scholarly journals Ki67 Protein expression and correlation with the histological grade and pTNM stage of colorectal carcinoma

2021 ◽  
Vol 11 (2) ◽  
pp. 204-208
Author(s):  
Indroneel Bhattacharya ◽  
Neepamanjari Barman ◽  
Ranu Sarkar

: Colorectal cancer, is third most frequently encountered malignancy worldwide. Histological grade, stage, and proliferative index act as vital prognostic markers, playing a decisive role in patient care and prognosis. While histopathological examination can determine grade and stage, Ki67 protein expression by immunohistochemistry represents the proliferative capacity of the malignant cell population. : This Study was conducted to immunohistochemically analyze expression of Ki67 protein and its change with respect to different grades and stage of colorectal adenocarcinoma. : A total of 66 histologically diagnosed cases of colorectal carcinoma underwent histopathological examination followed by immunohistochemistry for Ki67 protein. : A statistically significant (p=0.04) correlation was obtained between Ki67 labelling index and histopathological grade, with higher values of Ki67 labelling index in poorly differentiated carcinomas (43.2±1.7). The Ki67 labelling index value was lowest in stage IV disease (11.4±2.4) with metastatic burden, with higher values in lower stage diseases, however this correlation was not found to be significant statistically (p=0.07). : The rate of cell division and proliferation measured by Ki-67 antibody is related to histological grade of the malignancy, demonstrating higher mitotic activity with loss of differentiation and anaplasia. Stage IV disease have lower mitotic activity, thus may be less amenable to cytostatic chemotherapy drugs, and require multimodality treatment with addition of radiotherapy and other drug regimes.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 402-402
Author(s):  
Michael J. Overman ◽  
Keith F. Fournier ◽  
Chung-Yuan Hu ◽  
Robert A. Wolff ◽  
Cathy Eng ◽  
...  

402 Background: Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas; the prognostic impact of grade in localized disease, and the validity of the AJCC Cancer Staging Manual 7th edition decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known. Methods: Patients with adenocarcinoma of the appendix diagnosed between 1988-2007 were identified from the SEER database. Cancer-specific survival (CSS) stratified by histological subtype, stage and grade were calculated; and Cox proportional hazards regression analyses were performed. Results: We analyzed a total of 2,469 appendiceal adenocarcinomas, of which 1,375 had mucinous histology, 860 had non-mucinous histology, and 234 had signet-ring cell histology. Though overall CSS was similar for mucinous and non-mucinous subtypes, differences in stage distribution and stage-stratified CSS were seen. Female gender (57% vs.45%, P<0.01), stage IV disease (48% vs. 25%, P<0.01), and well differentiated histology (31% vs. 14%, P<0.01) were more common in mucinous as compared to non-mucinous adenocarcinomas. While histological grade for stage I-III cases was not statistically significant, it had strong prognostic impact for stage IV disease. The adjusted hazard ratios for stage IV well, moderately and poorly differentiated histological grade were 1 (reference), 1.63 (95%CI: 1.14-2.34) and 4.94 (95%CI: 3.32-7.35) for mucinous, in comparison to 1 (reference), 1.44 (95%CI: 0.82-2.52) and 1.90 (95%CI: 0.95-3.80) for non-mucinous histological subtypes, respectively. Conclusions: The strong prognostic impact of histological grade for mucinous adenocarcinomas is primarily restricted to stage IV disease. Stage IV moderately and poorly differentiated mucinous adenocarcinomas have distinctly different CSS and this data does not support the combination of these two histological grades in the recent AJCC 7th edition.


Author(s):  
Giovanni Capovilla ◽  
Renato Salvador ◽  
Luca Provenzano ◽  
Michele Valmasoni ◽  
Lucia Moletta ◽  
...  

Abstract Background Laparoscopic Heller myotomy (HM) has gained acceptance as the gold standard of treatment for achalasia. However, 10–20% of the patients will experience symptom recurrence, thus requiring further treatment including pneumodilations (PD) or revisional surgery. The aim of our study was to assess the long-term outcome of laparoscopic redo HM. Methods Patients who underwent redo HM at our center between 2000 and 2019 were enrolled. Postoperative outcomes of redo HM patients (redo group) were compared with that of patients who underwent primary laparoscopic HM in the same time span (control group). For the control group, we randomly selected patients matched for age, sex, FU time, Eckardt score (ES), previous PD, and radiological stage. Failure was defined as an Eckardt score > 3 or the need for re-treatment. Results Forty-nine patients underwent laparoscopic redo HM after failed primary HM. A new myotomy on the right lateral wall of the EGJ was the procedure of choice in the majority of patients (83.7%). In 36 patients (73.5%) an anti-reflux procedure was deemed necessary. Postoperative outcomes were somewhat less satisfactory, albeit comparable to the control group; the incidence of postoperative GERD was higher in the redo group (p < 0.01). At a median 5-year FU time, a good outcome was obtained in 71.4% of patients in the redo group; further 5 patients (10.2%) obtained a long-term symptom control after complementary PD, thus bringing the overall success rate to 81.6%. Stage IV disease at presentation was independently associated with a poor outcome of revisional LHD (p = 0.003). Conclusions This study reports the largest case series of laparoscopic redo HM to date. The procedure, albeit difficult, is safe and effective in relieving symptoms in this group of patients with a highly refractory disease. The failure rate, albeit not significantly, and the post-operative reflux are higher than after primary HM. Patients with stage IV disease are at high risk of esophagectomy.


Author(s):  
Kristina Lång ◽  
Solveig Hofvind ◽  
Alejandro Rodríguez-Ruiz ◽  
Ingvar Andersson

Abstract Objectives To investigate whether artificial intelligence (AI) can reduce interval cancer in mammography screening. Materials and methods Preceding screening mammograms of 429 consecutive women diagnosed with interval cancer in Southern Sweden between 2013 and 2017 were analysed with a deep learning–based AI system. The system assigns a risk score from 1 to 10. Two experienced breast radiologists reviewed and classified the cases in consensus as true negative, minimal signs or false negative and assessed whether the AI system correctly localised the cancer. The potential reduction of interval cancer was calculated at different risk score thresholds corresponding to approximately 10%, 4% and 1% recall rates. Results A statistically significant correlation between interval cancer classification groups and AI risk score was observed (p < .0001). AI scored one in three (143/429) interval cancer with risk score 10, of which 67% (96/143) were either classified as minimal signs or false negative. Of these, 58% (83/143) were correctly located by AI, and could therefore potentially be detected at screening with the aid of AI, resulting in a 19.3% (95% CI 15.9–23.4) reduction of interval cancer. At 4% and 1% recall thresholds, the reduction of interval cancer was 11.2% (95% CI 8.5–14.5) and 4.7% (95% CI 3.0–7.1). The corresponding reduction of interval cancer with grave outcome (women who died or with stage IV disease) at risk score 10 was 23% (8/35; 95% CI 12–39). Conclusion The use of AI in screen reading has the potential to reduce the rate of interval cancer without supplementary screening modalities. Key Points • Retrospective study showed that AI detected 19% of interval cancer at the preceding screening exam that in addition showed at least minimal signs of malignancy. Importantly, these were correctly localised by AI, thus obviating supplementary screening modalities. • AI could potentially reduce a proportion of particularly aggressive interval cancers. • There was a correlation between AI risk score and interval cancer classified as true negative, minimal signs or false negative.


2020 ◽  
Vol 154 (5) ◽  
pp. 635-644
Author(s):  
Yuhong Ye ◽  
Chengyu Lv ◽  
Songhua Xu ◽  
Yupeng Chen ◽  
Ru Qian ◽  
...  

Abstract Objective To explore the clinical and pathologic features of ovarian juvenile granulosa cell tumors (JGCTs). Methods Clinical data, histopathologic observations, immunohistochemical results, FOXL2 mutation status, and follow-up information of 7 JGCT cases were studied. Results The patients most commonly presented with abdominal distension and pain (5 cases), followed by precocious puberty (1 case) and a pelvic mass (1 case). Six patients had stage I disease, and 1 had stage IV disease. The microscopic examinations typically showed lobular growth punctuated by variably sized and shaped follicles. Rare features included a reticular-cystic appearance mimicking a yolk sac tumor (2 cases), a lobular appearance similar to a sclerosing stromal tumor (1 case), strands and cords (1 case), pseudopapillary appearance (2 cases), spindle cell appearance (1 case), microcystic appearance (1 case), hobnail cells (1 case), and rhabdomyoid cells (1 case). No FOXL2 mutation was encountered. After a median follow-up of 53 months, only 1 patient with a strongly diffuse TP53-positive tumor died of the disease, and 2 successfully had babies. Conclusions JGCT is a rare neoplasm with a wide morphologic spectrum and is easily confused with other tumors. Familiarity with the characteristics, rare atypical appearances, and immunohistochemical results may aid in obtaining a correct diagnosis.


2005 ◽  
Vol 54 (2) ◽  
pp. 145-155 ◽  
Author(s):  
Lara Maria Pasetto ◽  
Tamberi Stefano ◽  
Elena Rossi ◽  
Myriam Katya Paris ◽  
Silvio Monfardini

2022 ◽  
Author(s):  
Samo Rozman ◽  
Nina Ružić Gorenjec ◽  
Barbara Jezeršek Novaković

Abstract This retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of Hodgkin lymphoma (HL) patients with advanced stage disease receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 HL patients treated between 2004 and 2013 were enrolled for evaluation. RDI calculations were based on a Hryniuk's model. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, majority of patients were males and had stage IV disease. Fifty-four patients received ABVD and 60 received BEACOPP chemotherapy with 24 and 4 deaths, respectively. Patients in BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) in comparison with ABVD group, making the comparison of groups impossible. In ABVD group, RDI was not significantly associated with OS (p=0.590) or PFS (p=0.354) in a multivariate model where age was controlled. The low number of events prevented the analysis in the BEACOPP group. Patients' age was strongly associated with both OS and PFS: all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI) lost its effect in multivariate analyses where age was controlled. Based on our observations, we can conclude that RDI is not associated with the OS or PFS after the age is controlled, neither in all patients combined nor in individual chemotherapy groups.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10524-10524
Author(s):  
Alexandra Wehbe ◽  
Mark A. Manning ◽  
Hadeel Assad ◽  
Kristen Purrington ◽  
Michael S. Simon

10524 Background: Carriers of pathogenic variants in cancer susceptibility genes have an elevated risk of developing breast, ovarian, and other cancers.We conducted a medical record review to determine the uptake of genetic counseling and testing in a clinic-based population of women with breast cancer. Methods: Medical records of 150 women with breast cancer seen at the Karmanos Cancer Institute between January-December 2018 were reviewed to determine the proportion eligible for genetic testing according to National Comprehensive Cancer Network guidelines. We also assessed genetics referral rates, appointment completion and results of genetic testing. Using chi-square and ANOVA tests, we analyzed the association of demographic and clinical factors with eligibility and referral to genetic counseling. Results: The average age of diagnosis was 57.1 years old, with 68.7% of women diagnosed with stage I-III disease, and 31.3% diagnosed with stage IV disease. There were 91 (60.7%) women who met NCCN criteria for genetic testing, of which 46.2% ultimately underwent genetic testing. Eligible women were more likely to be younger (52.6 vs. 64.0 years old), White (75.0% vs. 54.5%), and have Medicaid (75.0%) or private insurance (72.9%) vs. Medicare (44.8%). Women who met NCCN criteria were 3.5 times more likely to be referred for genetic counseling than those that did not meet eligibility criteria. Women were also more likely to be referred if they had early-stage disease compared to stage IV (67.8% vs. 48.3%), and Medicaid or private insurance compared to Medicare (71.4%, 72.0% and 40.0%, respectively). Of eligible women, 59.3% had a genetic counseling appointment scheduled, and of those, 78.0% attended their appointment. There were no apparent differences in appointment completion based on race with similar percentages of Black and White women completing their appointments (74.0% and 77.0% respectively). Women with stage IV disease were more likely to complete their appointments (83.0%) compared to women with stages I-III (74.0%) and fewer women with Medicare completed their genetic counseling appointment (56.0%) compared to women with Medicaid (83.0%) and women with private insurance (83.0%). Among women who attended their appointment, 95.9% underwent genetic testing. Of women who had genetic testing, 8.5% had a pathogenic variant and 30.4% had a variant of unknown significance. Conclusions: The results of this study indicate that lack of genetic counseling referrals contribute to a gap between the need for and completion of genetic testing. By understanding barriers to genetic counseling and testing, future clinical initiatives could effectively improve accessibility to genetic counseling services.


2018 ◽  
Vol 51 (5) ◽  
pp. 2111-2122 ◽  
Author(s):  
Yi-Bing Hu ◽  
Xiao-Ting Ye ◽  
Qing-Qing Zhou ◽  
Rong-Quan Fu

Background/Aims: Sestrin 2 is associated with the pathophysiology of several diseases. The aim of this study was to investigate the effects and potential mechanisms of Sestrin 2 in rat hepatic stellate cells (HSCs) during liver fibrogenesis. Methods: In this study, Sestrin 2 protein expression was detected in rat HSC-T6 cells challenged with transforming growth factor-β (TGF-β) and in mice treated with carbon tetrachloride (CCl4), a well-known model of hepatic fibrosis. Next, HSC-T6 cells and fibrotic mice were transfected with lentivirus. The mRNA expression levels of markers of liver fibrosis [alpha-smooth muscle actin (α-SMA) and collagen 1A1 (Col1A1)] were analyzed by quantitative reverse transcription–polymerase chain reaction (RT-PCR). Cell death and proliferation were evaluated by the MTT assay, and biochemical markers of liver damage in serum [alanine transaminase (ALT) and aspartate transaminase (AST)] were also measured using a biochemical analyzer. Histopathological examination was used to evaluate the degree of liver fibrosis, and protein expression [phospho-adenosine monophosphate-activated protein kinase (p-AMPK), AMPK, phospho-mammalian target of rapamycin (p-mTOR), and mTOR] was determined by western blotting. Results: We found that Sestrin 2 was elevated in both the HSC-T6 cell and hepatic fibrosis models. In vitro, overexpression of Sestrin 2 attenuated the mRNA levels of α-SMA and Col1A1, suppressed α-SMA protein expression, and modulated HSC-T6 cell proliferation. In vivo, overexpression of Sestrin 2 reduced the ALT and AST levels as well as the α-SMA and Col1A1 protein expression in the CCl4 model of liver fibrosis. Moreover, the degree of liver fibrosis was ameliorated. Interestingly, overexpression of Sestrin 2 increased p-AMPK but decreased p-mTOR protein expression. Conclusion: Our findings indicate that Sestrin 2 may attenuate the activation of HSCs and ameliorate liver fibrosis, most likely via upregulation of AMPK phosphorylation and suppression of the mTOR signaling pathway.


2018 ◽  
Vol 103 (9) ◽  
pp. 3566-3573 ◽  
Author(s):  
Sri Harsha Tella ◽  
Anuhya Kommalapati ◽  
Subhashini Yaturu ◽  
Electron Kebebew

Abstract Context Adrenocortical carcinoma (ACC) is rare; knowledge about prognostic factors and survival outcomes is limited. Objective To describe predictors of survival and overall survival (OS) outcomes. Design and Patients Retrospective analysis of data from the National Cancer Database (NCDB) from 2004 to 2015 on 3185 patients with pathologically confirmed ACC. Main Outcome Measures Baseline description, survival outcomes, and predictors of survival were evaluated in patients with ACC. Results Median age at ACC diagnosis was 55 (range: 18 to 90) years; did not differ significantly by sex or stage of the disease at diagnosis. On multivariate analysis, increasing age, higher Charlson-Deyo comorbidity index score, high tumor grade, and no surgical therapy (all P &lt; 0.0001); and stage IV disease (P = 0.002) and lymphadenectomy during surgery (P = 0.02) were associated with poor prognosis. Patients with stage I-III disease treated with surgical resection had significantly better median OS (63 vs 8 months; P &lt; 0.001). In stage IV disease, better median OS occurred in patients treated with surgery (19 vs 6 months; P &lt; 0.001), and postsurgical radiation (29 vs 10 months; P &lt; 0.001) or chemotherapy (22 vs 13 months; P = 0.004). Conclusion OS varied with increasing age, higher comorbidity index, grade, and stage of ACC at presentation. There was improved survival with surgical resection of primary tumor, irrespective of disease stage; postsurgical chemotherapy or radiation was of benefit only in stage IV disease.


2012 ◽  
Vol 94 (7) ◽  
pp. 484-489 ◽  
Author(s):  
B Bisase ◽  
C Kerawala

INTRODUCTION Cervical metastases from breast carcinoma are rare and their management is controversial. Between 1987 and 2002 the American Joint Committee on Cancer (AJCC) staged patients with supraclavicular fossa nodal disease as M1 but the subsequent demonstration that patients with regional stage IV disease had better outcomes than visceral stage IV disease led to a reclassification of the former to stage IIIC in 2003. The literature remains inconsistent regarding the fate of these patients. Despite the attendant morbidity of treatment and lack of knowledge regarding long-term survival, we hypothesised that current practice varies in the UK and a unified approach does not exist. The aim of this study was therefore to determine current practice and opinion of both head and neck specialists and breast cancer clinicians in the UK. METHODS Questionnaires were disseminated to 185 head and neck surgeons, breast surgeons and their oncology counterparts. These outlined a clinical scenario of a patient with a history of T3 primary breast cancer presenting with cervical and supraclavicular nodal metastases, with opinion being sought regarding the significance of this status and the individual’s practical approach to the problem. The extent of any proposed neck dissection was also explored. RESULTS Of the 117 respondents, a noticeable variation in opinion was evident. Contrary to the current AJCC staging, 61% of clinicians felt that both level V and III metastases represented stage IV disease. There was a tendency towards aggressive surgical treatment with a third recommending comprehensive neck dissection despite a lack of evidence base. A disparity was noted between adjuvant treatments offered and the final pN stage. CONCLUSIONS This study suggests that at present there is widespread inconsistency in the management of breast carcinoma cervical metastases in the UK. There is a need to unify practice with an evidence base in order to improve informed multidisciplinary decision making and, ultimately, patient care. This study goes some way to supporting multicentre collaboration in order to achieve that aim.


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