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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.

Background The pectoralis major musculocutaneous flap (PMMF) is a pedicled flap often used as a reconstruction option in head and neck surgery, especially in cases with poor wound healing. However, applying PMMF after esophageal surgery is uncommon. We report here, the case of a successfully repaired refractory anastomotic fistula (RF) after total esophagectomy, by PMMF. Case presentation A 73-year-old man had a history of hypopharyngolaryngectomy, cervical esophagectomy, and reconstruction using a free jejunal graft for hypopharyngeal carcinosarcoma at the age of 54. He also received conservative treatment for pharyngo-jejunal anastomotic leakage (AL), then postoperative radiation therapy. This time, he was diagnosed with carcinosarcoma in the upper thoracic esophagus; cT3rN0M0, cStageII, according to the Japanese Classification of Esophageal Cancer 12th Edition. As a salvage surgery, thoracoscopic total resection of the esophageal remnant and reconstruction using gastric tube via posterior mediastinal route was performed. The distal side of the jejunal graft was cut and re-anastomosed with the top of the gastric tube. An AL was observed on the 6th postoperative day (POD), and after 2 months of conservative treatment was then diagnosed as RF. The 3/4 circumference of the anterior wall of the gastric tube was ruptured for 6 cm in length, and surgical repair using PMMF was performed on POD71. The edge of the defect was exposed and the PMMF (10 × 5 cm) fed by thoracoacromial vessels was prepared. Then, the skin of the flap and the wedge of the leakage were hand sutured via double layers with the skin of the flap facing the intestinal lumen. Although a minor AL was observed on POD19, it healed with conservative treatment. No complications, such as stenosis, reflux, re-leakage, were observed over 3 years of postoperative follow-up. Conclusions The PMMF is a useful option for repairing intractable AL after esophagectomy, especially in cases with large defect, as well as difficulties for microvascular anastomosis due to previous operation, radiation, or wound inflammation.

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).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.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.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.

Anastomotic leakage (AL) after esophagectomy is one of the major complications after esophagectomy. The aim of this study was to evaluate anastomotic procedure to reduce AL after esophagectomy with retrosternal gastric pull up. A total of 157 consecutive patients underwent thoracoscopic esophagectomy followed by retrosternal reconstruction with gastric tube in our hospital between January 2008 and December 2021. The anastomotic procedure was revised at January 2016. After cervical esophagogastric anastomosis using circular stapler, gastric tube was pulled down to linearize and place the anastomotic site below the suprasternal notch (SN). The sternum tracheal distance (STD) and the level of esophagogastric anastomosis (LEA) were measured using CT image. In comparison between the former (-December 2015, 65 cases) and later (January 2016-, 92 cases) group, AL was significantly reduced from 11/65 (16.9%) to 0/92 (0%) cases (p , p = 0.02) and LEA (0>, p Surgical procedure which avoids excessive compression on the gastric tube at the thoracic inlet may take an important role in reduction of AL.

BACKGROUND Distal pancreatectomy with en bloc celiac artery resection (DP-CAR) is a curative surgical method for locally advanced pancreatic body cancer; however, arterial reconstruction remains controversial in this procedure. This report presents the case of a 47-year-old man with advanced distal pancreatic carcinoma and initial partial response to chemotherapy who required celiac axis reconstruction of the common hepatic artery and left gastric artery. CASE REPORT A 47-year-old man had loss of appetite. He had a 40-mm hypovascular tumor extending from the pancreatic body to the tail, invading around the celiac artery, common hepatic artery, left gastric artery, and splenic artery. We initiated chemotherapy concurrent with chemo-radiotherapy with S-1 administration. After chemo-radiotherapy, computed tomography (CT) showed tumor shrinkage, indicating partial response, but soft tissue CT density surrounding the celiac axis arteries persisted. We conducted conversion surgery. When the common hepatic artery was clamped during surgery, the intrahepatic arterial blood flow reduced; thus, we reconstructed the middle hepatic artery to the common hepatic artery. The left gastric artery was also reconstructed using the second jejunal artery to prevent ischemic gastropathy. Histopathologic examination showed no tumor cells in the specimen; thus, R0 resection was achieved. CONCLUSIONS Arterial reconstruction can be an option for R0 resection in DP-CAR when hepatic arterial blood flow is reduced due to an intraoperative common hepatic artery clamping test.

680 Background: Multidisciplinary treatment of borderline resectable (BR)/unresectable locally advanced (UR-LA) pancreatic adenocarcinoma (PDAC) has not yet been established. The purpose of this study is to explore factors that improve prognosis in radical surgery after multidisciplinary treatment for pancreatic cancer. Methods: We evaluated the following prognostic factors in 240 PDAC patients who underwent radical resection after multidisciplinary treatment. Patients were classified into 3 groups according to NCCN guidelines (BR PDAC invading the portal vein (BR-PV), BR pancreatic cancer in contact with the major arteries such as the hepatic artery, celiac axis and superior mesenteric artery (BR-A), and UR-LA), and prognostic factors were investigated. Patients with BR PDAC were treated with chemotherapy followed by surgery, while radiation therapy was added preoperatively in most cases with arterial invasion. All patients with UR-LA underwent surgery after nab-paclitaxel plus gemcitabine (GnP) followed by chemoradiotherapy (CRT) with S-1. Results: BR-PV/BR-A/UR-LA patients were 88/111/41, respectively. Prognosis was significantly better in the NAT group than in the upfront surgery group for both BR-PV/A (P=0.004/42.5 (P=0.022). In univariate analysis in 39 patients with BR-A, the following factors were significantly favorable prognostic factors; TM normalization (P=0.033), preoperative PNI>42.5 (P=0.013), intraoperative blood loss>830 ml (P=0.013). Multivariate analysis revealed that high preoperative PNI was an independent prognostic factor (hazard ratio 0.15 [0.02-0.85]; P=0.014) in BR-A patients. In patients with UR-LA who underwent radical resection after GnP and subsequent CRT, median duration of NAT was 8.8 months, and R0 resection was achieved in 36 patients (88%). 3-year OS was 77.4%, and 5-year OS 58.6%. Multivariate analysis revealed that CA19-9 normalization (hazard ratio 0.23 [0.02-0.88]; P=0.032) and PNI≥41.7 (HR 0.05 [0.01-0.62]; P=0.021) were independent prognostic factors. Conclusions: In both BR/UR-LA pancreatic cancer, normalization of TM and maintenance of good nutritional status during NAT until surgery may contribute to prolonged prognosis.

674 Background: Positive peritoneal cytology has been reported to indicate a poor prognosis in patients with pancreatic cancer even if the primary tumor is surgically resected. This study investigated the clinical implications of peritoneal cytology by staging laparoscopy for patients with potentially resectable pancreatic cancer for whom initial treatment will be started. Methods: We retrospectively reviewed 113 consecutive patients with pancreatic cancer diagnosed as resectable by computed tomography in whom peritoneal cytology was evaluated by staging laparoscopy between December 2018 and August 2022. Patients with positive cytology received induction chemotherapy, and those in whom cytology converted to negative underwent surgical resection as needed when possible. We set best tumor marker cutoff values for predicting positive cytology by maximizing the Youden index. Results: Seventy-three patients were men and the mean age was 72 years. Thirty patients (26.5%) had positive cytology at initial staging laparoscopy. Minimal peritoneal metastases were detected in seven of these patients and liver metastases in two. Larger tumor diameter ( > 30 mm), location in the pancreatic body or tail, an elevated CA19-9 level ( > 138.5 U/ml), an elevated CA125 level ( > 13.5 U/ml), and an elevated CEA level ( > 5.1 ng/ml) were associated with a significantly increased risk of positive cytology (odds ratio 4.71 [confidence interval 1.87–12.2] P = 0.001, 2.49 [1.07–6.05] P = 0.038, 2.95 [1.26–7.12] P = 0.014, 3.89 [1.57-10.7] P = 0.005, and 3.52 [1.23–10.2] P = 0.018, respectively). Eighteen patients (60%) who received induction chemotherapy converted from positive to negative cytology; seven (38%) of these patients underwent surgery and all remain alive without recurrence. Interestingly, median overall survival in patients with negative cytology was not necessarily inferior to that in those with positive cytology (23.4 months vs. 24.2 months, P = 0.33). Conclusions: Over a quarter of patients with pancreatic cancer that is diagnosed as resectable by computed tomography may have positive peritoneal cytology at the initial assessment. These patients tend to have higher CA19-9, CA125, and CEA levels, larger tumors, and tumors located in the body or tail of the pancreas. A more favorable prognosis may be achieved by administering induction chemotherapy until cytology converts to negative than by upfront surgery.

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.

Anastomotic leakage (AL) is one of the major complications of gastro-esophageal anastomosis after esophagectomy, which causes short-term morbidity and mortality, as well as poor long-term survival. The aim of this study was to investigate factors which were associated with AL after esophagectomy in order to determine the optimal surgical technique to reduce AL. Methods A total of 128 patients with thoracic esophageal cancer underwent subtotal esophagectomy followed by retrosternal reconstruction with gastric conduit with cervical anastomosis using circular staple in our institute from January 2008 and January 2020. The relationship between AL and surgical procedures as well as clinicopathological characteristics of the patients were retrospectively investigated. In addition, we divided the patients into 65 cases in former period (December 2015) and 63 cases in later period (January 2016-) to compare the incidence of AL. Results AL was observed in 12 cases (9.4%) of the 128 patients. The incidence of AL decreased from 16.9% (11/65) in former period to 1.6% (1/63) in later period (p = 0.004). In comparison between the cases with and without AL (12 cases vs 116cases), statistically significant difference was seen in BMI (average ± SD, 24.2 ± 4.7 vs 21.6 ± 3.1; p = 0.02), anastomotic site (posterior wall/greater curvature, 11/1 vs 54/62; p = 0.004), and level of anastomosis (above/below superior border of manubrium of sternum, 12/0 vs 33/83; p Conclusion Surgical procedure which avoid excessive pressure on the gastric tube from the surrounding structures, such as sternum, may take an important role in reduction of AL after esophagectomy. However, multiple factors, such as nutritional status and obesity, also influence risk of anastomotic leakage.

The deep inferior epigastric perforator (DIEP) flap is widely recognized as safe for use as a first-choice option in autologous tissue breast reconstruction; however, DIEP is often not performed for breast reconstruction in the elderly. We report a case of an 85-year-old woman who underwent DIEP flap reconstruction. Immediate reconstruction was performed after mastectomy. The patient successfully underwent DIEP flap reconstruction with no complications. Other options for reconstruction include a latissimus dorsi flap, a transverse rectus abdominis flap and implant-based reconstruction. DIEP flap reconstruction was performed, which does not cause muscle damage and provides sufficient volume. To our knowledge, this study is the first to report DIEP breast reconstruction in a patient over 85 years of age. This case demonstrates the usefulness of DIEP flap reconstruction for elderly patients.

Introduction and importance Mediastinal cystic lesions, such as paratracheal air cyst (PTAC) and bronchogenic cyst (BC), are rare anomaly usually found incidentally in thoracic imaging. Special attention is needed in the case of thoracic surgery. Case presentation All three patients were male, 71, 73, and 76 years old. Preoperative CT showed each had a lobular cystic lesion at the right posterolateral side of trachea in the thoracic outlet 11, 14, and 19 mm in size, respectively, with air density and tracheal communication, leading to a diagnosis of PTACs. An oval cystic lesion, 7 mm in size, was found in one patient at the right lateral side of the upper esophagus with low density and without tracheal communication, leading to a diagnosis of paraesophageal BC. Intraoperative findings of the three PTACs demonstrated a soft bulge from the membranous portion of trachea that was left intact. The BC had an oval elastic structure, mimicking a metastatic lymph node, and was removed with the mediastinal lymph nodes. Histological examination showed ciliated columnar epithelium, confirming a diagnosis of BC. Clinical discussion PTACs are associated with increased intraluminal pressure due to chronic lung disease. BCs are congenital anomalies that originate from abnormal budding of the embryonic foregut. Conclusion PTACs and BCs need to be considered in preoperative image diagnosis in patients with esophageal cancer. PTACs should be left intact to avoid tracheal injury, while removal of isolated BCs is recommended as a diagnostic and therapeutic measure., Highlights • Paratracheal air cyst (PTAC) and bronchogenic cyst (BC) are rare anomaly. • Three PTACs and a BC were found in patients who received thoracoscopic esophagectomy for esophageal cancer. • PTACs were carefully left intact to avoid tracheal injury. • BC was removed for diagnostic and therapeutic measure. • PTACs and BCs need to be considered in preoperative image diagnosis in patients with esophageal cancer.

Background: The objective of this study was to investigate the optimal neoadjuvant therapy (NAT) for borderline resectable pancreatic cancer invading the portal vein (BR-PV) or abutting major arteries (BR-A). Methods: We retrospectively analyzed 88 patients with BR-PV and 111 patients with BR-A. Results: In BR-PV patients who underwent upfront surgery (n = 46)/NAT (n = 42), survival was significantly better in the NAT group (3-year overall survival (OS): 5.8%/35.5%, p = 0.004). In BR-A patients who underwent upfront surgery (n = 48)/NAT (n = 63), survival was also significantly better in the NAT group (3-year OS:15.5%/41.7%, p &lt, 0.001). The prognosis tended to be better in patients who received newer chemotherapeutic regimens, such as FOLFIRINOX and gemcitabine with nab-paclitaxel. In 36 BR-PV patients who underwent surgery after NAT, univariate analysis revealed that normalization of tumor marker (TM) levels (p = 0.028) and preoperative high prognostic nutritional index (PNI) (p = 0.022) were significantly associated with a favorable prognosis. In 39 BR-A patients who underwent surgery after NAT, multivariate analysis revealed that preoperative PNI &gt, 42.5 was an independent prognostic factor (HR: 0.15, p = 0.014). Conclusions: NAT using newer chemotherapy is essential for improving the prognosis of BR pancreatic cancer. These findings suggest that prognosis may be prolonged by maintaining good nutritional status during preoperative treatment.

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. 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. 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

530 Background: For borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC), upfront surgery was standard in the past, and the usefulness of neoadjuvant treatment (NAT) has been reported in recent years. However, few studies have been conducted to date on whether there is a difference in optimal treatment between BR-PDAC invading the portal vein (BR-PV) or abutting major arteries (BR-A). The objective of this study was to investigate the optimal treatment for BR-PV and BR-A. Methods: We retrospectively analyzed 199 patients with BR-PDAC (88 BR-PV and 111 BR-A). For each BR-PV and BR-A, we analyzed the following points. 1) Comparison of prognosis of upfront surgery vs. NAT, 2) Comparison of regimens in patients who underwent NAT, 3) Prognostic factors in patients who underwent resection after NAT. Results: 1) In BR-PV patients who underwent upfront surgery (n = 46)/NAT (n = 42), survival was significantly better in the NAT group (3-year overall survival (OS): 5.8%/35.5%, p = 0.004). In BR-A patients who underwent upfront surgery (n = 48)/NAT (n = 63), survival was also significantly better in the NAT group (3-year OS:15.5%/41.7%, p < 0.001). 2) The prognosis tended to be better in patients who received newer chemotherapeutic regimens, such as FOLFIRINOX and gemcitabine with nab-paclitaxel than older regimens such as gemcitabine and/or S-1, in each BR-PV and BR-A patients. The R0 rate was significantly higher (100%) when radiotherapy was used in combination with chemotherapy, regardless of the chemotherapeutic regimen. 3) In 36 BR-PV patients who underwent surgery after NAT, univariate analysis revealed that normalization of tumor marker levels ( p = 0.028) and preoperative high prognostic nutritional index (PNI) ( p = 0.022) were significantly associated with a favorable prognosis. In 39 BR-A patients who underwent surgery after NAT, multivariate analysis revealed that preoperative PNI > 42.5 was an independent prognostic factor (hazard ratio: 0.15, p = 0.014). The length of NAT was not a prognostic factor for either BR-PV or BR-A. Conclusions: NAT using newer chemotherapy is essential for improving the prognosis of BR pancreatic cancer. These findings suggest that prognosis may be improved by maintaining good nutritional status during preoperative treatment, not by the length of preoperative treatment. In addition, surgery after normalization of tumor markers levels by preoperative treatment contributes to the prolongation of survival.

Highlights • Mesenteric hematoma is a rare condition without specific symptoms. • Rivaroxaban is not affect to the value of PT or APTT. • It is difficult to diagnose mesenteric hematoma., Introduction Mesenteric hematoma is a rare condition caused by bleeding localized in the mesenteric vascular tree. This is a first report of spontaneous mesenteric hematoma caused by rivaroxaban. Presentation of case The patient was a 71-year-old man who had taken rivaroxaban for paroxysmal atrial fibrillation. He had experienced abdominal pain and diarrhea for the prior 3 days. He had little melena and was referred to our institute. He presented with hypotension on arrival. Computed tomography (CT) revealed a 10 cm mass in the mesentery of the sigmoid colon with extravasation. Active bleeding from the sigmoid colic arteries was embolized with angiography on the day of admission. On the second day, we operated on the patient. We detected 200 mL of bloody ascites accumulated in the abdomen. The serosa of the sigmoid colon was ruptured along the tenia due to the compression of the hematoma in the mesentery. The sigmoid colon was resected and a descending colostomy was reconstructed. Operative and pathological findings did not reveal the cause of bleeding. We finally diagnosed the patient with spontaneous mesenteric hematoma associated with rivaroxaban. Discussion Previous reports of mesenteric hematoma with anticoagulant were associated with warfarin. Since rivaroxaban is not affect to the value of prothrombin time (PT) and activated partial thromboplastin time (APTT) and mesenteric hematoma presents non-specific symptoms, it is difficult to diagnose mesenteric hematoma in the patients taking rivaroxaban. Conclusion It is important to keep in mind that mesenteric hematoma is one of the critical complications in patients taking rivaroxaban.

Background Epithelial cell adhesion molecule (EpCAM) is a marker for circulating tumor cells (CTCs) in various types of cancer. Cell surface antigens, such as CD90 and CD44, have been reported to be cancer stem cell (CSC) markers in esophageal squamous cell carcinoma (ESCC). The aim of this study was to assess the use of CD90 and CD44 as markers to identify clinically significant CTC subpopulations in ESCC. Methods We collected 3 mL of peripheral blood from 10 ESCC patients and 10 healthy volunteers to detect combined expression of EpCAM, CD90, and CD40 using flow cytometry. Results The number of EpCAM-positive cell counts (average ± SD) in the patients was significantly higher than healthy volunteers (29.1 ± 35.9 and 2.3 ± 2.5, P = 0.001). The proportions (average ±SD) of CD90- and CD44-positive cells in EpCAM-positive cells were 45.7% ± 42.4% and 98.7% ± 2.7%, respectively. EpCAM-positive/CD44-positive CTC counts, which was equivalent to EpCAM-positive CTC counts, correlated with pathologic V factors in the resected primary tumors (P > 0.01). EpCAM-positive/CD90-positive CTC counts, but not EpCAM-positive/CD90-negative CTC counts, correlated with pathologic V factors in the resected primary tumors (P = 0.01). Our results suggested that combined expression of EpCAM and CD90 may useful to detect CTC subsets, which have highly metastatic features in ESCC. CD44, on the other hand, is equivalent to EpCAM as a marker to detect CTCs in ESCC.

Background Multiple pancreaticoduodenal artery aneurysms in association with median arcuate ligament syndrome (MALS) are relatively rare. A treatment option, such as a median arcuate ligament (MAL) release or embolization of the aneurysms, should be considered in such cases, but the treatment criteria remain unclear. Case report A 75-year-old man was transferred to our hospital because of a ruptured pancreaticoduodenal aneurysm. Emergency angiography showed stenosis of the root of the celiac axis (CA), a ruptured aneurysm of the posterior inferior pancreaticoduodenal artery (PIPDA), and an unruptured aneurysm of the anterior inferior pancreaticoduodenal artery (AIPDA). Coil embolization of the PIPDA was performed. Five days after embolization, the gallbladder became necrotic due to decreased blood flow in the CA region, and an emergency operation was performed. We performed a cholecystectomy and released the MAL to normalize the blood flow of the CA region. However, the patient died on postoperative day 8 because of rupture of the untreated aneurysm of the AIPDA. Conclusions This is the first report of metachronous ruptures of multiple pancreaticoduodenal aneurysms due to MALS, even after a MAL release. Although rare, a residual aneurysm in the pancreatic head region may need to be embolized quickly.

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. The medical records of 1,016 patients who underwent general and digestive surgery between January 2016 and March 2019 in our hospital were reviewed. 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). 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.

Epithelial cell adhesion molecule (EpCAM) is a marker for circulating tumor cells (CTCs) in various types of cancer, while cluster of differentiation 44 (CD44) is a marker for gastric cancer (GC) stem cells. To evaluate the clinical significance of CD44+ CTCs in patients with GC in the present study, the number of EpCAM+CD44+ and EpCAM+CD44− cells were detected in the peripheral blood of 26 GC patients and 12 healthy volunteers using flow cytometry. The number (mean ± standard deviation) of EpCAM+CD44+ cells in the GC patients and healthy volunteers was 69.9±52.0 and 0.91±2.10, respectively (P=0.0001), while that of EpCAM+CD44− cells was 59.1±88.0 and 9.83±9.91, respectively (P=0.0313). The sensitivity and specificity of EpCAM+CD44+ cell detection for the identification of GC patients were 92.3 and 100%, respectively. By contrast, the values of EpCAM+CD44− cell detection were 76.9 and 83.3%, respectively. The number of EpCAM+CD44+ cells in the GC patients was correlated with the disease stage (P=0.0423), the depth of the tumor (P=0.0314) and venous invasion (P=0.0184) in the resected tumor specimens, while the number of EpCAM+CD44− cells did not correlate with any clinicopathological factors. The number of EpCAM+CD44+ cells significantly decreased following surgical resection of the tumor or induction of systemic chemotherapy. Additionally, atypical cells with a high nuclear to cytoplasmic ratio were morphologically detected in the sorted EpCAM+CD44+ cells. These results suggested that CD44+ CTCs, but not CD44− CTCs, reflect the malignant status of the primary tumor in patients with GC, providing a candidate biomarker for diagnosis and treatment response.

658 Background: Early studies raised concerns over whether preoperative treatment led to postoperative complications or even death. In contrast, recent studies have reported that initial treatment (IT) prior to resection of pancreatic ductal adenocarcinoma (PDAC) is safe, with no significant increase in overall morbidity or mortality, despite evidence for more advanced disease. In this study, we analyzed the clinical impact of chemotherapy or chemoradiotherapy as IT, focusing on treatment duration, on morbidity and mortality in patients with resected PDAC. Methods: We enrolled 509 consecutive patients, with 417 in the upfront surgery group and 92 in the IT group. The IT group was subdivided into 72 patients treated for < 8 months and 20 treated ≥8 months. We compared rates of postoperative Clavien–Dindo grade ≥III complications between the groups. Multivariate logistic regression analysis was used to find independent predictors of complications. Results: The upfront surgery and IT groups did not significantly differ in overall postsurgical complications. The rate of postoperative pancreatic fistula was significantly less in the IT group. Rates of other complications did not significantly differ, except for severe infection and delayed gastric emptying. Initiation of adjuvant chemotherapy was later in the IT group than in the upfront surgery group (43.2 vs 57.8 days, P < 0.001). In contrast, rates of overall complications significantly differed between the < 8 months and ≥8 months IT groups, although their background clinical factors did not differ. In multivariate analysis, operative procedure (distal pancreatectomy and distal pancreatectomy with celiac axis resection) (odds ratio [OR] 6.950, P = 0.0416) and IT ≥8 months (OR: 4.508, 95%, P = 0.0156) were independent predictive factors for postoperative complications. Conclusions: The incidence of postoperative complication was similar between the upfront surgery group and the IT group, however, it was significantly higher in the ≥8 months IT group in patients who underwent PDAC resection.

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.

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.

Highlights • A case showed perforation of gastric intramural metastasis from esophageal cancer. • Rapid tumor regression by preoperative chemotherapy may cause the perforation. • Minimally invasive curative resection was achieved by a two-step operation., Introduction Perforation of intramural metastasis to the stomach (IMS) from esophageal cancer during chemotherapy has not been reported. Presentation of case A 68-year-old male consulted our hospital due to appetite loss. He was diagnosed with advanced esophageal squamous cell carcinoma in the lower thoracic esophagus along with a large IMS in the upper stomach. The patient received preoperative chemotherapy of docetaxel, cisplatin, and 5-fluorouracil (DCF). During the second cycle of DCF, he had upper abdominal pain and was diagnosed with gastric perforation. Omental implantation repair for the perforation, peritoneal drainage, tube-gastrostomy, and tube-jejunostomy were performed. At 24 days after emergency surgery, he underwent thoracoscopic radical esophagectomy with total gastrectomy and reconstruction with colonic interposition. Pathological findings in the esophagus demonstrated complete replacement of the tumor by fibrosis. The gastric tumor was replaced by scar tissue with multinucleated giant cells along with a small amount of viable cancer cells. The patient was alive and healthy at 14 months after the radical operation, without tumor recurrence. Discussion The gastric perforation occurred due to rapid regression of the IMS which had involved the whole gastric wall before chemotherapy. Close monitoring to detect rapid tumor shrinkage during chemotherapy in patients with IMS may be warranted. A two-step operation was proposed to achieve safe curative treatment in patients with perforation of IMS during preoperative chemotherapy. Conclusion We describe the first reported case of a patient with esophageal squamous cell carcinoma who showed perforation of IMS during preoperative chemotherapy.

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. 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. 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

Background Mediastinoscopic esophagectomy is a minimally invasive surgery for thoracic esophageal cancer avoiding one-lung ventilation or transthoracic procedure. Methods We performed for the first time in the literature, salvage esophagectomy with combination of mediastinoscopic cervical approach and laparoscopic/mediastinoscopic transhiatal approach for recurrent thoracic esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT) in a patient who had previously undergone a left pneumonectomy for primary lung cancer. Results A 66-year-old man was diagnosed as local recurrence of lower ESCC (cT3N0M0 cStage II) at 9 years after dCRT. His medical history included left-sided pneumonectomy for lung adenocarcinoma 9 years previously. Then the patient was diagnosed as lower thoracic ESCC (cT3N1M0 cStage III) at 2 months after pneumonectomy. He received dCRT consisting of CDDP/5-FU infusion and irradiation (60 Gy) and achieved complete response. No evidence of tumor recurrence was observed at endoscopic surveillance up until 6 years after dCRT. For this present surgery, a cervical wound was made and the intramediastinal procedure was performed under pneumomediastinum. After mobilization of upper/middle thoracic esophagus, the esophageal wall was safely separated from the remaining part and the stump of the left main bronchus. Dense adhesions between the esophagus and fibrotic tissue at the site of previous left mediastinal pleural resection was divided using a sealing device. In the abdomen, 5 ports were inserted to perform abdominal and transhiatal procedures under CO2 insufflation. After mobilization of the stomach, fibrotic scar tissue around the lower esophagus was divided using a sealing device and the peri-esophageal space dissected from cervical and transhiatal approach were connected to completely mobilize the thoracic esophagus. The esophagectomy was uneventfully carried out followed by reconstruction with gastric conduit via retrosternal rout. Pathological findings demonstrated a moderately differentiated ESCC (pT3-AD pN1 M0 pStage III), indicating that R0 resection was successfully performed. The patient has been closely observed as an outpatient and was alive and healthy at 3 months after the operation without tumor recurrence. Conclusion Mediastinoscopic esophagectomy is a safe and curative treatment strategy for esophageal cancer patients who had a previous pneumonectomy, even in salvage surgery for recurrent cancer after dCRT. Disclosure All authors have declared no conflicts of interest.

219 Background: Recently, several nutritional and inflammatory markers have been reported to be involved in cancer progression. The aim of this study is to evaluate whether nutritional and inflammatory biomarkers such as the modified Glasgow prognostic score (mGPS), the neutrophil‐to-lymphocyte ratio (NLR), the platelet‐to-lymphocyte ratio, the systemic-immune-inflammation index (SIII), controlling nutritional status (CONUT) score, prognostic nutritional index, and the lymphocyte‐to-monocyte ratio (LMR) could predict the prognosis in patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) who underwent chemotherapy as first-line therapy, using disease-specific survival as the primary outcome. Methods: All UR-PDAC patients were retrospectively evaluated between January 2011 and May 2017 at Toyama University Hospital. Baseline clinicopathological characteristics and pre-treatment laboratory values such as absolute neutrophil, lymphocyte and platelet counts, C-reactive protein, albumin and CA19-9 levels, were collected. Results: A total of 184 patients were diagnosed as UR-PDAC. Among them, 151 patients who underwent chemotherapy were enrolled in this study. There were significant relationships between survival and elevated mGPS, elevated NLR, elevated SIII, decreased LMR, decreased serum cholinesterase level, and low CONUT score (p < 0.001, p < 0.001, p = 0.001, p < 0.001, p = 0.026 and p < 0.001, respectively, by log-rank test). The median survival time of patients with metastatic lesions was significantly shorter than that of patients with unresectable locally advanced PDAC (9.0 vs 15.5 months, respectively; p = 0.033). There was no significant difference in survival in pre-treatment CA19-9 level and tumor location. Multivariate analysis using Cox regression model revealed that NLR and CONUT score were independent prognostic factors. Conclusions: Pre-treatment NLR and CONUT score may predict clinical outcome in patients with UR-PDAC undergoing chemotherapy as first-line therapy.

The purpose of this study was to determine reliable predictors of outcome of biliary atresia (BA) after Kasai's operation.Fifty-four BA cases that underwent Kasai's operation at our institution over two decades were reviewed. The cases were divided into two groups: Group I: cases that required liver transplantation or died (n=30) and Group II: cases alive with the native liver. Serum levels of total bilirubin (TB), direct bilirubin (DB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) were measured sequentially after surgery. For cut-off determination, receiver operating characteristic (ROC) analysis was employed.Serum TB, DB, AST, and ALT in Group I were significantly higher than those in Group II at 1, 2, and 3 months after surgery (p.05). The most reliable cut-offs determined by ROC analysis were DB of 0.7 mg/dl at 2 months (sensitivity; 93%, specificity; 75%) and AST of 94 IU/L at 2 months (sensitivity; 87%, specificity; 71%). The 54 cases were re-divided into three groups according to the cut-off values: group G (good) with DB and ASTcut-offs (n=16; Group I:II=1:15), group M (moderate) with DB or ASTcut-offs (n=9; Group I:II=4:5), and group P (poor) with DB and AST ≥ cut-offs (n=29; Group I:II=25:4). The 15-year survival rate in groups G, M, and P was 94%, 44%, and 22%, respectively (p.001).The combination of serum DB and AST at 2 months after Kasai's operation is a reliable predictor of long-term BA outcome.

Mitotically quiescent cancer stem cells (CSC) are hypothesized to exhibit a more aggressive phenotype involving greater therapeutic resistance and metastasis. The aim of our study was to develop a method for identifying quiescent CSC in esophageal squamous cell carcinoma (ESCC) based on their expression of the p75 neurotrophin receptor (p75NTR) and other proposed CSC markers, such as CD44 and CD90. Double immunostaining of surgical ESCC specimens revealed that the mean Ki-67-labeling index of the p75NTR-positive cells was significantly lower than that of the p75NTR-negative cells. Real-time PCR analysis of sorted fractions of ESCC cell lines (KYSE cells) revealed that stem cell-related genes (Nanog, p63 and Bmi-1) and epithelial-mesenchymal transition (EMT)-related genes (N-cadherin and fibronectin) were expressed at significantly higher levels in the p75NTR-positive fractions than in the CD44-positive or CD90-positive fractions. In addition, the p75NTR-positive fractions exhibited significantly higher colony formation in vitro, significantly enhanced tumor formation in mice, and significantly greater chemoresistance against cisplatin (CDDP) than the CD44‑positive or CD90‑positive fractions. Furthermore, in both the cultured cells and those from the mouse xenograft tumors, the p75NTR‑positive/CD44-negative and p75NTR‑positive/CD90-negative KYSE cell fractions contained significantly higher proportions of mitotically quiescent cells. These results suggest that the mitotically quiescent CSC population in ESCC can be identified and isolated based on their p75NTR expression, providing researchers with a novel diagnostic and therapeutic target.

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.

No traditional Japanese and Chinese herbal preparations have been shown to be effective antitumor agents, and a Japanese herbal therapy (Kampo medicine) for cancer that causes fewer adverse drug reactions than orthodox pharmaceuticals is desired. Our present study demonstrated that a Kampo preparation Daikenchuto (DKT) exerts an antitumor effect against various cancer cells. We also discovered an antitumor factor in Japanese Zanthoxylum peel, which is an ingredient of DKT. Breast, esophageal, gastric, and colon cancer cell lines were individually incubated with DKT for 1-72 h, followed by assessment of tumor growth inhibition by MTT assay. The cancer cells were also analyzed for apoptotic changes after DKT treatment. Nude mice were used to establish a model of gastric cancer tumor growth and peritoneal disseminated metastasis, in which the number of peritoneal disseminations was evaluated after oral administration of DKT for 4 weeks. In addition, the antitumor effects of the individual DKT ingredients (viz., ginseng, Japanese Zanthoxylum peel, and processed ginger) and other Kampo preparations were also analyzed. The antitumor effect of DKT was demonstrated in gastric, breast, esophageal, and colon cancer cells. DKT treatment induced apoptosis in these cells. Oral administration of DKT had a tendency to reduce the growth and significantly reduced the peritoneal dissemination of gastric cancer in the nude mouse model compared with control. DKT exhibited a higher antitumor effect than other Kampo preparations. Furthermore, Japanese Zanthoxylum peel, an ingredient of DKT, showed a particularly potent antitumor effect. Our study indicated that DKT is useful as a Kampo preparation for cancer therapy. We also showed that Japanese Zanthoxylum peel, an ingredient of DKT, contains an antitumor factor.

Pancreatic carcinoma (PC) is among the most lethal types of carcinomas worldwide. We aimed to establish well-defined PC cell lines in order to determine their resistance to chemotherapy.Cells cultured from the tumors of two patients were analyzed for xenograft formation, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and TP53 mutations, chemosensitivity, and mRNAs encoding rate-limiting enzymes that metabolize anticancer drugs.The TYPK-1 and TYPK-2 cell lines were established from the lymph node of a locally advanced PC and from the ascites of a multi-metastatic and multi-chemoresistant PC, respectively. Each cell line generated tumors in nude mice. KRAS and TP53 mutations were detected in TYPK-1 but not TYPK-2 cells. TYPK-1 cells were resistant to gemcitabine, and TYPK-2 cells were resistant to oxaliplatin. The gemcitabine sensitivity of each cell line correlated with the expression of mRNAs encoding DCK and SLCAC29A1.TYPK-1 and TYPK-2 cells may contribute to investigations of resistance to anticancer drugs.

Small cell carcinoma of the esophagus (SCCE) is a rare but very aggressive disease with poor prognosis. The aim of the present study was to identify a molecular signature to predict postoperative outcomes in patients with SCCE.Expression of microRNA was detected in surgically-removed SCCE tumors using microarrays. A SCCE cell line (TYUC-1) was established to investigate the biological role of differentially expressed microRNAs.Hierarchical clustering of microRNA expression revealed two discrete clusters that were identical to the cases with rapid tumor relapse (n=3; median survival, 5.1 months) and the cases with long-term survival (n=3; median observation, 144.7 months), respectively. Eight microRNAs (miR-4323, miR-625, miR-3619-3p, miR-4419b, miR-1249, miR-4648, miR-4664-3p and miR-1203) showed significant correlation with tumor relapse (p0.01). Migration of TYUC-1 was significantly inhibited by down-regulation of miR-625.The expression profiles of microRNAs in tumors may represent a novel predictor for postoperative outcomes in patients with SCCE.

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).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.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.The prolonged fasting with PN is responsible for severe hepatocellular necrosis with fibrosis and consequent lethal portal hypertension.