Identification of hereditary cancer in the general population: development and validation of a screening questionnaire for obtaining the family history of cancer

Abstract

One of the challenges for Latin American countries is to include in their healthcare systems technologies that can be applied to hereditary cancer detection and management. The aim of the study is to create and validate a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The primary screening questionnaire (PSQ) was developed to identify families at-risk for HCPS. The PSQ was validated using discrimination measures, and the reproducibility was estimated through kappa coefficient. Patients with at least one affirmative answer had the pedigree drawn using three alternative interview approaches: in-person, by telephone, or letter. Validation of these approaches was done. Kappa and intraclass correlation coefficients were used to analyze data's reproducibility considering the presence of clinical criteria for HCPS. The PSQ was applied to a convenience sample of 20,000 women of which 3121 (15.6%) answered at least one affirmative question and 1938 had their pedigrees drawn. The PSQ showed sensitivity and specificity scores of 94.4% and 75%, respectively, and a kappa of 0.64. The strategies for pedigree drawing had reproducibility coefficients of 0.976 and 0.850 for the telephone and letter approaches, respectively. Pedigree analysis allowed us to identify 465 individuals (24.0%) fulfilling at least one clinical criterion for HCPS. The PSQ fulfills its function, allowing the identification of HCPS at-risk families. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.

This manuscript describes the creation and validation of a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The questionnaire was applied to a convenience sample of 20,000 women of which 3121 (15.6%) reported the presence of cancer cases in the family and 1938 had their pedigrees drawn. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.

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Identification of hereditary cancer in the general population: development and validation of a screening questionnaire for obtaining the family history of cancer

Abstract

One of the challenges for Latin American countries is to include in their healthcare systems technologies that can be applied to hereditary cancer detection and management. The aim of the study is to create and validate a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The primary screening questionnaire (PSQ) was developed to identify families at-risk for HCPS. The PSQ was validated using discrimination measures, and the reproducibility was estimated through kappa coefficient. Patients with at least one affirmative answer had the pedigree drawn using three alternative interview approaches: in-person, by telephone, or letter. Validation of these approaches was done. Kappa and intraclass correlation coefficients were used to analyze data's reproducibility considering the presence of clinical criteria for HCPS. The PSQ was applied to a convenience sample of 20,000 women of which 3121 (15.6%) answered at least one affirmative question and 1938 had their pedigrees drawn. The PSQ showed sensitivity and specificity scores of 94.4% and 75%, respectively, and a kappa of 0.64. The strategies for pedigree drawing had reproducibility coefficients of 0.976 and 0.850 for the telephone and letter approaches, respectively. Pedigree analysis allowed us to identify 465 individuals (24.0%) fulfilling at least one clinical criterion for HCPS. The PSQ fulfills its function, allowing the identification of HCPS at-risk families. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.

This manuscript describes the creation and validation of a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The questionnaire was applied to a convenience sample of 20,000 women of which 3121 (15.6%) reported the presence of cancer cases in the family and 1938 had their pedigrees drawn. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.

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Procaspase-activating compound-1 induces apoptosis in Trypanosoma cruzi

Abstract

Some therapeutics for parasitic, cardiac and neurological diseases activate apoptosis. Therefore, the study of apoptotic proteins in pathogenic organisms is relevant. However, the molecular mechanism of apoptosis in unicellular organisms remain elusive, despite morphological evidence of its occurrence. In Trypanosoma cruzi, the causative agent of Chagas disease, metacaspase 3 (TcMCA3), seems to have a key role in parasite apoptosis. Accordingly, this work provides data concerning TcMCA3 regulation through its interaction with procaspase-activating compound 1 (PAC-1), a procaspase 3 activator. Indeed, PAC-1 reduced T. cruzi epimastigote viability with an IC₅₀ of 14.12 µM and induced loss of mitochondrial potential and exposure of phosphatidylserine, features of the apoptotic process. Notwithstanding, those PAC-1-inducible effects were not conserved in metacyclic trypomastigotes. Moreover, PAC-1 reduced the viability of mammalian cells with a greater IC₅₀ (25.70 µM) compared to T. cruzi epimastigotes, indicating distinct modes of binding between caspases and metacaspases. To shed light on the selectivity of metacaspases and caspases, we determined the structural features related to the PAC-1 binding sites in both types of proteins. These data are important for improving the understanding of the apoptosis pathway in T. cruzi so that TcMCA3 could be better targeted with future pharmaceuticals.

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The Impact of Sentinel Node-Mapping in Staging High-Risk Endometrial Cancer

Abstract

Background

This study aimed to determine the impact of sentinel lymph node (SLN)-mapping on the staging of high-risk endometrial cancer (endometrioid grade 3, serous, clear cell, carcinosarcoma, deep myometrial invasion, or angiolymphatic invasion).

Methods

The study analyzed a series of 236 patients treated at AC Camargo Cancer Center from June 2007 to February 2017. The compared 75 patients who underwent SLN-mapping (SLN group) with 161 patients who received pelvic ± para-aortic lymphadenectomy (N-SLN group). Patients with adnexal, peritoneal, or suspicious node metastases were excluded from the study.

Results

The groups did not differ in terms of age, histologic type, or presence of deep myometrial invasion. The overall detection rate for SLNs was 85.3%, and bilateral SLNs were observed in 60% of the patients. Of 20 positive SLNs, 8 (40%) were detected only after immunohistochemistry (IHC). The findings showed an overall sensitivity of 90%, a negative predictive value of 95.7%, and a false-negative predictive value of 4.3%. The SLN group had more pelvic node metastases detected than the N-SLN group (26.7 vs 14.3%; p = 0.02). However, the rate of para-aortic node metastases did not differ between the two groups (13.5 vs 5.6%; p = 0.12). Five patients (3.5%) in the N-SLN group had isolated para-aortic node metastases versus none in the patients with SLN mapped. Additionally, the SLN group received more adjuvant chemotherapy (48 vs 33.5%; p = 0.03).

Conclusions

The data suggest that SLN-mapping identifies more pelvic node metastases than lymph node dissection alone and increases the node detection rate by 12.5% after IHC. Furthermore, no isolated para-aortic node metastases are observed when SLN is detected.

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Vitamin Status and the Development of Postoperative Cognitive Decline in Elderly Surgical Oncologic Patients

Abstract

Background

This study aimed to evaluate the influence that serum levels of vitamin B12, folate, and homocysteine have on the development of short-term postoperative cognitive decline in the elderly surgical oncology patient.

Methods

This study was part of a prospective cohort study focused on postoperative cognitive outcomes for patients 65 years of age or older undergoing surgery for a solid malignancy. Postoperative cognitive decline was defined as the change in the combined results of the Ruff Figural Fluency Test and the Trail-Making Test Parts A and B. Patients with the highest change in scores 2 weeks postoperatively compared with baseline were considered to be patients with cognitive decline. Patients with the lowest change were considered to be patients without cognitive decline. To analyze the effect of vitamin levels on the changes in postoperative cognitive scores, uni- and multivariate logistic regression analysis were performed.

Results

The study enrolled 61 patients with and 59 patients without postoperative cognitive decline. Hyperhomocysteinemia was present in 14.2% of the patients. Patients with postoperative cognitive decline more often had hyperhomocysteinemia (27.9 vs 10.2%). Hyperhomocysteinemia was associated with a higher chance for the development of postoperative cognitive decline (odds ratio_adjusted, 11.9; 95% confidence interval, 2.4–59.4). Preoperative vitamin B12 or folate deficiency were not associated with the development of postoperative cognitive decline.

Conclusion

Preoperative hyperhomocysteinemia is associated with the development of postoperative cognitive decline. The presence of preoperative hyperhomocysteinemia could be an indicator for an increased risk of postoperative cognitive decline developing in the elderly.

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Performance Analysis of the American Joint Committee on Cancer 8th Edition Staging System for Retroperitoneal Sarcoma and Development of a New Staging Algorithm for Sarcoma-Specific Survival

Abstract

Background

The American Joint Committee on Cancer (AJCC) recently published the 8th edition of the AJCC Cancer Staging Manual. Major changes were made to the staging algorithm for retroperitoneal sarcoma; however, whether these changes improve staging system performance is questionable.

Methods

This retrospective cohort analysis of 3703 adult patients with retroperitoneal sarcoma in the Surveillance, Epidemiology, and End Results (SEER) database compares a novel staging system incorporating histologic subtype of sarcoma with current and prior AJCC soft tissue sarcoma staging systems using multiple statistical techniques. The effect of tumor size on sarcoma-specific survival was also assessed by flexible, non-linear Cox proportional hazard regression using restricted cubic splines and fractional polynomials.

Results

The relationship between the covariate-adjusted log hazard for disease-specific survival and tumor size is non-linear. Although the new AJCC T classification approximates this hazard fairly well, the overall prognostic impact of tumor size is limited after accounting for other predictive factors. Predictive accuracy and concordance indices of the AJCC 8th edition staging system for retroperitoneal sarcoma are significantly lower than the prior 7th edition. A proposed staging system incorporating histologic grade, tumor size, and histologic subtype is superior to both the AJCC 7th and 8th editions in predicting sarcoma-specific survival.

Conclusion

AJCC committees should not revise tumor staging algorithms unless the changes actually improve the staging system. A proposed staging scheme incorporating data regarding histologic subtype of sarcoma performs significantly better than both the 7th and 8th AJCC staging systems.

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Rectal Gastrointestinal Stromal Tumor (GIST) in the Era of Imatinib: Organ Preservation and Improved Oncologic Outcome

Abstract

Background

Approximately 5% of gastrointestinal stromal tumors (GISTs) originate in the rectum, and historically, radical resection was commonly performed. Little is known about the outcome for rectal GIST in the era of imatinib.

Methods

Using a prospectively maintained database, this study retrospectively analyzed 47 localized primary rectal GISTs treated at our center from 1982 to 2016, stratified by when imatinib became available in 2000. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed by the Kaplan–Meier method.

Results

Rectal GISTs represented 7.1% of 663 primary GISTs. The findings showed 17 patients in the pre-imatinib era and 30 patients in the imatinib era. The two groups had similar follow-up evaluation, age, gender, Miettinen risk, and distance to the anal verge. In the imatinib era, tumors were smaller at diagnosis (median 4 vs. 5 cm; p = 0.029), and 24 of the 30 patients received perioperative imatinib. In the high-risk patients, organ preservation and negative margins were more common among the 13 patients treated with neoadjuvant imatinib than among the 21 patients treated directly with surgery. High-risk patients who received perioperative imatinib (n = 15) had greater (or nearly significantly greater) 5-year OS, DSS, local RFS, and distant RFS than those who did not (n = 19) (91, 100, 100, and 71% vs. 47, 65, 74, and 41%; p = 0.049, 0.052, 0.077, 0.051, respectively). In the imatinib era, no patient has had a local recurrence or death due to GIST.

Conclusions

The use of imatinib is associated with organ preservation and improved oncologic outcome for patients with rectal GIST.

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