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Medical Journal, Armed Forces India Sep 2022Colorectal cancer (CRC) is one of the commonest cancers worldwide, with incidence rates in India being around 4%. It is a heterogeneous disease with multiple established...
BACKGROUND
Colorectal cancer (CRC) is one of the commonest cancers worldwide, with incidence rates in India being around 4%. It is a heterogeneous disease with multiple established prognostic factors. Ten to fifteen percent originate from microsatellite instability (MSI) pathway, characterized by defect in mismatch repair (MMR) gene. Identification of MMR defective protein is relevant for diagnosis, prognosis, and prediction. Certain clinical and histological features are known to be associated with defective MMR genes. The objectives of this study are to find the prevalence of MSI in CRC to identify features associated with MSI and assess the value of histopathology in predicting MSI.
METHODS
We evaluated various clinical and histological parameters for identifying prognostically favorable colon cancers in a tertiary hospital. One hundred fifty colon cancers were evaluated, and MSI status was correlated with clinicopathologic variables.
RESULTS
The prevalence of MSI in CRC was found to be 11.3%. The factors associated with MSI were tumor differentiation, stage, tumor site, tumor size, tumor-infiltrating lymphocytes, Crohn's-like lymphoid reaction, and dirty necrosis. We have defined a "P" score for prediction of MSI using the clinicohistological parameters, which could be used to select patients who are to be tested for MSI.
CONCLUSION
Assessment of clinical and histopathological features will help in patient stratification and selection of patients for MSI testing. The evaluation is economical, reproducible, and easy to apply.
PubMed: 36147411
DOI: 10.1016/j.mjafi.2021.03.024 -
Cureus Apr 2024Background Microsatellite instability (MSI) is a genetic condition caused by errors in DNA repair genes that cause colorectal cancer (CRC). The literature contradicts...
Background Microsatellite instability (MSI) is a genetic condition caused by errors in DNA repair genes that cause colorectal cancer (CRC). The literature contradicts the frequency of MSI in sporadic CRCs and its effect on prognosis. This study investigated the distribution of clinicopathologic features and the relationship between MSI and survival outcomes. Methodology This is a retrospective study of 101 consecutive cases of CRC and immunohistochemical studies. All cases were retrospectively reviewed and reevaluated by histological grade, lymphovascular invasion, perineural invasion, tumor borders, dirty necrosis, tumor-infiltrating lymphocytes (TILs), Crohn's-like lymphoid reaction, mucinous and medullary differentiation, and tumoral budding from pathological slides. An immunohistochemical study was performed in appropriate blocks for using MLH-1, MSH-2, MSH-6, and PMS-2. We collected the clinical stage, pathological tumor stage, lymph node metastasis, age, sex, tumor diameter, distant metastasis, localization, and survival information from patients' clinical data. Results There was no statistically significant difference between the two groups regarding age, gender, tumor diameter, histological grade, tumor border, dirty necrosis, TILs, N and M stage, perineural and lymphovascular invasion, mucinous differentiation, medullary differentiation, and tumor budding characteristics of the patients. The MSI-H group was more frequently located in the right colon and transverse colon (p < 0.001), and the T stage was higher among them than in the MSI-L group (p = 0.014). Upon multivariate regression analysis, MSI status had no significant effect on survival time. Age and stage N and M were independent prognostic factors for colon cancer prognosis. Conclusions Our study presented the distribution of clinicopathological features and their relationship with MSI for 101 regional CRC patients. MSI status was detected by immunohistochemistry. Identifying MSI in CRCs may help personalize therapy planning. As the distribution of the features may vary from population to population, further investigations are needed on this topic.
PubMed: 38590982
DOI: 10.7759/cureus.57814 -
Journal of Clinical Pathology Jan 2024Pulmonary enteric adenocarcinoma (PEAC) is a rare variant of pulmonary adenocarcinoma. Due to its rarity, few pathological and molecular studies have been performed on...
AIMS
Pulmonary enteric adenocarcinoma (PEAC) is a rare variant of pulmonary adenocarcinoma. Due to its rarity, few pathological and molecular studies have been performed on PEAC. We herein conducted clinicopathological, immunohistochemical and molecular analyses of PEAC with a focus on its differentiation from invasive mucinous adenocarcinoma (IMA).
METHODS
We examined the clinicopathological features of 16 cases of PEAC and performed a genetic analysis using next-generation sequencing (NGS). The results obtained were compared with those for IMA.
RESULTS
The average age of patients with PEAC (seven men and nine women) was 72.9 years. A comparison of clinical data on PEAC and IMA revealed no significant differences in age, sex or smoking history. Fifteen PEAC cases had dirty necrosis. Immunohistochemically, the positive rates for each antibody in PEAC were as follows: CK7, 88% (14/16); CK20, 81% (13/16); CDX2, 88% (14/16); p53, 69% (11/16); MUC1, 100% (16/16); MUC2, 19% (3/16); MUC5AC, 69% (11/16); MUC6, 19% (3/16). The positive rates for these antibodies in IMA were 100%, 87%, 0%, 7%, 93%, 0%, 100% and 80%, respectively. mutations, the exon 14 skipping mutation, mutations, the fusion gene and fusion gene were not detected in any cases of PEAC or IMA. Among PEAC cases, NGS identified mutations in seven (44%, 7/16) and mutations in nine (56%, 9/16). Among IMA cases, the most commonly mutated gene was (90%).
CONCLUSIONS
The rates of dirty necrosis, immunopositivity for CDX2 and mutations were significantly higher, while that of mutations was significantly lower in PEAC cases than in IMA cases.
Topics: Male; Humans; Female; Aged; Lung Neoplasms; Proto-Oncogene Proteins p21(ras); Biomarkers, Tumor; Adenocarcinoma of Lung; Mutation; Adenocarcinoma, Mucinous; Necrosis
PubMed: 36456172
DOI: 10.1136/jcp-2022-208583 -
Journal of Fish Diseases Nov 2018Disease poses a major threat to aquaculture and commercial and recreational fisheries globally. Biosecurity measures have been implemented; however, empirical evidence...
Disease poses a major threat to aquaculture and commercial and recreational fisheries globally. Biosecurity measures have been implemented; however, empirical evidence of their efficacy in situ is lacking. Here, we present the results from a study conducted to examine the effectiveness of disinfectant net dips. Samples were collected from disinfectant net dips at 25 recreational fisheries in south-west England and assessed to determine (a) the level of bacterial contamination and (b) the reduction in titre of a target virus (infectious pancreatic necrosis virus, IPNV) following a contact time of 2 and 5 min. In addition, the study examined the reduction in target virus titre following exposure to laboratory prepared Virkon , representing "clean," "dirty" and "diluted and dirty" conditions, for 2 and 5 min. Bacterial contamination was high in 64% of disinfectant samples, and, 76% of disinfectant samples did not effectively reduce the target virus titre in 2 or 5 min. Virus titre was successfully reduced following exposure to laboratory prepared Virkon for 2 or 5 min, although dilution and contamination reduced the effectiveness. These results suggest that disinfectant net dips may not be working effectively on a high proportion of fishery sites. We provide recommendations for improving biosecurity.
Topics: Animals; Bacteria; Bacterial Infections; Birnaviridae Infections; Disinfectants; England; Equipment and Supplies; Fish Diseases; Fisheries; Infectious pancreatic necrosis virus
PubMed: 30091241
DOI: 10.1111/jfd.12868 -
Radiation Oncology (London, England) Oct 2022To introduce and compare multiple biological effectiveness guided (BG) proton plan optimization strategies minimizing variable relative biological effectiveness (RBE)...
BACKGROUND
To introduce and compare multiple biological effectiveness guided (BG) proton plan optimization strategies minimizing variable relative biological effectiveness (RBE) induced dose burden in organs at risk (OAR) while maintaining plan quality with a constant RBE.
METHODS
Dose-optimized (DOSEopt) proton pencil beam scanning reference treatment plans were generated for ten cranial patients with prescription doses ≥ 54 Gy(RBE) and ≥ 1 OAR close to the clinical target volume (CTV). For each patient, four additional BG plans were created. BG objectives minimized either proton track-ends, dose-averaged linear energy transfer (LET), energy depositions from high-LET protons or variable RBE-weighted dose (D) in adjacent serially structured OARs. Plan quality (RBE = 1.1) was assessed by CTV dose coverage and robustness (2 mm setup, 3.5% density), dose homogeneity and conformity in the planning target volumes and adherence to OAR tolerance doses. LET, D (Wedenberg model, α/β = 10 Gy, α/β = 2 Gy) and resulting normal tissue complication probabilities (NTCPs) for blindness and brainstem necrosis were derived. Differences between DOSEopt and BG optimized plans were assessed and statistically tested (Wilcoxon signed rank, α = 0.05).
RESULTS
All plans were clinically acceptable. DOSEopt and BG optimized plans were comparable in target volume coverage, homogeneity and conformity. For recalculated D in all patients, all BG plans significantly reduced near-maximum D to critical OARs with differences up to 8.2 Gy(RBE) (p < 0.05). Direct D optimization primarily reduced absorbed dose in OARs (average ΔD = 2.0 Gy; average ΔLET = 0.1 keV/µm), while the other strategies reduced LET (average ΔD < 0.3 Gy; average ΔLET = 0.5 keV/µm). LET-optimizing strategies were more robust against range and setup uncertaintes for high-dose CTVs than D optimization. All BG strategies reduced NTCP for brainstem necrosis and blindness on average by 47% with average and maximum reductions of 5.4 and 18.4 percentage points, respectively.
CONCLUSIONS
All BG strategies reduced variable RBE-induced NTCPs to OARs. Reducing LET in high-dose voxels may be favourable due to its adherence to current dose reporting and maintenance of clinical plan quality and the availability of reported LET and dose levels from clinical toxicity reports after cranial proton therapy. These optimization strategies beyond dose may be a first step towards safely translating variable RBE optimization in the clinics.
Topics: Humans; Proton Therapy; Protons; Radiotherapy Planning, Computer-Assisted; Necrosis; Blindness
PubMed: 36273132
DOI: 10.1186/s13014-022-02143-x -
Pathology, Research and Practice Oct 2021Current standard therapy for locally advanced rectal cancer (LARC) is neoadjuvant therapy followed by surgical resection; however, treatment response is variable among...
Current standard therapy for locally advanced rectal cancer (LARC) is neoadjuvant therapy followed by surgical resection; however, treatment response is variable among patients. This study aimed to identify histologic features that predict tumor response. This retrospective study included 105 patients with LARC, all of whom underwent biopsy followed by neoadjuvant therapy and subsequent surgical resection. Each patient's initial biopsy was evaluated for tumor grade, tumor budding, intraepithelial lymphocytes, intraepithelial neutrophils, desmoplasia, apoptosis, adjacent stromal lymphocytes, signet ring cells, mucinous features, tumoral Paneth cells, dirty necrosis, microscopic ulceration, and prominent lymphoid aggregates. These histologic features, along with patient age at diagnosis and tumor microsatellite status, were compared to tumor regression grades from the respective resection specimens. No histologic factors in tumor biopsies predictive of treatment response in post-therapy resection specimens were identified. Histologic features in pre-therapy biopsy samples of LARC do not predict subsequent response to neoadjuvant therapy. Effective and reliable methods to predict response to neoadjuvant therapy in rectal cancer remain elusive.
Topics: Adenocarcinoma; Adult; Aged; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Rectal Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 34530256
DOI: 10.1016/j.prp.2021.153608 -
Endoscopy Feb 2021
Topics: Endoscopy; Humans; Necrosis; Pancreatitis, Acute Necrotizing
PubMed: 33503664
DOI: 10.1055/a-1223-2341 -
PloS One 2021Emerging data suggest a negative role of cyclooxygenase-2 (COX-2) in colorectal carcinomas (CRC). Investigating this in developing communities such as ours helps to...
BACKGROUND
Emerging data suggest a negative role of cyclooxygenase-2 (COX-2) in colorectal carcinomas (CRC). Investigating this in developing communities such as ours helps to contribute to existing understanding of these lesions.
METHODS AND FINDINGS
Formalin-fixed paraffin-embedded CRC colectomy tissues and their corresponding non-tumour margins of resected tissues were sectioned and stained with COX-2 antibody. Adenomatous polyp tissues from non-cancer bearing individuals were similarly processed for comparison. COX-2 expression was scored for percentage (< 5% = 0; 6%-25% = 1; 26%-50% = 2; 51%-75% = 3; 76%-100% = 4) and intensity (no staining = 0; yellow = 2; yellowish-brown = 3, brown = 4). Total immunoscore (percentage + intensity score) ≥ 2 was regarded as positive COX-2 expression. Outcome was statistically evaluated with clinicopathological data to determine COX-2 expression-associated and predictor variables. Ninety-five CRC cases and 27 matched non-tumour tissues as well as 31 adenomatous polyps met the inclusion criteria. Individuals with CRC had a mean age of 56.1 ± 12.6 years while those with adenomatous polyps had a median age of 65 years (range 43-88). COX-2 was differentially overexpressed in CRCs (69/95; 72.6%) and in adenomatous polyps (17/31; 54.8%) than in non-tumour tissues 5/27 (18.5%); p < 0.001). The difference in COX-2 expression between CRC and polyps was non-significant (p > 0.065). Tumour grade, advanced pT-stage, tumour-infiltrating lymphocytes, and dirty necrosis were also significantly associated with COX-2 expression (p < 0.035; 0.043, 0.035 and 0.004, respectively). Only dirty necrosis and Crohns-like lymphocytic aggregates predicted COX-2 expression (p < 0.05).
CONCLUSION
This study showed a progressive increase in COX-2 expression from normal to adenomatous polyp and CRC tissues, this being associated with poorer prognostic indicators. Although COX-2 appears early in CRC, it may play a secondary role in promoting tumour growth and invasiveness.
Topics: Adenomatous Polyps; Adult; Aged; Aged, 80 and over; Black People; Case-Control Studies; Colorectal Neoplasms; Cyclooxygenase 2; Female; Humans; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Necrosis; Neoplasm Staging; Nigeria; Odds Ratio; Retrospective Studies
PubMed: 34314467
DOI: 10.1371/journal.pone.0255235 -
Postgraduate Medical Journal Apr 2015To review the clinical and pathological factors associated with fulminant amoebic colitis (FAC) requiring colonic resection and its outcome.
AIMS
To review the clinical and pathological factors associated with fulminant amoebic colitis (FAC) requiring colonic resection and its outcome.
METHODS
We retrospectively identified adult patients admitted to our centre between June 2007 and December 2011 with FAC who underwent colonic resection and were diagnosed with amoebic colitis based on the presence of trophozoites on histological examination. The clinical details were extracted from the medical notes and correlated with the pathological findings.
RESULTS
Thirty patients (18 men and 12 women) met the inclusion criteria. Their mean age was 50.1 years (range 21-89). The most frequent symptoms were abdominal pain, vomiting and fever. More than half the patients (16/30) had underlying conditions associated with immunosuppression including diabetes mellitus and tuberculosis. Pathological investigation of colonic resections showed predominantly right-sided involvement with geographic colonic ulcers covered with a creamy-white pseudomembrane, perforations, gangrenous changes, amoeboma and lesions mimicking inflammatory bowel disease. All showed basophilic dirty necrosis with abundant nuclear debris and amoebic trophozoites on histological examination. 21/30 patients (70%) had involvement beyond the caecum. 17/30 patients (57%) died. Those with involvement beyond the caecum were more likely to die (15/21, 71.4%) than those with less extensive disease.
CONCLUSIONS
FAC presents as acute abdomen and can mimic appendicitis, ischaemic bowel disease, tuberculosis and malignancy. Comorbidities causing immunosuppression frequently associated. Mortality remains high despite surgery, so FAC should be suspected in every case of acute abdomen with colonic perforation if associated with typical gross and microscopic findings and a history of stay in an endemic area.
Topics: Abdominal Pain; Adult; Aged; Aged, 80 and over; Cecum; Colectomy; Diagnosis, Differential; Dysentery, Amebic; Female; Fever; Humans; Immunohistochemistry; India; Length of Stay; Male; Middle Aged; Retrospective Studies; Survival Rate; Treatment Outcome; Vomiting
PubMed: 25748520
DOI: 10.1136/postgradmedj-2014-132597 -
Histopathology Jan 2017Colorectal carcinoma (CRC) with micropapillary (MP) features has only been described recently and is still being characterized.
AIMS
Colorectal carcinoma (CRC) with micropapillary (MP) features has only been described recently and is still being characterized.
METHODS AND RESULTS
We reviewed the clinicopathological and molecular features of 42 CRC with MP features. Twenty-nine cases were also evaluated for immunohistochemical evidence of epithelial-mesenchymal transition (EMT). The extent of MP features within our cohort ranged from 5% (13 cases) to 100% (one case). Twenty-seven cases featured prominent cribriforming with dirty necrosis in the non-MP component; nine displayed mucinous features. Twenty-four of 29 cases (83%) demonstrated evidence of EMT. Thirty-six cases (86%) showed advanced T-category (pT3 or pT4), 31 (74%) had lymph node metastases and 23 (55%) had distant metastases. Median overall follow-up was 36 months. Seventeen patients (40%) died of disease, with median survival of 23 months. Mutations were seen in 17 of 31 tested cases (55%), including 11 KRAS mutations and four BRAF V600E mutations. Microsatellite instability testing was performed on 21 cases; all were microsatellite-stable. Compared to a cohort of 972 conventional CRC, MP CRC was more likely to present as stage IV disease (P < 0.001), but patients with MP CRC showed no significant differences in overall survival after adjusting for stage.
CONCLUSIONS
Micropapillary features in CRC portend a high likelihood of advanced local disease and distant metastases. MP CRC is often associated with a cribriform pattern elsewhere in the tumour and cystic nodal metastases with prominent necrosis. They also show frequent mutations in KRAS and BRAF. Immunohistochemical evidence of EMT is common in MP CRC.
Topics: Adenocarcinoma, Papillary; Adult; Aged; Colorectal Neoplasms; DNA Mutational Analysis; Epithelial-Mesenchymal Transition; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged
PubMed: 27560620
DOI: 10.1111/his.13068