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Background: Anastomotic leakage following colorectal surgery remains a significant complication despite advances in surgical techniques. Recent findings on serosal injury repair in coelomic cavities, such as the peritoneum, challenge the current understanding of the cellular origins and mechanisms underlying intestinal anastomotic healing. Understanding the contribution of each layer of the intestinal wall during anastomotic healing is needed to find new therapeutic strategies to prevent anastomotic leakage. The aim of this experimental study was to investigate the role of the serosal layer of the intestinal wall in anastomotic healing., Materials and Methods: Comprehensive histologic analysis of human and murine anastomoses was performed to elucidate histologic changes in the different intestinal layers during anastomotic healing. In vivo staining of the extracellular matrix (ECM) in the serosal layer was performed using a fluorophore-conjugated N-hydroxysuccinimide-ester before anastomosis surgery in a murine model., Results: Histological examination of both human and murine anastomoses revealed that closure of the serosal layer occurred first during the healing process. In vivo serosal ECM staining demonstrated that a significant portion of the newly formed ECM within the anastomosis was indeed deposited onto the serosal layer. Furthermore, mesenchymal cells within the anastomotic scar were positive for mesothelial cell markers, podoplanin and Wilms tumour protein., Conclusions: In this experimental study, the results suggest that serosal scar formation is an important mechanism for anastomotic integrity in intestinal anastomoses. Mesothelial cells may significantly contribute to scar formation during anastomotic healing through epithelial-to-mesenchymal transition, potentially suggesting a novel therapeutic target to prevent anastomotic leakage by enhancing physiological healing processes., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background: We aimed to clarify the operative feasibility and oncological efficacy of a laparoscopic gastrectomy (LG) for pT4a gastric cancer through comparison with open gastrectomy (OG). Materials and Methods: We compared surgical and oncological outcomes in 178 patients with pT4a gastric cancer who underwent LG or OG between 2002 and 2016; the background was adjusted using propensity score matching. Results: After score matching, 45 patients were included in each group. The LG group had a significantly longer operation time (277 minutes versus 175 minutes, P  < .001) and lower estimated blood loss (50 mL versus 280 mL, P  < .001). The total number of dissected lymph nodes did not differ between groups (46 versus 38, P  = .119); however, the number of dissected suprapancreatic lymph nodes was significantly higher in the LG group (11 versus 7.5, P  = .011). Postoperative morbidity rates did not differ between groups. Postoperative hospitalization was significantly shorter in the LG group (7 days versus 13 days, P  < .01), whereas overall survival, disease-free survival, and cancer recurrence rates and patterns were similar between groups. Conclusions: LG for pT4a gastric cancer has feasible and acceptable outcomes compared with OG.

Myometrial invasion and its extent have been directly associated with the risk of relapse as well as the overall survival of endometrial cancer patients. Tumor free distance from the serosal surface of the uterine wall has been investigated the last years by several studies, however, to date, its importance remains unknown. The present meta-analysis is based on a systematic search of the Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases and has been designed according to the PRISMA guidelines. Nine studies were included in the present systematic review that recruited pathology slides from 1,598 endometrial cancer patients and their meta-analysis indicated that TFD was significantly associated with the progression free survival of patients with endometrial cancer (OR 0.36, 95% CI 0.20, 0.65). The disease specific survival was not affected by the TFD (OR 0.30, 95% CI 0.09, 1.01). Sensitivity analyses revealed, however, that both the progression free and overall survival rates were associated with TFD. Significant discrepancies were observed in terms of histological subtypes and stage of the disease among included patients, hence, the actual importance of TFD in specific subgroups remains unknown. Future studies must evaluate the importance of this pathology marker particularly in patients with endometrioid subtypes and early-stage disease, as it is believed that in this group its importance will be more predictive as it will not be skewed by the presence of more important factors such as more aggressive histology and advanced stage disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Indications for adjuvant chemotherapy for advanced gastric cancer are determined based on the pathological diagnosis. However, macroscopic diagnoses have been reported as predictors of peritoneal recurrence and survival. This study investigated the predictability of peritoneal recurrence and survival based on macroscopically (sT) and pathologically (pT) diagnosed serosal invasion to identify more sensitive predictors of peritoneal recurrence., Methods: This study included 396 patients who underwent R0 resection without adjuvant chemotherapy with S-1 in the JCOG0110 study. Tumor depth limited to the subserosa (SS) was defined as serosal invasion negative (T-), while tumors with serosal invasion (SE, SI) were defined as serosal invasion positive (T+). The predictability of peritoneal recurrence based on sT and pT was evaluated using the Fine and Gray model. Cox regression analyses were performed for overall survival (OS) and relapse-free survival (RFS) with sT or pT as covariates., Findings: A total of 150 patients (37.9%) were sT+ and 82 (26.3%) were pT+. Sixty-two patients (15.7%) were sT+/pT+, 88 (22.2%) were sT+/pT-, 20 (5.1%) were sT-/pT+, and 226 (57.1%) were sT-/pT-. Both sT and pT were found to be independent predictors of peritoneal recurrence, OS, and RFS. The 5-year RFS rates of sT+/pT+, sT+/pT-, sT-/pT+, and sT-/pT-patients were 45.2%, 63.6%, 55.0%, and 81.8%, respectively., Conclusion: Intraoperatively diagnosed macroscopic serosal invasion showed a similar predictive value for peritoneal recurrence as pathologically diagnosed serosal invasion. The establishment of a novel staging system incorporating macroscopic serosal invasion is recommended., Competing Interests: Declaration of competing interest MT reports lecture fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Yakult Honsha, Takeda Pharmaceutical, Eli Lilly Japan KK, Pfizer Pharmaceutical, Daiichi Sankyo, Johnson and Johnson, Medtronic Japan, Intuitive Japan, Olympus outside the submitted work. JM reports the funding from National Cancer Center, Japan and the Ministry of Labour and Welfare, Japan for the present study, and personal fees from Chugai Pharmaceutical, outside the submitted work. TS reports personal fees from Taiho Pharma, Chugai Pharma, Ono Pharma, Eli Lilly, outside the submitted work. TY reports grants from Eli Lilly japan, personal fees from MSD, BMS, Ono, Taiho, Lilly, Chugai, Pfizer, Nihon Kayaku, Terumo, Otsuka, Myarisan, EA pharma, Astra-Zeneca, Covidien, Johnson and Johnson outside the submitted work. NB received a research grant from Ono and Takeda and honorarium from Taiho, Ono, Bristol-Myers Squibb outside the submitted work. MS reports lecture fees from Taiho Pharmaceutical and Eli Lilly, travel support from Eli Lilly outside the submitted work, and has served as Chairman of the board of directors of the Japan Gastric Cancer Association and member of the Guideline committee of the Japan Gastric cancer Association during the study period. All the other authors declare no competing interests. Red lines represent serosal invasion positive and blue lines represent serosal invasion negative. The C-index was calculated using the Fine and Gray model., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background/aim: In the Japanese Classification of Gastric Carcinoma, T4a gastric cancer is defined as tumor invasion contiguous to the serosa or penetrating the serosa with exposure to the peritoneal cavity. The aim of this study was to assess the impact of T4a subclassification of gastric cancer on survival., Patients and Methods: A total of 326 patients with T4a cancer who had undergone gastrectomy were enrolled. The T4a tumors were classified into two groups: serosa-contiguous or serosa-exposed., Results: The serosa-exposed group had a significantly worse prognosis, and multivariate analysis identified the T4a subclass as an independent prognostic factor. Analysis of the risk factors for recurrence identified the T4a subclass as a significant risk factor for peritoneal recurrence in patients undergoing curative gastrectomy., Conclusion: The serosa-contiguous and serosa-exposed subgroups of T4a gastric cancer showed different biological behaviors. These groups may need to be treated as separate., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Liver transplantation is the most effective treatment for end-stage cirrhosis. However, due to serious donor shortages, new treatments to replace liver transplantation are sorely needed. Recent studies have focused on novel therapeutic methods using hepatocytes and induced pluripotent stem cells, we try hard to develop methods for transplanting these cells to the liver surface. In the present study, we evaluated several methods for their efficiency in the detachment of serous membrane covering the liver surface for transplantation to the liver surface. The liver surface of dipeptidyl peptidase IV (DPPIV)-deficient rats in a cirrhosis model was detached by various methods, and then fetal livers from DPPIV-positive rats were transplanted. We found that the engraftment rate and area as well as the liver function were improved in rats undergoing transplantation following serous membrane detachment with an ultrasonic homogenizer, which mimics the Cavitron Ultrasonic Surgical Aspirator ® (CUSA), compared with no detachment. Furthermore, the bleeding amount was lower with the ultrasonic homogenizer method than with the needle and electric scalpel methods. These findings provide evidence that transplantation to the liver surface with serous membrane detachment using CUSA might contribute to the development of new treatments for cirrhosis using cells or tissues.

Introduction: Studies on eosinophilic gastroenteritis have identified broad spectrums of disease. We aimed to characterize subtypes of disease and ascertain outcomes of each group., Methods: This is a retrospective cohort study from a large tertiary medical center including 35 patients diagnosed with eosinophilic gastroenteritis from 2007 to 2018. We defined 2 groups of patients based on clinical and laboratory findings at presentation. Severe disease was defined as having weight loss at time of presentation, hypoalbuminemia at presentation, serosal disease involvement, or anemia at diagnosis. The remaining patients were labeled as mild disease group. We collected and compared demographic data, clinical features, laboratory findings, an allergy history, and disease course of both cohorts., Results: Among 35 patients with eosinophilic gastroenteritis, 18 patients met the criteria for severe disease and 17 patients for mild disease. Of the patients with severe eosinophilic gastroenteritis, 6 (38%) had remission without chronic symptoms, whereas 10 (63%) had chronic symptoms requiring chronic medical therapy. Of the mild group, 12 patients (80%) had disease remission without chronic medications. An allergy history was more common in the severe disease group (83%) compared with the mild disease group (45%). Prednisone and open capsule budesonide were the most commonly used treatment medications in both groups., Discussion: Patients with eosinophilic gastroenteritis may be characterized into 2 forms. Patients with weight loss at time of presentation, hypoalbuminemia at presentation, serosal disease involvement, or anemia at diagnosis were associated with a chronic disease course requiring chronic medications., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Advanced gastric cancer sometimes causes macroscopic serosal change (MSC) due to direct invasion or inflammation. However, the prognostic significance of MSC remains unclear., Methods: A total of 1410 patients who had been diagnosed with deeper-than-pathological-T2 gastric cancer and undergone R0 gastrectomy with lymph node dissection at the National Cancer Center Hospital during January 2000 and December 2012 were restrospectively reviewed., Results: MSC was not found in 108 of the 506 patients with pathological T4a (21.3%), whereas it was detected in 250 of the 904 patients with pathological T2-T3 (27.7%). The sensitivity, specificity and accuracy for diagnosing pathological serosa exposed (SE) by MSC were 78.7, 72.3 and 74.6%, respectively. The MSC-positive cases had a worse 5-year overall survival (OS) than the MSC-negative cases in pT3 (72.9% vs. 84.3%, p = 0.001), pT4a (56.2% vs. 73.4%, p = 0.001), pStageIIB (76.0% vs. 88.4%, p = 0.005), pStageIIIA (63.4% vs. 75.6%, p = 0.019), pStageIIIB (53.6% vs. 69.2%, p = 0.029) and pStage IIIC (27.6% vs. 50.0%, p = 0.062). A multivariate analysis showed that MSC was a significant independent predictor for the OS (hazard ratio [HR]: 1.587, 95%CI 1.209-2.083, p = 0.001) along with the tumor depth (HR: 7.742, 95%CI: 2.935-20.421, p < 0.001), nodal status (HR:5.783, 95% CI 3.985-8.391, p < 0.001) and age (HR:2.382, 95%CI: 1.918-2.957, p < 0.001). Peritoneal recurrence rates were higher in the MSC-positive cases than in the MSC-negative cases at each pT stage., Conclusions: In this study, the MSC was one of the independent prognostic factors in patients with resectable locally advanced gastric cancer., (© 2021. The Author(s).)

Background: To develop and validate multivariate models integrating endoscopic biopsy, tumor markers, and CT findings based on late arterial phase (LAP) to predict serosal invasion in gastric cancer (GC)., Methods: The preoperative differentiation degree, tumor markers, CT morphological characteristics, and CT value-related and texture parameters of 154 patients with GC were analyzed retrospectively. Multivariate models based on regression analysis and machine learning algorithms were performed to improve the diagnostic efficacy., Results: The differentiation degree, carbohydrate antigen (CA) 199, CA724, CA242, and multiple CT findings based on LAP differed significantly between T1-3 and T4 GCs in the primary cohort (all P < 0.05). Multivariate models based on regression analysis and random forest achieved AUCs of 0.849 and 0.865 in the primary cohort, respectively., Conclusion: We developed and validated multivariate models integrating endoscopic biopsy, tumor markers, CT morphological characteristics, and CT value-related and texture parameters to predict serosal invasion in GCs and achieved favorable performance., (© 2021. The Author(s).)

Background: Whether laparoscopic gastrectomy is suitable for patients with serosa-invasive gastric cancer remains controversial. We performed this study to evaluate the short- and long-term outcomes after laparoscopic gastrectomy compared with after open gastrectomy., Methods: We retrospectively analyzed 906 consecutive patients with serosa-invasive gastric cancer from January 2004 to December 2014 in our center, who underwent laparoscopic gastrectomy or open gastrectomy with D2 lymphadenectomy. After propensity score matching, 334 patients were included in each group. Surgical conditions and short- and long-term results were compared., Results: Laparoscopic gastrectomy was associated with less estimated blood loss and longer operation time, while the number of harvested lymph nodes was not significantly different between laparoscopic gastrectomy and open gastrectomy. Patients who underwent laparoscopic gastrectomy had an earlier time to first flatus, first diet, and first ambulation and were discharged earlier. Overall and pulmonary postoperative complication rates were lower in the laparoscopic gastrectomy group. With a minimum follow-up of 60 months, the 5-year overall survival was 39.3% in the laparoscopic gastrectomy group and 34.3% in the open gastrectomy group, and the 5-year disease-free survival was 36.4% in the laparoscopic gastrectomy group and 32.7% in the open gastrectomy group. Laparoscopic gastrectomy was associated with better 5-year overall survival in patients aged ≥60 years. The overall recurrence rates and patterns were not significantly different between the 2 groups., Conclusion: Laparoscopic gastrectomy is an alternative surgical approach for patients with serosa-invasive gastric cancer in terms of short-term outcomes and long-term survival, and it might be more advantageous for certain populations., (Copyright © 2020. Published by Elsevier Inc.)

Diffuse malignant mesothelioma (MM) is an incurable tumour of the serosal membranes, which is often caused by exposure to asbestos and commonly diagnosed at advanced stage. Malignant mesothelioma in situ (MMIS) is now included as diagnostic category by the World Health Organization (WHO). However, our international survey of 34 pulmonary pathologists with an interest in MM diagnosis highlights inconsistency regarding how the diagnosis is being made by experts, despite published guidelines. Whilst the WHO restricts the diagnosis to surgical samples, the very concept has implication for cytological diagnosis, which is already regarded as controversial in itself by some. MMIS is currently only applicable as precursor to MM with an epithelioid component, and raises the possibility for different molecular pathways for different histological MM subtypes. The clinical implications of MMIS at this stage are uncertain, but aggressive therapies are being initiated in some instances. Based on the results of the survey we here present a critical appraisal of the concept, its clinical and conceptual implications and provide practice suggestions for diagnosis. A low threshold for ancillary testing is suggested. The designations of 'malignant mesothelioma, cannot exclude MMIS' or 'atypical mesothelial proliferation with molecular indicators of malignancy, so-called MMIS' could be used on cytology samples, adding 'no evidence of invasion in sample provided' for surgical samples. Clinical and radiological correlation are integral to diagnosis and best done at multidisciplinary meetings. Finally, collaborative studies are required to improve our understanding of MMIS., (Copyright © 2021. Published by Elsevier B.V.)

We evaluated the clinicopathologic features of 6 adenomatoid tumors of the uterus with unusual features. All the tumors differed grossly from the usual adenomatoid tumor, typically being ill-defined and occupying >50% of the myometrium, essentially replacing it in 4. The neoplasm extended to the endometrium in 2 cases and in one of these it formed an intracavitary mass; in both the tumor was first diagnosed in a curettage. In the other 4 cases, the adenomatoid tumor was discovered in a hysterectomy specimen performed for irregular vaginal bleeding (3 patients), and the finding of a pelvic mass on a computed tomography scan in a patient with right lower quadrant pain. The tumors extended to the uterine serosa in the form of small grape-like vesicles or cysts in 4 cases. All tumors contained the typical small often irregularly shaped spaces but also had prominent cysts. When cysts involved the serosa, the microscopic appearance mimicked that of peritoneal inclusion cysts. In one case with serosal involvement, a prominent papillary pattern was also present. The cysts were typically closely packed with minimal intervening stroma but were occasionally separated by conspicuous smooth muscle bundles. The stroma in one case was extensively hyalinized. Two tumors were focally infarcted. A striking, but minor, solid growth in which the tumor cells were arranged in tightly packed nests or interanastomosing cords and trabeculae was seen in 2 tumors. The unusual gross and microscopic features of these tumors can cause significant diagnostic difficulty and bring into the differential diagnosis entities that are usually not realistic considerations. The presentation of 2 tumors in a curettage specimen represents an unusual clinical aspect., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Airway submucosal gland serous cells are important sites of fluid secretion in conducting airways. Serous cells also express the cystic fibrosis (CF) transmembrane conductance regulator (CFTR). Protease-activated receptor 2 (PAR-2) is a G protein-coupled receptor that activates secretion from intact airway glands. We tested if and how human nasal serous cells secrete fluid in response to PAR-2 stimulation using Ca 2+ imaging and simultaneous differential interference contrast imaging to track isosmotic cell shrinking and swelling reflecting activation of solute efflux and influx pathways, respectively. During stimulation of PAR-2, serous cells exhibited dose-dependent increases in intracellular Ca 2+ . At stimulation levels >EC 50 for Ca 2+ , serous cells simultaneously shrank ∼20% over ∼90 s due to KCl efflux reflecting Ca 2+ -activated Cl - channel (CaCC, likely TMEM16A)-dependent secretion. At lower levels of PAR-2 stimulation (50 for Ca 2+ ), shrinkage was not evident due to failure to activate CaCC. Low levels of cAMP-elevating VIP receptor (VIPR) stimulation, also insufficient to activate secretion alone, synergized with low-level PAR-2 stimulation to elicit fluid secretion dependent on both cAMP and Ca 2+ to activate CFTR and K + channels, respectively. Polarized cultures of primary serous cells also exhibited synergistic fluid secretion. Pre-exposure to Pseudomonas aeruginosa conditioned media inhibited PAR-2 activation by proteases but not peptide agonists in primary nasal serous cells, Calu-3 bronchial cells, and primary nasal ciliated cells. Disruption of synergistic CFTR-dependent PAR-2/VIPR secretion may contribute to reduced airway surface liquid in CF. Further disruption of the CFTR-independent component of PAR-2-activated secretion by P. aeruginosa may also be important to CF pathophysiology.

Accurate prediction of peritoneal metastasis for gastric cancer (GC) with serosal invasion is crucial in clinic. The presence of collagen in the tumour microenvironment affects the metastasis of cancer cells. Herein, we propose a collagen signature, which is composed of multiple collagen features in the tumour microenvironment of the serosa derived from multiphoton imaging, to describe the extent of collagen alterations. We find that a high collagen signature is significantly associated with a high risk of peritoneal metastasis (P < 0.001). A competing-risk nomogram including the collagen signature, tumour size, tumour differentiation status and lymph node metastasis is constructed. The nomogram demonstrates satisfactory discrimination and calibration. Thus, the collagen signature in the tumour microenvironment of the gastric serosa is associated with peritoneal metastasis in GC with serosal invasion, and the nomogram can be conveniently used to individually predict the risk of peritoneal metastasis in GC with serosal invasion after radical surgery.

Low grade appendiceal mucinous neoplasm (LAMN) is the primary source of pseudomyxoma peritonei (PMP). PMP may develop after seemingly complete resection of primary tumor by appendectomy, which is unpredictable due to lack of reliable prognostic indicators. We retrospectively reviewed 154 surgically resected LAMNs to explore if any of the macroscopic and microscopic characteristics may be associated with increasing risk of PMP development. Our major findings include: (1) As compared to those without PMP, the cases that developed PMP were more frequent to have (a) smaller luminal diameter (<1 cm) and thicker wall, separate mucin aggregations, and microscopic perforation/rupture, all suggestive of luminal mucin leakage; (b) microscopic acellular mucin presenting on serosal surface and not being confined to mucosa; and (c) neoplastic epithelium dissecting outward beyond mucosa, however, with similar frequency of neoplastic cells being present in muscularis propria. (2) Involvement of neoplastic cells or/and acellular mucin at surgical margin did not necessarily lead to tumor recurrence or subsequent PMP, and clear margin did not absolutely prevent PMP development. (3) Coexisting diverticulum, resulted from neoplastic or non-neoplastic mucosa being herniated through muscle-lacking vascular hiatus of appendiceal wall, was seen in a quarter of LAMN cases, regardless of PMP. The diverticular portion of tumor involvement was often the weakest point where rupture occurred. In conclusion, proper evaluation of surgical specimens with search for mucin and neoplastic cells on serosa and for microscopic perforation, which are of prognostic significance, should be emphasized., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The bare area was reportedly formed by direct adhesion between the liver and diaphragm, meaning that the bare area lacked serosal components. This study aimed to analyze the structure of the bare area by an integrated study of surgical and laparoscopic images and pathological studies and describe surgical procedures focusing on the multilayered structure., Methods: Several surgical specimens of hepatectomy were analyzed histologically to evaluate the macroscopic structure of the bare area. Laparoscopic images and cadaver anatomy of the bare area were also examined., Results: The multilayered structure of the bare area comprised the liver, sub-serosal connective tissue, liver serosa, parietal peritoneum, retroperitoneal connective tissue, epimysium of the diaphragm, and diaphragm, in order from the liver to the diaphragm. The liver serosa and the parietal peritoneum fused with each other. This multilayered structure of the bare area is observed almost constantly. There are two layers in the dissection of the bare area in surgical procedures, an outer layer of the fused peritoneum (near the diaphragm) and an inner layer of the fused peritoneum (near the liver). Laparoscopic images enabled us to recognize the multilayered structure of the bare area., Conclusions: Histopathological findings showed the bare area to be a multilayered structure. In cases where tumors are located underneath the bare area, it could be important to dissect the bare area, with careful attention to its multilayered structure. Surgical dissection of the bare area in the outer layer of the fused peritoneum could allow a sufficient safety margin.

The peritoneal surface is the most frequent site of metastasis disease in patients with gastric cancer. Even after curative surgery and adjuvant chemotherapy, peritoneal recurrences often develop. Exosomes play pivotal roles in tumor metastasis via the transfer of microRNAs (miRNAs). In the present study, exosomes were isolated from peritoneal lavage fluid or ascites in 85 patients with gastric cancer and the relative expression levels of miR‑29s were examined. The expression of miR‑29a‑3p, miR‑29b‑3p and miR‑29c‑3p in peritoneal exosomes were all downregulated in patients with peritoneal metastases (PM) compared to those without PM. In 30 patients who underwent curative gastrectomy with serosa‑involved (T4) gastric cancer, 6 patients exhibited recurrence in the peritoneum within 12 months. The expression levels of miR‑29s at gastrectomy tended to be lower in these 6 patients than in the other 24 patients with significant differences in miR‑29b‑3p (P=0.003). When the patients were divided into two groups based on median levels of miR‑29s, peritoneal recurrence developed more frequently in patients with low expression of miR‑29b‑3p, and lower expression of miR‑29s were related with worse overall survival. miR‑29s are thought to play a suppressive role in the growth of disseminated peritoneal tumor cells. Reduced expression of miR‑29b in peritoneal exosomes is a strong risk factor of developing postoperative peritoneal recurrence.

Background: Peritoneal recurrence is one of the most frequent recurrent diseases in gastric cancer. Although the exposure of cancer cells to the serosal surface is considered a common risk factor for peritoneal recurrence, there are some cases of peritoneal recurrence without infiltration to the serosal surface even after curative surgery. This study sought to clarify the risk factors of peritoneal recurrence in the absence of invasion to the serosal surface., Materials and Methods: Ninety-six patients with gastric cancer who underwent curative surgery were enrolled. In all 96 cases, the depth of tumor invasion was subserosal (T3). The microscopic distance from the tumor invasion front to the serosa (DIFS) was measured using tissue slides by H&E staining and pan-cytokeratin staining. E-cadherin expression was evaluated by immunohistochemical staining., Results: Among the 96 patients, 16 developed peritoneal recurrence after curative surgery. The DIFS of the tumors with peritoneal recurrence (156±220 μm) was significantly shorter (p = 0.011) than that without peritoneal recurrence (360±478 μm). Peritoneal recurrence was significantly correlated with DIFS ≤234 μm (p = 0.023), but not with E-cadherin expression. The prognosis of DIFS ≤234 μm was significantly poorer than that of DIFS >234 μm (log rank, p = 0.007). A multivariate analysis of the patients' five-year overall survival revealed that DIFS ≤234 μm and lymph node metastasis were significantly correlated with survival (p = 0.005, p = 0.032, respectively)., Conclusion: The measurement of the DIFS might be useful for the prediction of peritoneal recurrence in T3-gastric cancer patients after curative surgery., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to elucidate the potential impact of "D2 plus" lymphadenectomy on the long-term survival of distal gastric cancer (GC) patients with clinical serosa invasion. A total of 394 distal GC patients with clinical serosa invasion who underwent at least standard D2 lymphadenectomy were enrolled. Patients were categorized into two groups according to the extent of lymphadenectomy: D2 group and "D2 plus" group. Propensity score matching was used to adjust for the differences in baseline characteristics. In the multivariate analysis for the whole study series, extent of lymphadenectomy was an independent prognostic factor for GC patients (P = 0.011). With the strata analysis, the significant prognostic differences between the two groups were only observed in patients at the IIIa-b or N1-3a stages. After matching, patients in "D2 plus" group still demonstrated a significantly higher 5-year overall survival rate than those in D2 group (55.3% versus 43.9%, P = 0.042). The common therapeutic value index of No. 12b, No. 12p, No. 14v and No. 13 LNs was 4.6, which was close to that of No. 5 LN station. In conclusion, "D2 plus" lymphadenectomy may be associated with improved overall survival in distal GC with clinical serosa invasion.

Background/aim: This study aimed to investigate the relationship between the iodine concentration (IC) of perigastric fat tissue as assessed by dual-energy computed tomography (DECT) and serosal invasion of gastric cancer., Materials and Methods: A total of 41 patients underwent preoperative staging evaluation for gastric cancer using DECT between July 2015 and March 2018. Patients were divided into 2 groups based on pathology results: serosal invasion (stage T4a) and intact serosa (stages T1–T3). Cutoff values, the diagnostic efficacy of IC in the perigastric fat tissue, and the perigastric fat tissue/tumor (P/T) ratio were determined., Results: Among the 41 patients, 22 had stage T4a gastric cancer and 19 patients had gastric cancer with a stage lower than T4a. The mean IC of perigastric fat tissue and the P/T ratio were significantly higher in patients with serosal invasion than in those with intact serosa (P < 0.001). During the arterial phase, the area under the curve (AUC) was 0.915 and 0.854 for the IC of perigastric fat tissue and the P/T ratio, respectively. During the venous phase, the AUC was 0.890 and 0.876 for the IC of perigastric fat tissue and the P/T ratio, respectively., Conclusion: The IC in the perigastric fat tissue seems to be a reliable indicator for serosal invasion of gastric cancer., (This work is licensed under a Creative Commons Attribution 4.0 International License)

Background: According to 8th AJCC/UICC TNM criteria, stage IIB includes pT1N3M0, pT2N2M0, pT3N1M0, and pT4aN0M0, which includes not only early gastric cancer but also locally advanced cancer. There are currently no data about whether there is any additional impact of serosal exposed cancer without nodal metastasis (pT4aN0) on patients' survival outcomes compared with other subgroups in IIB., Methods: Patients who underwent radical gastrectomy for gastric cancer patients were enrolled, including 427 patients in stage IIB; 20 (4.68%), 104 (24.35%), 172 (40.28%), and 131 (30.67%) patients were classified as pT1N3a, pT2N2, pT3N1, and pT4aN0, respectively. Clinicopathological characteristics, recurrence pattern, and survival and recurrence rates were analyzed according to the TNM subgroups., Results: Cancer-specific and relapse-free survival were significantly worse in serosal exposed cancer than in nonserosal exposed cancer in stage IIB (P = 0.019 and P = 0.015). Recurrence rate was highest in the pT4aN0 subgroup (29.0%) in stage IIB, and peritoneal metastasis was the most common pattern. Survival outcomes of the pT4aN0 subgroup were not significantly different from those of the stage IIIA or pT4aN1 subgroups., Conclusions: Patients with serosal exposed cancer without nodal metastasis shows worse cancer specific and disease-free survival with higher incidence of peritoneal metastasis than other subgroups in stage IIB. Further surveillance studies, including staging laparoscopy and active adjuvant therapy, are required in this subgroup of patients.

Membrane anatomy is in broad sense the anatomy of the mesentery and its bed, both of which are consisted of fascia membrane or/and serous membrane. Although the traditional mesentery has the definition of mesentery, people unconsciously identify them according to their "fan-shaped" and "free" characteristics. The "generalized mesentery" we propose refers to the fascia and/or serosa, envelope-like organs and their blood vessels, suspending to the posterior wall of the body, regardless of its shape, free or not. So the main points of the anatomy are as follows.(1) Organs or tissues with their feeding structures are enveloped by the fascia membrane or/and serous membrane, suspending to posterior wall of the body, to form different shapes of the mesentery in broad sense, and most of them are buried in the mesentery bed. (2) Cancer metastasis type V of in the gut moves in the envelop of the mesentery in broad sense.(3) Intraoperative breach of the envelop membrane not only results in intraoperative bleeding, but also cancer cell leakage from the mesentery. (4) The cancer of gut can be divided into cancer in the mesentery, cancer out of the mesentery and cancer at edge of the mesentery based on this anatomy. Radical tumor resection is effective for cancer in the mesentery, which should not be artificially breached into those of cancer out of the mesentery. The essence of neoadjuvant chemoradiation is to push cancer at edge of the mesentery back inside the mesentery.(5) Based on such anatomy, radical gut tumor operations are divided into D2/D3 procedure, without emphasizing the integrity of the mesentery during lymphatic dissection; CME procedure, which emphasizes the integrity of the mesentery but does not strictly define the extent of lymphatic dissection; D2/D3 + CME procedure, which strictly defines the integrity of the mesentery and the extent of lymphatic dissection.(6)For gastrointestinal tumors of the same T stage, shorter mesentery indicates worse prognosis.(7) For gastrointestinal tumors with the same T stage and the same length of mesentery, the more mesentery buried in the mesentery bed, the worse prognosis. (8) The above seven principles are universal in the organs of the body cavity (and even all internal organs).Membrane anatomy, unlike traditional "plane surgery" , is completely different from the "anatomy of the membrane..." described by Japanese scholars, but mainly bases on generalized mesentery and mesentery bed, meanwhile inherent life events can be accurately defined and confirmed.

Background and Aims: According to guidelines, endoscopic resection should only be performed for patients whose early gastric cancer invasion depth is within the mucosa or submucosa of the stomach regardless of lymph node involvement. The accurate prediction of invasion depth based on endoscopic images is crucial for screening patients for endoscopic resection. We constructed a convolutional neural network computer-aided detection (CNN-CAD) system based on endoscopic images to determine invasion depth and screen patients for endoscopic resection., Methods: Endoscopic images of gastric cancer tumors were obtained from the Endoscopy Center of Zhongshan Hospital. An artificial intelligence-based CNN-CAD system was developed through transfer learning leveraging a state-of-the-art pretrained CNN architecture, ResNet50. A total of 790 images served as a development dataset and another 203 images as a test dataset. We used the CNN-CAD system to determine the invasion depth of gastric cancer and evaluated the system's classification accuracy by calculating its sensitivity, specificity, and area under the receiver operating characteristic curve., Results: The area under the receiver operating characteristic curve for the CNN-CAD system was .94 (95% confidence interval [CI], .90-.97). At a threshold value of .5, sensitivity was 76.47%, and specificity 95.56%. Overall accuracy was 89.16%. Positive and negative predictive values were 89.66% and 88.97%, respectively. The CNN-CAD system achieved significantly higher accuracy (by 17.25%; 95% CI, 11.63-22.59) and specificity (by 32.21%; 95% CI, 26.78-37.44) than human endoscopists., Conclusions: We constructed a CNN-CAD system to determine the invasion depth of gastric cancer with high accuracy and specificity. This system distinguished early gastric cancer from deeper submucosal invasion and minimized overestimation of invasion depth, which could reduce unnecessary gastrectomy., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: For patients with gastric cancer intraoperative macroscopic serosal change is not always consistent with pathological T stage. We investigated whether macroscopic serosal change is associated with unfavourable prognosis of patients with gastric cancer., Methods: We reviewed 856 patients with stage T3 gastric cancer who underwent curative gastrectomy in our institution. All patients were classified as serosa negative and serosa positive according to the macroscopic serosal change during the operation. The prognostic difference between two groups was compared and clinicopathologic features were analysed., Results: The percentage of macroscopic serosal change accounted for 55.7% of all patients. Compared with normal serosal surface, the patients with macroscopic serosal change had larger tumour size, more extensive stomach involvement and more advanced stage N. The prognosis of stage T3 with macroscopic serosal change was significantly poorer than that of those with normal serosal surface, especially for those with stages T3N0 and T3N1. Multivariate analysis identified macroscopic serosal change as an independent factor associated with unfavourable prognosis of stage T3 cancer., Conclusion: Although the depth of tumour invasion mainly depends on pathological evaluation after surgery, the prognostic significance of intraoperative macroscopic serosal change should not be ignored for those patients with subserosal invasion.

Background: To date, it has been unclear whether laparoscopic gastrectomy (LG) is suitable for patients with serosa-positive (pT4a) gastric cancer. The purpose of this study was to compare the surgical and long-term oncologic outcomes of LG and open gastrectomy for pT4a gastric cancer., Methods: We prospectively collected data from 987 patients with pathological confirmed pT4a gastric cancer who underwent LG or OG at our institution between June 2009 and May 2015. A 1:1 matched propensity score matching (PSM) analysis was performed to reduce confounding bias. The primary outcome was 5-year overall survival (OS)., Results: After PSM, a well-balanced cohort of 202 pairs patients was analyzed. The LG group showed a longer operation time (261.42 vs. 171.00 min, P = 0.001), less blood loss (185.47 vs. 217.84 ml, P = 0.000), and shorter postoperative hospital stay (7.56 vs. 8.22 days, P = 0.007). The overall complication rate was 14.4% in the LG group and 16.3% in the OG group (P = 0.581). The minor (grade II) and severe (grade ≥ IIIa) complication rates were similar (LG, 6.9% vs. OG, 9.9%, P = 0.282; LG, 7.4% vs. OG, 6.4%, P = 0.695, respectively). The LG and OG groups showed similar survival 5-year OS and 5-year Disease-free survival (DFS) rates (44.6% vs. 42.1%, P = 0.403; 40.1 vs. 37.6%, P = 0.321, respectively). The recurrence rate and pattern did not differ between the two groups during the follow-up stage (P > 0.05)., Conclusions: For patients with pT4a gastric cancer, LG with D2 lymph node dissection can be a safe and feasible procedure in terms of surgical and long-term oncologic outcomes., (Copyright © 2019. Published by Elsevier Ltd.)

A 72-year-old woman presented with a mass on the right axilla. This was thought to be an occult breast cancer case, and the patient was treated with modified radical mastectomy, followed by hormonotherapy. Two years later she presented with incarcerated umbilical hernia. Pathology revealed Sister Mary Joseph's nodule inside the hernia sac. Further evaluation revealed that the primary tumor was papillary serous carcinoma of the peritoneal surface. The patient received adjuvant chemotherapy. Two years later the metastatic tumor was located on the other breast. The disease progressed gradually, and the patient eventually died from disseminated disease. This case is extraordinary in that it first presented with axillary metastasis without abdominal involvement and then later metastasized to the other breast after a long disease-free period.

BACKGROUND The POZ/BTB and AT-hook-containing Zinc finger protein 1 (PATZ1) is a ubiquitously expressed transcription factor belonging to the POZ domain Krüppel-like zinc finger (POK) family. It is involved in the pathogenesis of a growing list of human diseases, including cancer. The effect of PATZ1 on serous ovarian carcinoma (SOC) remains unclear. This study initially explored the clinical significance of PATZ1 in patients with SOC, the relationship between its expression and the prognosis of SOC patients, and its role in tumor proliferation and invasion. MATERIAL AND METHODS Immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR) were performed to characterize the expression of PATZ1 in SOC tissues. The relationship between PATZ1 expression and the clinicopathological features of patients with SOC was analyzed by chi-square test. Kaplan-Meier method and Cox regression analyses were utilized to evaluate the prognosis of SOC. PATZ1-constructed transfection-mediated overexpression was conducted. The CCK-8 assay was performed to examine the proliferation, while Transwell assay was used to detect the invasive capability. RESULTS The results of IHC and qPCR analyses showed that the expression of PATZ1 in cancerous tissue was significantly lower than that in non-cancerous tissues. Meanwhile, PATZ1 expression was significantly associated with tumor differentiation and LN metastasis. Survival analysis showed that PATZ1 expression was one of the independent prognosis factors for overall survival of SOC patients. In addition, overexpression of PATZ1 inhibited the proliferation and invasion of OVCAR3 cells by in vitro experiments. CONCLUSIONS Our data suggest that PATZ1 is a novel prognostic marker in SOC.

Background: The status of serosal invasion is often discordance between pathological and intraoperative evaluation. Our study sought to develop a risk-scoring system (RSS) to predict the probability of pT4a for macroscopic serosal invasion (MSI) positive patients and reevaluate the serosal invasion status., Patients and Methods: A total of 1301 pT3/pT4a gastric cancer patients with curative surgery were reviewed. We constructed the RSS to predict the probability of pT4a and assigned MSI-positive patients into different risk groups based on the risk scores. The prognostic significance of these risk groups was also evaluated., Results: Univariate and multivariate analyses identified that tumor location, Lauren type, Borrmann type, tumor size, lymphovascular invasion and pN stage were risk factors related to pT4a. Survival analyses showed that pT3 MSI-positive patients in high-risk group had similar survival with pT4a patients. We incorporated these two groups into one stage and proposed a novel revised-T stage. Two-step multivariate analyses indicated that the revised-T stage showed better prediction ability for prognosis and peritoneal recurrence assessment than original pT stage and MSI status., Conclusions: In our present study, we developed a RSS to predict the probability of pT4a for MSI-positive patients. Based on our RSS, we proposed a treatment algorithm to reevaluate the tumor invasion for MSI-positive patients in clinical practice. Future studies should include other preoperative predictors to improve the clinical utility of our model., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: The aims of this study were to evaluate the associations between peritoneal elastic lamina invasion (ELI) and the clinicopathological prognostic factors of colon cancer, to evaluate the feasibility of ELI with use of an elastic stain to help diagnose serosal invasion of colon cancer in routine practice, so as to help us to provide a more accurate estimate for prognosis and stage of patients and a marker for postoperative treatment., Methods: 254 cases with colon cancer were included in the study. According to the presence of elastic lamina (EL) and elastic lamina invasion (ELI), all cases were divided into four groups: pT3 EL negative (pT3 EL (-)), pT3 ELI positive (pT3 ELI (+)), pT3 ELI negative (pT3 ELI (-)) and pT4a. Statistical analysis was used to analyze the relationship between elastic lamina invasion and other established adverse histologic features., Results: The EL and ELI positive rates were 81.5% and 42.1% respectively. There were significant differences in mph node metastasis, venous invasion and tumor buds between pT3 ELI (-) and pT3 ELI (+), pT3 ELI (-) and pT4a. There was no significant difference in same factors between pT3 ELI (+) and pT4a. In pT3 stage, there were significant differences in lymph node metastasis, perineural invasion and tumor buds between EL (-) and ELI (+). There were no significant differences in same factors between EL (-) and ELI (-). EL was detected less frequently in right-sided tumors compared with left-sided tumors., Conclusions: ELI might be the prognostic factors of colon cancer with II stage and might be the marker of postoperative adjuvant chemotherapy. Patients with pT3 ELI (+) might have similar prognosis to patients with pT4a. For patients with pT3 colon cancer, EL(-) might have similar prognosis as ELI (-) and might take the same therapy. In addition, the right half colon EL positive rate was lower than the left colon. Elastic staining might be a useful tool to help determine the invasive depth and stage of colon cancer.

Objective: Our study aimed to explore the prognostic influence of tumor-to-background ratios (TBRs) of the maximum standardized uptake value (SUVmax) in advanced high-grade serous ovarian cancer (HGSC) patients., Patients and Methods: We retrospectively investigated 51 advanced HGSC patients who underwent PET/CT before primary surgery at our hospital between January 2010 and June 2015. None of these patients received neoadjuvant chemotherapy. SUVmax of ovarian tumor (SUVmax-P) and background (SUVmax-B) were measured using a PET/CT workstation. TBR was calculated by SUVmax-P/SUVmax-B. Backgrounds included the liver, mediastinum, and muscle, and TBRs were noted as TBR-L, TBR-Me, and TBR-Mu, respectively. The χ-test was used to analyze the relationships between PET/CT parameters and several clinical features. Progression-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank tests in univariate analyses., Results: The median (range) follow-up duration was 27 (8-61) months. The median (range) PET/CT parameter values were as follows: SUVmax, 11.41 (3.24-24.14), TBR-L, 2.84 (2.08-11.93), TBL-Me, 2.09 (1.33-9.07), and TBR-Mu, 1.04 (0.56-14.02). The patients were categorized into low and high groups by the median values of these parameters above separately. A larger proportion of patients in the high TBR-Me group were chemoresistant compared with the low-value group (P=0.039). Neither the residual disease nor the ascites levels correlated with SUVmax or TBR values. There were no differences in progression-free survival and overall survival between the patients in the high and low TBR level groups., Conclusion: TBRs of SUVmax were not prognostic indicators for advanced HGSC patients.

The mediastinal serous cavity is a normal anatomic space in the caudal mediastinum. Aims of this anatomic and case series study were to describe the signs of pathologic expansion of the mediastinal serous cavity observed during computed tomography (CT), review the underlying anatomy, perform a literature review, and evaluate the medical records of several dogs with mediastinal serous cavity empyema (paraesophageal empyema). The mesothelial lined mediastinal serous cavity is a cranial extension of the omental bursa, separated from the peritoneal cavity by the diaphragm, in the dorsal part of the caudal mediastinum, to the right of the esophagus, between the heart base and diaphragm. In five adult, large-breed dogs with surgically and histologically confirmed paraesophageal empyema, macroscopic plant material was found at surgery in two dogs, adherence to adjacent lung was present in three different dogs, accessory lobectomy was performed in two dogs with subacute-chronic pyogranulomatous pneumonia, and one dog had concurrent pyothorax and mediastinitis, but none had esophageal abnormalities. This study expands our understanding of the pathogenesis and basis for the imaging appearance of paraesophageal empyema in dogs by clarifying the underlying anatomic structures that direct development of this condition. The term empyema accurately describes this condition because the purulent material accumulates within an existing body cavity. The study also provides initial evidence that the development of paraesophageal empyema might be due to local extension of lung disease, such as foreign body migration or pneumonia. Computed tomography was helpful for diagnosis, assessing size, and determining the spread of disease., (© 2017 American College of Veterinary Radiology.)

The aim of this study is to describe an entity of primary hydrocele accompanied with fibrosis, thickening and hemorrhagic infiltration of parietal layer of tunica vaginalis (PLTV). During a 4-year period (2011-2014), 94 boys (2.5-14 years old) underwent primary hydrocele repair. Hydrocele was right sided in 55 (58.5 %), left sided in 26 (28.7%) and bilateral in 12 patients (13.8%). Eighty three out of 94 patients (88.30%) had communicating hydrocele and the rest eleven patients (11.7%) had non-communicating. Our case group consists of 8 patients (8.51%) based on operative findings consistent with PLTV induration, thickening and hemorrhagic infiltration. Preoperative ultrasonography did not reveal any pathology of the intrascrotal structures besides hydrocele. There weren't hyperechoic reflections or septa within the fluid. Evaluation of thickness of the PLTV was not feasible. Presence of lymph or exudate was excluded after fluid biochemical analysis. Tunica vaginalis histological examination confirmed thickening, hemorrhagic infiltration and inflammation, while there was absence of mesothelial cells. Immunochemistry for desmin was positive, excluding malignant mesothelioma. One patient underwent high ligation of the patent processus vaginalis and PLTV sheath fenestration, but one year later, he faced a recurrence. An elective second surgery was conducted via scrotal incision and Jaboulay operation was performed. The latter methodology was our treatment choice in other 7 out of 8 patients. During a 2-year postoperative follow-up, no other patient had any recurrence. We conclude that in primary hydrocele with macroscopic features indicative of tunica vaginalis inflammation, reversion of the tunica should be a part of operative strategy instead of sheath fenestration, in order to minimize the recurrence.

Background/aims: Several tumor factors seem to be related to the hepatocellular carcinoma (HCC) prognosis, but they are not definitive, except for major vascular invasion. We analyzed the impact of serosal invasion, which is histologically classified into four groups according to the definition of the Liver Cancer Study Group of Japan - S0: no tumor invasion of serosa, S1: tumor invasion of serosa, S2: tumor invasion of adjacent organs, S3: tumor rupture with intraperitoneal bleeding., Methods: This retrospective study included 421 consecutive patients who underwent hepatectomy as an initial treatment for HCC between September 2002 and December 2014., Results: Kaplan-Meier analysis and log-rank tests revealed that both recurrence-free survival (RFS) and disease-specific survival (DSS) worsened as the serosal invasion status advanced. Multivariate analyses showed that S2/S3 was independently correlated with RFS (hazard ratio [HR] 3.52; p  < 0.001) and DSS (HR 2.58; p  = 0.039). Another multivariate analysis showed that serosal invasion (S1-S3) was independently correlated with RFS (HR 1.70; p = 0.015) but not with DSS (HR 1.38; p = 0.27)., Conclusion: Invasion to adjacent organs and tumor rupture were crucial prognostic factors for both DSS and RFS. Serosal invasion was an independent prognostic factor only for RFS., (© 2017 S. Karger AG, Basel.)

The study aimed to investigate the role of Tanshinone IIA (Tan IIA) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in its regulation of TRPM7. Wistar male rats were randomly divided into the normal saline (NS), LPS, knockout (KO) + LPS, low-dose Tan IIA (Tan-L), middle-dose Tan IIA (Tan-M), high-dose Tan IIA (Tan-H) and KO + high-dose Tan IIA (KO + Tan-H) groups. The level of tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, TRPM7 protein expression, current density-voltage curve and Ca 2+ concentration were detected through ELISA, Western blotting, electrophysiological experiment and a calcium-imaging technique, respectively. The rats in the KO + LPS, Tan-L, Tan-M, Tan-H and KO + Tan-H groups all displayed lower levels of TNF-α, IL-1β and IL-6 than the LPS group. Rats in the KO + Tan-H group exhibited lower levels of NF-α, IL-1β and IL-6 than rats in the Tan-H group. Elevated levels of TRPM7 protein expression in the LPS and Tan groups were detected in comparison with the NS group. However, TRPM7 protein expression in Tan-M and Tan-H groups was notably lower than in that of the LPS group. In comparison with the NS group, the LPS and Tan groups had a greater PIMs cell density and a higher concentration of Ca 2+ . Contrary results were observed in the KO + LPS, Tan-H and KO + Tan-H groups. Tan IIA decreases calcium influx in PIMs and inhibits pro-inflammatory factors which provide an alleviatory effect in regards to LPS-induced ALI by suppressing TRPM7 expression., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: We sought to clarify the clinical value of the examination of cancer cells exposed to gastric serosa by our novel method of serosal stamp cytology and a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis., Method: A total of 70 patients who underwent gastrectomy were enrolled. Stamp cytology specimens were obtained by stamping the gastric serosa at the primary gastric tumor lesion, followed by Papanicolaou's staining. Samples obtained by brushing the serosa at the primary gastric tumor were analyzed by our RT-PCR of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20)., Results: Among the 70 patients, 11 patients were diagnosed as stamp cytology-positive. Eight and five patients were found to be CEA-positive and CK20-positive, respectively. Since 21 of the 70 patients were either stamp cytology-positive or RT-PCR analysis-positive, these 21 patients were considered to be positive for cancer cells exposed to serosa of primary gastric tumor. The 3-year recurrence-free survival rate of the patients with a single positive result by our method (41.7%) was significantly (log rank p = 0.0002) worse than that of the patients with both negative results (81.0%). Our method showed 58.8% sensitivity and 79.2% specificity. A multivariate analysis revealed that a stamp cytology and/or RT-PCR result was an independent prognostic factor for recurrence., Conclusion: The examination of cancer cells exposed to gastric serosa by our serosal stamp cytology and RT-PCR system will be useful for the identification of patients at high risk for peritoneal recurrence after curative surgery for gastric cancer., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Formyl peptide receptors (FPRs) are G protein-coupled chemoattractant receptors expressed mainly in phagocytic leukocytes. High expression of FPRs has also been detected in several cancers but the functions of FPR1 in tumor invasion and metastasis is poorly understood. In this study, we investigated the expression of FPRs in primary human colorectal cancer (CRC) and analyzed the association of FPRs expression with clinicopathological parameters. The levels of FPRs mRNA, especially those of FPR1, were significantly higher in colorectal tumors than in distant normal tissues and adjacent non-tumor tissues. FPR1 mRNA expression was also associated with tumor serosal infiltration. FPR1 protein expression was both in the colorectal epitheliums and tumor infiltrating neutrophils/macrophages. Furthermore, the functions of FPR1 in tumor invasion and tissue repair were investigated using the CRC cell lines SW480 and HT29. Higher cell surface expression of FPR1 is associated with significantly increased migration in SW480 cells compared with HT29 cells that have less FPR1 membrane expression. Finally, genetic deletion of fpr1 increased the survival rate of the resulting knockout mice compared with wild type littermates in a mouse model of colitis-associated colorectal cancer. Our data demonstrate that FPR1 may play an important role in tumor cell invasion in CRC patients.

Purpose: Although general surgeons normally perform laparoscopic colectomies in patients with colon cancer, the procedure is also indicated for serosa-negative tumors (≤ cT3). Serosal invasion (T4a) is regarded as a potential risk factor for peritoneal dissemination due to pneumoperitoneum effects and tumor manipulation during laparoscopic colectomy. We compared short- and long-term outcomes of patients who underwent laparoscopic and open colectomies for serosa-involving colon cancer (pT4a) and had a preoperative diagnosis of cancer without serosal invasion (≤cT3)., Methods: A total of 179 patients (102 patients treated with laparoscopic colectomies and 77 with open colectomies) who were treated between 2009 and 2015 were included. These patients were first diagnosed preoperatively with ≤ cT3 disease based on computed tomography, endoscopy, or endoscopic ultrasound, but they were diagnosed with pT4a disease based on final pathology results. Recurrence and survival rates between the two groups were compared., Results: Baseline characteristics, clinical stage, type of colectomy, and short-term outcome did not differ between the groups. Five-year overall survival (OS) (p=0.248) and disease- free survival (DFS) rates (p=0.113) were comparable between the laparoscopic and open groups. Recurrence patterns did not differ between groups. Moreover, laparoscopic colectomy did not increase peritoneal recurrence compared to open colectomy. By multivariate analysis, surgical approach was not an independent prognostic factor for OS or DFS., Conclusion: Similar survival and recurrence patterns were observed in patients with serosa-involving colon cancer (pT4a) who were preoperatively diagnosed with serosa negative disease (≤cT3) and underwent either laparoscopic or open colectomies. Laparoscopic colectomy may be safely performed in patients with serosa-positive tumors.

Signet ring cell change of intestinal epithelial cells is a rare but well-known mimicker of signet ring cell carcinoma and is often associated with ischemic and/or pseudomembranous colitis. Instead, signet ring cell change involving nonepithelial cells in the subserosa of the intestine is an extremely rare finding with only a single case report in the literature to date. We report a new case of benign signet ring cell change localized in the subserosa of the large bowel incidentally identified in a resection specimen for Clostridium difficile colitis mimicking a metastatic signet ring cell carcinoma. Based on the morphologic features and immunohistochemical profile, we propose that these signet ring cells may possibly represent modified/degenerated fat cells. Furthermore, we discuss how to differentiate benign signet ring cells from a signet ring cell carcinoma.

Objective: To explore whether CT value is useful in identifying different disease in tumors of rhinosinus parenchyma.
 Methods: The data of preoperation noncontrast CT in 277 patients were retrospectively reviewed. The final diagnosis and classification were based on the result of surgical histopathological examination. The CT value range for different classification was calculated and was compared. All patients were re-diagnosed according to CT value range combined with pathological results by the same doctor team. The diagnosis rates according to CT value range were compared.
 Results: The CT value was (25.3±3.5) Hu in nasal polyp, (7.9±3.5) Hu in serous cyst, (42.2±4.7) Hu in mucocele, (40.7±5.3) Hu in papilloma, (112.3±10.9) Hu in fungus ball, (41.7±4.8) Hu in hemangioma, (51.2±9.9) Hu in malignant melanoma, and (47.1±9.9) Hu in squamous carcinoma. The CT value in nasal polyp is significantly higher than that in serous cyst, which was significantly lower than that in mucocele, papilloma, fungus ball, hemangioma, malignant melanoma and squamous carcinoma (all P<0.05); the CT value in serous cyst was significantly lower than that in other classification diseases (all P<0.05); the CT value in fungus ball was significantly higher than that in other classification diseases (all P<0.05); there was no significant difference in CT value among mucocele, papilloma, hemangioma, malignant melanoma, squamous carcinoma (all P﹥0.05). The diagnosis rate was elevated (from 71.1% to 92.4%) according to CT value range, with significant difference (χ2=42.150, P<0.01).
 Conclusion: CT value in nasal polyp, serous cyst, fungus ball is different from other diseases, and the 3 diseases can be distinguished only by CT value range; the CT value in mucocele, papilloma, hemangioma, malignant melanoma and squamous carcinoma is similar, and their differential diagnosis should combine with imaging data and other clinical characters. The diagnosis rates can be improved when the CT value range is taken into account.

Background: Serious complications continue to occur in laparoscopic cholecystectomy (LC). The commonly used indicators of surgical difficulty such as the duration of surgery are insufficient because they are surgeon and institution dependent. We aimed to identify appropriate indicators of surgical difficulty during LC., Methods: A total of 26 Japanese expert LC surgeons discussed using the nominal group technique (NGT) to generate a list of intraoperative findings that contribute to surgical difficulty. Thereafter, a survey was circulated to 61 experts in Japan, Korea, and Taiwan. The questionnaire addressed LC experience, surgical strategy, and perceptions of 30 intraoperative findings listed by the NGT., Results: The response rate of the survey was 100%. There was a statistically significant difference among nations regarding the duration of surgery and adoption rate of safety measures and recognition of landmarks. The criteria for conversion to an open or subtotal cholecystectomy were at the discretion of each surgeon. In contrast, perceptions of the impact of 30 intraoperative findings on surgical difficulty (categorized by factors related to inflammation and additional findings of the gallbladder and other intra-abdominal factors) were consistent among surgeons., Conclusions: Intraoperative findings are objective and considered to be appropriate indicators of surgical difficulty during LC., (© 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

An incorrect approach to the critical view of safety can cause bile duct and/or vascular injury. However, only superficial anatomical features have been proposed as surgical landmarks to initiate laparoscopic cholecystectomy (LC) safely in previous reports. Accordingly, we have proposed a novel surgical anatomical definition of the gallbladder wall, in which the subserosal (SS) layer is divided into the inner layer of the SS (SS-Inner) layer consisting of vasculature and fibrous tissue, and the outer layer of the SS (SS-Outer) layer consisting of abundant fat tissue. By dissecting the gallbladder along the SS-Inner layer after exposure at a safe region, bile duct and/or vascular injury can be avoided, even in cholecystitis cases. Furthermore, recognition of this surgical anatomy reveals several aspects. In cholecystitis cases associated with severe fibrotic change, completion of LC by dissecting along the SS-Inner layer is impossible, resulting in abandonment of regular LC. An abscess in the liver bed associated with acute cholecystitis usually forms in the SS-Outer layer, thus, the gallbladder can be dissected easily. In the dome-down technique, the right hepatic duct is endangered by whole-layer dissection, in which the SS-Outer layer is also removed. The proposed procedure should become the universal standard for LC., (© 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

A real-time optical biopsy, which could determine tissue histopathology, would be of extraordinary benefit to staging laparoscopy for gastric cancer with serosal invasion (T4) that requires downstage treatment. We investigated the feasibility of using multiphoton imaging to perform a real-time optical diagnosis of gastric cancer with or without serosal invasion. First, a pilot study was performed to establish the optical diagnostic features of gastric cancer with or without serosal invasion using multiphoton imaging compared with hematoxylin-eosin staining and Masson's trichrome staining. Second, a blinded study was performed to compare the diagnostic sensitivity, specificity, and accuracy of multiphoton imaging and endoscopic ultrasonography (EUS) for T4 gastric cancer. In the pilot study, multiphoton imaging revealed collagen loss and degradation and cellular and nuclear pleomorphism in gastric cancer with serosal invasion. The collagen content in gastric cancer with or without serosal invasion was 0.36 ± 0.18 and 0.79 ± 0.16 (p < 0.001), respectively. In the blinded study, the sensitivity, specificity, and accuracy of EUS and multiphoton imaging for T4 gastric cancer were 70% and 90% (p = 0.029), 66.67% and 96.67% (p = 0.003), and 68.33% and 93.33% (p = 0.001), respectively. It is feasible to use multiphoton imaging to make a real-time optical diagnosis of gastric cancer with or without serosal invasion.

Background: Ischemic injury of an organ causes metabolic change from aerobic to anaerobic metabolism. It has been shown in experimental studies on the heart and liver that such conversion may be detected by conventional microdialysis probes placed intra-parenchymatously, as well as on organ surfaces, by assaying lactate, pyruvate, glucose, and glycerol in dialysate. We developed a microdialysis probe (S-μD) intended for use solely on organ surfaces. The aim of this study was to assess whether the newly developed S-μD probe could be used for detection and monitoring of small bowel ischemia., Methods: In anesthetized normoventilated pigs, a control S-μD probe was applied on the jejunal serosa 50 cm downstream from the duodenojejunal junction (DJJ). Starting 100 cm from DJJ, a 100-cm long ischemic segment was created by division of all mesenteric vessels. S-μDs were applied at 2.5, 5, 20, and 50 cm from the starting point of ischemia by serosal sutures. A standard μD probe was placed in the abdominal cavity as a further control. Dialysate was harvested before inducing ischemia and subsequently every 20 min for 4 h. Central venous blood was drawn every hour to monitor systemic lactate, C-reactive protein, and white blood cell count., Results: Microdialysis lactate levels were significantly higher than baseline from 20 min on into protocol time in the ischemic segment and in the control S-μD probe. The peritoneal cavity probe showed no significant elevation. Lactate levels from the ischemic segment reached a plateau at 60 min. Courses of pyruvate, glucose, and glycerol levels were in accordance with transition from an aerobic to anaerobic metabolism in the bowel wall. No statistically significant changes in hemoglobin, white blood cell count, or lactate values in central venous blood were recorded., Conclusions: Assaying the aforementioned compounds in dialysate, harvested by the newly developed S-μD probe, allowed detection and monitoring of small bowel ischemia from 20 min on following its onset., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The primary aim of our study was to determine the prevalence of macroscopic deciduosis Found randomly in Cesarean sections and the secondary objective to determine the association with any obstetrical complications or adverse effects., Methods: This is a unicenter prospective study from 01/08/2011 to 01/02/2014. During the study period 307 consecutive Cesarean sections were performed with 31 biopsy proven cases of macroscopic deciduosis in the ovary, uterine and fallopian tube serosa., Results: The mean age of the patients was 31.2 ± 5.4 years (range 13-43), the mean Body Mass Index was 26.3 ± 5.8 (range 15-48)kg/m(2), the mean term of Cesarean was 270 ± 25 days, and the mean fetal weight was 3094 ± 809 g. The majority of patients were Caucasian (n=175, 57.0%). Patients with deciduosis had a greater BMI (28.4 ± 5.3 kg/m(2) vs 25.7 ± 5.8 kg/m(2), p<0.05). The presence of pain was more frequent in the deciduosis group (10.1%, OR 5.78, 95%, CI [2.41-13.87], p<0.001)., Conclusion: Deciduosis is a benign lesion during pregnancy that is not correlated with obstetrical complications. Our study has shown that this physiological phenomenon is more frequent that originally thought, being present in 10% of the Cesarean sections, and is associated with abdominal pain during pregnancy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Macroscopic serosal classification (MSC) is an important clinicopathologic index of gastric cancer (GC). To investigate the prognostic significance of MSC status in patients with radically resected stage pT3-pT4b GC, we examined the relationship between MSC type and pT stage., Methods: Clinicopathologic and survival data of 1613 patients with stage pT3-pT4b GC were studied retrospectively, in the aftermath of radical surgery., Results: MSC types, including reactive, nodular, tendonoid, and color-diffused type, correlated significantly with overall survival (OS) in this cohort, but prognosis was similar for all stages of color-diffused type GC. We proposed a revised pT stage in which color-diffused type cancers at pT3 or pT4a stage were reclassified into pT4b stage. In two-step multivariate analysis, revised pT stage (stage pT4b for all color-diffused types) proved more suitable for determining prognosis, surpassing both Union for International Cancer Control/American Joint Committee on Cancer pT stage and MSC type as an independent prognostic index., Conclusions: MSC type is a significant and independent prognostic index of OS in patients with radically resected stage pT3-pT4b GC. For prognostic purposes, tumors of color-diffused type at pT3 or pT4a stage should be considered stage pT4b disease.

Overactive bladder is one of the major health problem especially in elderly people. Adenosine triphosphate (ATP) is released from urinary bladder cells and acts as a smooth muscle contraction and sensory signal in micturition but little is known about the role of ATP release in the pathophysiology of overactive bladder. To assess the relationship between ATP and overactive bladder, we used a partial bladder outlet obstruction (pBOO) model in rats. The bladder caused several changes by pBOO: An increase in bladder weight, hypertrophy of sub-urothelium and sub-serosal area, and frequent non-voiding bladder contraction during urine storage. Basal ATP release from urothelium and serosa of pBOO rats was significantly higher than that of normal rats. Distentioninduced ATP release from urothelium of normal and pBOO rats had no significant change. However, distention-induced ATP release from serosa of pBOO rats was higher than that of normal. These findings may identify ATP especially released from serosa as one of causes of non-voiding contractions and overactive bladder symptoms.