Clinical impact of intraoperative pancreatic transection margin analysis and additional resection during pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: The prognostic impact of additional resection based on intraoperative frozen section analysis (FSA) of the pancreatic transection margin in patients with pancreatic ductal adenocarcinoma (PDAC) is controversial. The purpose of this study was to evaluate the prognosis based on the results of the first FSA of the pancreatic transection margin (1st FSA) and the clinical significance of additional resection. METHODS: Patients who underwent pancreaticoduodenectomy for PDAC from 2000 to 2020 at a single center were included. Patients were divided into 3 groups based on the 1stFSA. Survival and prognostic factors were analyzed according to the 1stFSA. RESULTS: A total of 311 patients were included in this study. The 1stFSA was negative in 272 patients (1stFSA-R0) and positive in 39 patients [carcinoma in situ (1stFSA-CIS), 21 patients; invasive carcinoma (1stFSA-IC), 18 patients]. Additional resections were performed on 37 patients [1stFSA-CIS, 20 patients; 1stFSA-IC, 17 patients], and R0 resection was achieved in 34 patients intraoperatively. Comparing median survival time to 1stFSA-R0 (36.4 months), 1stFSA-CIS was comparable (27.8 months, p = 0.276), although 1stFSA-IC was significantly worse (18.8 months, p = 0.001). On multivariate analysis, 1stFSA-IC was an independent prognostic factor (hazard ratio 2.68, 95 % confidence interval 1.16-6.17, p = 0.020). CONCLUSIONS: 1stFSA-CIS and 1stFSA-R0 had similar OS, implying that additional resection may be acceptable for 1stFSA-CIS. 1stFSA-IC was still an independent prognostic factor based on additional resection, and the prognostic significance of additional resection is uncertain for 1stFSA-IC.

Hemodynamic Assessment of Infants With Congenital Heart Disease Using Ferumoxytol-Enhanced 4D Flow Cardiac Magnetic Resonance.

In complex congenital heart disease, characterization of the circulation is necessary to anticipate the clinical course. Four-dimensional cardiac magnetic resonance imaging enhanced by superparamagnetic iron oxide contrast agents (ferumoxytol) enables detailed and efficient assessment of both anatomy and physiology in neonates. We demonstrate this impact in 3 cases of neonates with congenital heart disease.

Impact of an Adult Congenital Heart Disease Order Set in a Pediatric Cardiac Intensive Care Unit.

Background: Patients with congenital heart disease (CHD) are increasingly surviving to adulthood. Given their age- and condition-specific needs, the optimal postoperative setting for these patients is not yet determined. This study aims to evaluate the utility of an adult-specific order set in improving clinical outcomes for these patients in a pediatric cardiovascular intensive care unit (ICU). Methods: Adults with CHD (ACHD) admitted to the cardiovascular ICU following cardiac surgery at a pediatric tertiary care center were identified for a retrospective cohort study. Health care delivery metrics and clinical outcomes of participants who received the adult-specific order set were compared with control patients admitted prior to the intervention. Categorical outcomes were compared using the χ2 test of independence or Fisher exact test, and continuous outcomes were assessed using the t test. Results: A total of 130 ACHD patients received the intervention, with no significant differences observed in clinical outcomes when compared with 89 controls. While there was additionally no reduction in hospital-related mortality (2.3% vs 7.8%, RR 0.3; P = .1), clinician ordering behaviors were better aligned with best-practices following the intervention. Among patients with moderate or greater anatomic complexity, a post hoc analysis demonstrated reduced in-hospital mortality from those who received the adult order set. Conclusions: The implementation of an adult-specific order set in a pediatric care setting did not improve clinical outcomes for all ACHD patients. Patients with moderate and greater anatomic complexity did see a mortality benefit, suggestive that targeted electronic tools may most benefit those who have the highest risk.

Significance of Lateral Pelvic Lymph Node Dissection in Resectable Stage IV Low Rectal Cancer: Experience from a Single Center in Japan.

Objectives: To investigate the significance of lateral pelvic lymph node dissection (LPLND) in resectable stage IV low rectal cancers, reviewing the treatment outcomes from a single cancer center dedicated to LPLND. Methods: Consecutive 56 patients with stage IV low rectal cancers who underwent primary tumor resection (PTR) between 2007 and 2022 were identified. Sixteen patients with non-curative PTR were excluded, and 40 with curative PTR were analyzed. Results: The dominant metastatic organ was the liver in 30 (75.0%) patients, followed by the lung in 9 (22.5%). Seven (17.5%) patients had multiple organ metastasis. Five of 40 patients had cT1bN0 or cT2N0 disease, 8 did not receive LPLND for other reasons, and accordingly, 27 (67.5%) finally received LPLND. A total of 15 patients (37.5% of all 40 cases and 55.5% of 27 LPLND cases) had LPLN metastasis. Six (15.0%) patients had bilateral metastasis, and 6 (15.0%) had LD3 metastasis. Eight (20.0%) patients developed local recurrence (LR), and the 5Y-LR rate was 22.3%. Twelve (30.0%) patients underwent preceding chemotherapy before PTR, 26 (65.0%) received chemotherapy after PTR, and 23 (57.5%) achieved complete resection. Twelve (52.2%) of 23 patients developed distant recurrence after complete resection. 5Y-overall survival for all patients was 42.4%. Conclusions: A high rate of LPLN metastasis implies the significance of management for LPLN metastasis; meanwhile, an unsatisfactory complete resection rate and overall survival implies that LPLN metastasis in this cohort should be dealt with as a systemic disease.

Significance of blood culture testing after pancreatoduodenectomy.

Aim: The aim of this study was to clarify the significance of blood culture testing in the postoperative period of pancreatoduodectomy (PD), a highly invasive surgery. Methods: Rates of blood culture sampling and positivity were investigated for febrile episodes (FEs) in patients who underwent PD (2016-2021). FEs were defined as body temperature of 38.0°C or higher occurring on or after the 4th postoperative day. Fever origin was diagnosed retrospectively, and FEs were classified as pancreatic fistula (PF)-related or PF-unrelated FEs. Factors correlated with blood culture positivity were explored. Results: Among 339 patients who underwent PD, 99 experienced 202 FEs. Blood culture testing was performed on 160 FEs occurring in 89 patients. The sampling and positivity rates were 79.2% and 17.5%, respectively, per episode and 89.9% and 28.1%, respectively, per patient. Thirty-six FEs were classified as PF-related and 124 were classified as PF-unrelated FEs. The blood culture positivity rate was significantly lower in PF-related vs. PF-unrelated FEs (1/36 vs. 27/124, respectively, p = 0.006). The blood culture positivity rate was significantly higher in patients with cholangitis, catheter-related blood stream infection, and urinary tract infection than PF-related FEs. Multivariate analysis showed that blood culture positivity was negatively associated with PF-related FEs and positively associated with accompanying symptoms of shivering, Pitt Bacteremia Score, and preoperative biliary drainage. Conclusions: Patients who underwent PD showed relatively high blood culture positivity rates. Based on these results, it may be possible to distinguish PF-related and -unrelated FEs.

Oncological similarities between large type 3 and type 4 tumors in patients with resectable gastric cancer: a propensity score-matched analysis of a multi-institutional dataset.

BACKGROUND: Large type 3 (diameter ≥ 8 cm) and type 4 gastric cancers have been arbitrarily combined in Japan as a single entity. However, whether these two types are oncologically similar remain unclear. This study aimed to clarify this issue. METHODS: In this retrospective study, we analyzed a database of 3,575 patients from nine institutions who underwent gastrectomy between 2010 and 2014. Using propensity scores to balance significant variables, we compared prognoses and tumor recurrences. RESULTS: Of patients with clinical T3/T4 who underwent R0 resection, 75 and 73 had large type 3 and 4 tumors, respectively. Patients with type 4 tumors had significantly lower overall survival rates than those of patients with large type 3 tumors (hazard ratio [HR] 1.77; 95% confidence interval [CI] 1.14-2.74). However, among the large type 3 tumors, a remarkable difference in prognosis was observed between the differentiated and undifferentiated histological types. A comparison was made between large type 3 with undifferentiated phenotype and type 4, each with 39 patients after propensity score matching. Outcomes in both groups were similar in terms of overall survival (HR 1.28; 95% CI 0.73-2.25) and relapse-free survival (HR 1.34; 95% CI 0.80-2.27). No statistically significant differences were observed in the incidence of peritoneal recurrence (35.9% vs. 46.1%, P = 0.36) and lymph node recurrence (25.6% vs. 12.8%, P = 0.15). CONCLUSIONS: Large type 3 tumors with undifferentiated phenotype and type 4 tumors were oncologically similar. This subgroup could be considered as a new entity for future clinical trials.

Thoracoscopic salvage esophagectomy with prophylactic mediastinal lymph node dissection after definitive chemoradiotherapy for patients with esophageal cancer.

BACKGROUND: Salvage esophagectomy for residual tumor and localized relapses after definitive chemoradiotherapy (dCRT) for patients with esophageal cancer is associated with a high rate of postoperative complications and in-hospital mortality. In addition, there are many controversial issues associated with salvage esophagectomy, such as the acceptability of minimally invasive surgery and the need for prophylactic dissection of mediastinal lymph nodes. The aim of this study was to evaluate the safety and usefulness of thoracoscopic salvage esophagectomy with prophylactic mediastinal lymph node dissection. METHODS: The study included 31 patients who underwent thoracoscopic salvage esophagectomy with prophylactic mediastinal lymph node dissection after dCRT between 2013 and 2022 (salvage patients) and 610 nonsalvage patients who underwent conventional thoracoscopic esophagectomy during the same time period. RESULTS: Differences between the median ages and sexes of the 2 patient groups were not significant. The dominant location of tumors in the salvage patients was the upper thoracic esophagus. More salvage patients had clinical T4 disease. The salvage patients had a lower median number of retrieved mediastinal lymph nodes than the nonsalvage patients. The differences between the rates of R0, postoperative complications, and in-hospital deaths in the 2 patient groups were not significant. The 3-year overall survival (OS) rates for the salvage patients were 73%, with 3-year OS rates for R0 vs non-R0 of 81% vs 0%, p < 0.01 and pN0 vs pN1-3 of 89% vs 49%, p < 0.01. CONCLUSION: Regarding short-term outcomes, prophylactic mediastinal lymph node dissection for patients undergoing thoracoscopic salvage esophagectomy was as safe as prophylactic dissection for patients undergoing conventional thoracoscopic esophagectomy. R0 surgery and pN0 are important factors for long-term survival in patients undergoing thoracoscopic salvage esophagectomy.

Combined Pubic Arch and Ischial Bone Resection for Metachronous and Frequent Local Recurrences of Rectal Cancer.

BACKGROUND/AIM: Complete surgical resection with negative margins remains the cornerstone for curative treatment of rectal cancer; however, local recurrence can pose a significant challenge. Herein, we aimed to introduce a novel surgical technique for combined resection of the pubic arch and ischial bone in the context of treating recurrent rectal cancer. CASE REPORT: We present a case of a patient with a fourth local recurrence of rectal cancer, with no evidence of distant metastasis. The tumor directly invaded the posterior wall of the pubic arch. To achieve complete tumor resection, an osteotomy was performed using a thread wire saw at the bilateral pubic rami and ischial bones. Intraoperative frozen section analysis (rapid tissue examination) was conducted on tissue samples from the lateral margins of the planned osteotomy line. Samples were negative for adenocarcinoma (cancerous cells). The combined resection of the pubic arch and ischial bone was successfully performed with negative margins for adenocarcinoma, as confirmed by frozen section analysis. CONCLUSION: Mastery of the surgical technique for combined resection of the pubic arch and ischial bone may be clinically significant for achieving complete resection in cases of multiple resections for locally recurrent rectal cancer.

Risk factors affecting delay of initiating adjuvant chemotherapy for stage III colorectal cancer.

PURPOSE: Delay in initiating adjuvant chemotherapy (AC) after curative resection of colorectal cancer (CRC) has been reported to lead to poor prognosis, but few studies have looked at associated factors. This study aimed to identify risk factors for delay in initiating AC. METHODS: Data from 200 consecutive patients who underwent curative resection and AC for stage III CRC between 2013 and 2018 were retrospectively collected and analyzed. RESULTS: AC was initiated more than 8 weeks after surgery in 12.5% of patients (the delay group). Compared to those with no delay (the non-delay group), patients in the delay group had significantly higher rates of synchronous double cancers (2.3% vs. 16.0%, p = 0.001), preoperative bowel obstruction (10.3% vs. 32.0%, p = 0.003), laparotomy (56.0% vs. 80.0%, p = 0.02), concomitant resection (2.9% vs. 24.0%, p < 0.001), and postoperative complications (32.0% vs. 56.0%, p = 0.02), and a significantly longer length of hospital stay (median 12 vs. 30 days, p < 0.001). In multivariate analysis, synchronous double cancers (odds ratio 10.2, p = 0.008), preoperative bowel obstruction (odds ratio 4.6, p = 0.01), concomitant resection (odds ratio 5.2, p = 0.03), and postoperative complications of Clavien-Dindo grade ≥ IIIa (odds ratio 4.0, p = 0.03) were identified as independent risk factors for delay in initiating AC. CONCLUSION: Careful preoperative treatment planning for CRC patients with synchronous double cancers, preoperative bowel obstruction, and concomitant resection, and management for postoperative complication are necessary to avoid delay in initiating AC.

Clinical impact of skeletal muscle mass change during the neoadjuvant chemotherapy period in patients with gastric cancer: An ancillary study of JCOG1002.

BACKGROUND: Recent studies have revealed that sarcopenia is associated with postoperative complications and poor prognosis. Although neoadjuvant chemotherapy is a promising treatment for gastric cancer, its toxicity may lead to the loss of skeletal muscle mass. This study investigates the changes in skeletal muscle mass during neoadjuvant chemotherapy and its clinical impact on patients with locally advanced gastric cancer. METHODS: Fifty patients who completed two courses of neoadjuvant chemotherapy followed by surgery were included. Skeletal muscle mass was measured using computed tomography images before and after chemotherapy. The proportion of skeletal muscle mass change (%SMC) during neoadjuvant chemotherapy and its cutoff value was explored using the receiver operating characteristic for the overall survival of patients undergoing R0 resection. Risk factors of skeletal muscle mass loss were also evaluated. RESULTS: Overall, 64% of patients had skeletal muscle mass loss during neoadjuvant chemotherapy (median %SMC -3.4%; range: -18.9% to 10.3%). Multivariable analysis identified older age (≥70 years) as an independent predictor of skeletal muscle mass loss (mean [95% confidence interval]: -4.70% [-8.83 to -0.58], p = 0.026). Among 43 patients undergoing R0 resection, %SMC <-6.9% was an independent poor prognostic factor for overall survival (hazard ratio, 11.53; 95% confidence interval, 2.78-47.80) and relapse-free survival (hazard ratio 4.54, 95% confidence interval 1.50-13.81). CONCLUSIONS: Skeletal muscle mass loss occurs frequently during neoadjuvant chemotherapy for locally advanced gastric cancer and could adversely affect survival outcomes.

A case of acinar cell carcinoma originating from the accessory papilla of the duodenum.

CASE PRESENTATION: A 61-year-old female was referred to our hospital with a neoplastic lesion in the duodenum. Computed tomography with contrast enhancement revealed a 10-mm tumor in the duodenum. Upper gastrointestinal endoscopy revealed a submucosal tumor-like lesion in the descending part of the duodenum. Endoscopic ultrasound revealed a well-defined hypoechoic tumor. Biopsy and immunohistochemical findings including negative Synaptophysin and Chromogranin A staining and positive Trypsin and BCL10 staining suggested a carcinoma with acinar cell differentiation. Pancreatoduodenectomy was performed, and the resected specimen had a 15-mm solid nodule in the submucosal layer of the duodenum. Pancreatogram of the resected specimen revealed a tumor localized in the accessory papilla region. In histopathological examination, the tumor was found in the submucosa of the duodenum with pancreatic tissue present nearby, and these were separated from the pancreatic parenchyma by the duodenal muscle layer. These findings led to a diagnosis of acinar cell carcinoma originating from the accessory papilla of the duodenum. CONCLUSION: Acinar cell carcinoma originating from the accessory papilla of the duodenum is exceptionally rare, with no reported cases to date. The origin was considered to be pancreatic tissue located in the accessory papilla region.

Meta-analysis: Incidence of cirrhosis and hepatocellular carcinoma in patients with Fontan palliation.

BACKGROUND AND AIMS: The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery. METHODS: A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy. RESULTS: A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis. CONCLUSION: The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.

Predictors of Atrial Arrhythmia in Adults with Repaired Tetralogy of Fallot.

Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease in adults, has excellent long-term survival. However, many patients (30-45%) develop late arrhythmias. Previous studies have identified predictors of arrhythmia (atrial or ventricular) using clinical markers that predate arrhythmia onset by many years. Our objective was to develop a predictive model for incident atrial arrhythmias within two years of clinical evaluation and diagnostic testing. A single-center nested unmatched case-control study of 174 adults with repaired TOF. We included only patients with results from ECG and echocardiogram data in the required time interval (3-24 months before first arrhythmia for cases; 24 months of follow-up for controls). A predictive multivariable model for risk of incident atrial arrhythmia was developed using logistic regression with a least absolute shrinkage and selection operator (LASSO). Of 41 demographic, surgical, and diagnostic variables, six were selected as having predictive value for atrial arrhythmia based on cross validation. The factors with the greatest predictive value in decreasing order were moderate / severe tricuspid regurgitation (adjusted odds ratio (OR) 149.42), QRS fragmentation (OR 28.08), severe pulmonary regurgitation (OR 8.22), RV systolic dysfunction (OR 2.95), 1st degree AV block (OR 2.59), and age at time of surgical repair (OR 1.02). Predictors for atrial arrhythmia in our study suggested abnormal right ventricle anatomical function and electrophysiologic properties (conduction and repolarization) as the primary underlying substrate.

Novel Repair Technique for Oral and Anal Side Stoma Prolapse of a Loop Colostomy With the Stapled Modified Altemeier Method Using Indocyanine Green Fluorescence Imaging.

BACKGROUND/AIM: Stoma prolapse is a common complication in the late phase after stoma creation. With advances in chemotherapy, a double-orifice colostomy or ileostomy and chemotherapy are used to treat primary unresectable colorectal cancer. Preoperative therapy with a double-orifice colostomy or ileostomy is performed to aid primary colorectal cancer miniaturization. Therefore, the number of stoma prolapses will likely increase in the future. Previous reports on the repair of stoma prolapse focused on unilateral stoma prolapse of loop colostomy, and there are no reports about the bilateral stoma prolapse of loop colostomy or ileostomy. CASE REPORT: We report a novel repair technique for oral and anal side (bilateral) stoma prolapse of a loop colostomy with the stapled modified Altemeier method using indocyanine green (ICG) fluorescence imaging considering the distribution of marginal artery in preventing marginal artery injury which has considerable clinical significance. CONCLUSION: Our novel technique for the oral and anal side prolapse of a loop colostomy is considered effective and safe.

Chronological improvement of survival in patients with advanced gastric cancer over 15 years.

Background: Recent trials have reported a median overall survival (OS) of 11-17 months in patients with advanced gastric cancer (AGC). However, it is unclear how recently approved drugs contribute to patient prognosis. Objectives: We aimed to evaluate the characteristics and survival in patients with AGC over the past 15 years. Design: Retrospective study. Methods: We evaluated data of 1355 patients with AGC who received first-line chemotherapy between January 2005 and March 2019 at a single institution. We compared the characteristics and survival rates across four periods: January 2005-December 2007 (period A), January 2008-February 2011 (period B), March 2011-May 2015 (period C), and June 2015-March 2019 (period D). The median follow-up duration was 13.1 months, with 312, 333, 393, and 317 patients in periods A, B, C, and D, respectively. Results: There were no significant differences in patient characteristics between the four periods, except for the proportion of patients who underwent prior gastrectomy and human epidermal growth factor receptor 2 (HER2) testing. Patients in period D had significantly longer OS than those in period A [median: 15.7 versus 12.4 months; adjusted hazard ratio (aHR): 0.79; p = 0.02]. The mean OS in patients with liver metastasis (LM) in period D was remarkably longer than that in patients in period A (median: 19.3 versus 12.4 months; aHR: 0.61; p < 0.01), while that in patients with peritoneal metastasis showed limited improvement. Conclusion: Clinical strategy changes, including gastrectomy, HER2 testing, and approval of new drugs, may be associated with improved OS in patients with AGC. In the last 4 years, a remarkable improvement has been observed in patients with LM.

Association between the antiadhesion membrane and small bowel obstruction after open gastrectomy: A supplemental analysis of the randomized controlled JCOG1001 trial.

Aim: Postoperative small bowel obstruction (SBO) is one of the major complications that is mainly caused by postoperative adhesion. Recently, the antiadhesion membrane has become popular for postoperative SBO prevention. However, its efficacy is yet to be confirmed in the gastric cancer surgery field. Here, we conducted the supplemental analysis of the randomized controlled trial JCOG1001 to investigate the efficacy of the antiadhesion membrane on SBO prevention in patients with open gastrectomy for gastric cancer. Methods: Of the 1204 patients enrolled in JCOG1001, 1200 patients were included. The development of SBO of Grade ≥ IIIa according to the Clavien-Dindo classification was recorded. Univariable and multivariable analyses were performed using the Fine and Gray model to determine the risk factors for SBO. Results: Fifty-one patients developed SBO (median follow-up duration: 5.6 years). Total gastrectomy, combined resection, and blood loss significantly increased the risk for SBO development in the univariable analysis. Large amount of blood loss was independently associated with SBO development in the multivariable analysis (hazard ratio [HR], 3.089; 95% confidence interval [CI], 1.562-6.109, p = 0.0012). Antiadhesion membrane did not reduce the risk for SBO (HR, 1.299; 95% CI 0.683-2.470; p = 0.4246). In the patients belonging to subgroup analyses who received distal and total gastrectomy, the antiadhesion membrane was not associated with the incidence of SBO. Conclusions: Antiadhesion membrane did not decrease SBO occurrence rate after open gastrectomy. Therefore, the use of antiadhesion membrane would not be effective for preventing SBO in gastric cancer surgery.

Early endpoints of a randomized phase II trial of preoperative chemotherapy with S-1/CDDP with or without trastuzumab followed by surgery for HER2-positive resectable gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study).

BACKGROUND: This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis. METHODS: Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006. RESULTS: This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively. CONCLUSIONS: Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis.

Risk factors for abdominal surgical infectious complications after distal gastrectomy for gastric cancer: A post-hoc analysis of a randomized controlled trial (JCOG0912).

BACKGROUND: Abdominal surgical infectious complications (ASIC) after gastrectomy for gastric cancer impair patients' survival and quality of life. JCOG0912 was conducted to compare laparoscopy-assisted distal gastrectomy with open distal gastrectomy for clinical stage IA or IB gastric cancer. The present study aimed to identify risk factors for ASIC using prospectively collected data. METHODS: We performed a post-hoc analysis of the risk factors for ASIC using the dataset from JCOG0912. All complications were evaluated according to the Clavien-Dindo classification (CD). ASIC was defined as CD grade I or higher anastomotic leakage, pancreatic fistula, abdominal abscess, and wound infection. Analyses were performed using the logistic regression model for univariable and multivariable analyses. RESULTS: A total of 910 patients were included (median age, 63 years; male sex, 61 %). Among them, ASIC occurred in 5.8 % of patients. In the univariable analysis, male sex (odds ratio [OR] 2.855, P = 0.003), diabetes (OR 2.565, P = 0.029), and Roux-en-Y (R-Y) reconstruction (vs. Billroth Ⅰ, OR 2.707, P = 0.002) were significant risk factors for ASIC. In the multivariable analysis, male sex (OR 2.364, P = 0.028) and R-Y reconstruction (vs. Billroth Ⅰ, OR 2.310, P = 0.015) were independent risk factors for ASIC. CONCLUSIONS: Male sex and R-Y reconstruction were risk factors for ASIC after distal gastrectomy. Therefore, when performing surgery on male patients or when R-Y reconstruction is selected after gastrectomy for gastric cancer, surgeons should pay special attention to prevent ASIC.

Brain-enriched guanylate kinase-associated protein, a component of the post-synaptic density protein complexes, contributes to learning and memory.

Brain-enriched guanylate kinase-associated protein (BEGAIN) is highly enriched in the post-synaptic density (PSD) fraction and was identified in our previous study as a protein associated with neuropathic pain in the spinal dorsal horn. PSD protein complexes containing N-methyl-D-aspartate receptors are known to be involved in neuropathic pain. Since these PSD proteins also participate in learning and memory, BEGAIN is also expected to play a crucial role in this behavior. To verify this, we first examined the distribution of BEGAIN in the brain. We found that BEGAIN was widely distributed in the brain and highly expressed in the dendritic regions of the hippocampus. Moreover, we found that BEGAIN was concentrated in the PSD fraction of the hippocampus. Furthermore, immunoelectron microscopy confirmed that BEGAIN was localized at the asymmetric synapses. Behavioral tests were performed using BEGAIN-knockout (KO) mice to determine the contribution of BEGAIN toward learning and memory. Spatial reference memory and reversal learning in the Barns circular maze test along with contextual fear and cued fear memory in the contextual and cued fear conditioning test were significantly impaired in BEGAIN-KO mice compared to with those in wild-type mice. Thus, this study reveals that BEGAIN is a component of the post-synaptic compartment of excitatory synapses involved in learning and memory.

Three cases of open surgical procedures on ileal conduits for the repair of benign ureteroenteric anastomotic strictures after total pelvic exenteration of rectal tumors.

Ureteroenteric anastomotic strictures (UEAS) are typical complications after creating an ileal conduit for total pelvic exenteration (TPE) of rectal tumors. We report the ileal conduit for reconstruction in three patients, in the age-range of 47-73 years. Case 1 was when a left-sided UEAS had sufficient length of ureter for anastomosis, Case 2 was a right-sided UEAS with sufficient length of ureter for anastomosis, and Case 3 was a left-sided UEAS with insufficient length of ureter for anastomosis. There were no complications after operation and no recurrence of UEAS. It is important to learn the open surgical procedures for repair of a benign UEAS after TPE of rectal cancers. This has fewer complications and is safe in the long term.