTION-3. Methods We reviewed the charts of Japanese patients who had discontinued second-line nivolumab in ATTRACTION-3 and started subsequent third-line taxanes between January 7, 2016, and November 12, 2018. The primary endpoint was objective response rate (ORR) to third-line taxanes. Results Of the 75 patients included in this study, 54 (72%), 18 (24%), and 3 (4%) patients received either paclitaxel, docetaxel, or combination therapy comprising docetaxel, cisplatin, and 5-fluorouracil, respectively. The ORR in the overall, paclitaxel, and docetaxel groups was 29.6%, 36.5%, and 12.5%, respectively; these numbers were comparable to those (20–44%) in patients receiving taxanes as first- and second-line therapy. The median OS in the overall, paclitaxel, and docetaxel groups was 9.9, 9.9, and 9.3 months, respectively, whereas the corresponding median PFS was 4.9, 4.7 and 6.5 months, respectively. Treatment-related adverse events were observed in 65 (87%) patients, of which grade 3–4 occurred in 37 (49%) patients. Conclusions Favorable effectiveness and safety profile of taxanes following second-line nivolumab was observed in Japanese patients with advanced esophageal squamous cell carcinoma. When a patient with advanced esophageal squamous cell carcinoma receiving nivolumab becomes refractory or intolerant, subsequent taxane treatment may be a promising option.

Although imaging surveillance after esophagectomy is required to achieve long-term survival for patients with esophageal cancer, the optimal surveillance timing and interval remain unclear. This study was designed to investigate the differences in oncological outcomes based on the detection method for recurrence and surveillance interval in patients with recurrence detected by routine imaging examination after esophagectomy.A total of 527 patients who underwent thoracic esophagectomy for esophageal cancer with R0 resection between 2003 and 2021 in our department were enrolled in this study. Postoperative, routine surveillance was conducted at an outpatient clinic every 3 months, thoracoabdominal computed tomography (CT) every 4-6 months, and esophagogastroduodenoscopy every 6 months. The detection method and optimal interval of imaging surveillance also were investigated.Of all patients, 161 patients developed recurrence during surveillance; 110 (68.3 %) by routine surveillance and 37 (23.0%) not detected by routine surveillance. Among patients who were diagnosed with recurrence following routine surveillance, patients with pStage IV disease on imaging surveillance by thoracoabdominal CT at an interval of ≤ 5 months had a better survival rate than those with an interval of 6 months (P = 0.004), whereas no significant difference among different intervals was observed in patients with pStage I-III disease.Recurrence may have been detectable by our routine surveillance in approximately 70% of patients who developed recurrence. These findings demonstrate the necessity of different imaging surveillance intervals for different pStages of esophageal cancer.

We herein investigated the association between early tumor shrinkage (ETS) and depth of response (DpR) and clinical outcomes in patients with metastatic esophageal cancer treated with 2-weekly docetaxel combined with cisplatin plus fluorouracil (bDCF) using data from the JCOG0807, a phase I/II trial of bDCF as first-line chemotherapy for metastatic esophageal cancer.ETS was defined as a percent decrease in the sum of the target lesions' longest diameter after 8 weeks, whereas DpR was defined as a percentage of the maximal tumor shrinkage during the treatment course. Multivariable analyses were conducted to identify significant prognostic variables in progression-free survival (PFS) and overall survival (OS): one for ETS and covariates, and another for DpR and covariates.Among 53 patients, 35 patients with ETS ≥ 20% (66.0%) had longer PFS (7.5 vs. 3.4 months, hazard ratio [HR]: 0.26, 95% confidence interval [95% CI] 0.14-0.49), OS (13.8 vs. 6.1 months, HR 0.20, 95% CI 0.11-0.39), and PPS (6.4 vs. 2.8 months, HR 0.38, 95% CI 0.20-0.72) than those with ETS 20%. In addition, 37 patients with DpR ≥ 30% (69.8%) had longer PFS (7.5 vs. 2.9 months, HR 0.17, 95% CI 0.08-0.34), OS (13.8 vs. 6.0 months, HR 0.14, 95% CI 0.07-0.27), and PPS (6.8 vs. 2.8 months, HR 0.30, 95% CI 0.15-0.58) than those with DpR 30%. Multivariable analyses revealed that each ETS and DpR was an independent factor of longer PFS and OS.ETS and DpR might be associated with clinical outcomes in patients with metastatic esophageal cancer treated with bDCF.

Two prominent patient positions during thoracoscopic esophagectomy are the left lateral decubitus position (LP) and the prone position (PP). However, whether the patient position during thoracoscopic esophagectomy influences short-term outcomes, especially postoperative pneumonia, remains unclear. We aimed to elucidate the impact of patient position on the occurrence of postoperative pneumonia.We analyzed 9850 patients who underwent oncologic thoracoscopic esophagectomies between 2016 and 2019 from the National Clinical Database. We compared the short-term outcomes between the LP and PP groups, and the primary outcome measure was the incidence of postoperative pneumonia.This study included 2637 (26.8%) and 7213 (73.2%) patients in the LP and the PP groups, respectively. The baseline characteristics of the two groups were well-balanced. Compared with the LP group, the PP group had a longer operative time and less blood loss. There were no significant differences in the incidences of postoperative pneumonia, recurrent laryngeal nerve palsy, anastomotic leakage, severe complications, and reoperation between the groups. Meanwhile, prolonged ventilation and surgery-related mortality occurred more frequently in the LP than in the PP group (P 0.001 and 0.046, respectively). After multivariable adjustment, the patient position did not significantly influence the incidence of postoperative pneumonia (odds ratio 0.91, 95% confidence interval 0.80-1.04).Although prolonged ventilation and surgery-related mortality occurred more frequently in the LP group than in the PP group, the patient position did not significantly influence the occurrence of postoperative pneumonia.

Studies have shown that epidural analgesia (EDA) is associated with a decreased risk of pneumonia and anastomotic leakage after esophagectomy, and several guidelines strongly recommend EDA use after esophagectomy. However, the benefit of EDA use in minimally invasive esophagectomy (MIE) remains unclear.The aim of this retrospective study was to compare the short-term outcomes between patients with and without EDA undergoing MIE for esophageal cancer.Data of patients who underwent oncologic MIE (April 2014-March 2019) were extracted from a Japanese nationwide inpatient database. Stabilized inverse probability of treatment weighting (IPTW), propensity score matching, and instrumental variable analyses were performed to investigate the associations between EDA use and short-term outcomes, adjusting for potential confounders.Among 12,688 eligible patients, EDA was used in 9954 (78.5%) patients. In-hospital mortality, respiratory complications, and anastomotic leakage occurred in 230 (1.8%), 2139 (16.9%), and 1557 (12.3%) patients, respectively. In stabilized IPTW, EDA use was significantly associated with decreased in-hospital mortality (odds ratio [OR] 0.46 [95% confidence interval 0.34-0.61]), respiratory complications (OR 0.74 [0.66-0.84]), and anastomotic leakage (OR 0.77 [0.67-0.88]). EDA use was also associated with decreased prolonged mechanical ventilation, unplanned intubation, nonsteroidal anti-inflammatory drug use, acetaminophen use, postoperative length of stay, and total hospitalization costs and increased vasopressor use. One-to-three propensity score matching and instrumental variable analyses demonstrated equivalent results.EDA use in oncologic MIE was associated with low in-hospital mortality as well as decreased respiratory complications, and anastomotic leakage, suggesting the potential advantage of EDA use in MIE.

One upside of cervical esophageal carcinoma is that radical surgery can be performed by laryngectomy, even for tumors with tracheal invasion. However, this approach drastically reduces the quality of life, such as by losing the vocal function. Cervical esophageal carcinoma is rare, and no comprehensive reports have described the current state of surgery. Using a Japanese nationwide web-based database, we analyzed the surgical outcomes of cervical esophageal carcinoma to evaluate the impact of larynx-preserving surgery.Based on the Japan National Clinical Database, 215 surgically treated cases of cervical esophageal carcinoma between January 1, 2018, and December 31, 2019, were enrolled. Clinical outcomes were compared between the larynx-preserved group and the laryngectomy group.Ninety-four (43.7%) patients underwent larynx-preserving surgery. A total of 177 (82.3%) patients underwent free jejunum reconstruction. More T4b patients and more patients who underwent preoperative radiotherapy were in the laryngectomy group. There were no significant differences in the frequency and the severity of morbidities between the two groups. However, in the laryngectomy group, in-hospital death within 30 days after surgery was observed in 1 patient, and the postoperative hospital stay was significantly longer (P = 0.030). In the larynx-preserved group, recurrent nerve paralysis was observed in 24.5%. Re-operation (35.3%, P = 0.016), re-intubation (17.6%, P = 0.019) and tracheal necrosis (17.6%, P = 0.028) were significantly more frequent in patients who underwent pharyngolaryngectomy with total esophagectomy and gastric tube reconstruction than in others.Larynx-preserving surgery was therefore considered to be feasible because it was equivalent to laryngectomy regarding the short-term surgical outcomes.

Postoperative complications after esophagectomy can be severe or fatal and impact the patient's postoperative quality of life and long-term outcomes. The aim of the present study was to develop the best possible model for predicting mortality and complications based on the Japanese Nationwide Clinical Database (NCD).Data registered in the NCD, on 32,779 patients who underwent esophagectomy via a thoracic approach for malignant esophageal tumor between January, 2012 and December, 2017, were used to create a risk model.The 30-day mortality rate after esophagectomy was 1.0%, and the operative mortality rate was 2.3%. Postoperative complications included pneumonia (13.8%), anastomotic leakage (13.2%), recurrent laryngeal nerve palsy (11.1%), atelectasis (4.9%), and chylothorax (2.5%). Postoperative artificial respiration for over 48 h was required by 7.8% of the patients. Unplanned intubation within 30 postoperative days was performed in 6.2% of the patients. C-indices evaluated using the test data were 0.694 for 30-day mortality and 0.712 for operative mortality.We developed a good risk model for predicting 30-day mortality and operative mortality after esophagectomy based on the NCD. This risk model will be useful for the preoperative prediction of 30-day mortality and operative mortality, obtaining informed consent, and deciding on the optimal surgical procedure for patients with preoperative risks for mortality.

Metformin has been reported to be associated with improved cancer prognosis when used in combination with chemotherapy and/or radiotherapy. In this study, we present a systematic review and meta-analyses of studies evaluating the association of tumor pathological response with the use of metformin during neoadjuvant chemoradiotherapy (NACRT) in rectal and esophageal/gastroesophageal cancer patients.We systematically searched databases for articles that compared concurrent metformin use with no metformin use in cancer patients treated with NACRT following the PRISMA 2020. The design and quality of the collected studies were reviewed, and meta-analyses were performed on the pathologic complete response (pCR) rate, tumor regression grade (TRG), T factor downstaging, and N factor downstaging.Three databases were searched, and 220 papers were screened. Five retrospective cohort study papers were eligible for the meta-analysis, with a total of 2041 patients. The included papers contained only rectal and esophageal/gastroesophageal cancers. In the metformin group, the pCR rate was 26% [20-32%], and metformin was associated with the pCR rate (odds ratio [OR] = 0.51 [0.34-0.76], p 0.01). Meta-regression analysis of the pCR rate showed a positive correlation with adenocarcinoma (coefficient = 0.13 [0.02-0.25], p = 0.03) and fluoropyrimidine anticancer drug use (coefficient = 0.01 [0.001-0.02], p = 0.03).The results suggest that metformin is associated with pCR rate when used in combination with NACRT. The association of metformin and pCR rate in combination with fluoropyrimidine anticancer drugs was observed mostly for adenocarcinoma patients.

Purpose In patients with esophageal cancer, skeletal muscle mass has been reported to decrease progressively after surgery and be independently associated with a poor prognosis. The purpose of this study was to investigate perioperative changes in dysphagia, oral intake status, and nutritional status and identify factors related to sarcopenia 6 months after esophagectomy. Methods A total of 134 patients who underwent radical resection for thoracic esophageal cancer between March 2016 and July 2019 were analyzed retrospectively. The diagnosis of sarcopenia was made by CT taken 6 months postoperatively using the cut-off criteria of skeletal muscle index (SMI) 2/m2 for male and SMI 2/m2 for female patients. As factors related to postoperative sarcopenia, dysphagia, oral intake status, nutritional status, and physical function were extracted from the medical records. Multivariate logistic regression analysis was performed to identify perioperative risk factors related to sarcopenia 6 months after surgery. Results Of the 134 patients, 34.3% were judged to be unable to start oral intake on swallowing assessment. At discharge, 30.6% received tube feeding with or without oral intake. In the non-oral intake group on swallowing assessment, a significantly higher proportion of patients received tube feeding at discharge (p = 0.014). Preoperative BMI, postoperative handgrip strength, and tube feeding at discharge were independent risk factors for sarcopenia 6 months after esophagectomy in male patients. Conclusion Tube feeding at discharge is significantly related to postoperative sarcopenia in patients with esophageal cancer. Identifying high-risk groups might allow early detection of malnutrition and provision of appropriate care.

One of the difficulties in the treatment of esophageal cancer surgery is the high rate of postoperative recurrence. After esophagectomy, distant metastatic recurrence frequently occurs in the lung. This study aimed to determine the clinical features of a recurrence pattern with lung metastasis.The current study analyzed data from 138 patients who had postoperative recurrence of esophageal cancer after a radical esophagectomy. According to the recurrence pattern at the time of initial diagnosis, the patients were classified into two groups as follows: those with lung metastasis and those without.Twenty-three of the 138 investigated patients had a recurrence pattern with lung metastasis. Salvage surgery and postoperative pneumonia (p = 0.041 and 0.030, respectively) were identified as risk factors for recurrence pattern with lung metastasis in multivariate analysis. When we compared the sites of primary esophageal tumors, we found that the frequencies of distant metastases, such as lung and liver metastases, as well as pleural/peritoneal dissemination, were higher in the mid and distal esophageal tumors. Patients with a recurrence pattern showing lung metastasis alone had a better overall and post-recurrence survival than those with other recurrence patterns (p 0.001 and p 0.001).In patients who had postoperative recurrence after esophagectomy for thoracic esophageal cancer, salvage surgery, and postoperative pneumonia were significantly related to recurrence pattern with lung metastasis. Postoperative recurrence with lung metastasis alone had a better prognosis than other recurrence patterns; therefore, when pulmonary recurrence is suspected, performing intensive examinations for early diagnosis is critical.

Purpose A collapse in regional healthcare through the maldistribution of physicians has been a long-debated issue in Japan and amidst this situation, a new system of board certification was initiated. The Japan Surgical Society (JSS) conducted a nation-wide survey to grasp the current distribution of surgeons in Japan, and their roles. Methods All 1976 JSS-certified teaching hospitals were invited to respond to a web-based questionnaire. The responses were analyzed to seek a solution to the current issues. Results Responses to the questionnaire were received from 1335 hospitals. The surgical departments of medical universities serve as an internal labor market and were the source of surgeons for most hospitals. More than 50% of teaching hospitals throughout the country claimed a shortage of surgeons even in well-populated prefectures such as Tokyo and Osaka. Hospitals rely on surgeons to cover the deficits in medical oncology, anesthesiology, and emergency medicine. These additional responsibilities were identified as significant predictors of a shortage of surgeons. Conclusions Surgeon shortage is a serious issue throughout Japan. Given the limited number of surgeons and surgical trainees, hospitals should make every effort to recruit specialists in the additional fields where surgeons are filling the gaps and allow surgeons to engage more in surgery.

Purpose: The postoperative mortality rate of distal pancreatectomy is lower than that of pancreaticoduodenectomy, although persistent complications may occur after distal pancreatectomy. Fluid collection (FC) is frequently observed after distal pancreatectomy; however, FC may occasionally progress to postoperative intra-abdominal abscess (PIAA), which requires conservative or progressive interventional treatment. This study aimed to compare the status between patients with or without PIAA, identify predictive factors for PIAA and clinically relevant postoperative pancreatic fistula, and investigate clinical characteristics of patients with PIAA with interventional drainage.Methods: We retrospectively reviewed data of patients who underwent distal pancreatectomy between January 2012 and December 2019 at two high-volume centers, where hepatobiliary-pancreatic surgeries were performed by expert specialist surgeons. Logistic regression analysis was performed to determine the predictive factors for PIAA.Results: Overall, 242 patients were analyzed, among whom 49 (20.2%) had PIAA. The median postoperative period of PIAA formation was 9 (range: 3–49) days. Among the 49 patients with PIAA, 25 (51.0%) underwent percutaneous ultrasound, computed tomography, or endoscopic ultrasound-guided interventions for PIAA. In the univariate analysis, preoperative indices representing abdominal fat mass (i.e., body mass index, subcutaneous fat area, and visceral fat area) were identified as predictive factors for PIAA; in the multivariate analysis, C-reactive protein (CRP) level (continuous variable) on postoperative day (POD) 3 (odds ratio: 1.189, 95.0% confidence interval: 1.111-1.274; PConclusions: CRP level on POD 3 was an independent and significant predictive factor for PIAA after distal pancreatectomy.

Background Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) is an alternative treatment approach. However, both treatments are associated with toxicity, and the optimal treatment for older patients with ESCC is unknown. This study aimed to evaluate the treatment strategies and prognosis of older patients with locally advanced ESCC in a real-world setting. Methods We retrospectively evaluated 381 older patients (≥ 65 years) with locally advanced ESCC (stage IB/II/III, excluding T4) who received anticancer therapy at 22 medical centers in Japan. Based on age, performance status (PS), and organ function, the patients were classified into two groups: clinical trial eligible and ineligible groups. Patients aged ≤ 75 years with adequate organ function and a PS of 0–1 were categorized into the eligible group. We compared the treatments and prognoses between the two groups. Results The ineligible group had significantly shorter overall survival (OS) than the eligible group (hazard ratio [HR] for death, 1.65; 95% confidence interval [CI], 1.22–2.25; P = 0.001). The proportion of patients receiving NAC followed by surgery was significantly higher in the eligible group than in the ineligible group (P = 1.07 × 10–11), whereas the proportion of patients receiving CRT was higher in the ineligible group than in the eligible group (P = 3.09 × 10–3). Patients receiving NAC followed by surgery in the ineligible group had comparable OS to those receiving the same treatment in the eligible group (HR, 1.02; 95% CI, 0.57–1.82; P = 0.939). In contrast, patients receiving CRT in the ineligible group had significantly shorter OS than those receiving CRT in the eligible group (HR, 1.85; 95% CI, 1.02–3.37; P = 0.044). In the ineligible group, patients receiving radiation alone had comparable OS to those receiving CRT (HR, 1.13; 95% CI, 0.58–2.22; P = 0.717). Conclusions NAC followed by surgery is justified for select older patients who can tolerate radical treatment, even if they are old or vulnerable to enrollment in clinical trials. CRT did not provide survival benefits over radiation alone in patients ineligible for clinical trials, suggesting the need to develop less-toxic CRT.

Purpose To assess the increase in hospital costs associated with postoperative complications after lower anterior resection (LAR) for rectal cancer. Methods The subjects of this retrospective analysis were patients who underwent elective LAR surgery between April, 2015 and March, 2017, collected from a Japanese nationwide gastroenterological surgery registry linked to hospital-based claims data. We evaluated total and category-specific hospitalization costs based on the level of postoperative complications categorized using the Clavien–Dindo (CD) classification. We assessed the relative increase in hospital costs, adjusting for preoperative factors and hospital case volume. Results We identified 15,187 patients (mean age 66.8) treated at 884 hospitals. Overall, 71.8% had no recorded complications, whereas 7.6%, 10.8%, 9.0%, 0.6%, and 0.2% had postoperative complications of CD grades I–V, respectively. The median (25th–75th percentiles) hospital costs were $17.3 K (16.1–19.3) for the no-complications group, and $19.1 K (17.3–22.2), $21.0 K (18.5–25.0), $27.4 K (22.4–33.9), $41.8 K (291–618), and $22.7 K (183–421) for the CD grades I–V complication groups, respectively. The multivariable model identified that complications of CD grades I–V were associated with 11%, 21%, 61%, 142%, and 70% increases in in-hospital costs compared with no complications. Conclusions Postoperative complications and their severity are strongly associated with increased hospital costs and health-care resource utilization. Implementing strategies to prevent postoperative complications will improve patients’ clinical outcomes and reduce hospital care costs substantially.

Several studies have reported a high incidence of metastasis to para-aortic station 16a2lat (no. 16a2lat) among patients with esophagogastric junction (EGJ) cancer. However, the risk factors for no. 16a2lat metastasis are unclear. This study aimed to clarify the risk factors for no. 16a2lat metastasis in patients with EGJ cancer.Among 371 prospectively enrolled patients with EGJ cancer, 344 patients who underwent no. 16a2lat lymph node dissection were analyzed. Background factors were compared between the patients with and those without no. 16a2lat metastasis. The association between the histologic status of 10 regional lymph node stations and that of no. 16a2lat metastasis was evaluated.Among the background factors, clinical N2-3 was the only independent risk factor for no. 16a2lat metastasis (odds ratio [OR], 5.90; p = 0.003). The metastasis rate of no. 16a2lat was 11.8% (11/93) for the patients with cN2-3 disease and 2.0% (5/251) for those with cN0-1 disease. The multivariate analysis showed that nos. 2 and 7 metastases were independent risk factors for no. 16a2lat metastasis, with respective ORs of 5.53 (p = 0.018) and 4.00 (p = 0.041). The patients with neither station no. 2 nor no. 7 metastasis did not exhibit no. 16a2lat metastasis, whereas the rate of no. 16a2lat metastasis was 23.7% for the patients with metastases of both stations.Clinical N2-3 and histologic positivity of station nos. 2 and 7 were independent risk factors for no. 16a2lat metastasis. These findings could potentially assist in determining the indication for no. 16a2lat dissection for patients with EGJ cancer.

The aim of this study was to evaluate clinical validity of the S-1 dosage formula based on body surface area (BSA) and creatinine clearance (CLcr) to achieve the target area under the concentration-time curve of 5-FU, which we had developed and refined in each prospective pharmacokinetic study.The recommended dose determined by the refined formula was assessed using data of the SPIRITS (S-1 vs. S-1 plus cisplatin [SP]) and the G-SOX (SP vs. S-1 plus oxaliplatin [SOX]) trials. Nine hundred and thirty-eight patients in these trials were classified into three groups according to their actual S-1 starting doses compared with the recommended doses (under-dosed, recommended dose; equal-dosed, =recommended dose; over-dosed, recommended dose).The patients in the under-dosed group in both trials showed similar tendencies: male, younger, higher BSA, and higher CLcr. The incidence of any grade neutropenia was significantly greater in the over-dosed group compared with the equal-dosed group in the S-1 and the SOX arms. The hazard ratios (HR) of overall survival (OS) (under-dosed vs. equal-dosed) were 1.361 (S-1 arm), 1.259 (SP arm) in the SPIRITS trial, and 1.381 (SOX arm), 0.999 (SP arm) in the G-SOX trial. Multivariate analysis in all the patients demonstrated that OS of the over-dosed group was equivalent (HR 1.002, 95% confidence interval [CI] 0.850-1.182, p = 0.980) and that of the under-dosed group was inferior (HR 1.267, 95% CI 1.005-1.597, p = 0.045) to the equal-dosed group.It is suggested that the refined S-1 dosage formula can recommend optimal dose in terms of safety and efficacy.

The contribution of postoperative coagulation-fibrinolysis status to prognosis is yet to be fully investigated. Thus, in this study, we aimed to elucidate the relationship between postoperative hypercoagulable state (PHS) after transthoracic esophagectomy and long-term outcome in patients with esophageal cancer.Patients with esophageal cancer who underwent transthoracic esophagectomy were selected from a prospectively maintained database. Based on the trend of postoperative plasma fibrin-fibrinogen degradation product (FDP) levels, patients with PHS were identified. The prognostic significance of PHS was evaluated via multivariate analysis using the Cox regression model.Based on the plasma FDP levels of 172 patients that reached a plateau between POD5 and POD7, we calculated the mean FDP value of POD5, 6, and 7, setting a median value as a cutoff. Consequently, 87 patients were classified as PHS. The overall survival (OS) in the PHS group was determined to be significantly lower than in the non-PHS group (5-year OS; 68% and 80%, p = 0.012). Recurrence-free survival (RFS) in the PHS group was significantly lower than in the non-PHS group (5-year RFS; 60% and 79%, p = 0.017). Using the pathological stage as a covariate in the multivariate analysis, PHS was an independent prognostic factor of OS [hazard ratio (HR) 2.517, p = 0.009] and RFS (HR 1.905, p = 0.041).PHS was found to be an independent negative prognostic factor in patients with esophageal cancer. Possible improvement of the oncological outcome by early postoperative intervention with anticoagulants should be explored in clinical trials.

Systematic inflammation has been reported to contribute to cancer progression through various mechanisms; however, the exact mechanism is still the subject of research. In this study, we evaluated the influence of systematic inflammation on lung metastasis, using a murine abdominal sepsis model, and assessed its relationship with pneumonia after curative esophagectomy in patients with esophageal cancer.We used a murine abdominal sepsis model given highly metastatic osteosarcoma, to reveal the mechanism of systematic inflammation and its potential for lung metastasis. The therapeutic effect of aspirin (ASA) in preventing distant metastasis was also investigated. Subsequently, we analyzed, retrospectively, the relationship between pneumonia and lung metastasis after esophagectomy in patients who underwent esophagectomy at Keio University between January, 2007 and October, 2020.Abdominal sepsis provoked lung injury in the acute phase. ASA inhibited the recruitment of neutrophils triggered by the lung injury, and it also suppressed lung metastasis. Our retrospective study revealed that lung metastasis was more frequent in patients with postoperative pneumonia.Postoperative acute lung injury is associated with a higher risk of lung metastasis. ASA may be a potential preoperative treatment for inhibiting lung metastasis by preventing the recruitment of neutrophils.

PURPOSE To appropriately adopt the organ preservation approach, including subsequent chemoradiotherapy (CRT) in patients who respond to neoadjuvant chemotherapy (NAC), the distribution of residual disease, including pathological lymph nodes (LNs) and recurrence site, needs to be recognized preoperatively. This study was designed to evaluate whether endoscopic response evaluation can predict residual tumor distribution. METHODS Patients with esophageal squamous cell carcinoma who underwent transthoracic esophagectomy (TTE) were retrospectively reviewed. Endoscopic responder (ER) to NAC was defined according to primary tumor endoscopic findings. Recurrence-free survival (RFS), overall survival (OS), and residual tumor patterns were compared between groups. RESULTS Of 193 patients, 40 (20%) were classified as ER. ERs showed significantly better RFS and OS. The pN location was found within the primary tumor and cN field in 88% of ERs, which was significantly higher than non-ERs at 63% (p = 0.004). Furthermore, the postoperative recurrence incidence in the distant organ was significantly lower in the ERs than the non-ERs (8%, 32%, respectively, p = 0.002). Residual disease, including postoperative initial recurrence, existed within the same field as the primary tumor and cN in 88% of ERs, significantly higher than 42% in the non-ERs (p < 0.001). CONCLUSIONS Endoscopic response evaluation can preoperatively predict distribution of residual tumors after NAC, which could help radiation field selection in subsequent definitive CRT when patients prefer to omit TTE. Along with improvements in NAC response rate, this could facilitate organ preservation in patients who respond to NAC.

Alcohol consumption is a major risk factor for esophageal cancer. In Asia, heavy drinkers are considered to have a higher risk of esophageal cancer than nondrinkers and light drinkers. However, no study has shown an association between alcohol reduction and the morbidity of esophageal cancer in Asian heavy drinkers. Therefore, this study investigated the significance of reducing alcohol consumption to prevent esophageal cancer in Asian heavy drinkers by conducting a systematic review and meta-analysis. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 1995 to December 2020. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a random-effects model. I2 statistics were used to detect heterogeneity. This study included 21 articles in the qualitative synthesis. Light drinkers and heavy drinkers were categorized based on alcohol consumption amount as ≤ 25 ethanol g/day and ≥ 66 ethanol g/day, respectively, as described in many previous studies, and five cohort studies were eligible for this meta-analysis. The HR of esophageal cancer among heavy drinkers versus nondrinkers was 4.18 (95% CI 2.34–7.47, I2 = 74%). On the other hand, the HR of esophageal cancer among light drinkers was 1.82 compared with nondrinkers (95% CI 1.57–2.10, I2 = 0%). Heavy drinkers have a higher esophageal cancer incidence than light drinkers and nondrinker. It is possible that alcohol reduction may decrease the risk of esophageal cancer in Asian heavy drinkers.

Esophagogastric junction (EGJ) cancers are resected thorough esophagectomy or gastrectomy, with the incidence of postoperative complications influenced by the chosen procedure. In this prospective nationwide multicenter study, patients with cT2–T4 EGJ cancers were enrolled before surgery. Based on the protocol, surgeons performed a transthoracic esophagectomy (TTE) or a transhiatal gastrectomy (THG) and dissected all lymph nodes prespecified as the standardized procedure. Postoperative complications were correlated with the clinical factors in each procedure. A total of 345 patients were eligible for this study. TTE and THG were performed in 120 and 225 patients, respectively. Complications of Clavien-Dindo ≥ Grade II were found in 115/345 (33.3%) patients. Recurrent laryngeal nerve palsy was found only in the TTE group (p

Risk stratification is required to improve the management of pouchitis with ulcerative colitis (UC) patients who undergo ileal pouch-anal anastomosis (IPAA). Recently, the colectomy risk score (CRS) has been used to assess UC severity and predict the need for surgery. We explored whether the CRS predicted pouchitis in patients with UC who underwent IPAA. This retrospective study included 168 UC patients who underwent IPAA. Pouchitis was diagnosed according to the pouchitis disease activity index. The primary endpoint was the cumulative incidence of pouchitis. The risk factors for pouchitis using preoperatively obtained data, including the CRS, were investigated. Based on their CRS, patients were assigned to low- (scores 0-3), intermediate- (scores 4-6), and high-risk (scores 7-9) groups. The incidence of pouchitis was estimated using the Kaplan-Meier curve. CRS validity was assessed using the Cox proportional hazards model. During the median 7.2 (interquartile range [IQR] 2.8-11.1) years' follow-up, 37 (28.5%) patients were diagnosed with pouchitis. Patients with pouchitis had significantly higher CRS than patients without pouchitis (median 7.0; IQR, 4.0-7.0 vs median 5.0; IQR, 3.0-7.0). The cumulative incidences of pouchitis in the low-, intermediate-, and high-risk groups were 10.3%, 18.3%, and 36.1% at 5 years, respectively. Thus, the incidence trended to increase significantly as CRS increased. Multivariate analysis revealed high-risk CRS status was an independent predictor of pouchitis (hazard ratio: 18.03; 95% confidence interval 1.55-210.05). CRS is useful in risk stratification for the development of subsequent pouchitis in patients with UC undergoing IPAA.

Pancreatic cancer is associated with both family and hereditary cancer syndromes. Multigene panel testing for pancreatic cancer detected the germline variants BRCA1/2, PALB2, ATM, TP53, MLH1, STK11/LKB1, APC, CDKN2A, and SPINK1/PRSS1 as high-risk genes. A latest genome-wide association study revealed the common, but low-risk germline variants in pancreatic cancer patients. Active pancreatic surveillance using magnetic resonance imaging and endoscopic ultrasound is recommended for high-risk individuals who have a family history of pancreatic cancer or harbor these germline pathogenic variants to improve the detection rate and prognosis of pancreatic cancer. Since poly-ADP-ribose polymerase (PARP) inhibitor has been shown to be effective in improving the prognosis of BRCA-positive pancreatic cancer as well as hereditary breast and ovarian cancer syndrome, PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring the BRCA1/2 germline variant. This review highlights the importance of surveillance for germline pathogenic variants in pancreatic cancer and is expected to lead to improvements in the diagnosis and prevention of pancreatic cancer as well as facilitate the development of effective therapeutic strategies and precision medicine.

Background The incidence of pancreatic neuroendocrine neoplasm (PNEN) has been increasing. Resection is typically indicated for PNEN, regardless of its size; however, the indications for its resection are controversial. This study aimed to evaluate the treatment results of surgical resection of PNEN at our institute. Methods In this single-center, retrospective, case-control study, 87 patients who underwent PNEN resection and 17 patients with PNEN who did not undergo surgical resection between 1993 and 2020 were included in this study. Clinical characteristics and outcomes were reviewed and statistically compared. Survival was also estimated for the patients in each cohort. Results Seventeen patients who underwent resection (20%) had lymph node metastasis. Tumors measuring ≥ 2.0 cm and multiple lesions were identified as independent predictors for lymph node metastasis (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.0–100.0, p = 0.001 and OR 8.7, 95% CI 1.5–52.0, p = 0.018, respectively). There was a significant difference in the survival curves depending on the presence or absence of lymph node metastasis (5-year overall survival 74.7% vs. 94.3%, p < 0.001; 5-year recurrence-free survival: 66.3% vs. 93.6%, p < 0.001). All 17 PNEN cases under observation with a median 8 mm (range 5–23) tumor size for a median of 34 (range 2.4–114) months showed slight morphological change with a median tumor growth rate of 0.15 mm (range 0–3.33) per year. Conclusion Patients with tumors measuring ≥ 2.0 cm have a high probability of lymph node metastasis or recurrence, thereby requiring resection. PNEN measuring < 1.0 cm may be acceptable for observation.

Background Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients. Methods This was a multicenter, retrospective cohort study; the database from the Japan COVID-19 Task Force was used. A total of 3314 COVID-19 patients were included in the study, and the data on respiratory symptoms were collected. The participants were classified according to their respiratory symptoms (Group 1: no respiratory symptoms, Group 2: only upper respiratory symptoms, Group 3: only lower respiratory symptoms, and Group 4: both upper and lower respiratory symptoms). The impacts of upper and lower respiratory symptoms on the clinical outcomes were compared. The primary outcome was the percentage of patients with poor clinical outcomes, including the need for oxygen supplementation via high-flow oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation or death. Results Of the 3314 COVID-19 patients, 605, 1331, 1229, and 1149 were classified as Group 1, Group 2, Group 3, and Group 4, respectively. In univariate analysis, patients in Group 2 had the best clinical outcomes among all groups (odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.11–0.39), while patients in Group 3 had the worst outcomes (OR: 3.27, 95% CI: 2.43–4.40). Group 3 patients had the highest incidence of pneumonia, other complications due to secondary infections, and thrombosis during the clinical course. Conclusions Upper and lower respiratory tract symptoms had vastly different impacts on the clinical outcomes of COVID-19.

Background C–C chemokine receptor type 7 (CCR7) participates in chemotactic and metastatic responses in various cancers, including in esophageal squamous cell carcinoma (ESCC). The microRNA (miRNA) let-7a suppresses migration and invasion of various types of cancer cells by downregulating CCR7 expression. Methods The expression levels of CCR7 and let-7a were measured in the cell lines, tumor, and peritumoral tissues of ESCC patients. KYSE cell lines were transfected with synthetic let-7a miRNA and a let-7a miRNA inhibitor, and their CCR7 expression levels as well as invasive ability were evaluated. A highly invasive cell line was established via an invasion assay, and CCR7 expression level along with let-7a level was subsequently evaluated. Cancer cells overexpressing CCR7 were injected subcutaneously into mice, and the animals were monitored for tumor growth along with lymph node metastasis. Results A negative correlation between CCR7 and let-7a expression was observed in the ESCC cell lines as well as in tissue samples from patients. Synthetic let-7a decreased CCR7 expression level, while the let-7a inhibitor increased it. In vitro, the established highly invasive cancer cells with high and low levels of CCR7 and let-7a expression, respectively, exhibited a greater invasive ability than the wild-type cell line. The cells were associated with tumor growth and lymph node metastasis in mice. Patients in the high-CCR7/low-let-7a group had the worst prognosis, with a five-year recurrence free survival (5-RFS) rate of 37.5%, followed by the high-CCR7/high-let-7a (5-RFS: 60.0%) and low-CCR7 (5-RFS: 85.7%; p = 0.038) groups. Conclusions The expression of CCR7 was downregulated by let-7a miRNA in esophageal cancer cells. The decrease in let-7a expression level led to the increased expression level of CCR7 in ESCC cells, consequently increasing their invasive ability and malignancy and resulting in a worse prognosis for ESCC patients. Trial registration. Retrospectively registered.

Background It has been reported that in conventional open surgery, approximately 10% of surgical gloves are perforated during surgery without being noticed. To protect both the patient and medical staff from harm, double gloving or changing gloves routinely at certain intervals during surgery is recommended. However, whether these protective measures are also necessary for laparoscopic colorectal surgery is unknown because the actual perforation rate during laparoscopic procedures is unclear. Methods Seventy-seven laparoscopic colorectal surgeries were evaluated, and a total of 616 surgical gloves used in the surgeries were collected for analysis. The presence of glove perforation was tested by the standard water-leak test method (EN455-1). Results Seven perforations were detected (1.1%). The duration of the laparoscopic procedure was not a statistically significant risk factor for glove perforation (p = 0.41). Postoperative surgical site infections (SSIs) were observed in 12 cases (15.6%), but there was no significant correlation between the presence of glove perforation and SSI (p = 0.92). According to the bacterial cultivation results, the majority of causative agents of SSI were enterobacteria, which belong to the major gut flora. Conclusion Although the perforation rate was considerably lower than that in open surgery, surgical glove perforation occurred during laparoscopic procedures. Double gloving in laparoscopic colorectal surgery is recommended not to prevent SSI but to protect medical workers from harmful infections after direct contact with the patient.

Sentinel node (SN) mapping based on the SN concept has been applied to early gastric cancer. However, it is still controversial whether or not the oncological safety is ensured in case pathological stage was advanced in these patients. The aim of this study was to investigate the validity of SN mapping in patients with clinically early staged gastric cancer diagnosed with pT2/deeper tumors. We retrospectively analyzed 40 patients with a diagnosis of cT1N0 or cT2N0 single-lesion gastric cancer who were shown to have pT2 or deeper tumors after gastrectomy with SN mapping. We adopted a dual-tracer method using a radioactive colloid and blue dye to detect SNs. The diagnostic accuracy and distribution of SNs at each tumor site were analyzed. Of the 40 patients, 24 (60%) were postoperatively diagnosed as pT2, and 16 (40%) as pT3 or T4. SNs were detected in all patients. The false negative rate was 9% (1/11), and in that patient, the non-SN metastasis was observed within the SN basin. Diagnostic accuracy was 98% (39/40). Overall distribution of SNs was similar to that for patients with early gastric cancer. No significant differences in overall and recurrence-free survival were observed between the patients who underwent standard gastrectomy and those who underwent function-preserving gastrectomy, based on the results of SN mapping. Our results confirmed validity of SN mapping for patients with clinically early staged gastric cancer diagnosed with pT2/deeper tumors after gastrectomy. Closed surveillance without additional surgical treatment is an option for these patients.

In laparoscopic surgery (LS) for colorectal cancer (CRC), the relationship between intraoperative end-tidal carbon dioxide concentration (EtCO2) and surgery-related complications remains unexplored. This study assessed the impact of intraoperative EtCO2 on postoperative complications in LS for CRC. In total, 909 patients who underwent LS for CRC were enrolled. Hypocapnia and hypercapnia were defined as EtCO2 40 mmHg, respectively, and the relationships between hypocapnia or hypercapnia duration and postoperative complications were analyzed. The median (range) durations of hypocapnia and hypercapnia were 2.0 (0–8.3) h and 0.3 (0–5.8) h, respectively. Complications were observed in 208 cases (23.0%), which included 37 (4.1%) instances of anastomotic leakage and 86 (9.5%) of superficial surgical site infection (SSI). While the hypercapnia duration was not associated with the short-term outcomes, prolonged hypocapnia was significantly correlated with complications (p = 0.02), specifically superficial SSI (p = 0.005). Multivariate analyses adjusted for confounding factors confirmed that hypocapnia prolongation was an independent risk factor for postoperative superficial SSI [OR 1.19; 95% confidence interval (Cl) 1.03–1.36, p = 0.01]. Intraoperative hypocapnia may be a risk factor for postoperative complications, in particular superficial SSI, in LS for CRC.

Invasive pulmonary aspergillosis (IPA) after liver transplantation (LT) is most often fatal. We analyzed the outcomes of IPA in a single center. We reviewed, retrospectively, the medical records of recipients of living donor LT (LDLT) or deceased donor LT (DDLT) performed between 1995 and 2019 at our institute. We analyzed the incidence of IPA and assessed the treatment courses of patients treated successfully and those not treatment successfully. Among 326 recipients, IPA was diagnosed in 6 (1.8%). The incidence of IPA was significantly higher in patients with acute liver failure (ALF, 9.8%) than in those without ALF (0.4%), after DDLT (8.8%) than after LDLT (1.0%), and in recipients who received preoperative steroid pulse therapy (16.0%) than in those who did not (0.7%). Complete cure of IPA was achieved in the most recent three patients, by administering voriconazole immediately after the diagnosis of IPA and performing lung resection, while the IPA lesion was single and localized. Patients with risk factors for IPA must be monitored closely. Our three successfully treated cases demonstrate that initiating immediate voriconazole treatment and making a calculated decision about lung resection can contribute to a favorable outcome.

Although radical esophagectomy with multifield lymph node dissection is a promising treatment to achieve long-term survival for resectable esophageal cancer, survival after postoperative recurrence remains poor. To select the optimal treatment for patients with recurrent esophageal cancer, simple, objective indicators for predicting of long-term outcomes are needed. We conducted a single-institution, retrospective cohort study between 2004 and 2019, wherein 586 patients underwent transthoracic esophagectomy for primary esophageal squamous cell carcinoma. Of these, 133 patients with postoperative recurrence were included in this analysis. Several predictors of survival after recurrence were investigated. Among all patients, the 1- and 3-year survival rates after recurrence were 48.0% and 23.1%, respectively. On multivariate analysis, the neutrophil to lymphocyte ratio (NLR) at recurrence was identified as a significant predictor of death after recurrence (hazard ratio 1.061; 95% confidence interval 1.002–1.125; p = 0.043). Time-dependent receiver operating characteristics curves showed that the area under the curve value of the NLR at recurrence was superior to the modified Glasgow Prognostic Score at recurrence in all terms. To simulate the clinical decision process, we set the cut-off NLR at recurrence for survival using survival classification and regression tree (CART) and defined the optimal cut-off value as 3.374. NLR at recurrence was a significant indicator of survival after recurrence in patients with recurrent esophageal cancer. CART analysis was used to determine the optimal cut-off value for the prediction of survival, allowing the NLR to be used clinically to facilitate decision making.