Inguinal lymph node metastases from rectal adenocarcinoma: a systematic review.

PURPOSE: Inguinal lymph nodes are a rare but recognised site of metastasis in rectal adenocarcinoma. No guideline or consensus exists for the management of such cases. This review aims to provide a contemporary and comprehensive analysis of the published literature to aid clinical decision-making. METHODS: Systematic searches were performed using the PubMed, Embase, MEDLINE and Scopus and Cochrane CENTRAL Library databases from inception till December 2022. All studies reporting on the presentation, prognosis or management of patients with inguinal lymph node metastases (ILNM) were included. Pooled proportion meta-analyses were completed when possible and descriptive synthesis was utilised for the remaining outcomes. The Joanna Briggs Institute tool for case series was used to assess the risk of bias. RESULTS: Nineteen studies were eligible for inclusion, encompassing 18 case series and one population-based study using national registry data. A total of 487 patients were included in the primary studies. The prevalence of ILNM in rectal cancer is 0.36%. ILNM are associated with very low rectal tumours with a mean distance from the anal verge of 1.1 cm (95% CI 0.92-1.27). Invasion of the dentate line was found in 76% of cases (95% CI 59-93). In patients with isolated inguinal lymph node metastases, modern chemoradiotherapy regimens in combination with surgical excision of inguinal nodes are associated with 5-year overall survival rates of 53-78%. CONCLUSION: In specific subsets of patients with ILNM, curative-intent treatment regimens are feasible, with oncological outcomes akin to those demonstrated in locally advanced rectal cancers.

Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe. METHODS: A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors. RESULTS: Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4-12.6), NAB+GEM 7.9 months (95%CI 6.2-10.0), other combinations 8.5 months (95%CI 7.7-9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4-5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1-3) with poor prognosis. CONCLUSION: Gemcitabine monotherapy was predominantly used in 2012-2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.

Potential effect of luteolin, epiafzelechin, and albigenin on rats under cadmium-induced inflammatory insult: In silico and in vivo approach.

Introduction: Cadmium(Cd) an industrial poison present abundantly in the environment, causes human toxicity by an inflammatory process. Chronic exposure of cadmium can cause a number of molecular lesions that could be relevant to oncogenesis, through indirect or epigenetic mechanisms, potentially including abnormal activation of oncogenes and suppression of apoptosis by depletion of antioxidants. As induction of cyclooxygenase (COX)-2 is linked to inflammatory processes, use of luteolin, epiafzelechin, and albigenin alone or in different combinations may be used as anti-inflammatory therapeutic agents. Methods: We, herein, performed in silico experiments to check the binding affinity of phytochemicals and their therapeutic effect against COX-2 in cadmium administered rats. Wistar albino rats were given phytochemicals in different combinations to check their anti-inflammatory activities against cadmium intoxication. The level of alanine aminotransferases (ALT), 4-hydroxynonenal (4HNE), 8-hydroxy-2-deoxyguanosine (8-OHdG), tumor necrosis factor-alpha (TNF-α), isoprostanes (IsoP-2α), COX-2, and malondialdehyde (MDA) were estimated with their respective ELISA and spectrophotometric methods. Results: The generated results show that phytocompounds possessed good binding energy potential against COX-2, and common interactive behavior was observed in all docking studies. Moreover, the level of ALT, 4HNE, 8-OHdG, TNF-α, IsoP-2α, malondialdehyde, and COX-2 were significantly increased in rats with induced toxicity compared to the control group, whereas in combinational therapy of phytocompounds, the levels were significantly decreased in the group. Discussion: Taken together, luteolin, epiafzelechin, and albigenin can be used as anti-inflammatory therapeutic agents for future novel drug design, and thus it may have therapeutic importance against cadmium toxicity.

Real-world comparison of curative open, laparoscopic and robotic resections for sigmoid and rectal cancer-single center experience.

There has been an increase in the utilization of robotic surgery in addition to traditional open or laparoscopic approaches. Aim of this study is to compare the short-term outcomes for open, laparoscopic, and robotic surgery for rectal and sigmoid cancer. One hundred and forty-seven patients (open n = 48, laparoscopic n = 49, robotic n = 50) undergoing curative resections by two surgeons between 2013 and 2020 were included. Data analyzed included patient demographics, tumor characteristics, length of stay, post-operative outcomes, and pathologic surrogates of oncologic results, including total mesorectal excision (TME) quality, circumferential resection margin (CRM) involvement and lymph node (LN) yield. Median age of population was 68 years (IQR 59-73), majority (68%) were males. Median distance from anal verge in the robotic surgery group was 8 cm, compared to 15 and 14.5 cm in the open and laparoscopic groups, respectively, p = 0.029, (laparoscopic vs robotic, p = 0.005 and open vs robotic, p = 0.027). Proportion of patients who received neoadjuvant radiotherapy in robotic surgery group was higher, p = 0.04. In sub-group of tumors between 3 and 7 cm from anal verge more patients in the robotic surgery group had sphincter preservation, p = 0.006. Length of stay, maximum C-reactive protein, and white blood cell rise favored minimally invasive approaches compared to open surgery. There were no differences in post-operative complications, lymph node yield or CRM positivity rate between the three groups. Robotic surgery approach is safe and allows sphincter preservation without compromising TME quality in rectal cancer surgery.

The Pakistan Risk of Myocardial Infarction Study: a resource for the study of genetic, lifestyle and other determinants of myocardial infarction in South Asia.

The burden of coronary heart disease (CHD) is increasing at a greater rate in South Asia than in any other region globally, but there is little direct evidence about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS) is an epidemiological resource to enable reliable study of genetic, lifestyle and other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over 5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over 5,000 matched controls aged 30-80 years. For each participant, information has been recorded on demographic factors, lifestyle, medical and family history, anthropometry, and a 12-lead electrocardiogram. A range of biological samples has been collected and stored, including DNA, plasma, serum and whole blood. During its next stage, the study aims to expand recruitment to achieve a total of about 20,000 cases and about 20,000 controls, and, in subsets of participants, to enrich the resource by collection of monocytes, establishment of lymphoblastoid cell lines, and by resurveying participants. Measurements in progress include profiling of candidate biochemical factors, assay of 45,000 variants in 2,100 candidate genes, and a genomewide association scan of over 650,000 genetic markers. We have established a large epidemiological resource for CHD in South Asia. In parallel with its further expansion and enrichment, the PROMIS resource will be systematically harvested to help identify and evaluate genetic and other determinants of MI in South Asia. Findings from this study should advance scientific understanding and inform regionally appropriate disease prevention and control strategies.

TRO40303 Ameliorates Alcohol-Induced Pancreatitis Through Reduction of Fatty Acid Ethyl Ester-Induced Mitochondrial Injury and Necrotic Cell Death.

OBJECTIVES: Mitochondrial permeability transition pore inhibition is a promising approach to treat acute pancreatitis (AP). We sought to determine (i) the effects of the mitochondrial permeability transition pore inhibitor 3,5-seco-4-nor-cholestan-5-one oxime-3-ol (TRO40303) on murine and human pancreatic acinar cell (PAC) injury induced by fatty acid ethyl esters (FAEEs) or taurolithocholic acid-3-sulfate and (ii) TRO40303 pharmacokinetics and efficacy in experimental alcoholic AP (FAEE-AP). METHODS: Changes in mitochondrial membrane potential (Δψm), cytosolic Ca ([Ca]c), and cell fate were examined in freshly isolated murine or human PACs by confocal microscopy. TRO40303 pharmacokinetics were assessed in cerulein-induced AP and therapeutic efficacy in FAEE-AP induced with palmitoleic acid and ethanol. Severity of AP was assessed by standard biomarkers and blinded histopathology. RESULTS: TRO40303 prevented loss of Δψm and necrosis induced by 100 µM palmitoleic acid ethyl ester or 500 µM taurolithocholic acid-3-sulfate in murine and human PACs. Pharmacokinetic analysis found TRO40303 accumulated in the pancreas. A single dose of 3 mg/kg TRO40303 significantly reduced serum amylase (P = 0.043), pancreatic trypsin (P = 0.018), and histopathology scores (P = 0.0058) in FAEE-AP. CONCLUSIONS: TRO40303 protects mitochondria and prevents necrotic cell death pathway activation in murine and human PACs, ameliorates the severity of FAEE-AP, and is a candidate drug for human AP.