Does total omentectomy prevent peritoneal seeding for advanced gastric cancer with serosal invasion?

BACKGROUND: Radical gastrectomy is composed of gastrectomy, lymph node dissection, and omentectomy. Total omentectomy (TO) is expected to reduce the incidence of peritoneal recurrence. We aimed to investigate the necessity of TO for advanced gastric cancer (AGC) with serosal invasion. METHODS: We retrospectively reviewed 310 patients who underwent radical gastrectomy with TO and 93 patients who underwent partial omentectomy (PO) for gastric cancer with serosal invasion between August, 2005 and December, 2017. Finally, 91 patients in the PO group and 91 in the TO group were enrolled based on a 1:1 propensity-score matching analysis. We evaluated surgical and oncological outcomes, including 5-year overall and recurrence-free survival rates. RESULTS: There was no statistically significant difference between the two groups in postoperative complications. Recurrence sites showed similar patterns in both groups, including peritoneal recurrence (PO vs. TO, 18.7% vs. 28.6%; p = 0.188). Five-year overall survival was better in the PO group (p = 0.018), while 5-year recurrence-free survival was similar in both groups (p = 0.066). CONCLUSION: TO might not be an essential part of preventing peritoneal recurrence for AGC with serosal invasion. PO could be considered a radical gastrectomy for T4a gastric cancer.

Effects of glutamine and omega-3 fatty acids on intestinal neomucosa formation on colon serosa in rats.

Background/aim: Intestinal neomucosa formation is a technique defined for the treatment of short bowel syndrome. This study evaluates the effect of glutamine and omega-3 fatty acids on the growth of intestinal neomucosa on the colonic serosal surface has been evaluated. Materials and methods: Thirty-two adult male Sprague-Dawley rats were randomly divided into 4 groups: sham, control, glutamine, and omega-3. Laparotomy was performed on all groups. For rats other than the sham group, a 1-cm full-thickness incision was made 4 cm proximal to the ileocecal valve, and colonic serosal surface was sutured as a serosal patch over these openings. By using the oral gavage technique, the glutamine group was ingested with 200 mg/kg/day of glutamine, and the omega-3 group was ingested with 100 mg/kg/day of omega-3 fatty acids. At the end of 14 days, the rats were euthanized, blood specimens were collected, and intestinal segments, including serosal patches, were excised. Results: Transforming growth factor-beta was significantly lower in the glutamine group compared to the control group. Similarly, fibroblast growth factor-2 was significantly lower in the glutamine group compared to the sham group. Intestinal neomucosa formation was observed in 100% of rats in the glutamine group. In the control and omega-3 groups, intestinal neomucosa formation was observed in 57.1% and 60% of rats, respectively. The inflammatory response, granulation tissue formation, and fibroblastic activity were more severe in the rats of the glutamine and omega-3 groups. Conclusion: The intestinal neomucosa formation is an experimental technique, and both glutamine and omega-3 fatty acids have the potential to positively affect inflammatory response, granulation tissue formation, and fibroblastic activity. Specifically, glutamine has a favorable effect on intestinal neomucosa formation.

Serosal Adhesion Ex Vivo of Hydrogels Prepared from Apple Pectin Cross-Linked with Fe3+ Ions.

The study aims to investigate the adhesion of a hydrogel made of cross-linked low-methyl esterified pectin to rat intestinal serosa ex vivo. The adhesivity of the FeP hydrogel, which was cross-linked by Fe3+ cations, exceeded that of hydrogels cross-linked by Ca2+, Zn2+, and Al3+ cations. The concentration of the cross-linking cation failed to influence the adhesion of the pectin hydrogel to the serosa. The mechanical properties and surface microrelief of the pectin hydrogel were influenced by the type and concentration of the cross-linking cations. Fe3+ cations form a harder and more elastic gel than Ca2+ cations. Scanning electron microscopy analysis revealed the characteristic surface pattern of FeP hydrogel and its denser internal structure compared to Ca2+ cross-linked hydrogel. The effect of the salt composition of the adhesion medium was shown since the FeP hydrogel's adhesion to the serosa was lower in physiological solutions than in water, and adhesion in Hanks' solution was higher than in phosphate buffered saline. Serum proteins and peritoneal leukocytes did not interfere with the serosal adhesion of the FeP hydrogel. Pre-incubation in Hanks' solution for 24 h significantly reduced the adhesion of the FeP hydrogel to the serosa, regardless of the pH of the incubation. Thus, serosal adhesion combined with excellent stability and mechanical properties in physiological environments appeared to be advantages of the FeP hydrogel, demonstrating it to be a promising bioadhesive for tissue engineering.

Localized bioelectrical conduction block from radiofrequency gastric ablation persists after healing: safety and feasibility in a recovery model.

Gastric ablation has demonstrated potential to induce conduction blocks and correct abnormal electrical activity (i.e., ectopic slow-wave propagation) in acute, intraoperative in vivo studies. This study aimed to evaluate the safety and feasibility of gastric ablation to modulate slow-wave conduction after 2 wk of healing. Chronic in vivo experiments were performed in weaner pigs (n = 6). Animals were randomly divided into two groups: sham-ablation (n = 3, control group; no power delivery, room temperature, 5 s/point) and radiofrequency (RF) ablation (n = 3; temperature-control mode, 65°C, 5 s/point). In the initial surgery, high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was performed to define the baseline slow-wave activation profile. Ablation (sham/RF) was then performed in the mid-corpus, in a line around the circumferential axis of the stomach, followed by acute postablation mapping. All animals recovered from the procedure, with no sign of perforation or other complications. Two weeks later, intraoperative high-resolution mapping was repeated. High-resolution mapping showed that ablation successfully induced sustained conduction blocks in all cases in the RF-ablation group at both the acute and 2 wk time points, whereas all sham-controls had no conduction block. Histological and immunohistochemical evaluation showed that after 2 wk of healing, the lesions were in the inflammation and early proliferation phase, and interstitial cells of Cajal (ICC) were depleted and/or deformed within the ablation lesions. This safety and feasibility study demonstrates that gastric ablation can safely and effectively induce a sustained localized conduction block in the stomach without disrupting the surrounding slow-wave conduction capability.NEW & NOTEWORTHY Ablation has recently emerged as a tool for modulating gastric electrical activation and may hold interventional potential for disorders of gastric function. However, previous studies have been limited to the acute intraoperative setting. This study now presents the safety of gastric ablation after postsurgical recovery and healing. Localized electrical conduction blocks created by ablation remained after 2 wk of healing, and no perforation or other complications were observed over the postsurgical period.

Validation of noninvasive body-surface gastric mapping for detecting gastric slow-wave spatiotemporal features by simultaneous serosal mapping in porcine.

Gastric disorders are increasingly prevalent, but reliable noninvasive tools to objectively assess gastric function are lacking. Body-surface gastric mapping (BSGM) is a noninvasive method for the detection of gastric electrophysiological features, which are correlated with symptoms in patients with gastroparesis and functional dyspepsia. Previous studies have validated the relationship between serosal and cutaneous recordings from limited number of channels. This study aimed to comprehensively evaluate the basis of BSGM from 64 cutaneous channels and reliably identify spatial biomarkers associated with slow-wave dysrhythmias. High-resolution electrode arrays were placed to simultaneously capture slow waves from the gastric serosa (32 × 6 electrodes at 4 mm spacing) and epigastrium (8 × 8 electrodes at 20 mm spacing) in 14 porcine subjects. BSGM signals were processed based on a combination of wavelet and phase information analyses. A total of 1,185 individual cycles of slow waves were assessed, out of which 897 (76%) were classified as normal antegrade waves, occurring in 10 (71%) subjects studied. BSGM accurately detected the underlying slow wave in terms of frequency (r = 0.99, P = 0.43) as well as the direction of propagation (P = 0.41, F-measure: 0.92). In addition, the cycle-by-cycle match between BSGM and transitions of gastric slow wave dysrhythmias was demonstrated. These results validate BSGM as a suitable method for noninvasively and accurately detecting gastric slow-wave spatiotemporal profiles from the body surface.NEW & NOTEWORTHY Gastric dysfunctions are associated with abnormalities in the gastric bioelectrical slow waves. Noninvasive detection of gastric slow waves from the body surface can be achieved through multichannel, high-resolution, body-surface gastric mapping (BSGM). BSGM matched the spatiotemporal characteristics of gastric slow waves recorded directly and simultaneously from the serosal surface of the stomach. Abnormal gastric slow waves, such as retrograde propagation, ectopic pacemaker, and colliding wavefronts can be detected by changes in the phase of BSGM.

Targeted ablation of gastric pacemaker sites to modulate patterns of bioelectrical slow wave activation and propagation in an anesthetized pig model.

Gastric motility is coordinated by underlying bioelectrical slow waves. Gastric dysrhythmias occur in gastrointestinal (GI) motility disorders, but there are no validated methods for eliminating dysrhythmias. We hypothesized that targeted ablation could eliminate pacemaker sites in the stomach, including dysrhythmic ectopic pacemaker sites. In vivo high-resolution serosal electrical mapping (16 × 16 electrodes; 6 × 6 cm) was applied to localize normal and ectopic gastric pacemaker sites in 13 anesthetized pigs. Radiofrequency ablation was performed in a square formation surrounding the pacemaker site. Postablation high-resolution mapping revealed that ablation successfully induced localized conduction blocks after 18 min (SD 5). Normal gastric pacemaker sites were eliminated by ablation (n = 6), resulting in the emergence of a new pacemaker site immediately distal to the original site in all cases. Ectopic pacemaker sites were similarly eliminated by ablation in all cases (n = 7), and the surrounding mapped area was then entrained by normal antegrade activity in five of those cases. Histological analysis showed that ablation lesions extended through the entire depth of the muscle layer. Immunohistochemical staining confirmed localized interruption of the interstitial cell of Cajal (ICC) network through the ablation lesions. This study demonstrates that targeted gastric ablation can effectively modulate gastric electrical activation, including eliminating ectopic sites of slow wave activation underlying gastric dysrhythmias, without disrupting surrounding conduction capability or tissue structure. Gastric ablation presents a powerful new research tool for modulating gastric electrical activation and may likely hold therapeutic potential for disorders of gastric function.NEW & NOTEWORTHY This study presents gastric ablation as a novel tool for modulating gastric bioelectrical activation, including eliminating the normal gastric pacemaker site as well as abnormal ectopic pacemaker sites underlying gastric dysrhythmias. Targeted application of radiofrequency ablation was able to eliminate these pacemaker sites without disrupting surrounding conduction capability or tissue structure. Gastric ablation presents a powerful new research tool for modulating gastric electrical activation and may likely hold therapeutic potential for disorders of gastric function.

Surgical and survival outcomes after laparoscopic and open gastrectomy for serosa-invasive Siewert type II/III esophagogastric junction carcinoma: a propensity score matching analysis.

BACKGROUND: The potential advantage of laparoscopic gastrectomy (LG) compared with open gastrectomy (OG) for serosa-invasive (pT4a) Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG) remains uncertain. Thus, the purpose of this study was to investigate the short- and long-term outcomes of LG compared to OG for pT4a Siewert type II/III AEG cancers. METHODS: We retrospectively evaluated 283 patients with pathological confirmed T4a Siewert type II and type III AEG who underwent LG or OG in our center between January 2004 and September 2015. The short- and long-term outcomes were compared between the groups using a 1:1 matched propensity score matching method (PSM). RESULTS: The LG group had a longer operation time, less estimated blood loss, less time to first flatus, less time to start liquid diet, less time to first ambulation, and shorter length of incision than the OG group. The conversion rates were 5.4% in the LG groups. There was no significant difference in the overall complication rate between the LG and OG groups. The 5-year overall survival (OS) and the 5-year disease-free survival (DFS) were comparable between the LG and OG groups (35.4% vs 32.1%, p = 0.541; 34.1% vs 31.0%, p = 0.523, respectively). There was no significant difference in the recurrence rate and pattern between the LG and OG groups. CONCLUSIONS: Laparoscopic gastrectomy is associated with better short-term outcomes and similar long-term outcomes for pT4a Siewert type II/III AEG. This study reveals that LG could be a safe and feasible option for pT4a Siewert type II/III AEG compared to OG.

PAR-2-activated secretion by airway gland serous cells: role for CFTR and inhibition by Pseudomonas aeruginosa.

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 Ca2+ 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 Ca2+. At stimulation levels >EC50 for Ca2+, serous cells simultaneously shrank ∼20% over ∼90 s due to KCl efflux reflecting Ca2+-activated Cl- channel (CaCC, likely TMEM16A)-dependent secretion. At lower levels of PAR-2 stimulation (

The prognostic impact of macroscopic serosal change on resectable advanced gastric cancer.

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.

Prediction of serosal invasion in gastric cancer: development and validation of multivariate models integrating preoperative clinicopathological features and radiographic findings based on late arterial phase CT images.

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.

Adenomatoid Tumor of the Uterus: A Report of 6 Unusual Cases With Prominent Cysts Including 4 With Diffuse Myometrial Involvement, 4 With Uterine Serosal Involvement, and 2 Presenting in Curettage Specimens.

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.

Comparisons of perioperative and survival outcomes of laparoscopic versus open gastrectomy for serosa-positive (pT4a) gastric cancer patients: a propensity score matched analysis.

BACKGROUND: Data about whether laparoscopic gastrectomy (LG) is applicable in serosa-positive (pT4a) gastric cancer patients remain rare. The purpose of this study is to compare the perioperative and long-term outcomes between the laparoscopic and open gastrectomy (OG) in pT4a gastric cancer patients who underwent curative resection. METHODS: A total of 1086 consecutive pT4a patients (101 patients with LG and 985 with OG) who underwent curative gastrectomy in a high-volume center between 2006 and 2016 were evaluated. Demographics, surgical, and oncologic outcomes were analyzed. Propensity score matching (PSM) analysis was performed to balance baseline confounders, and COX regression analysis was performed to identify independent prognostic factors. RESULTS: After PSM adjustment, a well-balanced cohort comprising 101 patients who underwent LG and 201 who underwent OG was analyzed. Operative time (288.7 vs. 234.2 min; P < 0.001) was significantly longer, while estimated blood loss (172.8 vs. 220.7 ml; P < 0.001) was significantly less in the LG group compared with the OG group. There were no significant differences between groups in total number of harvested lymph nodes, postoperative stays, readmission rate, and postoperative complication rate. The 3-year overall survival (OS) rate was not significant different in the LG and OG groups (66.7% vs. 62.8%, P = 0.668), and the subsequent multivariate analysis revealed that the surgical approach was not an independent prognostic factor for OS (HR = 1.123; 95%CI: 0.803-1.570; P = 0.499). In sensitivity analysis including 78 pairs well-matched patients operated by an experienced surgeon, the results were similar to these for the matched entire cohort. CONCLUSION: LG can be a safe and feasible approach for pT4a gastric cancer treatment. However, well-designed high-quality RCTs are expected to draw a definitive conclusion on this topic.

Dynamic Serosal Perfusion Assessment during Colorectal Resection Using Visible Light Spectroscopy.

INTRODUCTION: Anastomotic leakage (AL) in colorectal surgery occurs with an incidence of up to 20%. Bowel perfusion is deemed to be one of the most important factors for anastomotic healing. However, not much is known about its variability during colorectal surgery and its impact on the outcome. Therefore, this study aims to evaluate serosal oxygen saturation patterns during colorectal resections with visible light spectroscopy (VLS). MATERIALS AND METHODS: Bowel perfusion in patients undergoing left-sided colorectal resections was assessed at different timepoints during surgery using VLS on the colonic serosa. The primary outcome parameter was serosal oxygen saturation (StO2) at the anastomosis during different timepoints of surgery. RESULTS: We included 50 patients who underwent colorectal resection for bowel cancer (58%) and diverticular disease (34%). StO2 at the proximal site of the anastomosis increased significantly throughout the surgery (mean difference 3.61%; 95% CI -6.22 to -1.00; p = 0.008). However, aberrancy from this identified perfusion pattern had no impact on the postoperative outcome. CONCLUSION: During colorectal resections, we could demonstrate an increase of the colonic StO2 throughout surgery. Appearance of AL was not associated with lower StO2, underlining the multifactorial genesis of developing AL.

Nanomaterials and the Serosal Immune System in the Thoracic and Peritoneal Cavities.

The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the thoracic and peritoneal cavities, and they are crucial in first defense against pathogenic viruses and bacteria. Nanomaterials (NMs) can enter the cavities intentionally for medical purposes, or unintentionally following environmental exposure; subsequent serosal inflammation and cancer (mesothelioma) has gained significant interest. However, reports on adverse effects of NM on ILCs and other components of the serosal immune system are scarce or even lacking. As ILCs are crucial in the first defense against pathogenic viruses and bacteria, it is possible that serosal exposure to NM may lead to a reduced resistance against pathogens. Additionally, affected serosal lymphoid tissues and cells may disturb adipose tissue homeostasis. This review aims to provide insight into key effects of NM on the serosal immune system.

Serous Membrane Detachment with Ultrasonic Homogenizer Improves Engraftment of Fetal Liver to Liver Surface in a Rat Model of Cirrhosis.

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.

Intestine-specific deletion of metal transporter Zip14 (Slc39a14) causes brain manganese overload and locomotor defects of manganism.

Impaired manganese (Mn) homeostasis can result in excess Mn accumulation in specific brain regions and neuropathology. Maintaining Mn homeostasis and detoxification is dependent on effective Mn elimination. Specific metal transporters control Mn homeostasis. Human carriers of mutations in the metal transporter ZIP14 and whole body Zip14-knockout (WB-KO) mice display similar phenotypes, including spontaneous systemic and brain Mn overload and motor dysfunction. Initially, it was believed that Mn accumulation due to ZIP14 mutations was caused by impaired hepatobiliary Mn elimination. However, liver-specific Zip14-KO mice did not show systemic Mn accumulation or motor deficits. ZIP14 is highly expressed in the small intestine and is localized to the basolateral surface of enterocytes. Thus, we hypothesized that basolaterally localized ZIP14 in enterocytes provides another route for the elimination of Mn. Using wild-type and intestine-specific Zip14-KO (I-KO) mice, we have shown that ablation of intestinal Zip14 is sufficient to cause systemic and brain Mn accumulation. The lack of intestinal ZIP14-mediated Mn excretion was compensated for by the hepatobiliary system; however, it was not sufficient to maintain Mn homeostasis. When supplemented with extra dietary Mn, I-KO mice displayed some motor dysfunctions and brain Mn accumulation based on both MRI imaging and chemical analysis, thus demonstrating the importance of intestinal ZIP14 as a route of Mn excretion. A defect in intestinal Zip14 expresssion likely could contribute to the Parkinson-like Mn accumulation of manganism.NEW & NOTEWORTHY Mn-induced parkinsonism is recognized as rising in frequency because of both environmental factors and genetic vulnerability; yet currently, there is no cure. We provide evidence in an integrative animal model that basolaterally localized ZIP14 regulates Mn excretion and detoxification and that deletion of intestinal ZIP14 leads to systemic and brain Mn accumulation, providing robust evidence for the indispensable role of intestinal ZIP14 in Mn excretion.

A new methodologic approach for clinico-pathologic correlations in invasive placenta previa accreta.

BACKGROUND: The development of new management strategies for women presenting with placenta accreta spectrum requires quality epidemiology data, which have so far been limited by the high variability in clinical and histopathologic data confirming the diagnosis at birth. OBJECTIVE: To evaluate the role of a new methodologic approach for the correlation of clinical and pathological data for women with a history of prior cesarean delivery diagnosed prenatally with placenta previa accreta. MATERIALS AND METHODS: A modified pathologic technique for gross examination of hysterectomy specimens with placenta in situ consisting of intraoperative examination, immediate postoperative examination, and guided histologic sampling was used prospectively in a cohort of 24 patients with singleton pregnancies complicated by placenta low-lying/placenta previa accreta. Maternal characteristics, detailed ultrasound findings, surgical outcomes, and histopathologic examination were compared with those of a group of 24 patients with similar clinical characteristics and in whom a standard pathologic examination method was used. RESULTS: The median reporting time for obtaining the complete histopathology results including the microscopic examination was significantly shorter (7 versus 15 days; P < .001) and the median number of samples taken for histologic examination significantly lower (4 versus 14 samples; P < .001) in the study group than in the controls. The number of histologic slides showing villous invasion was significantly higher (2 versus 1 slide; P = .002), and the ratio of the number of samples taken to the numbers of slides confirming villous invasion was significantly lower (2 versus 9; P < .001) in the study group than in the controls. In all cases in the study group, intraoperative examination identified a dense tangled bed of vessels or multiple vessels running laterally and cranio-caudally in the uterine serosa above the placental insertion that were no longer visible during immediate gross postoperative examination of the hysterectomy specimens. Immediate postoperative dissection enables the differential diagnosis between focal and large increta areas, and between abnormally adherent placenta and invasive placenta accreta. CONCLUSION: Valuable clinical information on the serosal vascularity, uterine dehiscence, and extension of the accreta area is added with the description of the macroscopic examination during the surgical procedure and immediate dissection of the specimen. This methodological approach is cost-effective and increases the quality of the histologic sampling. It thus provides more accurate correlations with the clinical data and more accurate epidemiologic data collection. Perinatal pathologists should be part of multidisciplinary teams involved the management placenta accreta spectrum disorders.

Simultaneous computer-assisted assessment of mucosal and serosal perfusion in a model of segmental colonic ischemia.

BACKGROUND: Fluorescence-based enhanced reality (FLER) enables the quantification of fluorescence signal dynamics, which can be superimposed onto real-time laparoscopic images by using a virtual perfusion cartogram. The current practice of perfusion assessment relies on visualizing the bowel serosa. The aim of this experimental study was to quantify potential differences in mucosal and serosal perfusion levels in an ischemic colon segment. METHODS: An ischemic colon segment was created in 12 pigs. Simultaneous quantitative mucosal and serosal fluorescence imaging was obtained via intravenous indocyanine green injection (0.2 mg/kg), using two near-infrared camera systems, and computer-assisted FLER analysis. Lactate levels were measured in capillary blood of the colonic wall at seven regions of interest (ROIs) as determined with FLER perfusion cartography: the ischemic zone (I), the proximal and distal vascularized areas (PV, DV), and the 50% perfusion threshold proximally and distally at the mucosal and serosal side (P50M, P50S, D50M, D50S). RESULTS: The mean ischemic zone as measured (mm) for the mucosal side was significantly larger than the serosal one (56.3 ± 21.3 vs. 40.8 ± 14.9, p = 0.001) with significantly lower lactate values at the mucosal ROIs. There was a significant weak inverse correlation between lactate and slope values for the defined ROIs (r = - 0.2452, p = 0.0246). CONCLUSIONS: Mucosal ischemic zones were larger than serosal zones. These results suggest that an assessment of bowel perfusion from the serosal side only can underestimate the extent of ischemia. Further studies are required to predict the optimal resection margin and anastomotic site.

Activation and synchronization of the oscillatory morphodynamics in multicellular monolayer.

Oscillatory morphodynamics provides necessary mechanical cues for many multicellular processes. Owing to their collective nature, these processes require robustly coordinated dynamics of individual cells, which are often separated too distantly to communicate with each other through biomaterial transportation. Although it is known that the mechanical balance generally plays a significant role in the systems' morphologies, it remains elusive whether and how the mechanical components may contribute to the systems' collective morphodynamics. Here, we study the collective oscillations in the Drosophila amnioserosa tissue to elucidate the regulatory roles of the mechanical components. We identify that the tensile stress is the key activator that switches the collective oscillations on and off. This regulatory role is shown analytically using the Hopf bifurcation theory. We find that the physical properties of the tissue boundary are directly responsible for synchronizing the oscillatory intensity and polarity of all inner cells and for orchestrating the spatial oscillation patterns inthe tissue.

Macroscopic and microscopic characteristics of low grade appendiceal mucinous neoplasms (LAMN) on appendectomy specimens and correlations with pseudomyxoma peritonei development risk.

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.