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1.
CA Cancer J Clin ; 69(4): 258-279, 2019 07.
Article in English | MEDLINE | ID: mdl-31074865

ABSTRACT

Endometrial cancer is the most common gynecologic cancer in the United States, and its incidence is rising. Although there have been significant recent advances in our understanding of endometrial cancer biology, many aspects of treatment remain mired in controversy, including the role of surgical lymph node assessment and the selection of patients for adjuvant radiation or chemotherapy. For the subset of women with microsatellite-instable, metastatic disease, anti- programmed cell death protein 1 immunotherapy (pembrolizumab) is now approved by the US Food and Drug Administration, and numerous trials are attempting to build on this early success.


Subject(s)
Endometrial Neoplasms/therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant , Cytoreduction Surgical Procedures , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Female , Genetic Predisposition to Disease , Humans , Hysterectomy , Lymph Node Excision , Neoplasm Metastasis , Neoplasm Recurrence, Local/therapy , Prognosis , Radiotherapy, Adjuvant , Risk Factors , Sentinel Lymph Node/pathology , Sentinel Lymph Node/surgery
2.
J Natl Compr Canc Netw ; 22(2): 117-135, 2024 03.
Article in English | MEDLINE | ID: mdl-38503056

ABSTRACT

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.


Subject(s)
Vulvar Neoplasms , Female , Humans , Adenocarcinoma/pathology , Genital Neoplasms, Female , Paget Disease, Extramammary/diagnosis , Paget Disease, Extramammary/etiology , Paget Disease, Extramammary/therapy , Skin Neoplasms , Vulvar Neoplasms/diagnosis , Vulvar Neoplasms/epidemiology , Vulvar Neoplasms/etiology
3.
Curr Treat Options Oncol ; 25(4): 510-522, 2024 04.
Article in English | MEDLINE | ID: mdl-38472567

ABSTRACT

OPINION STATEMENT: Circulating tumor DNA (ctDNA) refers to small fragments of DNA released into the bloodstream by cancer cells. It is obtained through "liquid biopsy;" which most commonly refers to plasma or blood samples, but can be obtained from a number of bodily fluids including ascitic fluid, saliva, and even urine and stool. ctDNA is detected via polymerase chain reaction (PCR) or next-generation sequencing (NGS). The DNA from these samples is analyzed for the detection of point mutations, copy-number alterations, gene fusion, and DNA methylation. These results have the potential for use in cancer diagnosis, determining prognosis, targeting gene-specific therapies, and monitoring for/predicting disease recurrence and response to treatment. ctDNA offers an alternative to tissue biopsy; it is less invasive and can be monitored serially over time without multiple procedures. Moreover it may have the ability to detect disease recurrence or predict behavior in a way that solid tissue biopsies, tumor marker surveillance, and imaging cannot. Recent explosion in interest in ctDNA shows promising developments for widespread adoption of these techniques in cancer care. However, the use of ctDNA in diagnosis and treatment of gynecologic malignancies is currently limited, compared to adoption in other solid-organ tumors such as breast and colorectal cancers. Compared to other cancer types, there appear to be fewer comprehensive studies and clinical validations specifically focusing on the use of ctDNA in gynecologic cancers. More research is needed in this area to advance the potential for use of ctDNA in ovarian, endometrial, and cervical cancers before this can be routinely adopted to improve care for patients with gynecologic malignancies.


Subject(s)
Circulating Tumor DNA , Genital Neoplasms, Female , Humans , Female , Circulating Tumor DNA/genetics , Genital Neoplasms, Female/diagnosis , Genital Neoplasms, Female/genetics , Genital Neoplasms, Female/therapy , Neoplasm Recurrence, Local/genetics , DNA, Neoplasm/genetics , Liquid Biopsy/methods , Biomarkers, Tumor/genetics , High-Throughput Nucleotide Sequencing/methods , Mutation
4.
Gynecol Oncol ; 178: 69-79, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37806229

ABSTRACT

OBJECTIVE: Assess if MEK inhibitor blockade of RAS-ERK pathway adaptive response in high grade serous ovarian cancers (HGSOC) improves platinum sensitivity. METHODS: Three HGSOC cell lines and three patient derived organoid (PDOs) samples from ascites of platinum resistant HGSOC patients were collected. Cell lines and PDOs were exposed to carboplatin and MEK inhibitors cobimetinib or trametinib. Cytotoxic effects of MEK inhibitors alone or combined with carboplatin were established. Western blots demonstrated RAS-ERK pathway blockage after MEK inhibitor treatment. RNA sequencing assessed gene expression after MEK inhibitor treatment. Cell line NF1 gene knockdown was performed with corresponding chemosensitivity levels. RESULTS: High carboplatin IC50 levels indicated platinum resistance in cell lines and PDOs. Cobimetinib induced cytotoxicity in cell lines and PDOs, while trametinib was less effective. Western blot confirmed MEK-ERK pathway blockage at minimal concentrations of MEK inhibitors in cell lines and PDOs. Phosphorylated-ERK levels of untreated cells indicated higher levels of RAS-ERK pathway activation in OVSAHO and OVCAR7 compared to OVCAR3. OVSAHO harbors a NF1 mutation and had highest levels of RAS-ERK activation. Cotreatment with carboplatin and MEK inhibitors showed varying synergistic cytotoxic effects at different combinations. Synergistic effect was most prominent in the OVSAHO carboplatin and cobimetinib combination. RNA sequencing identified downregulation of c-MYC and FOXM1 gene expression after MEK inhibitor treatment. NF1 gene knockdown showed an acquired increased IC50 compared to parental cells. CONCLUSION: MEK inhibitors block RAS-ERK pathways in platinum resistant HGSOC cells and PDOs. MEK inhibitors with carboplatin have select synergistic effects which may indicate a strategy to improve platinum sensitivity.


Subject(s)
Antineoplastic Agents , Ovarian Neoplasms , Humans , Female , MAP Kinase Signaling System/physiology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Carboplatin/pharmacology , Carboplatin/therapeutic use , Apoptosis , Cell Line, Tumor , Antineoplastic Agents/therapeutic use , Protein Kinase Inhibitors/pharmacology , Carcinoma, Ovarian Epithelial/drug therapy , Mitogen-Activated Protein Kinase Kinases
5.
J Natl Compr Canc Netw ; 21(12): 1224-1233, 2023 12.
Article in English | MEDLINE | ID: mdl-38081139

ABSTRACT

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.


Subject(s)
Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
6.
J Natl Compr Canc Netw ; 21(2): 181-209, 2023 02.
Article in English | MEDLINE | ID: mdl-36791750

ABSTRACT

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.


Subject(s)
Adenocarcinoma, Clear Cell , Carcinoma, Endometrioid , Carcinosarcoma , Endometrial Neoplasms , Uterine Neoplasms , Female , Humans , Carcinoma, Endometrioid/pathology , Carcinosarcoma/diagnosis , Carcinosarcoma/therapy , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/therapy , Uterine Neoplasms/diagnosis , Uterine Neoplasms/therapy , Uterine Neoplasms/pathology
7.
Int J Gynecol Cancer ; 33(10): 1504-1514, 2023 10 02.
Article in English | MEDLINE | ID: mdl-37758451

ABSTRACT

Gestational choriocarcinoma accounts for 5% of gestational trophoblastic neoplasms. Approximately 50%, 25%, and 25% of gestational choriocarcinoma occur after molar pregnancies, term pregnancies, and other gestational events, respectively. The FIGO scoring system categorizes patients into low (score 0 to 6) and high risk (score 7 or more) choriocarcinoma. Single-agent and multi-agent chemotherapy are used in low- and high-risk patients, respectively. Chemotherapy for localized disease has a goal of eradication of disease without surgery and is associated with favorable prognosis and fertility preservation. Most patients with gestational choriocarcinoma are cured with chemotherapy; however, some (<5.0%) will die as a result of multi-drug resistance, underscoring the need for novel approaches in this group of patients. Although there are limited data due to its rarity, the treatment response with immunotherapy is high, ranging between 50-70%. Novel combinations of immune checkpoint inhibitors with targeted therapies (including VEGFR-2 inhibitors) are under evaluation. PD-L1 inhibitors are considered a potential important opportunity for chemo-resistant patients, and to replace or de-escalate chemotherapy to avoid or minimize chemotherapy toxicity. In this review, the Rare Tumor Working Group and the European Organization for Research and Treatment of Cancer evaluated the current landscape and further perspective in the management of patients diagnosed with gestational choriocarcinoma.


Subject(s)
Choriocarcinoma , Gestational Trophoblastic Disease , Uterine Neoplasms , Pregnancy , Female , Humans , Uterine Neoplasms/pathology , Treatment Outcome , Retrospective Studies , Choriocarcinoma/therapy , Choriocarcinoma/pathology , Gestational Trophoblastic Disease/drug therapy
8.
Acta Paediatr ; 112(3): 477-482, 2023 03.
Article in English | MEDLINE | ID: mdl-36495064

ABSTRACT

AIM: The major clinical manifestations multisystem inflammatory syndrome in children (MIS-C) are fever, gastrointestinal and cardiac. The aim of this study was to describe MIS-C in a series of patients who presented primarily with cervical manifestations. METHODS: We retrospectively reviewed medical records of all patients who met the Centers for Disease Control and Prevention and World Health Organization MIS-C diagnostic criteria treated at Hadassah-Hebrew University Medical Center between April 2020 and September 2021. RESULTS: Of 37 children diagnosed with MIS-C (median age: 10.2 years, range 1.5-18 years, 20 male) five, 13.5% (median age: 14.4 years, range 9.2-17.5 years) presented with cervical symptoms mimicking neck infections. One was hospitalised with a working diagnosis of retropharyngeal abscess, and four with acute cervical lymphadenitis that did not respond to early antibiotic treatment. All developed full MIS-C phenotype. CONCLUSION: MIS-C may present as cervical inflammation. An ill-appearing child with symptoms and/or signs of cervical inflammation should be evaluated for clinical and laboratory features of MIS-C, thereby facilitating prompt treatment of this potentially fatal disorder.


Subject(s)
COVID-19 , Male , Humans , COVID-19/complications , COVID-19/diagnosis , SARS-CoV-2 , Retrospective Studies , Systemic Inflammatory Response Syndrome/diagnosis , Inflammation
9.
Acta Paediatr ; 112(10): 2191-2198, 2023 10.
Article in English | MEDLINE | ID: mdl-37306590

ABSTRACT

AIM: To examine the clinical significance of thrombocytosis (platelets > 500 × 109 /L) in admitted children with an influenza-like illness. METHODS: We performed a database analysis consisting of patients evaluated at our medical centers with an influenza-like illness between 2009 and 2013. We included paediatric patients and examined the association between platelet count, respiratory viral infections, and admission outcomes (hospital length of stay and admission to the paediatric intensive care unit) using regression models adjusting for multiple variables. RESULTS: A total of 5171 children were included in the study cohort (median age 0.8 years; interquartile range, 0.2-1.8; 58% male). Younger age, and not the type of viral infection, was associated with a high platelet count (p < 0.001). Elevated platelet count independently predicted admission outcomes (p ≤ 0.05). The presence of thrombocytosis was associated with an increased risk for a prolonged length of stay (odds ratio = 1.2; 95% Confidence interval = 1.1 to 1.4; p = 0.003) and admission to the paediatric intensive care unit (odds ratio = 1.5; 95% Confidence interval = 1.1 to 2.0; p = 0.002). CONCLUSION: In children admitted with an influenza-like illness, a high platelet count is an independent predictor of admission outcomes. Platelet count may be used to improve risk assessment and management decisions in these paediatric patients.


Subject(s)
Influenza, Human , Thrombocytosis , Humans , Male , Child , Infant , Female , Platelet Count , Influenza, Human/complications , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Child, Hospitalized , Hospitalization , Thrombocytosis/etiology
10.
Rheumatology (Oxford) ; 61(12): 4667-4677, 2022 11 28.
Article in English | MEDLINE | ID: mdl-35377443

ABSTRACT

OBJECTIVES: To determine whether RA and interstitial lung disease (ILD) severity measures are associated with survival in patients with RA-ILD. METHODS: We studied US veterans with RA-ILD participating in a multicentre, prospective RA cohort study. RA disease activity (28-joint DAS [DAS28-ESR]) and functional status (multidimensional HAQ [MDHAQ]) were collected longitudinally while pulmonary function tests (forced vital capacity [FVC], diffusing capacity for carbon monoxide) were obtained from medical records. Vital status and cause of death were determined from the National Death Index and administrative data. Predictors of death were assessed using multivariable Cox regression models adjusting for age, sex, smoking status, ILD duration, comorbidity burden and medications. RESULTS: We followed 227 RA-ILD participants (93% male and mean age of 69 years) over 1073 person-years. Median survival after RA-ILD diagnosis was 8.5 years. Respiratory diseases (28%) were the leading cause of death, with ILD accounting for 58% of respiratory deaths. Time-varying DAS28-ESR (adjusted hazard ratio [aHR] 1.21; 95% CI: 1.03, 1.41) and MDHAQ (aHR 1.85; 95% CI: 1.29, 2.65) were separately associated with mortality independent of FVC and other confounders. Modelled together, the presence of either uncontrolled disease activity (moderate/high DAS28-ESR) or FVC impairment (<80% predicted) was significantly associated with mortality risk. Those with a combination of moderate/high disease activity and FVC <80% predicted had the highest risk of death (aHR 4.43; 95% CI: 1.70, 11.55). CONCLUSION: Both RA and ILD disease severity measures are independent predictors of survival in RA-ILD. These findings demonstrate the prognostic value of monitoring the systemic features of RA-ILD.


Subject(s)
Arthritis, Rheumatoid , Lung Diseases, Interstitial , Veterans , Humans , Male , Aged , Female , Cohort Studies , Prospective Studies , Arthritis, Rheumatoid/drug therapy , Severity of Illness Index
11.
Gynecol Oncol ; 167(2): 159-166, 2022 11.
Article in English | MEDLINE | ID: mdl-36154760

ABSTRACT

OBJECTIVE: To assess whether radiation completion within a planned timeframe in locally advanced squamous cell vulvar cancer impacts overall survival (OS). METHODS: The National Cancer Database from 2004 to 2017 was used to identify women ≥18 years old with stage II-IVA squamous cell vulvar cancer. We included women who received radiation alone (RT) or concurrent chemoradiation (CRT) for initial vulvar cancer treatment. Primary outcome was overall survival associated with time of delay in radiation completion. RESULTS: There were 2378 women identified (n = 856 RT and n = 1522 CRT). Median age was 67 (IQR 56-78), majority (88.35%) were white with advanced stage III or IVA (72.29%) disease. Median radiation dose was 5720 c-Gray (IQR 5040-6300). Radiation completion with delay ≥7 days resulted in reduction in survival compared to delay of <7 days (unadjusted HR 1.183 [95%CI: 1.066-1.313], p = 0.0016). When delays extended to ≥14 days compared to <14 days there was increased hazard of death (unadjusted HR: 1.263 [95%CI:1.126-1.416], p < 0.0001). Survival improved for patients with <7 versus ≥7 days delay whether treatment was with RT (median OS: 34.9 months versus 21.6 months, p < 0.01) or CRT (Median OS:58 months versus 41.3 months, p < 0.01). Stage IVA disease was associated with the greatest increase in hazard of death (HR 1.759 [95%CI 1.517-2.039], p < 0.0001) compared to stage II. CONCLUSION: Radiation completion with <7 days delay is associated with improved overall survival, independent of concurrent chemotherapy. This suggest that strategies to minimize delays in radiation are crucial in locally advanced vulvar cancer.


Subject(s)
Carcinoma, Squamous Cell , Vulvar Neoplasms , Humans , Female , Aged , Adolescent , Vulvar Neoplasms/radiotherapy , Vulvar Neoplasms/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/drug therapy , Vulva/pathology , Chemoradiotherapy/methods
12.
Pediatr Blood Cancer ; 69(3): e29549, 2022 03.
Article in English | MEDLINE | ID: mdl-34968007

ABSTRACT

BACKGROUND: Although hematopoietic stem cell transplantation (HSCT) is the only curative option for some children with malignant and nonmalignant disorders, the procedure itself carries a high risk of complications. A proportion of children undergoing HSCT develop severe transplant-related complications requiring hospitalization in the pediatric intensive care unit (PICU). METHODS: A retrospective cohort study included 793 children with malignant and nonmalignant diseases that underwent 963 HSCTs in two large pediatric hospitals over 15 years. Ninety-one patients needed 105 (11%) PICU admissions. The objective of the study was to analyze the risk factors associated with morbidity and mortality in children post HSCT who were admitted to the PICU. RESULTS: Survival rate of a single PICU hospitalization was 43%. Long-term survival rate (classified as 1 year and 3 years) was 29.1% and 14.9% among PICU hospitalized patients compared with 74.6% and 53.3% among patients who had undergone HSCT and did not require PICU hospitalization. Factors found to have a significant negative association with PICU survival were respiratory failure as indication for PICU admission, neutropenia, graft-versus-host disease, mechanical ventilation, inotropic support, need for dialysis, and multiple-organ failure (MOF) with more than one systemic intensive intervention. The strongest prognostic factors associated with mortality were MOF (p < .001) and the need for inotropic support (p = .004). CONCLUSIONS: Neutropenia was found to be negatively associated with survival, suggesting non-engraftment and late engraftment are important risk factors for HSCT patients hospitalized in PICU. MOF and inotropic support were found to be the main negatively associated predictive factors with survival.


Subject(s)
Hematopoietic Stem Cell Transplantation , Neutropenia , Child , Hematopoietic Stem Cell Transplantation/adverse effects , Hospitalization , Humans , Infant , Intensive Care Units, Pediatric , Multiple Organ Failure/etiology , Neutropenia/etiology , Prognosis , Retrospective Studies , Risk Factors
13.
Int J Gynecol Pathol ; 39(1): 8-18, 2020 Jan.
Article in English | MEDLINE | ID: mdl-30480644

ABSTRACT

Epithelioid trophoblastic tumor is a malignancy derived from the chorionic laeve-type intermediate trophoblast with sufficient rarity that the vast majority of literature on the topic exists in the form of case reports and small series. Classically, it is regarded as a well-circumscribed tumor with an expansile growth pattern that occurs in reproductive-aged women, usually after a normal pregnancy. However, we recently encountered a case of epithelioid trophoblastic tumor with aggressive spread throughout the abdomen and pelvis in a 68-yr-old female presenting 30 yr after her last delivery. Although to our knowledge this is the first report in a postmenopausal patient to be confirmed by molecular analysis of short tandem repeats, there are multiple similar case reports spanning a variety of clinical settings that deviate from the original description. We therefore sought to synthesize the clinicopathologic data among the available reports in the English literature, with emphasis on pathologic findings. While the overarching themes are largely unchanged, this series of 77 patients reveals a broader spectrum of disease and highlights frequent misdiagnosis. Here we present a clinicopathologic update on this rare entity, with emphasis on a practical approach to diagnosis.


Subject(s)
Epithelioid Cells/pathology , Trophoblastic Neoplasms/diagnosis , Trophoblastic Neoplasms/pathology , Uterine Neoplasms/diagnosis , Uterine Neoplasms/pathology , Adolescent , Adult , Aged , Female , Genotyping Techniques , Humans , Immunohistochemistry , Middle Aged , Postmenopause , Pregnancy , Rare Diseases/diagnosis , Rare Diseases/genetics , Rare Diseases/pathology , Time Factors , Trophoblastic Neoplasms/genetics , Uterine Neoplasms/genetics , Young Adult
14.
Gynecol Oncol ; 153(2): 335-342, 2019 05.
Article in English | MEDLINE | ID: mdl-30827726

ABSTRACT

OBJECTIVES: The ability to stratify a patient's risk of metastasis and survival permits more refined care. A proof of principle study was undertaken to investigate the relationship between single nucleotide polymorphisms (SNPs) in literature based candidate cancer genes and the risk of nodal metastasis and clinical outcome in endometrioid endometrial cancer (EEC) patients. METHODS: Surgically-staged EEC patients from the Gynecologic Oncology Group or Washington University School of Medicine with germline DNA available were eligible. Fifty-four genes represented by 384 SNPs, were evaluated by Illumina Custom GoldenGate array. Association with lymph node metastases was the primary outcome. Progression-free survival (PFS) and overall survival (OS) was also evaluated. RESULTS: 361 SNPs with high quality genotype data were evaluated in 337 patients with outcome data. Five SNPs in CXCR2 had an odds ratio (OR) between 0.68 and 0.70 (p-value ≤ 0.025). The A allele rs946486 in ABL had an OR of 1.5 (p-value = 0.01) for metastasis. The G allele in rs7795743 in EGFR had an OR for metastasis of 0.68 (p-value = 0.02) and hazard ratio (HR) for progression of 0.66 (p-value = 0.004). Importantly, no SNP met genome wide significance after adjusting for multiple test correcting and clinical covariates. The A allele in rs2159359 SNP in NME1 and the G allele in rs13222385 in EGFR were associated with worse OS. Both exhibited genome wide significance; rs13222385 remained significant after adjusting for prognostic clinical variables. CONCLUSION: SNPs in cancer genes including rs2159359 SNP in NME1 and rs13222385 in EGFR may stratify risk in EEC and are prioritized for further investigation.


Subject(s)
Biomarkers, Tumor/genetics , Endometrial Neoplasms/genetics , Lymphatic Metastasis/genetics , NM23 Nucleoside Diphosphate Kinases/genetics , Aged , Case-Control Studies , Disease Progression , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Endometrium/pathology , ErbB Receptors/genetics , Female , Humans , Lymphatic Metastasis/pathology , Middle Aged , Neoplasm Staging , Polymorphism, Single Nucleotide , Prognosis , Progression-Free Survival , Risk Assessment/methods
15.
Int J Gynecol Cancer ; 29(7): 1156-1163, 2019 09.
Article in English | MEDLINE | ID: mdl-31352365

ABSTRACT

OBJECTIVES: To compare clinical outcomes for stage IIIC and IV ovarian cancer patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery followed by up to three versus more cycles of post-operative chemotherapy. METHODS: We conducted a multi-institution retrospective cohort study of patients treated from January 2005 to February 2016 with neoadjuvant platinum-based therapy followed by interval surgery and post-operative chemotherapy. The following were exclusion criteria: more than four cycles of neoadjuvant chemotherapy, bevacizumab with neoadjuvant chemotherapy, non-platinum therapy, prior chemotherapy, and elevated CA125 values after three post-operative chemotherapy cycles. Progression-free and overall survival and toxicity profiles were compared between groups receiving up to three cycles versus more that three cycles post-operatively. RESULTS: A total of 100 patients met inclusion criteria: 41 received up to three cycles and 59 received more than three cycles. The groups were similar in terms of age, body mass index, performance status, tumor histology, optimal cytoreduction rates, and median number of neoadjuvant chemotherapy cycles. Median progression-free survival was 14 vs 16.6 months in those receiving up to three cycles versus more than three cycles, respectively (HR 0.99, 95% CI 0.58 to 1.68, p=0.97). Similarly, median overall survival was not different at 47.1 vs 69.4 months, respectively (HR 1.96, 95% CI 0.87 to 4.42, p=0.10). There were no differences in grade 2 or higher chemotherapy-related toxicities. CONCLUSIONS: Extending post-operative chemotherapy beyond three cycles in patients receiving neoadjuvant chemotherapy and interval cytoreductive surgery with normalization of CA125 levels was not associated with improved survival or greater toxicity. Future study in a larger cohort is warranted to define optimal length of cytotoxic treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carboplatin/therapeutic use , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/surgery , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Aged , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial/pathology , Chemotherapy, Adjuvant , Cohort Studies , Cytoreduction Surgical Procedures , Drug Administration Schedule , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , Progression-Free Survival , Randomized Controlled Trials as Topic , Retrospective Studies , Time Factors
16.
Skeletal Radiol ; 48(8): 1269-1274, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30446788

ABSTRACT

OBJECTIVE: To describe and evaluate the outcome following shoulder manipulation under rotator interval block for the treatment of adhesive capsulitis. MATERIALS AND METHODS: Patients with adhesive capsulitis referred by our local orthopaedic shoulder surgeons consented to targeted ultrasound-guided injection of the glenohumeral joint via the rotator interval. Inclusion criteria included a failure to respond to conservative treatment and the absence of a full-thickness rotator cuff tear. Twelve millilitres of a mixture of local anaesthetic and steroid was injected into the rotator interval using a 21-gauge needle, with a small volume of the same solution instilled into the subacromial bursa. Following injection, under local anaesthetic block, patients were gently manipulated into abduction, external rotation and internal rotation as far as they could comfortably tolerate. Patients were assessed pre-injection with documented pain scores from 0 to 10 on a visual analogue scale (VAS) and the Oxford Shoulder Score (OSS) questionnaire. Initial follow-up comprised a VAS pain score at 1 h, 24 h and 2 weeks. Clinical review by the referring orthopaedic surgeon was performed at 2 months post-injection. Long-term follow-up involved a VAS pain score and the OSS questionnaire at 5 months. RESULTS: Forty patients were suitable for inclusion in the study. Twenty-three were female (57.5%) and 17 were male. The mean age was 52 years (range, 31-73 years). Twelve patients were post-operative. The duration of symptoms ranged from 3 months to 18 months. Mean pre-procedure OSS was recorded as 23.3 (range, 4-36). The mean VAS pain score was 7.7 before the procedure (range, 4 - 10), 3.4 at 1 h (range, 0-8), 2.9 at 24 h (range, 0-8), and 1.8 at 2 weeks (range 1-4). Orthopaedic follow-up at an average of 66 days post-injection was recorded in 18 patients. All patients reported initial improvement of their shoulder pain and return to near full range of movement; however, recurrence of adhesive capsulitis symptoms was recorded in 5 patients. One case of rupture of the long head of the biceps tendon was reported, but the patient remained asymptomatic. Long-term follow-up at 5 months was obtained in 31 patients, with a mean OSS of 42 (range, 21-60) and VAS of 2.3 (range, 0-7). CONCLUSION: Manipulation under general anaesthesia is a well-recognised treatment for adhesive capsulitis. We report that targeted ultrasound-guided injection of the rotator interval and manipulation of the shoulder under local anaesthetic blockade result in good outcomes in reducing shoulder pain and symptoms of adhesive capsulitis with low recurrence and complication rates.


Subject(s)
Bursitis/diagnostic imaging , Bursitis/therapy , Manipulation, Orthopedic/methods , Adult , Aged , Anesthetics, Local/administration & dosage , Cohort Studies , Female , Humans , Injections, Intra-Articular , Male , Middle Aged , Nerve Block , Range of Motion, Articular , Ultrasonography
17.
J Pediatr ; 177: 316-320, 2016 10.
Article in English | MEDLINE | ID: mdl-27514238

ABSTRACT

Adenosine deaminase 2 deficiency is an autoinflammatory disease, characterized by various forms of vasculitis. We describe 5 patients with adenosine deaminase 2 deficiency with various hematologic manifestations, including pure red cell aplasia, with no evidence for vasculitis.


Subject(s)
Adenosine Deaminase/deficiency , Intercellular Signaling Peptides and Proteins/deficiency , Adenosine Deaminase/genetics , Child , Child, Preschool , Female , Humans , Infant , Intercellular Signaling Peptides and Proteins/genetics , Male , Metabolism, Inborn Errors/diagnosis , Metabolism, Inborn Errors/genetics , Phenotype
18.
Am J Obstet Gynecol ; 215(6): 766.e1-766.e9, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27457116

ABSTRACT

BACKGROUND: The incidence of endometrial cancer increases with age and is associated with medical comorbidities such as obesity and diabetes. Although a few cohort studies of <500 patients showed an association between comorbidity and survival in patients with endometrial cancer, the degree of association must be better described. The Adult Comorbidity Evaluation 27 is a validated comorbidity instrument that provides a score of 0-3 based on the number of and severity of medical comorbidities. OBJECTIVE: This study was performed to explore the association between medical comorbidities and survival of patients with endometrial cancer. STUDY DESIGN: Patients who were diagnosed with endometrial cancer from 2000-2012 were identified from the prospectively maintained Siteman Cancer Center tumor registry. Patients who underwent primary surgical treatment for endometrioid, serous, and clear cell endometrial carcinoma were included. Patients who primarily were treated with radiation, chemotherapy, or hormone therapy were excluded. Patients with uterine sarcomas or neuroendocrine tumors were excluded. Patients with missing Adult Comorbidity Evaluation 27 scores were also excluded from analysis. Information that included patient demographics, Adult Comorbidity Evaluation 27 score, tumor characteristics, adjuvant treatment, and survival data were extracted from the database. The association of Adult Comorbidity Evaluation 27 and overall and recurrence-free survival was explored in a multivariable Cox regression analysis after being controlled for variables that have been found to be associated significantly with survival in univariable analysis. RESULTS: A total of 2073 patients with a median age of 61 years (range, 20-94 years) at diagnosis were identified. The Adult Comorbidity Evaluation 27 score was 0, 1, 2, and 3 in 22%, 38%, 28%, and 12% of patients, respectively. Stage distribution was I (73%), II (5%), III (15%), and IV (7%), and grade distribution was 1 (52%), 2 (23%), and 3 (25%). Most patients had endometrioid histologic condition (87%) followed by serous (11%) and clear cell (3%) endometrial carcinoma. The median overall survival time for the entire cohort was 54 months (95% confidence interval, 3-154 months), and the median recurrence-free survival was 50 months (95% confidence interval, 2-154 months). On univariable analysis, age, race, marital status, stage, grade, histologic condition, and treatment type were associated significantly with overall survival and recurrence-free survival. After adjustment for these covariates, patients with an Adult Comorbidity Evaluation 27 score of 2 had a 52% higher risk of death (95% confidence interval, 1.16-2.00); patients with an Adult Comorbidity Evaluation 27 score of 3 had a 2.35-fold increased risk of death (95% confidence interval, 1.73-3.21) compared with patients with an Adult Comorbidity Evaluation 27 score of 0. Similarly, patients with an Adult Comorbidity Evaluation 27 score of 2 had a 38% higher risk of recurrence (95% confidence interval, 1.07-1.78); patients with Adult Comorbidity Evaluation 27 score of 3 had a 2.05-fold increased risk of recurrence (95% confidence interval, 1.53-2.75) compared with patients with an Adult Comorbidity Evaluation 27 score of 0. We found no interaction between Adult Comorbidity Evaluation 27 score and age, stage, or treatment type. CONCLUSION: Our findings demonstrate the importance of comorbidities in the estimation of the prognosis of patients with endometrial cancer, even after adjustment for age and known tumor-specific prognostic factors such as stage, grade, histologic condition, and adjuvant treatment.


Subject(s)
Adenocarcinoma, Clear Cell/mortality , Carcinoma, Endometrioid/mortality , Comorbidity , Endometrial Neoplasms/mortality , Neoplasms, Cystic, Mucinous, and Serous/mortality , Registries , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Clear Cell/therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/therapy , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Cohort Studies , Endometrial Neoplasms/pathology , Endometrial Neoplasms/therapy , Female , Humans , Hysterectomy , Middle Aged , Multivariate Analysis , Neoplasm Staging , Neoplasms, Cystic, Mucinous, and Serous/pathology , Neoplasms, Cystic, Mucinous, and Serous/therapy , Prognosis , Proportional Hazards Models , Retrospective Studies , Young Adult
19.
Am J Obstet Gynecol ; 214(4): 498.e1-498.e6, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26478102

ABSTRACT

BACKGROUND: Obesity significantly impacts the cost of cancer treatment, yet the impact of morbid obesity on inpatient hospital charges related to endometrial cancer treatment is not well-defined. OBJECTIVES: The purpose of this study was to determine the charges that are associated with inpatient surgery, hospitalization, and postoperative care of morbidly obese patients with endometrial cancer. STUDY DESIGN: Data were obtained from the National Inpatient Sample from 2010. Chi-square test, t-test, and linear regression were used for statistical analyses. RESULTS: Six thousand five hundred sixty patients who underwent hysterectomy for endometrial cancer were identified. Mean age was 62 years (range, 22-99 years). The majority were white (78%), and the remainder were black (10%), Hispanic, (8%), Asian (3%), and Native American (1%). Insurance types were private (45%), Medicare (45%), Medicaid (5%), and uninsured (7%). One thousand eighty-eight of these patients (17%) were coded as morbidly obese. The mean postoperative stay for the morbidly obese was 4.0 days (range, 0-46 days) compared with 3.5 days (range, 0-81 days) for the non-morbidly obese patients (P < .01). Morbidly obese patients required more intensive care with mechanical ventilation (5.5% vs 1.6%; P < .01). The median hospital charges were higher for morbidly obese patients compared with their counterparts ($46,654 vs $41,164; P < .01). After adjustment for charges that were associated with insurance type, hospital type, and the surgery that was performed, the incremental increase in hospital charges that were associated with treating the morbidly obese patient was $5096 per patient (95% confidence interval, $2593-$7598; P < .01). CONCLUSION: In this economic analysis, the health care charges that were associated with inpatient endometrial cancer treatment in the morbidly obese patient was significantly higher compared the non-morbidly obese patient. Resources are needed to support the needs of this population, and programs to encourage weight loss and optimize general health should be encouraged.


Subject(s)
Endometrial Neoplasms/economics , Endometrial Neoplasms/surgery , Hysterectomy/economics , Obesity, Morbid/economics , Adult , Aged , Aged, 80 and over , Critical Care , Female , Health Surveys , Hospital Charges/statistics & numerical data , Humans , Laparoscopy/economics , Laparoscopy/statistics & numerical data , Length of Stay/economics , Length of Stay/statistics & numerical data , Middle Aged , Respiration, Artificial/economics , Respiration, Artificial/statistics & numerical data , Robotic Surgical Procedures/economics , Robotic Surgical Procedures/statistics & numerical data , United States , Young Adult
20.
J Ultrasound Med ; 35(6): 1113-22, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27091918

ABSTRACT

The purpose of this review is to discuss the rationale and indications for transvaginal ultrasound-guided biopsy. Transvaginal ultrasound-guided biopsy can be a helpful tool for diagnosis and treatment planning in the evaluation of pelvic masses, particularly when the anatomy precludes a transabdominal or posterior transgluteal percutaneous biopsy approach. A step-by-step summary of the technique with preprocedure and postprocedure considerations is included.


Subject(s)
Pelvic Neoplasms/diagnostic imaging , Ultrasonography, Interventional/methods , Female , Humans , Image-Guided Biopsy/methods , Pelvis/diagnostic imaging , Vagina/diagnostic imaging
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