Role of expression of P63 and calponin in gastro-intestinal tract carcinomas

BACKGROUND: Gastrointestinal tract malignancies are causing significant morbidity and mortality constituting 27% of all cancer related deaths worldwide with highest burden of 62% in Asia. In developing countries like India, due to life style modifications and environmental factors the incidence of GIT malignancies are increasing nowadays. P63 and Calponin are the new immunohistochemical markers tried in GIT malignancies and the results were promising. So in our study, the expression of these two immunohistochemical markers were done and correlated with histopathological grading and lymph node status of these cases. OBJECTIVES: 1. To correlate the age, sex and anatomical site of distribution of gastrointestinal tract malignancies. 2. To study the histopathological features of gastrointestinal tract malignancies. 3. To study the role of expression of immunohistochemaical markers P63 and calponin in gastrointestinal tract malignancies. 4. To correlate the histopathological features with expression of immunohistochemical markers P63 and calponin. MATERIALS AND METHODS: A total of 60 cases of gastrointestinal tract carcinomas, 33 cases of GIT biopsies and 27 cases of GIT specimens were taken for the study. The study was conducted for three years (from June 2014 to June 2017). H & E sections and immunohistochemistry was done for the selected blocks of formalin fixed paraffin embedded sections. IHC done by using p63 and calponin for all the cases and the stastical analysis was done to evaluate the prognostic significance of these markers. RESULTS: In the present study, the most common age group involved in gastrointestinal tract malignancies was 61 – 70 years. Males are affected more than females with a sex ratio of 2.33:1. Stomach (antrum) is the most common anatomical site involved in GIT malignancies constituting 36.7% of all the cases followed by rectum with 16%.The most common histopathological diagnosis was adenocarcinoma, constituting around 88% of the total cases and the least common was malignant melanoma with 3.3%. The most common histopathological grade was moderately differentiated carcinomas constituting 36% of total cases (22 cases). The expression of IHC markers p63 and calponin were studied and compared with lymph node status and histopathological grade of tumors and the “p” values were found significant of < 0.05. p63 expression was found to be high in poorly differentiated carcinomas and calponin expression was low in poorly differentiated carcinomas. CONCLUSION: In this study, Increased expression of p63 is directly related to the lymph node metastases and the grade of the tumors. While calponin expression is inversely related to the grade and lymph node status of the cases studied. This study clearly showed that higher expression of calponin inhibits tumor metastases, tumor angiogenesis and tumor invasion, especially in patients with colorectal carcinomas. So targeted therapy with calponin will be prognostically beneficial to the patients with gastrointestinal tract carcinomas. Similarly p63 targeted therapy will be beneficial and improves the survival rate of the patients with gastrointestinal tract malignancies, especially in poorly differentiated esophageal carcinomas, gastric carcinomas and colorectal carcinomas

Improving surgery and prognostication in right-sided colon cancer

Bakgrunn Kreft i tykktarm er blant de vanligste kreftformene i Norge. Kirurgi er viktigste behandling for tykktarmskreft uten spredning, men har ikke gjennomgått samme forbedringer som behandling for endetarmskreft. En faktor som bidro til bedre overlevelse for endetarmskreft var standardisering av og mer radikal kirurgi. Det er på tide at behandling for tykktarmkreft gjennomgår tilsvarende forbedringer. Forskjeller i anatomi, biologi og prognose relatert til svulstens lokalisasjon i tykktarmen førte søkelyset til høyresidig tarmkreft. Kirurgi for proksimale svulster er teknisk vanskelig i tillegg til at de har en særegen biologi og dårlig prognose. Kjennskap til svulstens biologi er nødvendig for persontilpasset kreftbehandling, og inspirerte til en studie med flytende biopsi og analyse av sirkulerende DNA fra svulsten (ctDNA). Formål Målet med studien var å sammenlikne komplikasjoner etter radial kirurgi hos pasienter operert med åpen- eller kikkhullsoperasjon for høyresidig tykktarmskreft. Spesifikke komplikasjoner ble også undersøkt. Lengden på gjenværende karstump etter reseksjon ble vurdert som et mål på kvalitet. Målet med biomarkørstudien var å undersøke om ctDNA kan forutsi tilbakefall. Metode I studien ble 128 pasienter randomisert til åpen- eller kikkhulls-operasjon. Kirurgien ble utført standardisert og med mål om å fjerne de sentrale lymfeknutene i operasjonsområdet. De første 40 pasientene, 20 fra hver gruppe, ble undersøkt med måling av gjenværende stump fra blodkaret etter operasjon. Målingen ble utført på CT tatt 6 måneder etter operasjon, og ble utført to ganger av to uavhengige radiologer. I den prospektive observasjonsstudien for biomarkører ble 50 pasienter undersøkt med neste generasjons sekvensering og digital dråpe PCR (ddPCR) for kreftrelaterte mutasjoner i svulst og blod. Resultat Det var ingen forskjeller i komplikasjoner mellom de to gruppene. Det var ingen livstruende komplikasjoner og få alvorlige komplikasjoner med 8 % i den åpne gruppen og 5 % i kikkhulls-gruppen. Ingen pasienter ble reoperert for lekkasje i tarmskjøten. Blodoverføring eller infusjon av jern var den vanligste komplikasjonen (22 % åpen vs. 15 % kikkhull). Postoperativ tarmparalyse var den nest vanligste komplikasjonen, og ble registret hos 16 % operert åpent og 19 % operert med kikkhull. Det ble i gjennomsnitt fjernet like mange lymfeknuter ved åpen operasjon (n=32) som ved kikkhullsoperasjon (n=29). Gjenværende karstump var kort og lik i begge grupper (4mm). Det var godt samsvar mellom målingene til hver radiolog, mens det var forskjeller mellom de to. Forskjellene forekom i den åpne gruppen hvor det ikke var markør på karet som var delt. Kreftrelaterte mutasjoner ble funnet hos 49/50 pasienter, og 47 av disse var mulig å følge med ddPCR. ctDNA kunne påvises hos 31/47 pasienter før operasjon, og ble redusert etter operasjon hos 27/31. Risiko for tilbakefall var forhøyet hos pasienter hvor ctDNA kunne påvises etter operasjon (justert hazard ratio: 173). Konklusjon/implikasjoner Høyresidig kolektomi med sentral lymfeknutedisseksjon foran vena mesenterica superior er en anvendelig, trygg og reproduserbar metode som kan bli fremtidig standard ved høyresidig tykktarmskreft. Lengden av gjenværende karstump kan være kvalitetsmarkør for omfang av lymfeknutedisseksjon. ctDNA kan forutsi tidlig tilbakefall ved høyresidig tykktarmskreft.Background The incidence of colon cancer is high in Norway. Surgery is the mainstay in the treatment of colon cancer but has not undergone the same improvements as rectal cancer. Standardisation of and more radical surgery was one of the measures that lead to increased survival for rectal cancer. It is time for colon cancer to undergo the same improvements. Differences in tumour biology, anatomy and prognosis related to localisation of the tumour in colon, led to focus on right-sided colon cancer. The proximal tumours have a distinct tumour biology with poor prognosis in addition to technical demanding surgery. Knowledge of tumour biology is necessary to personalize cancer treatment and inspired to launch a project with liquid biopsy and analysis of circulating tumour DNA (ctDNA). Aim The aim of the study was to compare the differences in complications after radical surgery between open and laparoscopic surgery for right-sided colon cancer. Specific complications were also explored. Surgical quality was evaluated by comparing length of remaining vascular stump length after resection. The aim of the biomarker study was to investigate ctDNA as a predictor of recurrence. Method In the trial, 128 patients were randomised to receive either open or laparoscopic colectomy. The surgery was standardized and focused on central lymphadenectomy. The first 40 patients, 20 in each group were explored for length of remaining vascular stump length after resection by measurements in computed tomography 6 months postoperative. The measurements were conducted twice by two independent radiologists. In the prospective observational biomarker study 50 patients were explored by next generation sequencing and digital droplet PCR (ddPCR) for cancer related mutations in tumour and blood. Results There was no difference in complications between the two groups. There were no life-threatening complications and a low incidence of serious complications with 8 % in the open group and 5 % in the laparoscopic group. No patients were reoperated due to anastomotic leaks. Transfusion or infusion of i.v iron was the most common complication (22 % open vs 15 % laparoscopic). Postoperative ileus was the second most common complications and occurred in 16 % after open and 19 % after laparoscopic surgery. Equal number of mean lymph nodes was removed in open (n=32) and laparoscopic (n=29) group. The remaining vascular stump length after resection was short and equal in the two groups (4 mm). Interclass correlation for each observer was good but interclass correlation between observers was poor. The discrepancy occurred in the open group where no marker was present at the vessel stump. Cancer related mutations was detected in 49/50 patients of which 47 available for surveillance with ddPCR assays. ctDNA was present in liquid biopsy prior to surgery in 31/47 patients and was reduced after surgery in 27/31 patients. Risk for recurrence was elevated in the patients with postoperative positive ctDNA (adjusted hazard ratio: 173). Conclusion/implications Right-sided colectomy with central lymphadenectomy along superior mesenteric vein is applicable, safe, and reproducible and can be the future standard for right-sided colon cancer. Vascular stump length can be a quality marker for central lymph node dissection. ctDNA is a strong predictor for early recurrence in right sided colon cancer and must be further explored in clinical trials to establish its role in routine diagnostics.Doktorgradsavhandlin

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p &lt; 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p &lt; 0.001). Males were significantly more likely to be admitted than females (p &lt; 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted

Diseases of the Abdomen and Pelvis 2018-2021: Diagnostic Imaging - IDKD Book

Gastrointestinal disease; PET/CT; Radiology; X-ray; IDKD; Davo

Ultrasound Imaging

Ultrasound Imaging - Current Topics presents complex and current topics in ultrasound imaging in a simplified format. It is easy to read and exemplifies the range of experiences of each contributing author. Chapters address such topics as anatomy and dimensional variations, pediatric gastrointestinal emergencies, musculoskeletal and nerve imaging as well as molecular sonography. The book is a useful resource for researchers, students, clinicians, and sonographers looking for additional information on ultrasound imaging beyond the basics

A study on Gastro Intestinal Polyps.

INTRODUCTION : The polyposis syndromes, a heterogeneous group of diseases, have been a major focus of study for the last decade and provide critical insight into the molecular pathogenesis of cancel'. Despite intense study, these important syndromes are still clinically confusing and proper objective identification is necessary for appropriate clinical management. The term "polyp" derives from the Greek for "multiple feet" or "little nipple". In current clinical practice a polyp is defined as any nodule or mass that projects above the level of the surrounding mucosa, as in the gut, to form a macroscopically visible structure. Traction on the mass may create a stalked, or pedunculated, polyp. Alternatively, the polyp may be sessile, without a definable stalk. The polyps that are formed as a result of abnormal mucosal maturation, inflammation, or architecture, are non-neoplastic and do not have malignant potential, but those that arise as the result of epithelial proliferation and dysplasia are termed adenomatous polyps or adenomas. They are true neoplastic lesions and are precursors of carcinoma. Some polypoid lesions may be caused by submucosal or mural tumors. However, as with the stomach, the term polyp, unless otherwise specified, refers to lesions arising from the epithelium of the mucosa. Gastrointestinal polyps are being identified more frequently today because of increased awareness, screening and improved diagnostic tools. The entire gastrointestinal tract is at risk for polyp development but the adult colon and rectum account for the majority of polyps. Painless, bright red, rectal bleeding with normal stool frequency and consistency is the hallmark presentation of colorectal polyps at any age. Gastric polyps are uncommon and are most frequently hyperplastic polyps, fundic gland polyps and adenomatous polyps. Hyperplastic and fundic gland polyps are essentially innocuous. In contrast, there is a definite risk of an adenomatous polyp harboring adenocarcinoma, which increases with polyp size. AIMS AND OBJECTIVES : To study the incidence and prevalence of gastrointestinal polyps with a clinical, endoscopic and histopathologic correlation. CONCLUSION : This study has highlighted the importance of screening for patients with upper Gastro Intestinal Symptoms by detection of unsuspected polyps (44% upper GI polyps). Regarding lower gastrointestinal polyps colonoscopic screening has helped to detect polyps and the histopathological types has helped us in offering proper management options like polypectomy is many. In two patients which appeared as non malignant histopathological examination detected malignancy in them and further investigations helped us to offer curative resections for these patients