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OBJECTIVE: To investigate if underrepresentation of racial and ethnic minorities exists in metastatic colorectal carcinoma (CRC) clinical trials. SUMMARY BACKGROUND DATA: Representation of vulnerable subpopulations is essential for generalizability of clinical trials. Limited studies to date have investigated racial and ethnic representation of patients enrolled in clinical trials for metastatic CRC. METHODS: ClinicalTrials.gov was queried for metastatic CRC clinical trials in the United States from 2000-2020. Incidence data were extracted from the SEER Database. Enrollment fraction (EF) was defined as number of trial participants divided by U.S. incidence of metastatic CRC in each race, ethnicity, and gender. Representation Quotient (RQ) was defined as the proportion of trial participants divided by proportion of U.S. metastatic CRC incidence for each subgroup. RESULTS: 8084 patients from 135 clinical trials were analyzed. 49.6% of clinical trials reported race data and 34.8% reported ethnicity data. Compared to 2000-2009, 2010-2019 had increased representation data reporting for race (61.2% vs. 38.8%) and ethnicity (64.6% vs. 35.4%). Of trials with race data, White patients represented 77.0%, Black patients 6.6%, Asian/Pacific Islander (API) patients 16.1%, American Indian/Alaska Native (AIAN) patients 0.2%, and Hispanic patients 6.8%. Black patients (median RQ 0.54), API patients (median RQ 0.19), AIAN patients (median RQ 0.00), and Hispanic patients (median RQ 0.26) were underrepresented. Black patients had a higher degree of underrepresentation in clinical trials with serum creatinine inclusion criteria (RQ 0.40 vs. 0.86, P=0.034). CONCLUSIONS: Strategies are needed to increase minority enrollment in clinical trials for metastatic CRC. Identification of systemic barriers is integral in public policy advocacy to increase representation.
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Background: Extrahepatic biliary neuroendocrine tumors (EBNETs) are rare. We aimed to characterize EBNETs including factors associated with survival. Methods: The National Cancer Database was queried for patients with EBNETs from 2004 to 2016. Patients who underwent resection were examined using Cox proportional hazards regression and the Kaplan-Meier method. We compared overall survival (OS) among patients with EBNETs to those with NETs from other primary sites. Results: Overall, 223 patients with EBNETs were identified. Patients were predominantly male (n = 113, 50.7 %), white (n = 177, 79.4 %) and presented without distant metastasis (n = 182, 81.6 %). The majority underwent operation (n = 127, 57.9 %) with resection of the primary tumor (n = 89, 70 %). Among patients who underwent resection (n = 71), multivariable regression demonstrated older age (HR 1.11, 95 % C.I. 1.04-1.17), lymph node metastases (HR 1.19, 95 % C.I. 1.02-1.38) and poorly/undifferentiated tumors [HR 22.3, 95 % C.I. 3.78-131]) were associated with worse overall survival. Patients with EBNETs experienced abbreviated OS compared to patients with small bowel or pancreas NETs (p < 0.001), but improved OS when compared to patients with gallbladder NETs (p = 0.001). Conclusions: Tumor differentiation and lymph node status significantly impact overall survival.
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Background: Treatment of advanced liver tumors remains challenging. Although immune checkpoint inhibition has revolutionized treatment for many cancers, responses in colorectal liver metastases and biliary tract cancers remain suboptimal. Investigation into additional immunomodulatory therapies for these cancers is needed. Interleukin-12 (IL-12) is a pro-inflammatory cytokine with robust anti-tumor activity, but systemic adverse effects largely terminated therapeutic development of recombinant human IL-12 (rhIL-12). PDS01ADC is a novel human monoclonal antibody (NHS76) conjugated to two IL-12 heterodimers with established safety in phase I trials. The NHS76 antibody specifically targets histone/DNA complexes which are accessible only in regions of cell death and this antibody has been shown to accumulate locally in tumors. Methods: Patients with unresectable metastatic colorectal cancer (mCRC) or unresectable intrahepatic cholangiocarcinoma (ICC) will receive synchronization of subcutaneous PDS01ADC with floxuridine delivered via a hepatic artery infusion pump (HAIP). The primary outcome measured in this study will be overall response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Secondary outcomes measured in this study will include hepatic and non-hepatic progression-free survival (PFS), overall survival, and safety of PDS01ADC combination therapy with HAIP. Discussion: Poor clinical response of these liver tumors to immunotherapy is likely due to various factors, including poor immune infiltrate into the tumor and immunosuppression by the tumor microenvironment. By exploiting the tumor cell death induced by HAIP locoregional therapy in combination with systemic chemotherapy, PDS01ADC is poised to modulate the tumor immune microenvironment to improve outcomes for patients undergoing HAIP therapy. Trial Registration: ClinicalTrials.gov (ID NCT05286814 version 2023-10-18); https://clinicaltrials.gov/study/NCT05286814?term=NCT05286814&rank=1.
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BACKGROUND: There is variation in the probability of nodal metastases from low-grade appendiceal adenocarcinomas, and the role of right colectomy is unclear. We aimed to define the prevalence and utility of lymphovascular invasion in predicting the risk of nodal metastases to help stratify patients who may benefit from right hemicolectomy. METHODS: Patients with nonmetastatic low-grade appendiceal adenocarcinomas were identified from the National Cancer Database (2010-2017). The primary outcome was probability of nodal metastases. Logistic regression was used to identify independent predictors of nodal metastases. A 4-tier risk model-the COH Composite Score-was calculated by assigning 1 point each for a high-risk feature (lymphovascular invasion, T3/T4 T stage, or nonmucinous histology). Survival analysis was performed using the Kaplan-Meier method. Multivariate Cox regression analysis was used to identify independent predictors of survival. RESULTS: A total of 1,303 patients with nonmetastatic low-grade appendiceal adenocarcinomas (64.2% mucinous) were identified. Of the 1,133 patients with known lymphovascular invasion status, 78 (6.9%) were lymphovascular invasion positive. In multivariate analysis, lymphovascular invasion was independently associated with nodal metastases (odds ratio, 8.68; P < .001). Overall accuracy of lymphovascular invasion in predicting nodal metastases was 86%. The COH Composite Score stratified patients in 4 categories with increasing risk of nodal metastases and incrementally worse survival. For patients with the COH Composite Score of 0 (12%), the nodal metastasis rate was 3.1%, and a right hemicolectomy in this group did not improve survival. CONCLUSION: The presence of lymphovascular invasion is strongly predictive of nodal metastases. Lymphovascular invasion as part of the COH Composite Score may help guide the extent of surgery in low-grade appendiceal adenocarcinomas.
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Adenocarcinoma , Neoplasias del Apéndice , Colectomía , Metástasis Linfática , Invasividad Neoplásica , Humanos , Colectomía/métodos , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/cirugía , Neoplasias del Apéndice/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Invasividad Neoplásica/patología , Estudios Retrospectivos , Estadificación de Neoplasias , Clasificación del Tumor , Medición de Riesgo , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugíaAsunto(s)
Adenocarcinoma Mucinoso , Neoplasias del Apéndice , Humanos , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/mortalidad , Neoplasias del Apéndice/terapia , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/terapia , Tasa de Supervivencia , PronósticoRESUMEN
Importance: Approximately 1% to 3% of gastric cancers and 5% of lobular breast cancers are hereditary. Loss of function CDH1 gene variants are the most common gene variants associated with hereditary diffuse gastric cancer and lobular breast cancer. Previously, the lifetime risk of gastric cancer was estimated to be approximately 25% to 83% and for breast cancer it was estimated to be approximately 39% to 55% in individuals with loss of function CDH1 gene variants. Objective: To describe gastric and breast cancer risk estimates for individuals with CDH1 variants. Design, Setting, and Participants: Multicenter, retrospective cohort and modeling study of 213 families from North America with a CDH1 pathogenic or likely pathogenic (P/LP) variant in 1 or more family members conducted between January 2021 and August 2022. Main Outcomes and Measures: Hazard ratios (HRs), defined as risk in variant carriers relative to noncarriers, were estimated for each cancer type and used to calculate cumulative risks and risks per decade of life up to age 80 years. Results: A total of 7323 individuals from 213 families were studied, including 883 with a CDH1 P/LP variant (median proband age, 53 years [IQR, 42-62]; 4% Asian; 4% Hispanic; 85% non-Hispanic White; 50% female). In individuals with a CDH1 P/LP variant, the prevalence of gastric cancer was 13.9% (123/883) and the prevalence of breast cancer among female carriers was 26.3% (144/547). The estimated HR for advanced gastric cancer was 33.5 (95% CI, 9.8-112) at age 30 years and 3.5 (95% CI, 0.4-30.3) at age 70 years. The lifetime cumulative risk of advanced gastric cancer in male and female carriers was 10.3% (95% CI, 6%-23.6%) and 6.5% (95% CI, 3.8%-15.1%), respectively. Gastric cancer risk estimates based on family history indicated that a carrier with 3 affected first-degree relatives had a penetrance of approximately 38% (95% CI, 25%-64%). The HR for breast cancer among female carriers was 5.7 (95% CI, 2.5-13.2) at age 30 years and 3.9 (95% CI, 1.1-13.7) at age 70 years. The lifetime cumulative risk of breast cancer among female carriers was 36.8% (95% CI, 25.7%-62.9%). Conclusions and Relevance: Among families from North America with germline CDH1 P/LP variants, the cumulative risk of gastric cancer was 7% to 10%, which was lower than previously described, and the cumulative risk of breast cancer among female carriers was 37%, which was similar to prior estimates. These findings inform current management of individuals with germline CDH1 variants.
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BACKGROUND: Mucinous adenocarcinoma of the appendix (MACA) follows a complex disease course with variable survival. Large-scale predictive modeling may determine subtle yet important prognostic factors otherwise unseen in smaller cohort analyses. METHODS: Patients with MACA were identified from the Surveillance, Epidemiology, and End Results (SEER) Research Plus database (2005-2019). Primary, secondary, and tertiary outcomes were disease-specific survival (DSS), overall survival (OS), and average annual percent change (AAPC) in incidence. RESULTS: Among 4,258 included patients, MACA was most frequently diagnosed at 50 to 69 years (52.0%), with female preponderance (55.9%). MACA incidence AAPC was 3.8 (95% confidence interval [CI] 1.9-5.9). For patients with exclusive, first-diagnosis MACA included in survival analysis (3,222 patients), median DSS and OS were 118 and 88 months, respectively. In DSS-based multivariable analysis, worse prognosis was associated with non-Hispanic Black background (HR 1.36, 95% CI 1.02-1.82; p = 0.036), high grade (grade 3 HR 3.10, 95% CI 2.44-3.92; p < 0.001), lymphatic spread (HR 2.73, 95% CI 2.26-3.30; p < 0.001), and distant metastasis (HR 5.84, 95% CI 3.86-8.83; p < 0.001). In subcohort analysis of patients with rationale for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC, 2,387 patients), CRS-HIPEC was associated with survival benefit compared with surgery alone but only for moderate-grade tumors (median DSS/OS 138/138 vs. 116/87 months; p < 0.001). CONCLUSIONS: Mucinous adenocarcinoma of the appendix incidence is increasing in the United States. Survival rates are affected by both demographics and classical risk factors, and CRS-HIPEC-associated survival benefit predominantly occurs in moderate-grade tumors. Further exploration of biologic and clinicopathologic features may enhance risk stratification for this disease.
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Adenocarcinoma Mucinoso , Neoplasias del Apéndice , Programa de VERF , Humanos , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Neoplasias del Apéndice/mortalidad , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/terapia , Femenino , Masculino , Persona de Mediana Edad , Anciano , Tasa de Supervivencia , Pronóstico , Estudios de Seguimiento , Adulto , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Quimioterapia Intraperitoneal Hipertérmica , IncidenciaRESUMEN
Importance: BRCA1-associated protein (BAP1) tumor predisposition syndrome (TPDS) is a cancer genodermatosis associated with high risk of uveal and cutaneous melanoma, basal cell carcinoma, and multiple internal malignant neoplasms, including mesothelioma and renal cell carcinoma. Early detection of the syndrome is important for cancer surveillance and genetic counseling of family members who are at risk. Objective: To determine the prevalence of nail abnormalities in individuals with pathogenic germline variants in BAP1. Design, Setting, and Participants: In this prospective cohort study, individuals who were known carriers of pathogenic BAP1 germline variants were consecutively enrolled between October 10, 2023, and March 15, 2024. Dermatologic evaluation for nail abnormalities was performed, including a history of nail abnormalities and associated symptoms, physical examination, medical photography, and nail biopsy for histopathology. This was a single-center study conducted at the National Institutes of Health Clinical Center. Main Outcomes and Measures: Primary outcomes were the prevalence and spectrum of nail changes and histopathologic characterization. Results: Among 47 participants (30 female [63.8%]; mean [SD] age, 46.4 [15.1] years) ranging in age from 13 to 72 years from 35 families, nail abnormalities were detected in 41 patients (87.2%) and included leukonychia, splinter hemorrhage, onychoschizia, and distal nail hyperkeratosis. Clinical findings consistent with onychopapilloma were detected in 39 patients (83.0%), including 35 of 40 individuals aged 30 years or older (87.5%). Nail bed biopsy was performed in 5 patients and was consistent with onychopapilloma. Polydactylous involvement with onychopapillomas was detected in nearly all patients who had nail involvement (38 of 39 patients [97.4%]). Conclusions and Relevance: This study found that BAP1 TPDS was associated with a high rate of nail abnormalities consistent with onychopapillomas in adult carriers of the disease. Findings suggest that this novel cutaneous sign may facilitate detection of the syndrome in family members who are at risk and patients with cancers associated with BAP1 given that multiple onychopapillomas are uncommon in the general population and may be a distinct clue to the presence of a pathogenic germline variant in the BAP1 gene.
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Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Neoplasias Cutáneas , Proteínas Supresoras de Tumor , Ubiquitina Tiolesterasa , Humanos , Ubiquitina Tiolesterasa/genética , Femenino , Proteínas Supresoras de Tumor/genética , Masculino , Persona de Mediana Edad , Adulto , Estudios Prospectivos , Anciano , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Adulto Joven , Adolescente , Enfermedades de la Uña/genética , Enfermedades de la Uña/patología , Enfermedades de la Uña/epidemiología , Enfermedades de la Uña/diagnóstico , Prevalencia , Papiloma/patología , Papiloma/genética , Papiloma/epidemiología , Papiloma/diagnóstico , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/patología , Uñas Malformadas/genética , Uñas Malformadas/epidemiología , Uñas Malformadas/diagnósticoRESUMEN
BACKGROUND: Colorectal adenosquamous carcinoma (ASC) is a rare subtype of colorectal carcinoma. This study presents findings from a large database query to highlight the demographic, clinical, and pathological factors, prognosis, and survival of colorectal ASC. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with colorectal ASC diagnosed between 2000 and 2020 and assess factors associated with overall survival (OS) and cause-specific survival (CSS). RESULTS: Among 284 identified cases, the median age of diagnosis was 64 years. The majority of patients were White (69.0%), with income ≤ $70,000 ( 62.3%), and lived in metropolitan areas (85.6%). Regarding tumor characteristics, the majority of tumors were poorly differentiated (49.6%), regional stage (39.8%), size of > 4.0 cm ( 41.5%), and had a negative lymph node status (47.2%). Primary sites were the rectum (35.2%) and colon ( 64.8%). In patients with primary site to the rectum, the majority of treatment modality was multimodal therapy (40.0%). The main treatment modality for the primary site to the colon was surgery only (46.2%), followed by surgery + chemotherapy (34.2%). The overall 5-year survival was 31.3 (95% C.I. 28.4-34.2) and the 5-year cause-specific survival (CSS) was 40.1% (95% C.I. 36.9-43.3). Multivariate analysis showed age ≥ 60 years, regional stage, and distant stage were negative prognostic factors. An income of > $70,000, multimodal therapy, and surgery with chemotherapy were positive prognostic factors. CONCLUSION: Colorectal adenosquamous carcinomas are more common in the non-Hispanic White populations and appear more frequently later in life (based on the median age of diagnosis at 64). Factors that contributed to a worse prognosis were an age of diagnosis ≥ 60 years, regional stage, and distant stage.
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Carcinoma Adenoescamoso , Quimioradioterapia , Neoplasias Colorrectales , Programa de VERF , Humanos , Carcinoma Adenoescamoso/mortalidad , Carcinoma Adenoescamoso/terapia , Carcinoma Adenoescamoso/patología , Persona de Mediana Edad , Masculino , Femenino , Anciano , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Programa de VERF/estadística & datos numéricos , Quimioradioterapia/estadística & datos numéricos , Quimioradioterapia/métodos , Pronóstico , Tasa de Supervivencia , Adulto , Estados Unidos/epidemiología , Estadificación de Neoplasias , Anciano de 80 o más AñosRESUMEN
PURPOSE: Risk-reducing surgery for cancer prevention in solid tumors is a pressing clinical topic because of the increasing availability of germline genetic testing. We examined the short- and long-term outcomes of risk-reducing total gastrectomy (RRTG) and its lesser-known impacts on health-related quality of life (QOL) in individuals with hereditary diffuse gastric cancer syndrome. METHODS: Individuals who underwent RRTG as part of a single-institution natural history study of hereditary gastric cancers were examined. Clinicopathologic details, acute and chronic operative morbidity, and health-related QOL were assessed. Validated questionnaires were used to determine QOL scores and psycho-social-spiritual measures of healing. RESULTS: One hundred twenty-six individuals underwent RRTG because of a pathogenic or likely pathogenic germline CDH1 variant between October 2017 and December 2021. Most patients (87.3%; 110/126) had pT1aN0 gastric carcinoma with signet ring cell features on final pathology. Acute (<30 days) postoperative major morbidity was low (5.6%; 7/126) and nearly all patients (98.4%) lost weight after total gastrectomy. At 2 years after gastrectomy, 94% (64/68) of patients exhibited at least one chronic complication (ie, bile reflux, dysphagia, and micronutrient deficiency). Occupation change (23.5%), divorce (3%), and alcohol dependence (1.5%) were life-altering consequences attributed to total gastrectomy by some patients. In patients with a median follow-up of 24 months, QOL scores decreased at 1 month after gastrectomy and returned to baseline by 6-12 months. CONCLUSION: RRTG is associated with life-changing adverse events that should be discussed when counseling patients with CDH1 variants about gastric cancer prevention. The risks of cancer-prevention surgery should not only be judged in the context of likelihood of death due to disease if left untreated, but also based on the real consequences of organ removal.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Calidad de Vida , Gastrectomía/efectos adversos , Pruebas Genéticas , Adenocarcinoma/cirugía , Cadherinas/genética , Mutación de Línea Germinal , Predisposición Genética a la EnfermedadRESUMEN
Women with germline pathogenic variants in CDH1, which encodes E-cadherin protein, are at increased lifetime risk of invasive lobular carcinoma (ILC). The associated tumor characteristics of hereditary lobular breast carcinoma (HLBC) in this high-risk population are not well-known. A single-center prospective cohort study was conducted to determine the imaging and pathologic features of HLBC compared to population-based ILC using Surveillance, Epidemiology, and End Results (SEER) data. One hundred fifty-eight women with CDH1 variants were evaluated, of whom 48 (30%) also had an ILC diagnosis. The median age at CDH1 diagnosis was 45 years [interquartile range, IQR 34-57 years] whereas the median age at diagnosis of CDH1 with concomitant ILC (HLBC) was 53 [IQR 45-62] years. Among women with HLBC, 83% (40/48) were identified with CDH1 mutation after diagnosis of ILC. Among 76 women (48%, 76/158) undergoing surveillance for ILC with breast magnetic resonance imaging (MRI), 29% (22/76) had an abnormal MRI result with available biopsy data for comparison. MRI detected ILC in 7 out of 8 biopsy-confirmed cases, corresponding with high sensitivity (88%), specificity (75%), and negative predictive value (98%); however, false-positive and false-discovery rates were elevated also (25% and 68%, respectively). HLBC was most frequently diagnosed at age 40-49 years (44%, 21/48), significantly younger than the common age of diagnosis of ILC in SEER general population data (most frequent age range 60-69 years, 28%; p < 0.001). HLBC tumors were smaller than SEER-documented ILC tumors (median 1.40 vs. 2.00 cm; p = 0.002) and had a higher incidence of background lobular carcinoma in situ (88% vs. 1%; p < 0.001) as well as progesterone receptor positivity (95% vs. 81%, p = 0.032). These findings suggest that HLBC is often detected via conventional screening methods as an early-stage hormone receptor-positive tumor, thus the clinical benefit of intensive screening with MRI may be limited to a subset of women with germline CDH1 variants.
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Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have diverse tumor biology. Succinate dehydrogenase (SDH)-deficient GIST, comprise less than 10% of all GIST, with mutational loss of the catalytic SDHA subunit being the most common subtype. Contrary to typical GISTs harboring inactivating mutations in KIT/PDGFRA, SDH-deficient GIST has varying biology and behavior, occurring at a younger age, often metastatic on presentation and frequently refractory to conventional tyrosine kinase inhibitors (TKI). Liver and peritoneum are their most common sites of metastases, and extra-abdominal spread to the diaphragm or mediastinum has not been previously described. Case Description: Herein, we present a case of a 44-year-old female patient with a history of SDHA-deficient GISTs with multiple previous metastasectomies who presented with recurrence to the paraesophageal region and diaphragm which was identified upon routine positron emission tomography (PET) surveillance. Patient subsequently underwent a robotic assisted metastasectomy using a thoracic approach. Follow up was obtained 2 months following procedure and there was no evidence of recurrence. Conclusions: SDHA-deficient GISTs have unique tumor biology and management of metastatic lesions remains an area of debate and discovery. Overall, this report highlights the need for comprehensive knowledge of the disease, a skilled surgical team, and multi-disciplinary involvement in order to optimize care and ensure favorable outcomes in this patient population.
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INTRODUCTION: Patients with germline variants in CDH1 who undergo prophylactic total gastrectomy (TG) are at risk of altered nutrient and drug absorption due to modified gastrointestinal anatomy. Bone mineral density loss and micronutrient deficiencies have not been described previously in this patient population. METHODS: In this study we included 94 patients with germline CDH1 variants who underwent prophylactic TG between October 2017 and February 2022. We examined pre- and post-gastrectomy bone mineral density (BMD); serum biomarkers including calcium, phosphorus, alkaline phosphatase, and 25 (OH)-vitamin D; and postoperative adherence to calcium and multivitamin supplementation. RESULTS: Almost all patients (92/94, 98%) lost a substantial amount of weight post-TG, with an average weight loss of 26.5% at 12 months post-surgery. Serum biomarkers of mineral metabolism, namely calcium and phosphorus, did not change significantly after TG. However, average BMD was decreased in all patients at 12 months post-TG. Nonadherence to calcium supplementation was associated with a decrease in BMD. Nonadherence to multivitamin supplementation was associated with greater percent BMD loss in the femoral neck and total hip. CONCLUSIONS: Appropriate micronutrient supplementation and nutritional counseling pre- and postoperatively in patients undergoing prophylactic TG are important to mitigate the long-term effects of gastrectomy on bone health.
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Densidad Ósea , Calcio , Humanos , Calcio/farmacología , Vitaminas/farmacología , Vitamina D , Calcio de la Dieta , Biomarcadores , Cuello Femoral , Suplementos Dietéticos , Gastrectomía/efectos adversos , Fósforo , Antígenos CD , CadherinasRESUMEN
Chronic granulomatous disease (CGD) is a rare inborn error of immunity, resulting from a defect in nicotinamide adenine dinucleotide phosphate oxidation and decreased production of phagocyte reactive oxygen species. The main clinical manifestations are recurrent infections and chronic inflammatory disorders. Current approaches to management include antimicrobial prophylaxis and control of inflammatory complications. Hematopoietic stem cell transplantation or gene therapy can provide definitive treatment. Gastrointestinal and hepatic manifestations are common in CGD and include structural changes, dysmotility, CGD-associated inflammatory bowel disease, liver abscesses, and noncirrhotic portal hypertension. The findings can be heterogeneous, and the management is complex in light of the underlying immune dysfunction. This review describes the various clinical findings and the latest studies in management of gastrointestinal and hepatic manifestations in CGD, as well as the management experience at the National Institutes of Health.
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Enfermedad Granulomatosa Crónica , Trasplante de Células Madre Hematopoyéticas , Hipertensión Portal , Humanos , Enfermedad Granulomatosa Crónica/complicaciones , Enfermedad Granulomatosa Crónica/terapia , Enfermedad Granulomatosa Crónica/genética , Tracto Gastrointestinal , Trasplante de Células Madre Hematopoyéticas/efectos adversos , NADPH Oxidasas/genéticaRESUMEN
INTRODUCTION: Prophylactic total gastrectomy (PTG) can eliminate gastric cancer risk and is recommended in carriers of a germline CDH1 pathogenic variant. PTG has established risks and potential life-long morbidity. Decision-making regarding PTG is complex and not well-understood. METHODS: Individuals with germline CDH1 pathogenic or likely pathogenic variants who underwent surveillance endoscopy and recommended for PTG were evaluated. Factors associated with decision to pursue PTG (PTGpos) or not (PTGneg) were queried. A decision-regret survey was administered to patients who elected PTG. RESULTS: Decision-making was assessed in 120 patients. PTGpos patients (63%, 76/120) were younger than PTGneg (median 45 vs 58 years) and more often had a strong family history of gastric cancer (80.3% vs 34.1%). PTGpos patients reported decision-making based on family history more often and decided soon after diagnosis (8 vs 27 months) compared with PTGneg. Negative endoscopic surveillance results were more common among PTGneg patients. Age >60 years, male sex and longer time to decision were associated with deferring PTG. Strong family history, a family member who died of gastric cancer and carcinoma on endoscopic biopsies were associated with decision to pursue PTG. In the PTGpos group, 30 patients (43%) reported regret which was associated with occurrence of a postoperative complication and no carcinoma detected on final pathology. CONCLUSION: The decision to undergo PTG is influenced by family cancer history and surveillance endoscopy results. Regret is associated with surgical complications and pathological absence of cancer. Individual cancer-risk assessment is necessary to improve pre-operative counselling and inform the decision-making process. TRIAL REGISTRATION NUMBER: NCT03030404.