Impact of positive microscopic resection margins (R1) after gastrectomy in diffuse-type gastric cancer.

INTRODUCTION: Diffuse-type gastric cancer (DTGC) is associated with poor outcome. Surgical resection margin status (R) is an important prognostic factor, but its exact impact on DTGC patients remains unknown. The aim of this study was to assess the prognostic value of microscopically positive margins (R1) after gastrectomy on survival and tumour recurrence in DTGC patients. METHODS: All consecutive DTGC patients from two tertiary centers who underwent curative oncologic gastrectomy from 2005 to 2018 were analyzed. The primary endpoint was overall survival (OS) for R0 versus R1 patients. Secondary endpoints included disease-free survival (DFS), recurrence patterns as well as the overall survival benefit of chemotherapy in this DTGC patient cohort. RESULTS: Overall, 108 patients were analysed, 88 with R0 and 20 with R1 resection. Patients with negative lymph nodes and negative margins (pN0R0) had the best OS (median 102 months, 95% CI 1-207), whereas pN + R0 patients had better median OS than pN + R1 patients (36 months 95% CI 13-59, versus 7 months, 95% CI 1-13, p < 0.001). Similar findings were observed for DFS. Perioperative chemotherapy offered a median OS of 46 months (95% CI 24-68) versus 9 months (95% CI 1-25) after upfront surgery (p = 0.022). R1 patients presented more often early recurrence (< 12 postoperative months, 30% vs 8%, p = 0.002), however, no differences were observed in recurrence location. CONCLUSION: DTGC patients with microscopically positive margins (R1) presented poorer OS and DFS, and early tumour recurrence in the present series. R0 resection should be obtained whenever possible, even if other adverse biological features are present.

Crohn's versus Cancer: Comparison of Functional and Surgical Outcomes after Right-Sided Resections.

BACKGROUND: The objective of this study was to compare functional and surgical outcomes of patients undergoing ileocecal resection for Crohn's disease (CD) to patients undergoing oncological right colectomy. METHODS: Retrospective single-center cohort study including consecutive patients undergoing right colectomy for adenocarcinoma (oncological resection) or CD (mesentery-sparing resection) between July 2011 and November 2017. Outcome measures were pathological details (lymph node yield), postoperative recovery (pain levels, return to flatus and stool, intake of fluids, weight change, and mobilization), and early (30-day) outcomes (surgical/medical complications, hospital stay, readmissions). RESULTS: A total of 195 patients (153 [78%] with cancer and 42 [22%] with CD) were included. Overall compliance with the institutional enhanced recovery protocol was comparable between the 2 groups (compliance ≥70%: 60% in CD patients vs. 62% in cancer, p = 0.458). The adenocarcinoma group had a larger lymph node yield than the CD group (26 ± 13 vs. 2.4 ± 5, respectively, p < 0.001). While the CD group experienced significantly more pain (3.7 ± 1.9/10 vs. 2.8 ± 2.5/10, p = 0.007, patients requiring opioids: 65 vs. 28%, p = 0.001), return of flatus (2.3 ± 1.2 days vs. 2.4 ± 2.8 days, p = 0.642) and stool (4.1 ± 6.0 vs. 3.0 ± 1.8 days, p = 0.292) was no different in both groups. No difference was observed regarding postoperative complications, length of stay, and readmission rate. CONCLUSION: This study revealed no differences in both functional and surgical outcomes in CD and cancer patients undergoing mesentery-sparing or formal oncological right colectomy, respectively.

Early and delayed neurological manifestations of cardiac myxomas.

Cardiac myxoma can embolize and cause early and delayed sequelae including stroke, growth into intracranial fusiform aneurysms and cerebral tumors with risk of hemorrhage and mass effect. Here, we report the rare coincidence of all these manifestations in a 63-year-old man who presented with cognitive and behavioral changes, and seizures 9 months after an embolic stroke from the heart tumor. C-reactive protein (CRP) was elevated at the time of stroke and cardiac myxoma diagnosis but was normal at late neurologic manifestation with isolated myxoma-related intracranial tumors and aneurysms. Low-dose whole-brain radiotherapy can be helpful to diminish cerebral myxoma tumors and fusiform aneurysms despite reported increased risk of aneurysm rupture.

Reproducibility of the peritoneal regression grading score for assessment of response to therapy in peritoneal metastasis.

AIMS: The four-tiered peritoneal regression grading score (PRGS) assesses the response to chemotherapy in peritoneal metastasis (PM). The PRGS is used, for example, to assess the response to pressurised intraperitoneal aerosol chemotherapy (PIPAC). However, the reproducibility of the PRGS is currently unknown. We aimed to evaluate the inter- and intraobserver variability of the PRGS. METHODS AND RESULTS: Thirty-three patients who underwent at least three PIPAC treatments as part of the PIPAC-OPC1 or PIPAC-OPC2 clinical trials at Odense University Hospital, Denmark, were included. Prior to each therapy cycle, peritoneal quadrant biopsies were obtained and three haematoxylin and eosin (H&E)-stained step sections were scanned and uploaded to a pseudonymised web library. For determining interobserver variability, eight pathologists assessed the PRGS for each quadrant biopsy, and Krippendorff's alpha and intraclass correlation coefficients (ICCs) were calculated. For determining intraobserver variability, three pathologists repeated their own assessments and Cohen's kappa and ICCs were calculated. A total of 331 peritoneal biopsies were analysed. Interobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was moderate to good/substantial. The intraobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was good to excellent/almost perfect. CONCLUSIONS: Our data support the PRGS as a reproducible and useful tool to assess response to intraperitoneal chemotherapy in PM. Future studies should evaluate the prognostic and predictive role of the PRGS.

Synchronous tumors of the pancreas and the gallbladder: a case report with targeted NGS evaluation.

Synchronous tumors of the pancreas and gallbladder are rare and often attributed to an abnormal pancreato-biliary junction, which results in a persistent reflux of pancreatic secretions leading to chronic biliary inflammation. We present the case of a 73-year-old woman with synchronous lesions of the pancreas and gallbladder initially considered as two primary localized cancers and treated with curative intent. At relapse, targeted next generation sequencing (NGS), performed in search of potential therapeutic targets, uncovered the fact that the two lesions appeared to be clonally related. This case illustrates the problem of synchronous lesions of the pancreas and gallbladder. New pathologic assessments with comparative molecular analysis of mutational profiles may be helpful in this context.

Eosinophilic Esophagitis: Relationship of Subepithelial Eosinophilic Inflammation With Epithelial Histology, Endoscopy, Blood Eosinophils, and Symptoms.

OBJECTIVES: For technical reasons, the histologic characterization of eosinophilic esophagitis (EoE)-specific alterations is almost exclusively based on those found in the esophageal epithelium, whereas little is known about subepithelial abnormalities. In this study, we aimed to systematically assess the nature of subepithelial histologic alterations, and analyze their relationship with epithelial histologic findings, endoscopic features, and symptoms. METHODS: Adult patients with established EoE diagnosis were prospectively included during a yearly follow-up visit. Patients underwent assessment of clinical, endoscopic, and histologic disease activity using EoE-specific scores. RESULTS: We included 200 EoE patients (mean age 43.5±15.7 years, 74% males) with a median peak count of 36 intraepithelial eosinophils/hpf (IQR 14-84). The following histologic features were identified in the subepithelial layer: eosinophilic infiltration (median peak count of 20 eosinophils/hpf (IQR 10-51)), eosinophil degranulation (43%), fibrosis (82%), and lymphoid follicles (56%). Peak intraepithelial eosinophil counts were higher, identical, and lower when compared to the subepithelial layer in 62.5%, 7%, and 30.5% of patients, respectively. Anti-eosinophilic treatment at inclusion did not influence the relation between subepithelial and epithelial peak eosinophil counts. Subepithelial histologic activity correlated with epithelial histologic activity (rho 0.331, P<0.001), endoscopic severity (rho 0.208, P=0.003), and symptom severity (rho 0.179, P=0.011). Forty percent (21/52) of patients with <15 intraepithelial eosinophils/hpf had subepithelial peak counts of ≥15/hpf. CONCLUSIONS: There is a significant but modest correlation between subepithelial histologic activity and epithelial histologic activity, endoscopic severity, and symptom severity. The long-term clinical impact of assessing subepithelial alterations in EoE needs to be further elucidated.

An unusual location of gouty panniculitis: A case report.

RATIONALE: Gouty panniculitis, characterised by the deposition of monosodium urate crystals in subcutaneous tissue, is a rare clinical manifestation of gout. PATIENT CONCERNS: The case of a 67-year-old man is reported, who presented an erythematous nodule on the upper part of the right buttock suspicious for an abscess. This was in the context of chemotherapy for non-Hodgkin's lymphoma. DIAGNOSES: Histopathologic examination demonstrated gouty panniculitis. INTERVENTIONS: Because infection was suspected, an incision was performed. The lesion was found to be densely calcified and friable, without purulent discharge. Therefore, a surgical en-bloc resection was performed. OUTCOMES: The wound healed slowly initially due to a combination of malnutrition, chemotherapy and infection. A wound infection with Enterococcus faecium was treated with antibiotic therapy (carbapenem for seven days) and local therapy. At 6-week follow up the wound showed good granulation tissue and was healing well by secondary intention. The patient was instructed to continue anti-hyperuricaemic treatment. LESSONS SUBSECTIONS: In patients known to have long-standing hyperuricaemia and gout with nonspecific subcutaneous erythematous nodules, gouty panniculitis should be considered.

[Curative treatment for esophageal cancer: results of a multidisciplinary consensus]. / Traitement curatif du cancer de l'oesophage: consensus multidisciplinaire multicentrique.

The management of patients with resectable cancer of the esophagus or gastroesophageal junction is currently not standardized. A multi- disciplinary regional consensus has been developed and is presented in this article. The standard workup includes an upper endoscopy, ultrasonography and a CT-scan. For locally advanced tumors, surgery should be associated with either preoperative radiochemotherapy orperioperative chemotherapy after discussion in multidisciplinary tumor board. Before the operation, smoking and alcohol cessation is imperative and nutritional status should be optimized. Nowadays, surgery is well standardized and generally performed minimally invasive accesses. After surgery, clinical and oncological follow-up is necessary.

Mouse Model of Respiratory Tract Infection Induced by Waddlia chondrophila.

Waddlia chondrophila, an obligate intracellular bacterium belonging to the Chlamydiales order, is considered as an emerging pathogen. Some clinical studies highlighted a possible role of W. chondrophila in bronchiolitis, pneumonia and miscarriage. This pathogenic potential is further supported by the ability of W. chondrophila to infect and replicate within human pneumocytes, macrophages and endometrial cells. Considering that W. chondrophila might be a causative agent of respiratory tract infection, we developed a mouse model of respiratory tract infection to get insight into the pathogenesis of W. chondrophila. Following intranasal inoculation of 2 x 108 W. chondrophila, mice lost up to 40% of their body weight, and succumbed rapidly from infection with a death rate reaching 50% at day 4 post-inoculation. Bacterial loads, estimated by qPCR, increased from day 0 to day 3 post-infection and decreased thereafter in surviving mice. Bacterial growth was confirmed by detecting dividing bacteria using electron microscopy, and living bacteria were isolated from lungs 14 days post-infection. Immunohistochemistry and histopathology of infected lungs revealed the presence of bacteria associated with pneumonia characterized by an important multifocal inflammation. The high inflammatory score in the lungs was associated with the presence of pro-inflammatory cytokines in both serum and lungs at day 3 post-infection. This animal model supports the role of W. chondrophila as an agent of respiratory tract infection, and will help understanding the pathogenesis of this strict intracellular bacterium.

[Eosinophilic gastrointestinal disorders]. / Gastroentérite à éosinophiles.

The term « eosinophilic gastrointestinal disorders ¼ describes a group of diseases that comprises eosinophilic esophagitis, gastritis, enteritis, and colitis. Eosinophilic esophagitis is the most prevalent form while eosinophilic gastritis, enteritis, and colitis are rare. Food antigens have increasingly been found to trigger the inflammatory response. This review will highlight the epidemiology, clinical manifestations, diagnostic modalities and therapeutic options of eosinophilic gastritis, enteritis, and colitis.

L'œsophagite à éosinophiles, la gastrite, l'entérite, et la colite à éosinophiles représentent un ensemble de pathologies appartenant au groupe des « eosinophilic gastrointestinal disorders ¼. Contrairement à l'œsophagite à éosinophiles, qui présente une incidence en nette augmentation, la gastrite, l'entérite et la colite à éosinophiles, rassemblées sous le nom de gastroentérite à éosinophiles (GEE), sont des entités rares. Dans de nombreux cas, l'inflammation est déclenchée par des allergènes ingérés. Cet article fait le point sur les dernières connaissances concernant l'épidémiologie, les manifestations cliniques, les modalités diagnostiques et les options thérapeutiques de la GEE.

Is the formula of Traub still up to date in antemortem blood glucose level estimation?

According to the hypothesis of Traub, also known as the 'formula of Traub', postmortem values of glucose and lactate found in the cerebrospinal fluid or vitreous humor are considered indicators of antemortem blood glucose levels. However, because the lactate concentration increases in the vitreous and cerebrospinal fluid after death, some authors postulated that using the sum value to estimate antemortem blood glucose levels could lead to an overestimation of the cases of glucose metabolic disorders with fatal outcomes, such as diabetic ketoacidosis. The aim of our study, performed on 470 consecutive forensic cases, was to ascertain the advantages of the sum value to estimate antemortem blood glucose concentrations and, consequently, to rule out fatal diabetic ketoacidosis as the cause of death. Other biochemical parameters, such as blood 3-beta-hydroxybutyrate, acetoacetate, acetone, glycated haemoglobin and urine glucose levels, were also determined. In addition, postmortem native CT scan, autopsy, histology, neuropathology and toxicology were performed to confirm diabetic ketoacidosis as the cause of death. According to our results, the sum value does not add any further information for the estimation of antemortem blood glucose concentration. The vitreous glucose concentration appears to be the most reliable marker to estimate antemortem hyperglycaemia and, along with the determination of other biochemical markers (such as blood acetone and 3-beta-hydroxybutyrate, urine glucose and glycated haemoglobin), to confirm diabetic ketoacidosis as the cause of death.

Fatal tolperisone poisoning: autopsy and toxicology findings in three suicide cases.

Tolperisone (Mydocalm) is a centrally acting muscle relaxant with few sedative side effects that is used for the treatment of chronic pain conditions. We describe three cases of suicidal tolperisone poisoning in three healthy young subjects in the years 2006, 2008 and 2009. In all cases, macroscopic and microscopic autopsy findings did not reveal the cause of death. Systematic toxicological analysis (STA) including immunological tests, screening for volatile substances and blood, urine and gastric content screening by GC-MS and HPLC-DAD demonstrated the presence of tolperisone in all cases. In addition to tolperisone, only the analgesics paracetamol (acetaminophen), ibuprofen and naproxen could be detected. The blood ethanol concentrations were all lower than 0.10 g/kg. Tolperisone was extracted by liquid-liquid extraction using n-chlorobutane as the extraction solvent. The quantification was performed by GC-NPD analysis of blood, urine and gastric content. Tolperisone concentrations of 7.0 mg/l, 14 mg/l and 19 mg/l were found in the blood of the deceased. In the absence of other autopsy findings, the deaths in these three cases were finally explained as a result of lethal tolperisone ingestion. To the best of our knowledge, these three cases are the first reported cases of suicidal tolperisone poisonings.

An unusual case of accidental poisoning: fatal methadone inhalation.

In this report, the authors present a case of unusual, accidental methadone intoxication in a 40-year-old man, who had inhaled methadone powder. The drug dealer was a pharmacy technician; methadone had been stolen from a pharmacy and sold as cocaine. After having inhaled methadone powder, he suffered cardiopulmonary arrest. He was admitted to hospital where he died after 24 h of intensive care. The autopsy revealed congestion of internal organs and cerebral and pulmonary edema. Microscopically, the heart showed no changes. The toxicological analyses performed on blood and urine taken at the hospital revealed methadone, cannabinoids, and ethanol. The blood methadone concentration was 290 µg/L. The urine methadone concentration was 160 µg/L. Midazolam and lidocaine, which were administered to the patient at the hospital, were also detected in the blood. The cause of death was determined to be methadone intoxication. The literature has been reviewed and discussed. To date, and to our knowledge, only very few cases of accidental death resulting from methadone inhalation have been described up to the case presented herein.

Homicidal and suicidal sharp force fatalities: autopsy parameters in relation to the manner of death.

A retrospective, comparative study was carried out on 118 sharp force fatalities, including 70 homicides and 48 suicides, and covering a 22-year period from 1986 to 2008. The objective was to identify relevant parameters that may be used to distinguish between these two manners of death. The following parameters were analysed: age, gender, number of wounds, type of wounds, anatomical sites of the wounds, presence of wounds affecting bones or cartilage, the longitudinal axis of stab wounds located at the anterior part of the trunk, Injury Severity Score (ISS) and associated traumatic injuries. Our statistical analyses revealed several relevant parameters that may help differentiate the two manners of death. Homicide victims were younger than those who had committed suicide. Homicide cases showed associated stab and cut wounds, whereas suicide cases predominantly showed isolated cut wounds. Wounds located at the head, limbs, hands, nape of the neck, or back were predictive of a homicide, whereas wounds located solely at the anterior parts of the trunk, neck, or forearms were predictive of a suicide. The presence of bone or cartilage wounds was predictive of a homicide and their absence was predictive of a suicide. A vertical longitudinal axis of stab wounds located at the anterior part of the trunk was predictive of a homicide whereas a horizontal axis was predictive of a suicide. ISS was found to be significantly higher in homicide cases than in suicide cases. The presence of defensive or violence-associated traumatic wounds was predictive of a homicide whereas the presence of hesitation-associated wounds or the absence of associated traumatic wounds was predictive of a suicide.