The second article in this 2-part continuing medical education series reviews the following malignant causes of flushing: mastocytosis, medullary thyroid carcinoma, pheochromocytoma, carcinoid tumors, gastroenteropancreatic neuroendocrine tumors, bronchogenic carcinoma, vasointestinal polypeptide secreting tumors, and renal cell carcinoma. The information provided will allow physicians to better distinguish patients who have worrisome presentations that require a more thorough investigation. Appropriate diagnostic workup and treatment options for these malignancies are reviewed.
Carcinoma (4), Pheochromocytoma (3), Mastocytosis (3), more mentions
RATIONALE: Retroperitoneal bronchogenic cysts without specific clinical manifestations are extremely rare and difficult to diagnose preoperatively and are easily misdiagnosed as left adrenal or pancreatic tumors.
PATIENT CONCERNS: A 48-year-old woman with the chief complaint of obscure epigastric pain for 1 month and with no other gastrointestinal symptoms and no significant medical history. The patient had signed informed consent for publication of this case report.
DIAGNOSIS: The serum level of carbohydrate antigen 19-9 (CA 19-9) in the patient was >1200 U/mL, which far exceeded the normal level of <37 U/mL. Computed tomography (CT) initially suggested the presence of an adrenal tumor. However, endoscopic ultrasound (EUS) showed that the adrenal gland had an intact capsule and that the mass originated in the retroperitoneal space and did not involve the paranephros.
INTERVENTIONS: Surgical resection was performed on the patient.
OUTCOMES: Histopathological examination demonstrated that the mass was a retroperitoneal bronchogenic cyst. At the 2-month postoperative follow-up, the level of CA 19-9 had returned to normal.
LESSONS: EUS appears to be superior to CT because it clearly delineated the mass from the surrounding structures of the retroperitoneal region. EUS-fine needle aspiration can be used for diagnosis or determining whether the mass is malignant or benign. To the best of our knowledge, retroperitoneal bronchogenic cysts with significantly elevated serum CA 19-9 have not been reported. Measurement of serum CA 19-9 may be helpful in the diagnosis of retroperitoneal bronchogenic cysts. However, this was a rare case, and the mechanism behind CA 19-9 elevation is not clear and needs further investigation.
AbstractText: The prognostic value of WHO grade in pancreatic neuroendocrine tumors (PanNETs) in patients with Multiple EndocrineNeoplasia Type 1 (MEN1) is unknown AbstractText: We performed a cohort study using the Dutch National MEN1 database, which includes >90% of the Dutch MEN1 population with ... Keyword: Multiple endocrineneoplasia type 1.
Neoplasms (4), Multiple Endocrine Neoplasia Type 1 (3), Neuroendocrine Tumors (2), more mentions
Background: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear.
Objective: To examine whether coffee consumption is associated with all-cause and cause-specific mortality.
Design: Prospective cohort study.
Setting: 10 European countries.
Participants: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition).
Measurements: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800).
Results: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; γ-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels.
Limitations: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once.
Conclusion: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country.
Primary Funding Source: European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer.
AbstractText: Gastric neuro-endocrinetumours are rare. European guidelines for the management of neuro-endocrinetumours have been published in 2012... We reviewed all the individual medical reports of gastric neuro-endocrinetumours in order to collect data on treatment AbstractText: One hundred and ninety seven gastric neuro-endocrinetumours diagnosed between 1964 and 2013 in 20 centres were registered ...
AbstractText: Since prognosis and treatment of pancreatic endocrinetumors (pNET) are based on tumor grade, contrast-enhanced multidetector computed tomography (MDCT) features of solid non-functioning pNETs were studied and correlated with pathology tumor grading AbstractText: MDCTs of diagnosed pNETs were reviewed retrospectively. Each tumor was analyzed for location, size, homogeneity, margins, arterial and venous phase enhancement, main pancreatic duct ...
Neoplasms (13), Primitive Neuroectodermal Tumors (1), more mentions
This is why more penetrant mutations were overrepresented in early multiple endocrineneoplasia 2 (MEN2) studies, whereas less penetrant mutations went underrepresented. Enrichment of genetic association studies with advanced disease may produce a flawed understanding of disease evolution, precipitating far-reaching surgical strategies like bilateral total adrenalectomy and 4-gland parathyroidectomy in MEN2.
Pheochromocytoma (2), Multiple Endocrine Neoplasia (1), Hyperparathyroidism (1), more mentions
Abstract: We describe a family with multiple endocrineneoplasia type 2A (MEN2A) caused by the D631Y RET mutation resulting in an atypical phenotype... Keyword: multiple endocrineneoplasia type 2. Keyword: pheochromocytoma.
Oncology (3) Multiple Endocrine Neoplasia Type 2a (5), Pheochromocytoma (3), Thyroid Carcinoma (3), more mentions
... quality of life and financial burden among patients with multiple endocrineneoplasia type 1 is poorly described... We hypothesized that the financial burden attributable to multiple endocrineneoplasia type 1 is associated with worse health-related quality of life.United States adults (≥18 years) with multiple endocrineneoplasia type 1 were recruited from the AMENSupport MEN online support ...
Pheochromocytoma and/or paraganglioma associated with neurofibromatosis type 1, multiple endocrineneoplasia type 2A, and von Hippel-Lindau disease have different catecholamine ... through 2016.Eighty-one patients underwent pheochromocytoma/paraganglioma resection (multiple endocrineneoplasia type 2A, n = 36; neurofibromatosis type 1, n = 26; von ... 0.67, P = .033; and r = 0.89, P < .001 for multiple endocrineneoplasia type 2A, von Hippel-Lindau disease, and neurofibromatosis type 1 ...
Neurofibromatosis 1 (9), von Hippel-Lindau Disease (6), Multiple Endocrine Neoplasia Type 2a (6), more mentions
Physical and psychosocial morbidity of multiple endocrineneoplasia type-1 is ill-defined... impacts health-related quality of life in adults with multiple endocrineneoplasia type-1.Adults (≥18 years) with multiple endocrineneoplasia type-1 completed an online survey of demographics, disease features ... factors associated with decreased health-related quality of life.Multiple endocrineneoplasia type-1 patients (n = 207) reported worse health-related quality ...
Multiple Endocrine Neoplasia (5), Hyperparathyroidism (1), Multiple Endocrine Neoplasia Type 1 (1), more mentions
Previous meta-analysis has not shown different effects of miR-608 rs4919510 polymorphism in specific cancer types and reported no significant association between rs4919510 and cancer risk among Chinese. However, more recent findings have been inconsistent. Therefore, we performed an updated meta-analysis to examine whether this polymorphism is associated with cancer risk based on ethnicity and type. A total of 18 case-control studies, comprising 12,517 cases and 15,624 controls, were included in our study. Surprisingly, in contrast with previous meta-analysis, a significant association between the rs4919510 polymorphism and cancer risk was observed in Chinese (CG vs CC: odds ratio = 1.11; 95% confidence interval = 1.04-1.19). In further stratified analyses based on cancer type, rs4919510 was significantly associated with an increased risk of papillary thyroid cancer (CG vs CC: odds ratio = 1.25; 95% confidence interval = 1.01-1.54) and exhibited borderline significant associations with increased risk of gastric cancer (GG vs CC: odds ratio = 1.27; 95% confidence interval = 1.00-1.62) and lung cancer (CG vs CC: odds ratio = 1.14; 95% confidence interval = 0.99-1.32), but a decreased risk of colorectal cancer (GG vs CC: odds ratio = 0.74; 95% confidence interval = 0.60-0.91). Moreover, the RegulomeDB database indicated that rs4919510 may affect the expression of two nearby genes ( SEMA4G and MRPL43), and the Cancer Genome Atlas database revealed that the expression level of SEMA4G was significantly lower in colorectal cancer and lung cancer tissues than that in adjacent non-tumour tissues, while the expression level of SEMA4G was significantly higher in gastric cancer tissues than that in adjacent non-tumour tissues. These findings provide evidence that the miR-608 rs4919510 polymorphism may modify cancer susceptibility in a type-specific manner. Furthermore, SEMA4G may function as an oncogene or tumour suppressor to regulate tumour development in a type-specific manner. Further studies with experimental evaluations are warranted.
This study aimed to investigate the clinical features and outcomes of skin metastasis in ovarian and fallopian tube carcinomas.We studied patients with epithelial ovarian or fallopian tube carcinoma who developed skin metastasis from 2001 through 2012, and were also treated with chemotherapy and/or surgery.Skin metastases were classified as umbilical metastasis (Sister Joseph nodule [SJN]) and nonumbilical metastasis. Patients who developed skin metastases at paracentesis sites were excluded.Of the 206 patients treated, 12 (5.8%) developed skin metastasis: 7 developed SJN, and 5 developed nonumbilical metastasis. Six patients had serous carcinoma, 3 had clear cell carcinoma, 2 had endometrioid carcinoma, and 1 had adenocarcinoma. Four patients out of the 7 who developed SJN had skin metastasis at initial diagnosis, and all 4 patients had SJN with concomitant peritoneal dissemination. Of the 4 patients, 3 received chemotherapy, and their survival ranged from 22 to 42 months. Of the 7 patients who developed SJN, 3 patients with stage IIIC disease developed an SJN at recurrence and were treated with surgery and/or chemotherapy. Their survival duration after recurrence ranged from 26 to 43+ months. Five patients developed nonumbilical metastases 3 to 53 months (median 34 months) after initial diagnosis: 3 cases occurred in incisional scars of primary surgery, and 2 in subcutaneous metastasis in the other sites. Survival after recurrence ranged from 56 to 140+ months in 3 patients with incisional scar recurrence, and it was 5 months in 2 other patients.Sister Joseph nodule developed only in patients with peritoneal dissemination, and most patients with SJN survived for >24 months. Nonumbilical metastases occurring in incisional scars of primary surgery may carry a favorable prognosis.
OBJECTIVE: To compare 30-day postsurgical readmission rates and associated risk factors for readmission among women undergoing gynecologic surgery for benign and malignant conditions.
METHODS: In a retrospective cohort study, we identified patients after surgery for benign and malignant gynecologic conditions in the National Surgical Quality Improvement Program database between January 1, 2011, and December 31, 2012. Data collected included surgical factors, perioperative characteristics, surgical complications, and 30-day readmissions. The primary study outcome was readmission rates after gynecologic surgery for benign and oncologic conditions. Secondary study outcomes were risk factors associated with readmission among gynecologic surgeries performed for benign and oncologic conditions.
RESULTS: Approximately 3% (1,444/46,718) compared with 8.2% (623/7,641) of patients who underwent gynecologic surgery for benign and malignant indications, respectively, were readmitted (P<.01). Compared with patients with benign surgical indications, those with uterine cancer (readmission rate 6.6%; odds ratio [OR] 2.21, 95% CI 1.95-2.51), ovarian cancer (readmission rate 10.9%; OR 3.82, 95% CI 3.29-4.45), and cervical cancer (readmission rate 10.1%; OR 3.51, 95% CI 2.71-4.53) were more likely to be readmitted. In multivariable models, independent risk factors for readmission for gynecologic cancer surgery included worse preoperative conditions (OR 1.49, 95% CI 1.17-1.90) and major complications (OR 17.84, 95% CI 14.19-22.43). In comparison, independent risk factors for readmission after surgery for benign indications included comorbid conditions (OR 1.36, 95% CI 1.18-1.57), operative time (15-59 minutes: referent; 60 minutes or greater: 1.37, 95% CI 1.14-1.63) and major complications (OR 53.91, 95% CI 46.98-61.85).
CONCLUSION: Among gynecologic surgeries, those performed for oncologic indications were associated with readmission rates 2.8 times that of surgeries performed for benign indications. In adjusted models, worse preoperative conditions and surgical complications remained independent risk factors associated with the higher rate of readmission among patients with gynecologic cancer.
BACKGROUND: The biological mechanisms underlying early- and advanced-stage epithelial ovarian cancers (EOCs) are still poorly understood. This study explored kinase-driven metabolic signalling in early and advanced EOCs, and its role in tumour progression and response to carboplatin-paclitaxel treatment.
METHODS: Tumour epithelia were isolated from two independent sets of primary EOC (n=72 and 30 for the discovery and the validation sets, respectively) via laser capture microdissection. Reverse phase protein microarrays were used to broadly profile the kinase-driven metabolic signalling of EOC with particular emphasis on the LBK1-AMPK and AKT-mTOR axes. Signalling activation was compared between early and advanced lesions, and carboplatin-paclitaxel-sensitive and -resistant tumours.
RESULTS: Advanced EOCs were characterised by a heterogeneous kinase-driven metabolic signature and decreased phosphorylation of the AMPK-AKT-mTOR axis compared to early EOC (P<0.05 for AMPKα T172, AMPKα1 S485, AMPKβ1 S108, AKT S473 and T308, mTOR S2448, p70S6 S371, 4EBP1 S65, GSK-3 α/β S21/9, FOXO1 T24/FOXO3 T32, and FOXO1 S256). Advanced tumours with low relative activation of the metabolic signature and increased FOXO1 T24/FOXO3 T32 phosphorylation (P=0.041) were associated with carboplatin-paclitaxel resistance.
CONCLUSIONS: If validated in a larger cohort of patients, the decreased AMPK-AKT-mTOR activation and phosphorylation of FOXO1 T24/FOXO3 T32 may help identify carboplatin-paclitaxel-resistant EOC patients.
We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8(+) and CD4(+) T cells and exhibited oligoclonal expansion of specific T cell subsets. We also detected CD8(+) T cell reactivity against predicted neoepitopes after isolation of cells from a blood sample taken almost 3 years after the tumors were resected. These findings suggest that multiple distinct tumor immune microenvironments co-exist within a single individual and may explain in part the heterogeneous fates of metastatic lesions often observed in the clinic post-therapy. VIDEO ABSTRACT.
Platinum resistance is a critical barrier for clinicians to improve the survival of ovarian cancer. Our study evaluated the correlation between copy number variations (CNVs) of neurotrophic tyrosine receptor kinase 3 (NTRK3) and the prognosis of ovarian cancer, which might predict platinum resistance in ovarian cancer patients.Array comparative genomic hybridization (CGH) was used to test gene backgrounds between platinum-sensitive and platinum-resistant relapsed populations and CNVs of NTRK3 were indicated by cluster analysis. Fluorescence in situ hybridization (FISH) was adopted in 41 cases for further verification, which confirmed the results of array CGH. Spearman's rank correlation analysis and χ test were used to evaluate the accuracy of CNVs of NTRK3 which predicted platinum-sensitive or platinum-resistant recurrence.We detected CNVs of NTRK3 between 2 groups by array CGH, and amplification of NTRK3 was confirmed by FISH in the platinum-sensitive recurrence group with enlarged samples. The test concordance of 2 methods was 78.6%. Among 41 cases with satisfied FISH results, the median time to recurrence (TTR) of patients with amplified and nonamplified NTRK3 were respectively 18 and 5 months (P <.01). The cut-off value of TTR to differentiate platinum-sensitive or platinum-resistant recurrence was 6 months in accordance with clinical practice. According to the above standard, 15 cases with NTRK3 amplification were platinum-sensitive and 12 cases without NTRK3 amplification were platinum-resistant recurrences which demonstrated that the accuracy of NTRK3 amplification/nonamplification to predict recurrent types was 65.9% (27/41).CNVs of NTRK3 were associated with platinum-sensitive and platinum-resistant recurrences. Amplification of NTRK3 perfectly predicted platinum-sensitive relapse of ovarian cancer.
OBJECTIVE: To examine the cumulative incidence of subsequent ovarian cancer among young women with stage I endometrioid endometrial cancer who had ovarian conservation at surgical treatment.
METHODS: This retrospective study examined the Surveillance, Epidemiology, and End Results Program to identify women aged younger than 50 years who underwent hysterectomy with ovarian conservation for stage I endometrioid endometrial cancer between 1983 and 2013. Time-dependent risk of ovarian cancer diagnosed during the follow-up after endometrial cancer diagnosis was examined.
RESULTS: Among 1,322 women in the study cohort, 16 women developed subsequent ovarian cancer with 5- and 10-year cumulative incidences of 1.0% and 1.3%, respectively. Median time to develop subsequent ovarian cancer was 2.4 years, and the majority of subsequent ovarian cancer was diagnosed within the first 3 years from the diagnosis of endometrial cancer (68.8%). The majority of subsequent ovarian cancer was endometrioid type (81.3%) and stage I disease (75.0%). With a median follow-up time of 11.6 years, there were no ovarian cancer deaths. Younger age at endometrial cancer diagnosis was significantly associated with increased risk of subsequent ovarian cancer (10-year cumulative incidences: age younger than 40 compared with 40-49 years, 2.6% compared with 0.4%, hazard ratio 5.00, 95% confidence interval [CI] 1.60-15.7, P=.002).
CONCLUSION: Young women with stage I endometrioid endometrial cancer have an approximately 1% risk of developing subsequent ovarian cancer after ovarian conservation at the time of hysterectomy that was associated with favorable tumor factors resulting in good ovarian cancer-specific survival. Our results endorse the importance of genetic testing and close follow-up when counseling about this procedure, especially for those who are younger than 40 years.