Factors, Including Clinical Trial Eligibility, Associated with Induction of Third-Line Treatment for Advanced Gastric Cancer.

INTRODUCTION: Third-line chemotherapy has been suggested to improve survival in patients with gastric cancer. This study aimed to identify factors associated with the induction of third-line chemotherapy for advanced gastric cancer, focusing on patient eligibility for clinical trial. METHODS: We retrospectively analyzed 335 patients treated for unresectable or recurrent gastric cancer between April 2009 and May 2020. The patients were grouped into those that met the key eligibility criteria for clinical trial (136 patients, 40.6%) and those that did not (199 patients, 59.4%) before receiving first-line chemotherapy. RESULTS: The overall survival (OS) was 16.8 months (95% CI: 14.0-19.6) and 9.3 months (95% CI: 7.8-11.0) in the eligible and ineligible group, respectively. Multivariate analyses to identify the risk factors associated with the induction of third-line chemotherapy revealed ineligibility of clinical trial (OR 1.95; 95% CI: 1.15-3.31), number of metastatic sites (OR 1.99; 95% CI: 1.23-3.22), low albumin concentration (OR 2.24; 95% CI: 1.14-4.38), and a lack of complete or partial response to first-line treatment (OR 1.85; 95% CI: 1.05-3.26). Indeed, in responders to first-line treatment for ineligible patients, the median OS was 17.7 months (95% CI: 10.6-27.9), respectively. CONCLUSIONS: Treatment outcomes were different for those eligible for clinical trials and those who were not. However, this study suggested that patients who responded to first-line treatment have more favorable prognosis when treated with salvage chemotherapy, even if they were deemed ineligible for clinical trials.

Efficacy and feasibility of scheduled intravenous acetaminophen administration after pancreatoduodenectomy: a propensity score-matched study.

PURPOSE: The efficiency and safety of routine intravenous administration of acetaminophen after highly invasive hepatobiliary pancreatic surgery remain unclear. In particular, there have been no studies focusing on pancreatoduodenectomy. The present study clarified its clinical utility for patients undergoing pancreatoduodenectomy. METHODS: We retrospectively collected 179 patients who underwent open pancreatoduodenectomy from 2015 to 2020. The analgesic effects and adverse events in patients with scheduled intravenous administration of acetaminophen were evaluated using propensity score matching. RESULTS: After 40 patients from each group were selected by propensity score matching, the postoperative liver function tests were not significantly different between the control and acetaminophen groups. No significant differences were found in the self-reported pain intensity score or postoperative nausea and vomiting; however, the rate of pentazocine use and the total number of additional analgesics were significantly lower in the acetaminophen group than in the control group (p = 0.003 and 0.002, respectively). CONCLUSION: The scheduled intravenous administration of acetaminophen did not affect the postoperative liver function and had a good analgesic effect after pancreatoduodenectomy.

Clip-guided local duodenectomy for safe and minimal local resection of nonampullary duodenal neoplasms.

BACKGROUND: Local duodenectomy and primary closure is a simple option for some nonampullary duodenal neoplasms. Minimizing the resection area while ensuring curability is necessary for safe primary duodenal closure. However, it is often difficult to determine the appropriate resection line from the serosal side. We developed clip-guided local duodenectomy to easily determine the resection range and perform local duodenectomy safely, then performed a retrospective observational study to confirm the safety of clip-guided local duodenectomy. METHODS: The procedure is as follows: placing endoscopic metal clips at four points on the margin around the tumor within 3 days before surgery, identifying the tumor extent with the clips under X-ray imaging during surgery, making an incision to the duodenum just outside of the clips visualized by X-ray imaging, full-thickness resection of the duodenum with the clips as guides of tumor demarcation, and transversely closure by Gambee suture. We evaluated clinicopathological data and surgical outcomes of patients who underwent clip-guided local duodenectomy at two surgical centers between January 2010 and May 2020. RESULTS: Eighteen patients were included. The pathological diagnosis was adenoma (11 cases), adenocarcinoma (6 cases), and GIST (1 case). The mean ± SD tumor size was 18 ± 6 mm, and the tumor was mainly located in the second portion of the duodenum (66%). In all cases, the duodenal defect was closed with primary sutures. The mean operation time and blood loss were 191 min and 79 mL, respectively. The morbidity was 22%, and all complications were Clavien-Dindo grade II. No anastomotic leakage or stenosis was observed. In the 6 adenocarcinoma patients, all were diagnosed with pT1a, and postoperative recurrence was not observed. The 1-year overall and recurrence free survival rate was 100%. CONCLUSIONS: Clip-guided local duodenectomy is a safe and useful surgical option for minimally local resection of nonampullary duodenal neoplasms such as duodenal adenoma, GIST, and early adenocarcinoma.

Early ambulation after general and digestive surgery: a retrospective single-center study.

PURPOSE: Postoperative early ambulation contributes to the improvement of postoperative outcomes; however, the definition of "early" ambulation is unclear. In this study, we aimed to define desirable "early" ambulation after digestive surgery in terms of short-term outcomes and to identify the risk factors for delayed ambulation. METHODS: We retrospectively analyzed 718 patients who underwent major digestive surgery between January 2016 and May 2019 in our hospital. The timing of first ambulation after surgery was reviewed and correlated with short-term postoperative outcomes and perioperative patient characteristics. RESULTS: Of 718 patients, 55% underwent first ambulation at postoperative day (POD) 1, 31% at POD 2, and the remaining patients at POD 3 or later. Whereas short-term outcomes were equivalent among patients with first ambulation at POD 1 and those at POD 2, patients who delayed ambulation until POD 3 or after had an increased incidence of infectious complications (P = 0.004), longer hospitalization (P < 0.001), and a decreased home discharge rate (P < 0.001). Multivariate analysis showed that significant predictors of delayed ambulation (POD ≥ 3) were poor Eastern Cooperative Oncology Group performance status (ECOG-PS), low controlling nutritional status (CONUT), nonlaparoscopic surgery, and transvenous opioid use. Of these factors, the combination of ECOG-PS, CONUT, and nonlaparoscopic surgery clearly stratified patients into four-grade risk groups regarding delayed ambulation (P for trend < 0.001). CONCLUSION: Our results suggest that first ambulation before POD 2 could be desirable for better short-term outcomes. Active preoperative intervention, such as nutritional care and prehabilitation, in patients with multiple risk factors for delayed ambulation could improve the postoperative course.

Risk factors for postoperative pneumonia after general and digestive surgery: a retrospective single-center study.

PURPOSE: Pneumonia is the second-most common complication in postoperative patients and is associated with significant morbidity and high costs of care. We aimed to determine the risk factors for pneumonia after general and digestive surgery. METHODS: The medical records of 1,016 patients who underwent general and digestive surgery between January 2016 and March 2019 in our hospital were reviewed. RESULTS: Of the 1,016 patients, 67 (6.6%) developed postoperative pneumonia. The multivariate analysis showed that significant predictors of postoperative pneumonia were a poor Eastern Cooperative Oncology Group performance status (ECOG-PS), low forced vital capacity and low forced expiratory volume in one second in the spirometry test, malnutrition (low serum albumin levels and low controlling nutritional status scores and prognostic nutritional index [PNI] values), esophagectomy, upper gastrointestinal surgery, and nonlaparoscopic surgery. Of these factors, the combination of PNI and ECOG-PS clearly stratified patients into low-, intermediate-, and high-risk groups with respect to developing postoperative pneumonia (area under the curve: 0.709). CONCLUSIONS: Although postoperative pneumonia is associated with many clinical variables, active medical intervention for the prevention of pneumonia in patients with multiple risk factors can improve the postoperative course. In particular, perioperative nutritional care may prevent postoperative pneumonia in patients with malnutrition and a poor PS.

[Laparoscopic Surgery for an Intussusception Caused by Rectosigmoid Colon Cancer after Pre-Operative Reduction by Transanal Insertion of a Circular Sizer - A Case Report].

An octogenarian man complaining of bloody stool was referred to our hospital. A digital examination, abdominal enhanced CT and endoscopy led to a diagnosis of intussusception due to rectosigmoid colon cancer, but he was not suffering from bowel obstruction. An elective laparoscopic Hartmann's operation was performed after reduction by transanal insertion of a circular sizer. It may be difficult to reduce an intussusception induced by rectal cancer. We report this case with a review of the relevant literature.

Detection of circulating tumor cells by p75NTR expression in patients with esophageal cancer.

BACKGROUND: The p75 neurotrophin receptor (p75NTR) is a cancer stem cell (CSC) marker in esophageal squamous cell carcinoma (ESCC). This study aimed to assess the use of p75NTR in detecting circulating tumor cells (CTCs) in ESCC. METHODS: Peripheral blood mononuclear cell expression of epithelial cell adhesion molecule (EpCAM) and p75NTR was detected in 23 ESCC patients (13 received chemo- or chemoradiotherapy and 10 received curative surgery) and 10 healthy controls by flow cytometry. RESULTS: EpCAM+p75NTR+ cell counts (average±SD) were significantly higher in patients (n=23, 16.0±18.3) compared to controls (n=10, 0.4±0.9, p=0.013). The sensitivity and specificity to differentiate ESCC patients from controls were 78.3 and 100% (cut-off value 4.0), respectively. EpCAM+p75NTR+, but not EpCAM+p75NTR- cell counts, correlated with clinically diagnosed distant metastasis (n=13, p=0.006) and pathological venous invasion in resected primary tumors (n=10, p=0.016). Malignant cytology was microscopically confirmed in isolated EpCAM+p75NTR+ cells with immunocytochemical double staining. CONCLUSIONS: p75NTR is suggested to be a useful marker for clinically significant CTCs, which exhibit highly metastatic features in ESCC.

Parenteral nutrition-associated liver disease in extremely low-birthweight infants with intestinal disease.

BACKGROUND: The aim of this study was to investigate factors associated with the development of parenteral nutrition-associated liver disease (PNALD) and to examine the clinicopathological relationship of PNALD in extremely low-birthweight infants (ELBWI). METHODS: The subjects were 13 ELBWI who had received PN because of intestinal perforation or functional ileus between 2000 and 2013. We measured the serum levels of biochemical parameters, including aspartate aminotransferase, alanine aminotransferase, and direct bilirubin. Liver histopathology was examined in relation to outcome. The subjects were categorized into two groups on liver histopathology: F(+), development of hepatic fibrosis and necrosis with/without cholestasis; and F(-), no hepatic fibrosis. RESULTS: Of 13 ELBWI, five died of hepatic failure, five died of sepsis, and the other three were alive at the time of the study. Of the five infants who died of hepatic failure, two developed fulminant hepatitis without cholestasis, and the other three developed chronic cholestasis and finally hepatic failure. Postmortem histopathology in F(+) indicated not only massive hepatic necrosis, but also massive hepatic fibrosis. These histopathological findings explained the clinical presentation of portal hypertension. There were significant differences in the fasting period after intestinal disease onset between the two groups. CONCLUSION: The prolonged fasting with PN is responsible for severe hepatocellular necrosis with fibrosis and consequent lethal portal hypertension.

Efficacy and safety of strong acid electrolyzed water for peritoneal lavage to prevent surgical site infection in patients with perforated appendicitis.

PURPOSE: Our previous experimental study of perforated peritonitis in rats proved that peritoneal lavage with strong acid electrolyzed water (SAEW) has no adverse effects, reduces the bacteria count in the ascitic fluid more effectively than saline, and increases the survival rate significantly. Thus, we conducted a randomized controlled study, applying SAEW in the treatment of perforated appendicitis in children. METHODS: Forty-four patients, aged 3-14 years, were randomly divided into two groups: Group S (n = 20), in which the peritoneal cavity was lavaged with 100 ml/kg saline and the wound was washed out with 200 ml saline; and Group E (n = 24), in which the peritoneal cavity was lavaged with 100 ml/kg SAEW and the wound was washed out with 200 ml SAEW. RESULTS: No adverse effect of SAEW was observed in Group E. There was no difference in the bacterial evanescence ratio of ascitic fluid after lavage between Groups S and E (11.1 and 15.8%, respectively). A residual abscess developed in one patient from each group (5.0 and 4.2%, respectively). The incidence of surgical site infection (SSI) was significantly lower in Group E than in Group S (0 and 20%, respectively; P < 0.05). There was no difference in the duration of pyrexia, positive C-reactive protein, leukocytosis, or hospital stay between the groups. CONCLUSION: Peritoneal lavage and wound washing with SAEW have no adverse effects and are effective for preventing SSI.

[Identification of Circulating Tumor Cell（CTC）in Breast Cancer Patients Using a Newly Established CTC Detecting System].

We developed a new circulating tumor cell (CTC) chip in order to identify CTCs in the peripheral blood of cancer patients. In this study, we aimed to identify CTCs in the blood of breast cancer patients by using this CTC detecting system. In addition, we used this system to evaluate the response to anticancer agents. We were able to identify CTCs in 5 of 6 patients. In addition, the system showed that the number of CTCs had decreased after chemotherapy. Thus, the CTC detecting system was useful in the identification of CTCs in the breast cancer patients and in the early prediction of response to anticancer agents.

A Neonatal Case of Lower Urinary Tract Obstruction and Imperforate Anus: Urethral Decompression Due to Rectourinary Fistula.

Lower urinary tract obstruction (LUTO) is a rare fetal condition associated with significant perinatal morbidity and mortality. Herein, we report a neonatal case of LUTO with anal atresia complicated by anhydramnios and pulmonary hypoplasia. After treatment for severe postnatal respiratory distress, the neonate underwent vesicostomy and colostomy. Postoperatively, respiratory status and renal function improved. This case highlights a unique feature where a large rectovesical fistula channeled fetal urine into the colon, which minimized obstructive damage to the urinary tract and preserved renal morphology. Fetal colonic dilatation and numerous enteroliths indicate urine influx into the intestinal tract. Our case suggests the importance of recognizing such exceptions in complete LUTO to predict postnatal outcomes diagnosed in utero.

A case of BRCA1-mutated giant pancreatic acinar cell carcinoma successfully treated with modified FOLFIRINOX therapy and radical resection.

Pancreatic acinar cell carcinoma (PACC) is a rare type of pancreatic cancer; further, its pathogenesis and treatment strategies remain unclear. We report the case of a 70-year-old man who presented with a chief complaint of abdominal distention. Computed tomography scans revealed a large lobulated mass (tumor diameter: 150 mm) in the pancreatic body tail, which was diagnosed as a PACC through endoscopic ultrasonography fine needle aspiration. The other imaging modalities did not reveal distant metastases, and the tumor was classified as resectable. Neoadjuvant chemotherapy was planned after staging laparoscopy ruled out microscopic distant metastasis. First-line chemotherapy with gemcitabine + nab-paclitaxel failed due to tumor growth and worsening abdominal distention. Evaluation using the BRACAnalysis® device indicated that the patient was positive for BRCA1 mutation. Second-line modified FOLFIRINOX (mFFX) resulted in a marked decrease in elastase 1 levels; moreover, a partial antitumor response was observed, which prompted radical resection. After distal pancreatectomy, the patient has survived for 3.5 years without recurrence. BRCA-mutated pancreatic cancer is more likely to respond to mFFX, including platinum, and BRCA mutations have been reported to be highly prevalent in PACC. It is important to evaluate the presence of BRCA mutations in patients with PACC prior to treatment.

Novel choledochojejunostomy technique "T-shaped anastomosis" for preventing the development of postoperative cholangitis in pancreatoduodenectomy: A propensity score matching analysis.

Background: There have been few studies of countermeasures against postoperative cholangitis, a serious complication after pancreaticoduodenectomy (PD) that impairs quality of life. Objective: To evaluate our recently developed, novel method of choledochojejunostomy with a larger anastomotic diameter, the "T-shaped anastomosis." Methods: The study included 261 cases of PD. The T-shaped choledochojejunostomy technique was performed with an additional incision for a distance greater than half the diameter of the bile duct at the anterior wall of the bile duct and the anterior wall of the elevated jejunum. To compensate for potential confounding biases between the standard anastomosis group (n = 206) and the T-shaped anastomosis group (n = 55), we performed propensity score matching (PSM). The primary endpoint was the incidence of medium-term postoperative cholangitis adjusted for PSM. Results: In the PSM analysis, 54 patients in each group were matched, and the median bile duct diameter measured by preoperative CT was 8.8 mm versus 9.3 mm, the rate of preoperative biliary drainage was 31% versus 37%, the incidence of cholangitis within 1 month before surgery was 9% versus 13%, and the incidence of postoperative bile leakage was 2% versus 2%, with no significant differences. The incidence of medium-term postoperative cholangitis was 15% versus 4%, and multivariate logistic regression revealed that T-shaped choledochojejunostomy was an independent predictor of a reduced incidence of cholangitis (odds ratio, 0.17, 95% CI 0.02-0.81; p = 0.024). Conclusions: The T-shaped choledochojejunostomy technique was shown to be effective with a significant reduction in the incidence of medium-term postoperative cholangitis. Clinical trial identification: UMIN000050990.

Thoracoscopic enucleation of an esophageal glomus tumor in the prone position: a case report and literature review.

BACKGROUND: Glomus tumors (GT) generally occur in the skin. However, esophageal GT, an extremely rare condition, has no established standardized treatment guidelines. Herein, we report the case of an esophageal GT successfully removed by thoracoscopic enucleation in the prone position using intra-esophageal balloon compression. CASE PRESENTATION: A 45-year-old man underwent an annual endoscopic examination and was found to have a submucosal tumor in the lower esophagus. Endoscopic ultrasound (EUS) revealed a hyperechoic mass originating from the muscular layer. Contrast-enhanced computed tomography identified a 2 cm mass lesion with high contrast enhancement in the right side of the lower esophagus. Pathologic findings of EUS-guided fine needle aspiration biopsy (EUS-FNA) revealed round to spindle shaped atypical cells without mitotic activity. Immunohistochemically, the tumor was positive for alpha-smooth muscle actin, but negative for CD34, desmin, keratin 18, S-100 protein, melan A, c-kit, and STAT6. He was diagnosed with an esophageal GT and a thoracoscopic approach to tumor resection was planned. Under general anesthesia, a Sengstaken-Blakemore (SB) tube was inserted into the esophagus. The patient was placed in the prone position and a right thoracoscopic approach was achieved. The esophagus around the tumor was mobilized and the SB tube balloon inflated to compress the tumor toward the thoracic cavity. The muscle layer was divided and the tumor was successfully enucleated without mucosal penetration. Oral intake was initiated on postoperative day (POD) 3 and the patient discharged on POD 9. No surgical complications or tumor metastasis were observed during the 1-year postoperative follow-up. CONCLUSIONS: As malignancy criteria for esophageal GT are not yet established, the least invasive procedure for complete resection should be selected on a case-by-case basis. Thoracoscopic enucleation in the prone position using intra-esophageal balloon compression is useful to treat esophageal GT on the right side of the esophagus.

Impact of cow's milk allergy on enterocolitis associated with Hirschsprung's disease.

PURPOSE: To investigate the impact of cow's milk allergy (CMA) on infants with Hirschsprung's disease (HD). METHODS: Twenty-four patients, who developed gastrointestinal symptoms before the age of 60 days and underwent surgery for HD in the period between January 2003 and December 2012, were enrolled in this study. They were divided into two groups based on CMA-related findings: stimulation index of lymphocyte stimulation test >300 % and the presence of eosinophilic infiltration in the resected colon. Ten patients were determined specimen as not having CMA (Group A), because they did not satisfy any of the criteria. The remaining 14 were determined as having possible CMA (Group B), because they satisfied either or both findings. Patient background characteristics, pre- and postoperative clinical history, and laboratory data were compared between Groups A and B. RESULTS: Pre- and postoperative enterocolitis did not occur in Group A patients. Postoperative enterocolitis was more frequent in Group B than in Group A (p = 0.04). Other clinical and laboratory data did not show significant difference between the two groups. CONCLUSION: CMA is a possible risk factor for postoperative enterocolitis in patients with HD.

Perioperative Management of Congenital Diaphragmatic Hernia Repair in a Patient With Univentricular Circulation: A Case Report.

The survival rate in congenital diaphragmatic hernia (CDH) with complex heart defects is low. Although the current consensus on the indications for surgical repair of CDH without heart defects has improved surgical outcomes, the surgical indication for CDH with complex heart defects remains unclear. Herein, we report the perioperative management of a patient with univentricular circulation who underwent CDH repair. Thus, patients with CDH complicated by univentricular anatomy may tolerate surgery depending on preserved respiratory function.

Usefulness of the femoral vein as a graft for portal vein/superior mesenteric vein reconstruction during pancreatectomy.

Shibuya and colleagues describe their innovative technique using the femoral vein as a graft for portal vein/superior mesenteric vein reconstruction during pancreatectomy. The femoral vein has an appropriate diameter and is particularly useful when long resection of the superior mesenteric vein is required in surgery for locally advanced pancreatic ductal adenocarcinoma.

Laparoscopic distal pancreatectomy for pancreatic tail cancer in a 100-year-old patient.

We present the case of a 100-year-old man with no specific symptoms. Computed tomography (CT) revealed a 34 mm tumor in the pancreatic tail, which was diagnosed as pancreatic cancer by biopsy. CT and magnetic resonance imaging showed that the tumor was resectable, and there were no noncurative factors on staging laparoscopy (cT3N0M0: cStage IIA). His performance status was good, and hypertension was the only comorbidity. A cardiologist, respiratory physician, and anesthesiologist examined the patient and determined that his condition was suitable for surgery. His postoperative predicted mortality rate was 0.9% using the American College of Surgeons risk calculator. We administered synbiotics and nutrients before surgery and introduced preoperative rehabilitation to improve his activities of daily living (ADL) as well as respiratory training to prevent postoperative pneumonia. Regarding the invasiveness of the surgery, we performed laparoscopic distal pancreatectomy with D1 lymphadenectomy. The patient was discharged on postoperative day 17, without any major complications. When performing pancreatectomy in older adults, it is important to fully assess preoperative tolerance and perioperative risk and prevent worsening of ADL by introducing nutritional therapy and rehabilitation.

A case of squamous cell carcinoma of the breast achieved a pathological complete response after dose-dense AC + dose-dense PTX.

BACKGROUND: Squamous cell carcinoma (SCC) of the breast is a rare form of breast cancer, accounting for approximately 0.1% of all breast cancers. It is known for its rapid tumor growth and poor prognosis with no established treatment. CASE PRESENTATION: A 56-year-old woman was diagnosed with breast SCC with axillary, supraclavicular and internal thoracic lymph node metastases. She received neoadjuvant chemotherapy (NAC) with dose-dense doxorubicin and cyclophosphamide (AC) followed by dose-dense paclitaxel (PTX). This treatment resulted in a pathological complete response (pCR) after breast-conserving surgery. The patient was then treated with radiotherapy. She remained free of recurrence for three years postoperatively. CONCLUSIONS: We report a rare case of breast SCC treated with preoperative dose-dense chemotherapy, resulting in pCR and allowing breast-conserving surgery.

miR-877-3p as a Potential Tumour Suppressor of Oesophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: MicroRNAs (miRNAs) are abnormally expressed and involved in the pathogenesis of various carcinomas. The present study aimed to identify novel miRNA genes associated with the pathogenesis and prognosis of oesophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: The miRNA profiling of 873 genes was performed using surgically resected oesophageal tissues from 35 patients with ESCC to identify candidate miRNAs. To examine the biological activities of candidate miRNAs, their proliferative, invasive, and migratory abilities were evaluated in ESCC cells subjected to miRNA mimic-mediated over-expression. The miRNA expression levels of the selected candidate miRNAs were analysed in the resected oesophageal tissues of 76 patients with ESCC from the two cohorts and correlated with the clinicopathological parameters. RESULTS: Among the four candidate miRNAs identified by miRNA profiling, miR-877-3p was selected for subsequent analyses. In vitro analyses showed that the over-expression of miR-877-3p significantly suppressed the proliferation, invasion, and migration of ESCC cell lines compared with those of control cells. In the analyses of clinical specimens, the expression of miR-877-3p was down-regulated in ESCC tissues compared with that in adjacent normal oesophageal tissues. The down-regulation of miR-877-3p expression in ESCC tissues was significantly associated with advanced local progression and lymphatic involvement. The miR-877-3p down-regulation was also significantly associated with poor disease-free and disease-specific survival. CONCLUSION: miR-877-3p acts as a tumour suppressor gene in ESCC cells, and its down-regulation in ESCC tissues is associated with a poor prognosis. Thus, miR-877-3p may serve as a novel prognostic marker and promising therapeutic target.