Characterization and clinical outcomes of mismatch repair deficient (dMMR) small bowel adenocarcinoma (SBA).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1511-1511
Author(s):  
Alicia Latham ◽  
Diane Lauren Reidy ◽  
Neil Howard Segal ◽  
Rona Yaeger ◽  
Karuna Ganesh ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Clinical Outcomes ◽  
Age Of Onset ◽  
Early Stage ◽  
Preliminary Evaluation ◽  
Small Bowel Adenocarcinoma ◽  
Recurrence Rates ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Clinical Records

1511 Background: SBA is a rare cancer known to be associated with Lynch syndrome (LS). The prevalence, tumor characteristics, and clinical course of SBAs in the setting of LS is not well understood. We sought to characterize SBA according to mismatch repair and germline mutation status, comparing clinical outcomes. Methods: A retrospective review of SBAs at a single institution identified 74 SBAs that were assessed for dMMR either via immunohistochemical staining (IHC) or microsatellite instability status (MSI) using NGS. Germline DNA was analyzed for mutations in LS-associated mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, EPCAM) and when available, clinical records were reviewed. Results: Of 74 individuals with SBA, 28.4% (21/74) of tumors exhibited dMMR and/or high-frequency MSI (MSI-H). The overall prevalence of LS in SBA was 9.5% (7/74), with all LS patients having dMMR/MSI-H tumors. 33.3% (7/21) of dMMR/MSI-H SBA patients had LS. The distribution of germline mutations among LS patients was 57.1% (4/7) in MLH1, 28.6% (2/7) in MSH2, and 14.3% (1/7) in PMS2. One patient with an dMMR/MSI-H tumor was found to have a high-penetrance APC mutation, diagnostic of familial adenomatous polyposis (FAP). In the 38 patients with available clinical follow-up, median age of onset was similar in the dMMR/MSI-H vs the pMMR/MSS group (62 vs 57, p = 0.8). The prevalence of synchronous/metachronous cancers was 5.9% (1/17) in the pMMR/MSS group and 38% (8/21) in the dMMR/MSI-H group (p = 0.02), with 62.5% (5/8) of these in LS (p = 0.001; synchronous/metachronous in LS (5/7) vs. non-LS (4/31)). In the pMMR/MSS group, 58.8% (10/17) of patients presented with metastatic disease at diagnosis, compared to 19% (4/21) in the dMMR/MSI-H group (p = 0.01). In dMMR/MSI-H SBA patients with early-stage disease, 11.8% (2/17) recurred, compared to 71.4% (5/7) in the pMMR/MSS group (p = 0.009). Conclusions: This preliminary evaluation suggests that SBA exhibiting dMMR/MSI-H status is more closely associated with early-stage disease and lower recurrence rates, similar to prior observations in colon cancer. LS was found in 9.5% of all SBA and in 33.3% of dMMR/MSI-H tumors, suggesting that germline assessment for LS in SBA is warranted.

scholarly journals Study protocol: A multi-centre, double blind, randomised, placebo-controlled, parallel group, phase II trial (RIDD) to determine the efficacy of intra-nodular injection of anti-TNF to control disease progression in early Dupuytren’s disease, with an embedded dose response study.

2017 ◽  
Vol 2 ◽  
pp. 37 ◽  
Author(s):  
Jagdeep Nanchahal ◽  
Catherine Ball ◽  
Jennifer Swettenham ◽  
Susan Dutton ◽  
Vicki Barber ◽  
...  
Keyword(s):  
Disease Progression ◽  
Early Stage ◽  
Dupuytren’S Disease ◽  
Recurrence Rates ◽  
Double Blind ◽  
Dupuytren's Disease ◽  
Early Stage Disease ◽  
Matrix Deposition ◽  
Stage Disease

Dupuytren’s disease is a common fibrotic condition of the hand affecting 4% of the population and causes the fingers to curl irreversibly into the palm. It has a strong familial tendency, there is no approved treatment for early stage disease, and patients with established digital contractures are most commonly treated by surgery. This is associated with prolonged recovery, and less invasive techniques have high recurrence rates. The myofibroblasts, the cells responsible for the excessive matrix deposition and contraction, are aggregated in nodules. Using excised diseased and control human tissue, we found that immune cells interspersed amongst the myofibroblasts secrete cytokines. Of these, only tumour necrosis factor (TNF) promoted the development of myofibroblasts. The clinically approved anti-TNF agents led to inhibition of the myofibroblast phenotype in vitro. This clinical trial is designed to assess the efficacy of the anti-TNF agent adalimumab on participants with early disease. The first part is a dose-ranging study where nodules of participants already scheduled for surgery will be injected with either placebo (saline) or varying doses of adalimumab. The excised tissue will then be analysed for markers of myofibroblast activity. The second part of the study will recruit participants with early stage disease. They will be randomised 1: 1 to receive either adalimumab or placebo at 3 month intervals over 1 year and will then be followed for a further 6 months. Outcome measures will include nodule hardness, size and disease progression. The trial will also determine the cost-effectiveness of adalimumb treatment for this group of participants.

Primary adenocarcinoma of the ileum causing obstruction in an 84-year-old patient – a case report

Nowa Medycyna ◽  
2018 ◽  
Vol 25 (4) ◽  
Author(s):  
Krzysztof Łampika ◽  
Paweł Dutkiewicz ◽  
Przemysław Ciesielski
Keyword(s):  
Case Report ◽  
Small Bowel ◽  
Early Stage ◽  
Tumour Progression ◽  
Correct Diagnosis ◽  
Primary Adenocarcinoma ◽  
Intestinal Fistula ◽  
Small Bowel Adenocarcinoma ◽  
Early Stage Disease ◽  
Stage Disease

Although small bowel adenocarcinoma is a rare cancer, with estimated incidence rate of 4 cases per million persons it is the most common small bowel tumour. Diagnosis of early-stage disease is difficult due to non-specific symptoms. Patients are usually treated on an emergency basis due to gastrointestinal obstruction or bleeding. The paper presents a case report of an 84-year-old female who underwent surgical treatment due to bowel obstruction caused by ileum cancer, and in whom diagnostic imaging did not allow for a correct diagnosis. The surgery was complicated by intestinal fistula. Histopathology confirmed local tumour progression. After treatment completion, the patient was referred for further anti-cancer treatment.

Clinical Profile of a New Monoclonal Antibody-Based Immunoassay for Tissue Polypeptide Antigen

1994 ◽  
Vol 9 (4) ◽  
pp. 231-238 ◽  
Author(s):  
M. Correale ◽  
H. Arnberg ◽  
P. Blockx ◽  
E. Bombardieri ◽  
M. Castelli ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bladder Cancer ◽  
Early Stage ◽  
Roc Curves ◽  
Preliminary Evaluation ◽  
Tissue Polypeptide Antigen ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Wide Range ◽  
Disease Stages

Our preliminary evaluation of a new monoclonal antibody-based assay for tissue polypeptide antigen (TPA) has shown it to be clinically equivalent to the polyclonal antibody-based assay for TPA. The new assay (TPA-M) employs three monoclonal antibodies to epitopes on cytokeratins 8, 18 and 19. This multicenter, multinational study included 266 patients with newly diagnosed carcinomas of the lung, breast, large bowel and urinary bladder. TPA values from the two assays were compared with three other cytokeratin markers (TPS, CYFRA 21–1 and TPACyk) and with the established reference markers for these malignancies (CEA and NSE for lung, CA 15–3 for breast, CEA and CA 19–9 for colorectal tumors). Analysis of receiver operating characteristic (ROC) curves in lung, colorectal and bladder cancer showed similar sensitivities for the two assays, ranging from 50% to 80% with a specificity of 95%. In breast cancer all the markers studied showed poor sensitivity. However, TPA determination by either method could discriminate advanced stage (stages III and IV) from early stage disease (stages 0 to II). TPA showed similar discriminating ability in bladder cancer. On the basis of the results obtained in our patient series, it seems that of the cytokeratin markers studied, TPA and TPA-M are the most sensitive and offer a wide range of clinical applications.

Postoperative surveillance recommendations for early-stage colon cancer based on results from the clinical outcomes of surgical therapy trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4013-4013
Author(s):  
V. L. Tsikitis ◽  
K. Malireddy ◽  
E. A. Green ◽  
B. Christensen ◽  
R. Whelan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Clinical Outcomes ◽  
Surgical Therapy ◽  
Late Stage ◽  
Early Stage ◽  
Early Stage Disease ◽  
Postoperative Surveillance ◽  
Stage Disease ◽  
Therapy Trial ◽  
Early Stage Colon Cancer

4013 Background: Intensive postoperative surveillance is associated with improved survival and recommended for patients with late stage (stage IIB & III) colon cancer. We hypothesized that stage I & IIA colon cancer patients would experience similar benefits. Methods: Secondary analysis of data from the Clinical Outcomes of Surgical Therapy trial was performed by analyzing results according to TNM stage; early (stage I & IIA; 537 patients) and late (stage IIB & III; 254 patients) stage disease. Five-year recurrence rates were higher in patients with late (35.7%) versus early stage disease (9.5%). Early and late stage salvage rates, recurrence patterns and methods of first detection were compared by χ2 test. Results: Salvage rates for early and late stage disease patients with recurrence were the same (35.9% versus 37%, p=0.9 respectively). Median survival following second surgery after recurrence was 35.8 months late stage and 51.2 months for early stage patients respectively. Sites of first recurrence did not significantly differ between late and early stage disease: liver (37.4% vs. 27.2%); lung (29.7% vs.23.6%); intraabdominal (24.2% vs.10.9%); and locoregional (12.1% vs.10.9%). Methods of first detection of recurrence were also not significantly different: CEA (37.4% vs. 29.1%); CT scan (26.4% vs. 23.6%); chest X-ray (12.1% vs. 7.3%); and colonoscopy (8.8% vs. 12.7%), for late versus early stage disease, respectively. Conclusions: Patients with early stage colon cancer have similar sites of recurrence, and receive similar benefit from post-recurrence therapy as later stage patients; implementation of existing surveillance guidelines for early stage patients is appropriate. No significant financial relationships to disclose.

Novel approaches to improve prostate cancer diagnosis and management in early-stage disease

2012 ◽  
Vol 109 ◽  
pp. 1-7 ◽  
Author(s):  
Michael Marberger ◽  
Jelle Barentsz ◽  
Mark Emberton ◽  
Jonas Hugosson ◽  
Stacy Loeb ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Diagnosis ◽  
Early Stage ◽  
Early Stage Disease ◽  
Prostate Cancer Diagnosis ◽  
Diagnosis And Management ◽  
Stage Disease ◽  
Novel Approaches ◽  
Improve Prostate Cancer

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

scholarly journals Female Breast Cancer in Suriname: Pathways to Treatment—A Patient’s Perception

2020 ◽  
Vol 6 (Supplement_1) ◽  
pp. 49-49
Author(s):  
Euridice R. Irving ◽  
Dennis R. A. Mans ◽  
Els Th. M. Dams ◽  
Maureen Y. Lichtveld
Keyword(s):  
Breast Cancer ◽  
Health Care ◽  
Access To Health Care ◽  
Early Stage ◽  
Diagnosis And Treatment ◽  
Related Factors ◽  
Entire Interval ◽  
Early Stage Disease ◽  
Resource Setting ◽  
Stage Disease

PURPOSE Delays across the entire cancer care continuum are not uncommon. This cross-sectional study explored the health care trajectories of Surinamese women with breast cancer and identified predictors of timely diagnosis and treatment initiation. METHODS One hundred women age 30 years or older who were newly diagnosed with breast cancer in 2017 to 2018 were recruited from all 4 hospitals in Paramaribo. Data on their demographics, lifestyle, reproductive and medical history, health status, and family history of breast cancer and other malignancies were collected using a validated semistructured questionnaire. Using Anderson’s Model of Pathways to Treatment, we defined a patient interval (from detection to first consultation), diagnostic interval (from consultation to histopathologic diagnosis), and treatment interval (from diagnosis to first treatment). Log-transformed data were analyzed using linear regression, and variables with P ≤ .05 were considered statistically significant predictors of intervals. RESULTS All participants had health insurance and access to health care. Eighty-five percent of patients presented with early-stage disease. Ninety percent of patients had self-detected their disease, with 70% finding a lump. Average age was 55.6 years (± 11.8 years). Median durations of patient, diagnostic, and treatment intervals were 13 days (interquartile, range, 4-63 days), 40 days (IQR, 21-57 days), and 18 days (IQR, 8-38 days), respectively. Median duration of the entire interval was 95 days (IQR, 59-272 days). Patient-related factors associated with the intervals were religion (β = −530; P = .003), being employed (β = 149.4; P = .007), and age 50 years and older (β = −195.8; P = .037). Disease-related factors were lump as first symptom (β = −175.6; P = .038) and late-stage disease at diagnosis (β = 213.5; P = .004). CONCLUSION Given the limited-resource setting, delays in Suriname’s health care can be minimized by programs aimed at increasing breast cancer awareness and education; however, delays may have been underestimated as a result of the over-representation of early-stage disease and recall bias regarding the first symptom detected.

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