Immunohistochemical characterization of bipolar cells in four distantly related avian species

Visual (and probably also magnetic) signal processing starts at the first synapse, at which photoreceptors contact different types of bipolar cells, thereby feeding information into different processing channels. In the chicken retina, 15 and 22 different bipolar cell types have been identified based on serial electron microscopy and single‐cell transcriptomics, respectively. However, immunohistochemical markers for avian bipolar cells were only anecdotally described so far. Here, we systematically tested 12 antibodies for their ability to label individual bipolar cells in the bird retina and compared the eight most suitable antibodies across distantly related species, namely domestic chicken, domestic pigeon, common buzzard, and European robin, and across retinal regions. While two markers (GNB3 and EGFR) labeled specifically ON bipolar cells, most markers labeled in addition to bipolar cells also other cell types in the avian retina. Staining pattern of four markers (CD15, PKCα, PKCβ, secretagogin) was species‐specific. Two markers (calbindin and secretagogin) showed a different expression pattern in central and peripheral retina. For the chicken and European robin, we found slightly more ON bipolar cell somata in the inner nuclear layer than OFF bipolar cell somata. In contrast, OFF bipolar cells made more ribbon synapses than ON bipolar cells in the inner plexiform layer of these species. Finally, we also analyzed the photoreceptor connectivity of selected bipolar cell types in the European robin retina. In summary, we provide a catalog of bipolar cell markers for different bird species, which will greatly facilitate analyzing the retinal circuitry of birds on a larger scale

Worldwide Practice in Gastric Cancer Surgery: A 6-Year Update

OBJECTIVES: The aim of the study was to evaluate the current status of gastric cancer surgery worldwide and update the changes compared to a previous survey in 2014. METHODS: A cross-sectional survey was sent to surgical members of the International Gastric Cancer Association, pilot centers of the World Organization for Specialized Studies on Diseases of the Esophagus, and the Australian and New Zealand Gastric and Oesophageal Surgeons Association in addition to participants of the 2019 International Gastric Cancer and European Society for Diseases of the Esophagus congresses. Topics addressed included hospital volume, staging, perioperative treatment, surgical approach, anastomotic techniques, lymphadenectomy, and palliative management. RESULTS: Between June 2019 and January 2020, 165 respondents from 44 countries completed the survey. In total, 80% worked in a hospital performing >20 gastrectomies annually. Staging laparoscopy and 18F-fluorodeoxyglucose positron emission tomography with computed tomography were preferred by 68 and 26% for advanced cancer, and 90% offered perioperative chemo(radio)therapy to patients. For early cancer, a minimally invasive surgical approach was preferred by 65% for distal and by 50% for total gastrectomy. For advanced cancer, this was preferred by 39% for distal and by 33% for total gastrectomy. And 84% favored a stapled anastomosis, and 14% created a jejunal pouch as reconstruction during total gastrectomy. A D2 lymphadenectomy was preferred for distal as well as for total gastrectomy, in both early (62 and 71%) and advanced (84 and 89%) cancer. CONCLUSION: This international survey demonstrates that perioperative chemotherapy and a D2 lymphadenectomy have now become the preferred treatment for gastric cancer. A minimally invasive surgical approach has gained popularity

Pain and Opioid Consumption After Laparoscopic Versus Open Gastrectomy for Gastric Cancer:A Secondary Analysis of a Multicenter Randomized Clinical Trial (LOGICA-Trial)

Background:Laparoscopic gastrectomy could reduce pain and opioid consumption, compared to open gastrectomy. However, it is difficult to judge the clinical relevance of this reduction, since these outcomes are reported in few randomized trials and in limited detail. Methods: This secondary analysis of a multicenter randomized trial compared laparoscopic versus open gastrectomy for resectable gastric adenocarcinoma (cT1-4aN0-3bM0). Postoperative pain was analyzed by opioid consumption in oral morphine equivalents (OME, mg/day) at postoperative day (POD) 1–5, WHO analgesic steps, and Numeric Rating Scales (NRS, 0–10) at POD 1–10 and discharge. Regression and mixed model analyses were performed, with and without correction for epidural analgesia. Results: Between 2015 and 2018, 115 patients in the laparoscopic group and 110 in the open group underwent surgery. Some 16 patients (14%) in the laparoscopic group and 73 patients (66%) in the open group received epidural analgesia. At POD 1–3, mean opioid consumption was 131, 118, and 53 mg OME lower in the laparoscopic group, compared to the open group, respectively (all p &lt; 0.001). After correcting for epidural analgesia, these differences remained significant at POD 1–2 (47 mg OME, p = 0.002 and 69 mg OME, p &lt; 0.001, respectively). At discharge, 27% of patients in the laparoscopic group and 43% patients in the open group used oral opioids (p = 0.006). Mean highest daily pain scores were between 2 and 4 at all PODs, &lt; 2 at discharge, and did not relevantly differ between treatment arms. Conclusion: In this multicenter randomized trial, postoperative pain was comparable between laparoscopic and open gastrectomy. After laparoscopic gastrectomy, this was generally achieved without epidural analgesia and with fewer opioids. Trial Registration: NCT02248519.</p

Laparoscopic versus open gastrectomy for gastric cancer, a multicenter prospectively randomized controlled trial (LOGICA-trial)

Background: For gastric cancer patients, surgical resection with en-bloc lymphadenectomy is the cornerstone of curative treatment. Open gastrectomy has long been the preferred surgical approach worldwide. However, this procedure is associated with considerable morbidity. Several meta-analyses have shown an advantage in short-term outcomes of laparoscopic gastrectomy compared to open procedures, with similar oncologic outcomes. However, it remains unclear whether the results of these Asian studies can be extrapolated to the Western population. In this trial from the Netherlands, patients with resectable gastric cancer will be randomized to laparoscopic or open gastrectomy. Methods: The study is a non-blinded, multicenter, prospectively randomized controlled superiority trial. Patients (≥18 years) with histologically proven, surgically resectable (cT1-4a, N0-3b, M0) gastric adenocarcinoma and European Clinical Oncology Group performance status 0, 1 or 2 are eligible to participate in the study after obtaining informed consent. Patients (n = 210) will be included in one of the ten participating Dutch centers and are randomized to either laparoscopic or open gastrectomy. The primary outcome is postoperative hospital stay (days). Secondary outcome parameters include postoperative morbidity and mortality, oncologic outcomes, readmissions, quality of life and cost-effectiveness. Discussion: In this randomized controlled trial laparoscopic and open gastrectomy are compared in patients with resectable gastric cancer. It is expected that laparoscopic gastrectomy will result in a faster recovery of the patient and a shorter hospital stay. Secondly, it is expected that laparoscopic gastrectomy will be associated with a lower postoperative morbidity, less readmissions, higher cost-effectiveness, better postoperative quality of life, but with similar mortality and oncologic outcomes, compared to open gastrectomy. The study started on 1 December 2014. Inclusion and follow-up will take 3 and 5 years respectively. Short-term results will be analyzed and published after discharge of the last randomized patient

Technical Feasibility of TachoSil Application on Esophageal Anastomoses

Purpose. Sealing esophageal anastomoses with a sealant patch (TachoSil) containing human fibrinogen and thrombin may improve mechanical strength. The aim was to evaluate the technical feasibility of the application of a sealant patch in upper gastrointestinal surgery. Methods. In total 15 patients, 18–80 years old, undergoing thoracolaparoscopic esophagectomy with esophagogastrostomy or laparoscopic total gastrectomy with esophagojejunostomy was included. Different techniques of anastomotic TachoSil patch application were tested and recorded on video. Results. TachoSil was successfully applied to the esophagogastrostomy (n=11) and to the esophagojejunostomy (n=4). A median of 2 (1–6) attempts was necessary to reach successful application. The median duration was 7 (3–26) minutes before successful application was accomplished. The best technique in esophagectomy was the application of TachoSil with the use of 2 cellophane sheets. For total gastrectomy, the patch was folded into a harmonica shape and wrapped around the esophagojejunostomy. Although not significant, the number of attempts and time to success showed a decreasing trend along with the increased experience. Conclusion. Application of TachoSil as a sealant of esophageal anastomoses was technically feasible. Future studies may investigate the value of TachoSil application on the prevention of anastomotic leakage

Worldwide practice in gastric cancer surgery

AIM: To evaluate the current status of gastric cancer surgery worldwide. METHODS: An international cross-sectional survey on gastric cancer surgery was performed amongst international upper gastro-intestinal surgeons. All surgical members of the International Gastric Cancer Association were invited by e-mail to participate. An English web-based survey had to be filled in with regard to their surgical preferences. Questions asked included hospital volume, the use of neoadjuvant treatment, preferred surgical approach, extent of the lymphadenectomy and preferred anastomotic technique. The invitations were sent in September 2013 and the survey was closed in January 2014. RESULTS: The corresponding specific response rate was 227/615 (37%). The majority of respondents: originated from Asia (54%), performed > 21 gastrectomies per year (79%) and used neoadjuvant chemotherapy (73%). An open surgical procedure was performed by the majority of surgeons for distal gastrectomy for advanced cancer (91%) and total gastrectomy for both early and advanced cancer (52% and 94%). A minimally invasive procedure was preferred for distal gastrectomy for early cancer (65%). In Asia surgeons preferred a minimally invasive procedure for total gastrectomy for early cancer also (63%). A D1+ lymphadenectomy was preferred in early gastric cancer (52% for distal, 54% for total gastrectomy) and a D2 lymphadenectomy was preferred in advanced gastric cancer (93% for distal, 92% for total gastrectomy) CONCLUSION: Surgical preferences for gastric cancer surgery vary between surgeons worldwide. Although the majority of surgeons use neoadjuvant chemotherapy, minimally invasive techniques are still not widely adapted

Management and outcome of cervical versus intrathoracic manifestation of cervical anastomotic leakage after transthoracic esophagectomy for cancer

The aim of this study was to evaluate management strategies and related outcomes for cervical versus intrathoracic manifestation of cervical anastomotic leakage after transthoracic esophagectomy for cancer with gastric conduit reconstruction. Patients with esophageal cancer undergoing transthoracic esophagectomy with cervical anastomosis from October 2003 to December 2014 were identified from a prospectively acquired database. Management strategies and related outcomes among patients with anastomotic leakage confined to the neck were compared to patients with intrathoracic manifestation of anastomotic leakage. From a total of 286 patients, leakage of the cervical anastomosis occurred in 60 patients (21%) at a median time of 7 days after esophagectomy. Leakage was confined to the neck in 23 of 60 patients (38%), whereas 37 of 60 patients (62%) presented with intrathoracic spread. Leakages with intrathoracic manifestation were more frequently accompanied by a positive SIRS score compared to leakages confined to the neck (73% vs. 35%, respectively; P = 0.004). Drainage of the anastomotic leakage through the neck wound was effective in all of 23 patients (100%) with cervical manifestation. In patients with intrathoracic manifestation, mediastinal drainage through the neck was successful in 15 of 37 patients (41%), whereas 22 patients (59%) required an intervention through the thoracic cavity. Compared to patients with leakage confined to the neck, patients with intrathoracic manifestation showed prolonged intensive care unit (ICU) stay (median 6 vs. 2 days, respectively; P = 0.001), hospital stay (median 34 vs. 19 days, respectively; P < 0.001), and time to oral intake (32 vs. 23 days, respectively; P = 0.018). Intrathoracic manifestation of cervical anastomotic leakage occurs in more than half of patients with anastomotic leakage after transthoracic esophagectomy for cancer. A SIRS reaction should raise the suspicion of intrathoracic spread of leakage. Intrathoracic manifestation can be managed effectively by mediastinal drainage through the neck in 41% of patients, but a reintervention through the thoracic cavity is required in 59%. Intrathoracic manifestation of leakage results in prolonged ICU/hospital stay and delays time to oral intake compared with leakage confined to the neck

The Oncological Value of Omentectomy in Gastrectomy for Cancer

AIM: The aim of this study was to determine the oncologic value of omentectomy in patients undergoing gastrectomy for gastric cancer. METHODS: All consecutive patients with gastric cancer that underwent gastrectomy with curative intent between April 2012 and August 2015 were prospectively analyzed. The greater omentum was separately marked during operation and pathologically evaluated for the presence of omental lymph nodes and tumor deposits. RESULTS: In total, 50 patients were included. The greater omentum harbored lymph nodes in nine (18 %) patients. The omental lymph nodes contained metastases in one (2 %) patient, still free of disease after 20 months. Omental tumor deposits were found in four (8 %) patients; one died <30 days postoperative and three developed peritoneal carcinomatosa after 4, 4, and 8 months. Patients with omental tumor deposits had a significantly reduced 1-year disease-free survival compared to patients without tumor deposits (0 vs. 58.7 %, p = 0.003). No predictive factors for omental tumor involvement could be identified. CONCLUSION: Omental lymph node metastases or tumor deposits are present in 10 % of Western European patients undergoing gastrectomy for gastric cancer. Omentectomy has a prognostic and oncologic value in the curative treatment of patients with gastric cancer. As no predictive factors for omental tumor involvement could be identified, omentectomy should be the standard in gastrectomy for gastric cancer patients

Definition of an Normal Tissue Complication Probability Model for the Inner Ear in Definitive Radiochemotherapy of Nasopharynx Carcinoma

Background: Definitive radiochemotherapy is the treatment of choice for locally advanced nasopharyngeal carcinoma. Due to the vicinity of the nasopharynx to the inner ear and the use of ototoxic platinum-based chemotherapy, there is a risk for irreversible damage to the auditory system. To avoid or minimize these critical side effects, radiation exposure to each inner ear must be balanced between target volume coverage and toxicity. However, normal tissue complication probability (NTCP) models of the inner ear validated by clinical data are rare. Patients and Methods: This retrospective study investigates the inner ear toxicity of 46 patients who received radio(chemo-)therapy for nasopharyngeal carcinoma at our institution from 2004 to 2021 according to CTCAE 5.0 criteria. For each inner ear, the mean (Dmean) and maximum (Dmax) dose in Gray (Gy) was evaluated and correlated with clinical toxicity data. Based on the data, an NTCP model and a cutoff dose logistic regression model (CDLR) were created. Results: In 11 patients (23.9%) hearing impairment and/or tinnitus was observed as a possible therapy-associated toxicity. Dmean was between 15&ndash;60 Gy, whereas Dmax was between 30&ndash;75 Gy. There was a dose-dependent, sigmoidal relation between inner ear dose and toxicity. A Dmean of 44 Gy and 65 Gy was associated with inner ear damage in 25% and 50% of patients, respectively. The maximum curve slope (m) was found at 50% and is m=0.013. The Dmax values showed a 25% and 50% complication probability at 58 Gy and 69 Gy, respectively, and a maximum slope of the sigmoid curve at 50% with m=0.025. Conclusion: There is a sigmoidal relation between radiation dose and incidence of inner ear toxicities. Dose constraints for the inner ear of &lt;44 Gy (Dmean) or &lt;58 Gy (Dmax) are suggested to limit the probability of inner ear toxicity &lt;25%

Calcification of Arteries Supplying the Gastric Tube : A New Risk Factor for Anastomotic Leakage after Esophageal Surgery

PURPOSE: To evaluate the association between the amount and location of calcifications of the supplying arteries of the gastric tube, as determined with a vascular calcification scoring system, and the occurrence of anastomotic leakage after esophagectomy with gastric tube reconstruction in patients with esophageal cancer. MATERIALS AND METHODS: Institutional review board approval was obtained, and the informed consent requirement was waived for this retrospective study. Consecutive patients who underwent elective esophagectomy for cancer with gastric tube reconstruction and cervical anastomosis between 2003 and 2012 were identified from a prospective database. Vascular calcification scores were retrospectively assigned by reviewing the routine preoperative computed tomographic (CT) images. In patients with anastomotic leakage, presence and severity of calcifications of the aorta (score of 0-2), celiac axis (score of 0-2), right postceliac arteries (common hepatic, gastroduodenal, and right gastroepiploic arteries; score of 0-1), and left postceliac arteries (splenic and left gastroepiploic arteries, score of 0-1) along with patient- and procedure-related characteristics were compared with those of patients without leakage by using multivariate logistic regression analysis. RESULTS: Of 246 patients, 58 (24%) experienced anastomotic leakage. No significant differences in patient-related factors were found between patients with leakage and those without leakage, with the exception of more chronic use of steroids in the leakage group (7% [four of 58] vs 0% [0 of 188], P = .003). At univariate analysis, leakage was more common in patients with calcification of the aorta (27% [28 of 102] and 35% [13 of 37] vs 16% [17 of 107], P = .029) and the right postceliac arteries (55% [six of 11] vs 22% [52 of 235], P = .013). At multivariate analysis, both minor (odds ratio, 2.00; 95% confidence interval: 1.02, 3.94) and major (odds ratio, 2.87; 95% confidence interval: 1.22, 6.72) aortic calcifications were associated with leakage. Also, an independent association with leakage was found for calcifications of the right postceliac arteries (odds ratio, 4.22; 95% confidence interval: 1.24, 14.4). CONCLUSION: Atherosclerotic calcification of the aorta and right postceliac arteries that supply the gastric tube is an independent risk factor for anastomotic leakage after esophagectomy