Substratifying the risk of covert malignancy in significant rectal polyps: Outcomes from a specialist multidisciplinary team (MDT).

AIM: A treatment strategy for patients with a significant polyp or early colon cancer (SPECC) of the rectum presents a challenge due to the significant rate of covert malignancy and lack of standardized assessment. For this reason, NICE recommends multidisciplinary meetings to improve outcomes. The primary aim of the present study was to report the performance of our specialist early rectal cancer (SERC) multidisciplinary team (MDT) in correctly substratifying the risk of cancer and to discuss the limitations of staging investigations in those patients with "poor outcomes". METHOD: This was a retrospective review of patients referred to our SERC MDT from 2014 to 2019. Lesions were assigned by the MDT to three pre-resection categories (low, intermediate, high) according to the risk of covert malignancy. Resection method and final histology were compared to the pre-resection categories. RESULTS: Of 350 SPECC lesions, 174 were assessed as low-risk, 108 intermediate-risk and 68 high-risk. The cancer incidence was 4.8%, 8.3% and 53%, respectively (15.5% overall). Eight lesions were categorized as low-risk but following piecemeal resection were found to be malignant. Five lesions, three of which were categorized as high-risk, were ultimately benign following conventional surgery. One pT1sm1 cancer, removed by anterior resection, may have been treated by local excision. CONCLUSION: A total of 83% of malignant polyps were triaged to an en bloc resection technique and surgical resection avoided for nearly all benign lesions. However, 12 patients from this cohort were deemed to have a poor outcome because of miscategorization. Further comparative research is needed to establish the optimum strategy for rectal SPECC lesion assessment. ORIGINALITY STATEMENT: There is currently no consensus for staging significant polyps of the rectum. This paper reports the effectiveness of a specialist early rectal cancer MDT to correctly risk-stratify significant rectal polyps. It underscores the importance of accurate categorization for treatment decision-making, while acknowledging the limitations of current staging modalities.

Evaluation of Different Regimens of Palliative Radiation Therapy for Symptomatic Bone Metastases: An Audit From a Tertiary Care Hospital in Jharkhand, India.

Background This study aimed to assess the efficacy of different radiation therapy regimens in treating patients with symptomatic bone metastases. Methodology A retrospective study was conducted by assigning patients with symptomatic bone metastases from different primary cancers into three groups, namely, Arms A, B, and C. The radiation dose delivered in each arm was as follows: 8 Gray (Gy) in a single fraction for Arm A, 20 Gy in five fractions at the rate of 4 Gy per fraction for Arm B, and 30 Gy in 10 fractions at the rate of 3 Gy per fraction for Arm C. Each arm consisted of 15 patients. A comparison was conducted across all three arms to evaluate pain relief based on the Visual Analog Scale (VAS), performance score improvement based on the Eastern Cooperative Oncology Group (ECOG), and analgesic requirement based on the World Health Organization (WHO) step ladder at one week, one month, and three months. Results The pain relief was measured using the VAS in three different arms, i.e., Arm A, B, and C. After one week, the pain relief was 66.67%, 60%, and 60%, respectively. After one month, it was 73.33% in all three arms. At three months, it was 80%, 86.67%, and 86.67%, respectively. The study also measured the improvement in the ECOG performance score. The improvement in all three arms was 60% after one week and 66.67% in Arm A and 73.33% in Arms B and C after one month. After three months, the improvement was 73.33%, 80%, and 80% in Arms A, B, and C, respectively. The decrease in analgesic usage was also measured in all three arms. After one week, it was 60% in all three arms. After one month, it was 66.67%, 73.33%, and 73.33% in Arms A, B, and C, respectively. At three months, it was 73.33%, 80%, and 80% in Arms A, B, and C, respectively. No significant statistical difference was found between the three arms. Conclusions The efficacy of a single 8 Gy arm was almost equivalent to that of other arms of multifractionated regimens in terms of improvement in pain and performance score and decreased use of analgesics for a short duration of follow-up. For high-volume cancer centers and patients with economic constraints, a single-fraction regime provides effective palliation for painful bone metastases.

Accumulation of resveratrol, ferulic acid and iron in seeds confer iron deficiency chlorosis tolerance to a novel genetic stock of peanut (Arachis hypogaea L.) grown in calcareous soils.

Peanut is mostly grown in calcareous soils with high pH which are deficient in available iron (Fe2+) for plant uptake causing iron deficiency chlorosis (IDC). The most pertinent solution is to identify efficient genotypes showing tolerance to limited Fe availability in the soil. A field screening of 40 advanced breeding lines of peanut using NRCG 7472 and ICGV 86031 as IDC susceptible and tolerant checks, respectively, was envisaged for four years. PBS 22040 and 29,192 exhibited maximum tolerance while PBS 12215 and 12,185 were most susceptible. PBS 22040 accumulated maximum seed resveratrol (5.8 ± 0.08 ppm), ferulic acid (378.6 ± 0.31 ppm) and Fe (45.59 ± 0.41 ppm) content. Enhanced chlorophyll retention (8.72-9.50 µg ml-1), carotenoid accumulation (1.96-2.08 µg ml-1), and antioxidant enzyme activity (APX: 35.9-103.9%; POX: 51- 145%) reduced the MDA accumulation (5.61-9.11 µM cm-1) in tolerant lines. The overexpression of Fe transporters IRT1, ZIP5, YSL3 was recorded to the tune of 2.3-9.54; 1.45-3.7; 2.20-2.32- folds respectively in PBS 22040 and 29,192, over NRCG 7472. PBS 22040 recorded the maximum pod yield (282 ± 4.6 g/row), hundred kernel weight (55 ± 0.7 g) and number of pods per three plants (54 ± 1.7). The study thus reports new insights into the roles of resveratrol, ferulic acid and differential antioxidant enzyme activities in imparting IDC tolerance. PBS 22040, being the best performing line, can be the potent source of IDC tolerance for introgression in high yielding but susceptible genotypes under similar edaphic conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01321-9.

Exploring scientific validation of Triphala Rasayana in ayurveda as a source of rejuvenation for contemporary healthcare: An update.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayurveda remains the classical and comprehensive part of the ancient Indian medicine system for well-being promotive, disease preventive, and revival approach for the human body. Triphala Rasayana is mentioned in Ayurveda, comprising fruits of three plant species viz. Phyllanthus emblica L. (P. emblica), Terminalia chebula Retz (T. chebula), and Terminalia bellirica Roxb (T.bellirica). Triphala Rasayana has been utilized in various traditional medicine systems, viz., Ayurveda, Siddha, and Unani. Traditionally Rasayana based drugs are utilized in different kinds of diseases without pathophysiological associations as indicated by current medication. Various medicinal attributes of Triphala Rasayana include antioxidant, anticancer, antidiabetic, antimicrobial, immunomodulatory, and anticataract and is also considered as a pillar for gastrointestinal treatment, specifically in functional gastrointestinal disorders (FGIDs). Due to Rasayana's accessible mode of administration, availability, and affordability, there is an increase in its global acceptance. AIM OF REVIEW: This review article summarizes the scientific validation, traditional uses, bioactive compounds, and ethnopharmacological properties of Triphala Rasayana. It also documents recent data on in vivo and in vitro pharmacological studies and clinical effects of Triphala Rasayana. MATERIAL AND METHOD: A literature review is carried out using PubMed, ScienceDirect, Scopus, web of science, Ayush Research Portal, and Clinical Trials Registry-India. In addition to an electronic search, traditional ayurvedic texts and books were used as sources of information. RESULTS: Traditionally, "Triphala Rasayana" is classified as a tridoshic rasayana and one of the most well-studied ayurvedic Rasayana. It showed various pharmacological activities such as anticancer, antioxidant, antibacterial, immunomodulatory, cardioprotective, and antidiabetic. Besides this, Rasayana has reported ethnopharmacological activities such as antimicrobial, anticataract, wound healing, and radioprotection. It has shown a good impact on the gastrointestinal tract (GIT) system with the reported pharmacological activities in gastrointestinal disorders such as constipation, gastric ulcer, and inflammatory bowel disease (IBD). Phytochemical studies of Triphala Rasayana revealed chemical constituents like gallic acid, ellagic acid, chebulic acid, chebulinic acid, methyl gallate, emblicanin A, and emblicanin B. Additionally, clinical studies found Triphala Rasayana to be effective against diabetes, constipation, and obesity. CONCLUSION: The present review revealed that Triphala Rasayana may treat a diverse range of diseases, especially GIT disorders. Considering the beneficial properties of Triphala Rasayana and it's proven non-toxic nature could be a source of rejuvenation in contemporary healthcare. Nevertheless, its clinical data effectively provided precious signals to correlate ayurvedic biology and modern medicine.

Collagenous panenteritis: a rare cause of chronic diarrhoea.

Collagenous panenteritis is a rare inflammatory condition that causes profound diarrhoea and weight loss. There has only been a handful of cases reported in the literature. We report this rare case and the diagnostic difficulties encountered in securing the diagnosis. A 59-year-old woman presented with an 8-month history of diarrhoea and weight loss on a background of a family history of coeliac disease. Her presentation was complicated with acute kidney injury secondary to prerenal losses. Repeated gastroscopies and colonoscopies along with biopsies were inconclusive. It was not until histology of biopsies taken at endoscopies were reviewed that a diagnosis of collagenous panenteritis was secured. Her management revolved around combination of budesonide, gluten-free diet and antidiarrhoeals, which has achieved clinical remission.

Developing a protocol for gastrostomy tube insertion in patients diagnosed with head and neck cancer.

Selecting patients with head and neck cancer requiring a pretreatment gastrostomy feeding tube is not straightforward. The nutritional status and functional deficits associated with the cancer, its treatment, and the long-term side effects predicate the need for gastrostomy tube placement. However, gastrostomy tubes are not without morbidity and are an added burden to the patient. The aim of this retrospective case series review was to evaluate the clinical characteristics of newly diagnosed patients with head and neck cancer treated with curative intent having gastrostomy placement, with the intent of developing a protocol to help with the timely selection of patients for pretreatment gastrostomy insertion. A gastrostomy tube was placed in 32%. A regression model identified 5 independent predictors (P < .001) to predict gastrostomy tube placement: overall clinical stage, tumor site, clinical T stage, patient age, and clinical N stage. A protocol to help the multidisciplinary team to decide whether a pretreatment gastrostomy tube should be placed is suggested.

The role of matrix metalloproteinase-7 in redefining the gastric microenvironment in response to Helicobacter pylori.

BACKGROUND & AIMS: Interactions between epithelial and stromal cells are important determinants of mucosal organization, but the signaling mechanisms are understood incompletely. Matrix metalloproteinase (MMP)-7 is produced uniquely in epithelia, may act on growth factors and matrix proteins, and in the stomach is increased with Helicobacter pylori infection. We have studied the role of MMP-7 in signaling between epithelial cells and a key stromal cell type, the myofibroblast. METHODS: Immunohistochemistry and Western blotting were applied to gastric corpus biopsy specimens; primary cultures of human gastric glands and myofibroblasts were used to study the role of MMP-7 in regulating proliferation and migration of the latter, and MMP-7 substrates were identified by proteomic methods. RESULTS: Increased abundance of the myofibroblast marker alpha-smooth muscle actin was identified in H. pylori-positive biopsy specimens. Media from H pylori-infected gastric epithelial cultures stimulated proliferation and migration of primary human gastric myofibroblasts and antisense oligonucleotide treatment indicated a role for MMP-7. Proteomic methods identified insulin-like growth factor binding protein (IGFBP)-5 as a substrate for MMP-7 in medium from gastric myofibroblasts. Knockdown of IGFBP-5 by small interfering RNA or immunoneutralization of IGF-II, abolished myofibroblast responses to MMP-7. Proliferation of gastric epithelial cells also was stimulated by MMP-7-treated myofibroblasts via IGF-II. CONCLUSIONS: MMP-7 acts as an epithelial-derived signal increasing the bioavailability of IGF-II released from myofibroblasts. Because IGF-II acts on both stromal and epithelial cells, the findings suggest that increased MMP-7 expression contributes to redefining the niche occupied by dividing cells and leading to hyperproliferation in H pylori infection.

Identification of plasminogen activator inhibitor-2 as a gastrin-regulated gene: Role of Rho GTPase and menin.

BACKGROUND & AIMS: The gastric hormone gastrin regulates acid secretion, gene expression, and the functional development and cellular composition of the gastric mucosa. Using a gene array, we sought to identify major, novel, gastrin-regulated genes. METHODS: A cancer gene array was probed with samples from the gastric cancer cell line AGS, expressing the gastrin-cholecystokinin(B) receptor and stimulated with gastrin. The expression of gastrin-regulated genes was further characterized by Western blots and enzyme-linked immunosorbent assay in tissue and blood of hypergastrinemic patients. Gene expression was studied using promoter-luciferase reporter constructs. RESULTS: Plasminogen activator inhibitor 2 (PAI-2) was identified as a major, previously unknown target of gastrin in the gastric cancer cell line AGS. The relevance was confirmed by showing elevated tissue and plasma PAI-2 in hypergastrinemic patients (pernicious anemia and multiple endocrine neoplasia type 1). PAI-2 promoter-luciferase constructs showed that gastrin stimulated expression via pathways involving Galpha and Gbetagamma subunits, protein kinase C, RhoA, and the transcription factors CREB and AP1. The tumor suppressor menin inhibited transcription. In addition, gastrin stimulated expression in adjacent cells via a paracrine mechanism involving protein kinase C and RhoA but not CREB. CONCLUSIONS: A gene array showed PAI-2 to be a novel gastrin-regulated gene, stimulated in part through CREB and AP-1 and inhibited by the tumor suppressor menin.