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Alstonia scholaris (L.) R. Br., an evergreen tropical plant rich in indole alkaloids with significant physiological activity, is traditionally used to treat respiratory diseases in China. This study was conducted to establish the toxicity profile of the alkaloid extract (TA) of A. scholaris leaves in non-rodents. After oral administration of a single dose (4 g/kg.bw), a number of transient symptoms, such as unsteady gait, drooling, emesis, and reddening of peri-oral mucosa, were observed, but no treatment-related mortality. A sub-chronic toxicity study with a range of doses of TA (20, 60 and 120 mg/kg.bw) was conducted for a 13-week treatment period, followed by 4-week recovery observation. Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group, no clinical changes were observed in TA-treated animals. Data from electrocardiography, bone marrow, urine, fecal, hematology and clinical chemistry analyses were comparable between TA-treated and control animals. No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups. Accordingly, the non-observed-adverse-effect-level (NOAEL) of TA was established as 120 mg/kg.bw. Our results add further knowledge to the safety database for indole alkaloid extracts from A. scholaris with potential utility as novel drug candidates.Case report A 45-year-old female presented to the surgery emergency department with complaints of pain in the whole abdomen, vomiting and non-passage of flatus and stools for the past one day. Physical examination revealed tachycardia with a normal blood pressure. Staurosporine mw The abdomen showed diffuse tenderness and guarding and bowel sounds were absent. After appropriate fluid resuscitation, the patient underwent a non-contrast computed tomography, which showed intra-abdominal free air. She was then prepared for exploratory laparotomy. Intraoperatively, three jejunal diverticula were identified at the mesenteric side, with perforation of the distal two. Segmental resection of the jejunum, including three diverticula, with primary end-to-end anastomosis was performed. Histopathology report confirmed the diagnosis of jejunal diverticula. Conclusion Jejunal diverticula are extremely rare and are usually asymptomatic. However, such presentation warrants their inclusion under the differential diagnosis of acute abdomen, albeit lower down the order. Isolated jejunal diverticular perforation is a rare complication and may present as a surprise intraoperative finding to the operating surgeon.Breast-conserving surgery, a major achievement in surgical oncology, has allowed an increasing number of breast cancer patients to avoid the mutilation of mastectomy. However, mastectomy still is performed in certain circumstances although breast-conserving surgery would be equally safe. Many reasons, including patients' and surgeons' personal motivations, influence the decision-making process before the final choice between breast preservation and mastectomy. The importance of quality measurement and reporting in medicine is increasingly recognized, and breast surgery is no exception. The substantial variability of re-excision rates for positive surgical margins after a first attempt at breast-conserving surgery suggests that improvement is possible. Therefore, the re-excision rate has been proposed as a quality metric for assessing and comparing the performance of different institutions. Indeed, re-excision rates can be reduced by actionable factors such as accurate preoperative local staging, localization of occult lesions, and intraoperative assessment of the oriented specimen. However, equally important non-actionable risk factors pertaining the biology, detectability, and resectability of the tumor also should be taken into account. Therefore, if the re-excision rate has to be used as a performance indicator of breast surgical care, critical interpretation of results with accurate case-mix adjustment are mandatory, and reasonable targets must be appropriately set so that surgeons treating patients at higher risk of positive margins are not unduly penalized.Background Pathological complete response (pCR) following neoadjuvant treatment for locally advanced rectal cancer (LARC) is associated with better survival, less local recurrence, and less distant failure. Furthermore, pCR indicates that the rectum may have been preserved. This meta-analysis gives an overview of available neoadjuvant treatment strategies for LARC and analyzes how these perform in achieving pCR as compared with the standard of care. Methods Pubmed, Embase, and Cochrane Central bibliographic databases were searched. Randomized controlled trials in which patients received neoadjuvant treatment for MRI-staged nonmetastatic resectable LARC were included. The primary outcome was pCR, defined as ypT0N0. A meta-analysis of studies comparing an intervention with standard fluoropyrimidine-based chemoradiation (CRT) was performed. Results Of the 17 articles included in the systematic review, 11 were used for the meta-analysis. Addition of oxaliplatin to fluoropyrimidine-based CRT resulted in significantly more pCR compared with fluoropyrimidine-based CRT only (OR 1.46), but at the expense of more ≥ grade 3 toxicity. Other treatment strategies, including consolidation/induction chemotherapy and short-course radiotherapy (SCRT), did not improve pCR rates. None of the included trials reported a benefit in local control or OS. Five-year DFS was significantly worse after SCRT-delay compared with CRT (59% vs. 75.1%, HR 1.93). Conclusions All included trials fail to deliver high-level evidence to show an improvement in pCR compared with standard fluoropyrimidine-based CRT. The addition of oxaliplatin might result in more pCR but at the expense of more toxicity. Furthermore, this benefit does not translate into less local recurrence or improved survival.Background Sentinel lymph node biopsy (SLNB) is recommended for intermediate thickness melanoma, but for thick melanoma, guidelines are less definitive about the use of SLNB in this population. We present a study on thick melanoma evaluating for prognostic factors. Patients and methods The Sentinel Lymph Node Working Group database was queried for thick (> 4 mm) melanoma cases that had a SLNB from 1993 to 2018. Clinicopathologic characteristics were correlated with SLN status and melanoma-specific survival (MSS). Results There were 1235 patients. Median follow-up was 28 months. Median thickness was 5.9 mm, with 956, 175, and 104 cases presenting thickness > 4-8, > 8-12, and > 12 mm, respectively. SLN metastases were seen in 439 of 1235 (35.5%) cases and in 33.9%, 40.6%, and 42.3% of melanomas > 4-8, > 8-12, and > 12 mm, respectively. In each thickness group, MSS was significantly worse for SLN-positive compared with SLN-negative cases (all P 12 mm HR 3.58, 95% CI 1.56-8.22, p less then 0.0027). Conclusions Thick melanoma patients with SLN metastasis have significantly worse MSS compared with SLN-negative patients, even in the thickest cases, and SLN status is the most powerful and/or only predictor of MSS. Given these results, SLNB shows important prognostic value in this population and is indicated for clinically localized thick melanoma.Background Surgery alone is standard-of-care for stage I gastric adenocarcinoma; however, clinicians can offer preoperative therapy for clinical stage I disease with signet ring cell histology, given its presumed aggressive biology. We aimed to assess the validity of this practice. Methods The National Cancer Database (2004-2015) was reviewed for patients with clinical stage I signet ring cell gastric adenocarcinoma who underwent treatment with surgery alone, perioperative chemotherapy, neoadjuvant therapy, or adjuvant therapy. Analysis was stratified by preoperative clinical/pathologic stage. Primary outcome was overall survival (OS). Results Of 1018 patients, median age was 60 years (±14); 53% received surgery alone (n = 542), 5% received perioperative chemotherapy (n = 47), 12% received neoadjuvant therapy (n = 125), and 30% received adjuvant therapy (n = 304). For clinical stage I disease, surgery alone was associated with an improved 5-year OS rate (71%) versus perioperative chemotherapy (58%), neoadjuvaastric adenocarcinoma.Background Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment for peritoneal carcinomatosis. Objective The aim of this study was to determine the predictive value of postoperative inflammatory biomarkers in assessing complications after CRS and HIPEC. Methods A prospective database of 181 patients, who underwent CRS-HIPEC between March 2014 through April 2018 in the Erasmus MC, was retrospectively analyzed. Postoperative complications were defined according to the serious adverse event (SAE) grading system. Levels of C-reactive protein (CRP) and white blood cell (WBC) count were compared between patients with SAE grade less then 3 and SAE grade ≥ 3. The area under the receiver operating characteristic curve (AUC) was calculated for CRP and WBC against SAE ≥ 3 and various intra-abdominal complications. Results SAE ≥ 3 postoperative complications occurred in 50 patients. From the second until the fifth postoperative day (POD), CRP levels were significantly higher (p = 0.023, p less then 0.001, p = 0.002, and p = 0.002, respectively) in these patients. CRP concentrations above 166 mg/L on POD3 (AUC 0.75) and 116 mg/L on POD4 (AUC 0.70) were associated with the highest risk of an SAE ≥ 3. Postoperative WBC levels were not significantly different between patients with SAE less then 3 and SAE ≥ 3 complications. Conclusion Data from our hospital suggest that CRP levels that continue to rise after POD2 or that are ≥ 166 mg/L at POD3 or ≥ 116 mg/L at POD4, indicate a considerable risk for developing high-grade SAEs. The cut-off values we found can potentially be used as a threshold for additional diagnostic interventions, after they have been validated in external data.Background Although squamous cell carcinoma antigen (SCC-Ag) is a tumor marker widely used to estimate the progression of esophageal SCC (ESCC), only a few studies have focused on the relationship between serum SCC-Ag levels and the therapeutic effect of neoadjuvant chemotherapy (NAC). Objective This study aimed to elucidate the clinical significance of pretherapeutic serum SCC-Ag levels in patients who underwent NAC followed by esophagectomy. Methods Data of 453 patients who underwent NAC followed by esophagectomy were collected from the esophageal cancer database of two high-volume Japanese centers. Serum SCC-Ag levels were measured prior to NAC, and the pathological therapeutic effect of NAC and patient survival were evaluated. Patients were classified according to the tertiles of the serum SCC-Ag value (low, middle, and high groups), and the outcomes among the groups were compared. Results The levels of serum SCC-Ag were significantly associated with tumor stage (p less then 0.01). With regard to the pathological therapeutic effect, the levels of serum SCC-Ag were negatively correlated with the therapeutic effect (p = 0.02). Moreover, increased levels of serum SCC-Ag negatively influenced relapse-free survival (p less then 0.01). Multivariate analyses revealed the 'high' group as the independent factor for both the unfavorable therapeutic effect (p = 0.01) and the increased risk of disease recurrence (p less then 0.01) when compared with the 'low' group. Conclusion Elevated levels of pretherapeutic serum SCC-Ag are significantly associated with advanced tumor stage, poor response to NAC, and increased risk of disease recurrence.

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