RESUMEN
Germline pathogenic loss-of-function (pLOF) variants in DICER1 are associated with a predisposition for a variety of solid neoplasms, including pleuropulmonary blastoma and Sertoli-Leydig cell tumor (SLCT). The most common DICER1 pLOF variants include small insertions or deletions leading to frameshifts, and base substitutions leading to nonsense codons or altered splice sites. Larger deletions and pathogenic missense variants occur less frequently. Identifying these variants can trigger surveillance algorithms with potential for early detection of DICER1-related cancers and cascade testing of family members. However, some patients with DICER1-associated tumors have no pLOF variants detected by germline or tumor testing. Here, we present two patients with SLCT whose tumor sequencing showed only a somatic missense DICER1 RNase IIIb variant. Conventional exon-directed germline sequencing revealed no pLOF variants. Using a custom capture panel, we discovered novel intronic variants, ENST00000343455.7: c.1752+213A>G and c.1509+16A>G, that appear to interfere with normal splicing. We suggest that when no DICER1 pLOF variants or large deletions are discovered in exonic regions despite strong clinical suspicion, intron sequencing and splicing analysis should be performed.
Asunto(s)
Neoplasias Ováricas , Tumor de Células de Sertoli-Leydig , Masculino , Femenino , Humanos , Tumor de Células de Sertoli-Leydig/genética , Tumor de Células de Sertoli-Leydig/patología , Neoplasias Ováricas/genética , Intrones/genética , Mutación de Línea Germinal/genética , Mutación , Ribonucleasa III/genética , ARN Helicasas DEAD-box/genéticaRESUMEN
â¢Primary angiosarcoma of the ovary historically has no standard treatment due to its rarity, and outcomes have been variable.â¢Olaparib may represent a viable treatment option for primary angiosarcoma of the ovary with a somatic BRCA mutation.â¢Next-generation sequencing may play an important component in treatment of very rare cancers to guide new or uncommon therapies.
RESUMEN
â¢Acquired lymphangioma circumscriptum may arise in adulthood as a result of blunt trauma.â¢Large scale surgical excision may effectively treat recalcitrant lymphangioma circumscriptum.â¢Patients with large lymphangioma circumscriptum lesions may benefit from earlier surgical intervention.
RESUMEN
OBJECTIVE: Recent reports in both cervical and endometrial cancer suggest that minimally invasive surgery (MIS) had an unanticipated negative impact on long-term clinical outcomes, including recurrence and death. Given increasing use of robotic surgery since the LAP2 trial, we sought to compare the intermediate and long-term outcomes between those who underwent robotic surgery or laparoscopy for Stage I endometrial cancer. METHODS: We performed a retrospective review of patients from a single, large, academic, urban practice who underwent either laparoscopic or robot-assisted MIS (RA-MIS) for the treatment of endometrial carcinoma between 2006 and 2016, ensuring at least 5 years of potential follow-up. To adjust for differences in confounding variables between groups, propensity score-based inverse probability of treatment weighting (IPTW) was performed. Overall and recurrence-free survival were compared using Cox proportional hazards regression models adjusting for confounding weights. RESULTS: 1027 patients were included; 461 received laparoscopy and 566 received RA-MIS. RA-MIS use increased steadily during the study window, which resulted in longer mean surveillance in laparoscopy group (median 8.7 years versus 6.3 years, p < 0.001). RA-MIS was associated poorer recurrence-free (HR: 1.41, 95% CI: 1.12, 1.77) and overall survival (HR: 1.39, 95% CI: 1.06, 1.83). Disease-specific survival was also poorer in the RA-MIS group (HR: 3.51, 95% CI: 2.19, 5.63). Among those who recurred, median time to first recurrence was shorter in the RA-MIS group than the laparoscopy group (16.3 vs. 28.7 months, p = 0.07). CONCLUSION: RA-MIS was associated with poorer long-term patient outcomes. Our data in this lower-risk population indicate relevant clinical endpoints may be occurring during intermediate and long-term follow-up windows. These findings support a prospective evaluation of the long-term outcomes of RA-MIS.
Asunto(s)
Neoplasias Endometriales , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Robótica , Neoplasias Endometriales/patología , Femenino , Humanos , Histerectomía/métodos , Laparoscopía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
BACKGROUND: The purpose of this study was to determine whether the residual fixative from a liquid-based Pap test or a swab of the cervix contained proteins that were also found in the primary tumor of a woman with high grade serous ovarian cancer. This study is the first step in determining the feasibility of using the liquid-based Pap test or a cervical swab for the detection of ovarian cancer protein biomarkers. METHODS: Proteins were concentrated by acetone precipitation from the cell-free supernatant of the liquid-based Pap test fixative or eluted from the cervical swab. Protein was also extracted from the patient's tumor tissue. The protein samples were digested into peptides with trypsin, then the peptides were run on 2D-liquid chromatography mass spectrometry (2D-LCMS). The data was searched against a human protein database for the identification of peptides and proteins in each biospecimen. The proteins that were identified were classified for cellular localization and molecular function by bioinformatics integration. RESULTS: We identified almost 5000 proteins total in the three matched biospecimens. More than 2000 proteins were expressed in each of the three biospecimens, including several known ovarian cancer biomarkers such as CA125, HE4, and mesothelin. By Scaffold analysis of the protein Gene Ontology categories and functional analysis using PANTHER, the proteins were classified by cellular localization and molecular function, demonstrating that the Pap test fluid and cervical swab proteins are similar to each other, and also to the tumor extract. CONCLUSIONS: Our results suggest that Pap test fixatives and cervical swabs are a rich source of tumor-specific biomarkers for ovarian cancer, which could be developed as a test for ovarian cancer detection.
RESUMEN
PURPOSE: Limitations of the paclitaxel-doxorubicin-cisplatin (TAP) regimen in the treatment of endometrial cancer include tolerability and cumbersome scheduling. The Gynecologic Oncology Group studied carboplatin plus paclitaxel (TC) as a noninferior alternative to TAP. METHODS: GOG0209 was a phase III, randomized, noninferiority, open-label trial. Inclusion criteria were stage III, stage IV, and recurrent endometrial cancers; performance status 0-2; and adequate renal, hepatic, and marrow function. Prior radiotherapy and/or hormonal therapy were permitted, but chemotherapy, including radiosensitization, was not. Patients were treated with doxorubicin 45 mg/m2 and cisplatin 50 mg/m2 (day 1), followed by paclitaxel 160 mg/m2 (day 2) with granulocyte colony-stimulating factor or paclitaxel 175 mg/m2 and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles. The primary endpoint was overall survival (OS; modified intention to treat). Progression-free survival (PFS), health-related quality of life (HRQoL), and toxicity were secondary endpoints. RESULTS: From 2003 to 2009, 1,381 women were enrolled. Noninferiority of TC to TAP was concluded for OS (median, 37 v 41 months, respectively; hazard ratio [HR], 1.002; 90% CI, 0.9 to 1.12), and PFS (median, 13 v 14 months; HR, 1.032; 90% CI, 0.93 to 1.15). Neutropenic fever was reported in 7% of patients receiving TAP and 6% of those receiving TC. Grade > 2 sensory neuropathy was recorded in 26% of patients receiving TAP and 20% receiving TC (P = .40). More grade ≥ 3 thrombocytopenia (23% v 12%), vomiting (7% v 4%), diarrhea (6% v 2%), and metabolic (14% v 8%) toxicities were reported with TAP. Neutropenia (52% v 80%) was more common with TC. Small HRQoL differences favored TC. CONCLUSION: With demonstrated noninferiority to TAP, TC is the global first-line standard for advanced endometrial cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Endometriales/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Neoplasias Endometriales/mortalidad , Femenino , Filgrastim/administración & dosificación , Filgrastim/efectos adversos , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Supervivencia sin Progresión , Calidad de Vida , Resultado del TratamientoRESUMEN
Primary incisional carcinoma (PIC) is a rare, delayed complication of surgery, usually attributed to the malignant transformation of endometriosis. We report a case of incisional carcinoma with nodal metastases in a 55-year-old woman, 18 years after cesarean section. She underwent extirpative surgery, including hysterectomy and bilateral salpingo-oophorectomy, without intraperitoneal disease identifed. Adjuvant treatment included sandwiched platinum-based chemotherapy (carboplatin and paclitaxel) and radiation. She remains disease-free 8 months after completing therapy. We identified 46 additional reported cases. Of these, >90% had undergone an "endometrium-exposing" surgery, most commonly cesarean section; while no cases followed adnexal-only surgery. The median time between antecedent surgery and presentation was 18 years. At presentation, tumors were often large (median 8 cm), and symptomatic with pain (63%) and/or mass (26%). Serum CA125 levels were commonly, albeit slightly, elevated (median 57U/ml (IQR 22-96, Range 6-1690)). Lymph node metastases were common (35%), with most following a vulvar-type spread pattern (inguinal first). Most patients (63%) were treated with chemotherapy +/- radiation. Approximately 50% of patients recurred promptly (median < 6 months), but long-term survival was reported following combined chemotherapy/radiation. Lymph node metastases portended a shorter disease-free interval, with 73% of cases recurring (median 5 months) despite chemotherapy-based treatment. These data suggest that some incisional carcinomas may result from displacement of healthy endometrium followed by delayed malignant transformation. Chemotherapy-only and radiation-only treatments are attended by modest prognosis. Taken together, these data suggest there is both need and potential avenues for improved prevention, detection, and treatment of this condition.
RESUMEN
OBJECTIVE: Endometrial cancer can be diagnosed early and cured, yet cases that recur portend a very poor prognosis with over 10,000 women succumbing to the disease every year. In this study we addressed the question of how to recognize cases likely to recur early in the course of therapy using dysregulation of tumor microRNAs (miRNAs) as predictors. METHODS: Using the tissue collection from Gynecologic Oncology Group Study-210, we selected and analyzed expression of miRNAs in 54 recurrent and non-recurrent cases. The three most common histologic types, endometrioid adenocarcinoma (EEA), serous adenocarcinoma (ESA) and carcinosarcoma (UCS), were analyzed as three independent sets and their miRNA expression profiles compared. RESULTS: Only one miRNA was statistically different between recurrent and non-recurrent cases, and in only one histologic type: significant down-regulation of miR-181c was observed in EEA recurrence. Using several well-known databases to assess miR-181c targets, one target of particular relevance to cancer, NOTCH2, was well supported. Using The Cancer Genome Atlas and our validation tumor panel from the GOG-210 cohort, we confirmed that NOTCH2 is significantly over-expressed in EEA. In the most relevant endometrial adenocarcinoma cell model, Ishikawa H, altering miR-181c expression produces significant changes in NOTCH2 expression, consistent with direct targeting. CONCLUSIONS: Our findings suggest that increased NOTCH2 via loss of miR-181c is a significant component of EEA recurrence. This presents an opportunity to develop miR-181c and NOTCH2 as markers for early identification of high risk cases and the use of NOTCH inhibitors in the prevention or treatment of recurrent disease.
Asunto(s)
Carcinoma Endometrioide/genética , Neoplasias Endometriales/genética , MicroARNs/biosíntesis , Recurrencia Local de Neoplasia/genética , Receptor Notch2/biosíntesis , Carcinoma Endometrioide/metabolismo , Neoplasias Endometriales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Recurrencia Local de Neoplasia/metabolismo , Receptor Notch2/genéticaRESUMEN
PURPOSE: We examined disparities in prognosis between patients with ovarian clear cell carcinoma (OCCC) and serous epithelial ovarian cancer (SOC). METHODS: We reviewed data from FIGO stage I-IV epithelial ovarian cancer patients who participated in 12 prospective randomized GOG protocols. Proportional hazards models were used to compare progression-free survival (PFS) and overall survival (OS) by cell type (clear cell versus serous). RESULTS: There were 10,803 patients enrolled, 9531 were eligible, evaluable and treated with platinum, of whom 544 (6%) had OCCC, 7054 (74%) had SOC, and 1933 (20%) had other histologies and are not included further. In early stage (I-II) patients, PFS was significantly better in OCCC than in SOC patients. For late stage (III, IV) patients, OCCC had worse PFS and OS compared to SOC, OS HR=1.66 (1.43, 1.91; p<0.001). After adjusting for age and stratifying by protocol and treatment arm, stage, performance status, and race, OCCC had a significantly decreased OS, HR=1.53 (1.33, 1.76; p<0.001). In early stage cases, there was a significantly decreased treatment effect on PFS for consolidative therapy with weekly Paclitaxel versus observation in OCCC compared to SOC (p=0.048). CONCLUSIONS: This is one of the largest analyses to date of OCCC treated on multiple cooperative group trials. OCCC histology is more common than SOC in early stage disease. When adjusted for prognostic factors, in early stage patients, PFS was better for OCCC than for SOC; however, in late-stage patients, OCCC was significantly associated with decreased OS. Finally, treatment effect was influenced by histology.
Asunto(s)
Adenocarcinoma de Células Claras/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cistadenocarcinoma Seroso/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/patología , Adulto , Anciano , Carboplatino/administración & dosificación , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Pronóstico , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de SupervivenciaAsunto(s)
Cirugía Bariátrica/economía , Neoplasias Endometriales/prevención & control , Costos de la Atención en Salud , Obesidad/economía , Obesidad/cirugía , Análisis Costo-Beneficio , Neoplasias Endometriales/epidemiología , Femenino , Humanos , Incidencia , Masculino , Personal Militar , Movimiento y Levantamiento de Pacientes/efectos adversos , Obesidad/complicaciones , Obesidad/epidemiología , Prevalencia , Resultado del Tratamiento , Estados Unidos/epidemiología , Pérdida de PesoRESUMEN
OBJECTIVE: To report clinical and pathologic relationships with disease spread in endometrial cancer patients. METHODS: Surgical candidates with uterine cancer (adenocarcinoma or carcinosarcoma) who were eligible to participate in a surgical pathological study to create a clinically annotated tissue biorepository to support translational and clinical research studies. All patients were to undergo a hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. From 2003-2007, open eligibility enrollment was conducted, and from 2007-2011, eligibility was restricted to enrich underrepresented patients or those at high risk. RESULTS: This report details clinical pathological relationships associated with extra uterine disease spread of 5866 evaluable patients including those with endometrioid histology as well as papillary serous, clear cell and carcinosarcoma histologies. Review of unrestricted enrollment was constructed in an effort to capture a cross-section population representative of endometrial cancers seen by the GOG participating members. Evaluation of this group of patients suggested the more natural incidence of different surgical pathological findings as well as demographic information. The addition of 2151 patients enrolled during the restricted time interval allowed a total of 1630 poor histotype patients available for further analysis. As expected, endometrioid (E) cancers represented the largest enrollment and particularly E grade 1 and 2 (G1 and 2) were more frequently confined to the uterus. Grade 3 (G3) endometrioid cancers as well as the poor histotype (papillary serous, clear cell and carcinosarcoma) had a much greater propensity for extant disease. CONCLUSIONS: This study confirms the previously reported surgical pathological findings for endometrioid cancers but in addition, using a large database of papillary serous, clear cell and carcinosarcoma, surgical pathological findings substantiate the categorization of poor histotypes for these cancers.
Asunto(s)
Carcinoma Endometrioide/patología , Carcinoma Endometrioide/cirugía , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/epidemiología , Carcinoma Endometrioide/etnología , Estudios Transversales , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/etnología , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Estados Unidos/epidemiologíaRESUMEN
We previously showed that the cell adhesion molecule Nectin-4 is overexpressed in ovarian cancer tumors, and its cleaved extracellular domain can be detected in the serum of ovarian cancer patients. The ADAM (adisintegrin and metalloproteinase) proteases are involved in ectodomain cleavage of transmembrane proteins, and ADAM17 is known to cleave Nectin-4 in breast cancer. However, the mechanism of Nectin-4 cleavage in ovarian cancer has not yet been determined. Analysis of ovarian cancer gene microarray data showed that higher expression of Nectin-4, ADAM10, and ADAM17 is associated with significantly decreased progression-free survival. We quantified Nectin-4 shedding from the surface of ovarian cancer cells after stimulation with lysophosphatidic acid. We report that ADAM17 and ADAM10 cleave Nectin-4 and release soluble Nectin-4 (sN4). Small molecule inhibitors and siRNA knockdown of both ADAM proteases confirmed these results. In matched samples from 11 high-grade serous ovarian cancer patients, we detected 2-20-fold more sN4 in ascites fluid than serum. Co-incubation of ovarian cancer cells with ascites fluid significantly increased sN4 shedding, which could be blocked using a dual inhibitor of ADAM10 and ADAM17. Furthermore, we detected RNA for Nectin-4, ADAM10, and ADAM17 in primary ovarian carcinoma tumors, secondary omental metastases, and ascites cells isolated from serous ovarian cancer patients. In a signaling pathway screen, lysophosphatidic acid increased phosphorylation of AKT, EGF receptor, ERK1/2, JNK1/2/3, and c-Jun. Understanding the function of Nectin-4 shedding in ovarian cancer progression is critical to facilitate its development as both a serum biomarker and a therapeutic target for ovarian cancer.
Asunto(s)
Proteína ADAM10/metabolismo , Proteína ADAM17/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Moléculas de Adhesión Celular/metabolismo , Proteínas de la Membrana/metabolismo , Neoplasias Ováricas/metabolismo , Proteína ADAM10/genética , Proteína ADAM17/genética , Secretasas de la Proteína Precursora del Amiloide/genética , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/genética , Proteínas de la Membrana/genética , Metástasis de la Neoplasia , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Dominios Proteicos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-jun/genética , Proteínas Proto-Oncogénicas c-jun/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismoRESUMEN
OBJECTIVE: To estimate whether a rapid recovery program would reduce length of stay among patients undergoing laparotomy on a gynecologic oncology service. METHODS: We conducted a prospective, randomized, controlled trial comparing an enhanced recovery after surgery protocol with routine postoperative care among women undergoing laparotomy on the gynecologic oncology service. Protocol elements included: preoperative counseling, regional anesthesia, intraoperative fluid restriction, and early postoperative ambulation and feeding. A sample size of 50 per group (N=100) was planned to achieve 80% power to detect a two-day difference in our primary outcome, length of hospital stay; secondary outcomes included: total daily narcotics used, time to postoperative milestones, and complications. RESULTS: A total of 112 women were enrolled between 2013 and 2015. Nine patients did not undergo laparotomy and were excluded, leaving 52 and 51 patients in the control and intervention groups, respectively. There was no difference in length of stay between the two groups (median 3.0 in both groups; P=.36). Enhanced recovery after surgery patients used less narcotics on day 0 (10.0 compared with 5.5 morphine equivalents in the control and intervention arms, respectively, P=.09) and day 2 (10.0 compared with 7.5 morphine equivalents, respectively; P=.05); however, there was no statistically significant difference between groups in any of the secondary outcomes. Post hoc analysis based on actual anesthesia received also failed to demonstrate a difference in time to discharge. CONCLUSION: When compared with usual care, introducing a formal enhanced recovery after surgery protocol did not significantly reduce length of stay. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01705288.
Asunto(s)
Neoplasias de los Genitales Femeninos/cirugía , Procedimientos Quirúrgicos Ginecológicos/rehabilitación , Laparotomía/rehabilitación , Tiempo de Internación , Cuidados Posoperatorios/métodos , Anestesia/métodos , Anestesia/estadística & datos numéricos , Ambulación Precoz/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/epidemiología , Periodo Posoperatorio , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/estadística & datos numéricos , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer therapy with few efficacious treatments. METHODS: We enrolled 70 patients with CIPN in a randomized, double-blinded, sham-controlled, cross-over trial to determine if photobiomodulation (PBM)±physiotherapy reduced the symptoms of neuropathy compared to sham treatment. At the conclusion of follow-up, sham-arm patients could cross-over into a third arm combining PBM and physiotherapy to determine if multimodal treatment had additive effects. Treatment included 30minute sessions 3-times weekly for 6weeks using either PBM or sham therapy. Neuropathy was assessed using the modified total neuropathy score (mTNS) at initiation and 4, 8, and 16weeks after initiating treatment. RESULTS: Sham-treated patients experienced no significant change in mTNS scores at any point during the primary analysis. PBM patients experienced significant reduction in mTNS scores at all time points. Mean changes in mTNS score (and corresponding percent drop from baseline) for sham and PBM-group patients respectively were -0.1 (-0.7%) and -4.2 (-32.4%) at 4weeks (p<0.001), 0.2 (0.0%) and -6.8 (-52.6%) at 8weeks (p<0.001), and 0.0 (0.1%) and -5.0 (-38.8%) at 16weeks (p<0.001). Patients who crossed over into the PBM/PT-group experienced similar results to those treated primarily; changes in mTNS score from baseline were -5.5 (-40.6%) 4weeks (p<0.001), -6.9 (-50.9%) at 8weeks (p<0.001), and -4.9 (-35.9%) at 16weeks (p<0.001). The addition of physiotherapy did not improve outcomes over PBM alone. CONCLUSION AND RELEVANCE: Among patients with CIPN, PBM produced significant reduction in neuropathy symptoms.
Asunto(s)
Antineoplásicos/efectos adversos , Terapia por Luz de Baja Intensidad , Neoplasias/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/terapia , Modalidades de Fisioterapia , Anciano , Anciano de 80 o más Años , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Prevention of surgical site infections (SSIs) can improve surgical quality through reductions in morbidity and cost. We sought to determine whether the abdominal closure protocol, in isolation, decreases SSI at an academic teaching hospital. METHODS: Adult patients undergoing laparotomy were prospectively randomized to an abdominal closure protocol, which includes unused sterile instruments and equipment at fascial closure, or usual care. A 30-day SSI rates were compared. General surgery, colorectal, urology, or gynecologic oncology patients undergoing anticipated wound classification II cases were eligible. RESULTS: Overall SSI rates were 11.6% in patients randomized to protocol closure vs 12.4% for usual care (total n = 233; P = .85). The abdominal closure protocol and usual care groups had similar rates of superficial (4.5% vs 4.1%; P = .9), deep (.9% vs 0%, P = .3), organ-space SSI rates (6.2% vs 8.3%, P = .55), and wound dehiscence (2.7% vs 5.3%; P = .24). CONCLUSIONS: An abdominal closure protocol did not decrease the rate of SSI and is likely not a key intervention for SSI reduction.
Asunto(s)
Técnicas de Cierre de Herida Abdominal/normas , Neoplasias de los Genitales Femeninos/cirugía , Infección de la Herida Quirúrgica/prevención & control , Cicatrización de Heridas/fisiología , Abdomen/cirugía , Técnicas de Cierre de Herida Abdominal/tendencias , Adulto , Anciano , Neoplasias Colorrectales/cirugía , Cirugía Colorrectal/efectos adversos , Cirugía Colorrectal/métodos , Femenino , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Laparotomía/efectos adversos , Laparotomía/métodos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Mejoramiento de la Calidad , Medición de Riesgo , Resultado del Tratamiento , Procedimientos Quirúrgicos Urológicos/efectos adversos , Procedimientos Quirúrgicos Urológicos/métodosRESUMEN
BACKGROUND: Obesity has been linked to abnormal estrogen regulation, endometrial hyperplasia, and endometrial cancer (EC). Our group has shown that hormone receptor expression profiles in the endometria of morbidly obese women change with weight loss, in some cases concordantly with resolving hyperplasia; however other potential drivers of neoplasia, including altered immunologic tolerance exist. The objective of this study was to evaluate the effect of bariatric surgery induced weight loss on the expression patterns of nonhormone receptor biomarkers associated with cancer and immunity. METHODS: Endometrial biopsies were obtained from 59 asymptomatic, morbidly obese women at the time of bariatric surgery and again 1 year postsurgery. Tissue microarrays were created and immunohistochemical stains for CD3, CD20, and PTEN were performed on all samples and evaluated by 2 blinded pathologists independently. Approximately 50% of participants had sufficient tissue for analysis at both visits. McNemar/Bowker tests of symmetry were performed to compare proportions between categories for matched pairs (pre- and post-treatment). RESULTS: Endometrial hyperplasia was identified in 4 women despite negative clinical histories and resolution of hyperplasia after weight loss occurred in 3 women. While overall no significant differences were observed between matched pre and postsurgery levels of CD20 and CD3 positive cells, a tendency toward decreased expression levels from baseline status was observed for CD20. No differences were observed for PTEN. CONCLUSION: Our data demonstrate that the prevalence of endometrial pathology appears to be partially mitigated by weight loss. Weight loss is associated with alterations in the hormone receptor profiles, but these data suggest that changes in the immune response, as measure be expression of CD20+, may be relevant targets for EC prevention research.
Asunto(s)
Cirugía Bariátrica/métodos , Endometrio/inmunología , Obesidad Mórbida/cirugía , Pérdida de Peso/inmunología , Adulto , Antígenos CD20/metabolismo , Biomarcadores/metabolismo , Complejo CD3/metabolismo , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/inmunología , Femenino , Humanos , Hallazgos Incidentales , Persona de Mediana Edad , Obesidad Mórbida/inmunología , Fosfohidrolasa PTEN/metabolismo , Cuidados Posoperatorios , Cuidados Preoperatorios , Análisis de Matrices TisularesRESUMEN
OBJECTIVE: We sought to evaluate an electronic referral form to increase referral for genetic risk assessment of women with newly diagnosed epithelial ovarian cancer. METHODS: A form summarizing referral for genetic counseling for women with ovarian cancer was introduced into the electronic medical record allowing gynecologic oncologists to electronically submit a request for genetic services. Analysis compared patient and provider characteristics for women newly diagnosed with ovarian, fallopian tube, and primary peritoneal cancer referred 1 year before and after introducing the form. All patients were seen in a single fee-for-service university-based cancer center clinic. RESULTS: There were 86 newly diagnosed ovarian cancer patients seen before and 83 seen after the introduction of the electronic referral form. Most lived in the metropolitan area and had stage III to IV disease, serous histology, a documented family history, and a treating oncologist who was less than 10 years from completion of fellowship. Postintervention referral rates increased from 17% to 30% (P = 0.053). Factors best predicting referral were whether the patient was seen after the intervention (P = 0.009), resided in the metropolitan area (P = 0.006), and had been identified as at high hereditary risk (P < 0.0001). Sixty percent of the referred patients participated in counseling. There were no differences in baseline characteristics of the referred patients before and after the intervention. CONCLUSIONS: Referral rates increased with the introduction of an electronic medical record referral form suggesting that streamlining the physician referral process might be effective at increasing referrals for cancer genetic risk assessment.
Asunto(s)
Cistadenocarcinoma Seroso/genética , Registros Electrónicos de Salud/estadística & datos numéricos , Asesoramiento Genético , Neoplasias Ováricas/genética , Neoplasias Peritoneales/genética , Derivación y Consulta , Adulto , Anciano , Anciano de 80 o más Años , Cistadenocarcinoma Seroso/prevención & control , Cistadenocarcinoma Seroso/psicología , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/prevención & control , Neoplasias Ováricas/psicología , Neoplasias Peritoneales/prevención & control , Neoplasias Peritoneales/psicología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Adulto JovenRESUMEN
OBJECTIVES: Ileostomy results in a relatively poorer water reabsorption and is associated with dehydration and renal injury. These problems may be exacerbated in the setting of gynecologic cancers owing to both patient and disease-related factors. We evaluated the rate and reasons for hospital readmission within 30 days of ileostomy creation in patients with a gynecologic malignancy. METHODS: We performed a retrospective review of women with gynecologic malignancies who underwent ileostomy creation between 2002 and 2013. RESULTS: Fifty-three patients were eligible for analysis. The mean age was 63.3 years. Most patients had ovarian cancer (86.5%). Indications for ileostomy included small bowel obstruction (45.3%), as part of primary debulking (18.9%), or treatment of an anastomotic leak (15.1%). The 30-day readmission rate was 34%. Co-morbid diseases such as hypertension (p=0.008) and chronic kidney disease (p=0.010) were more common among women who were readmitted. The most common reasons for readmission were dehydration (38.9%) and acute renal failure (33.3%); women readmitted for these conditions had higher average serum creatinine levels at initial postoperative discharge (1.00 mg/dL versus 0.71 mg/dL, p=0.017) than women who did not require readmission. Readmitted women had a trend toward shorter overall survival (0.41 years versus 1.67 years, p=0.061). CONCLUSIONS: Readmission rates for gynecologic oncology patients undergoing ileostomy were similar to, but higher than those previously reported in the colorectal literature. In our population, patients with preexisting cardiovascular or renal disease were at the highest risk of readmission and may benefit from preemptive strategies to decrease high ostomy output and dehydration.
Asunto(s)
Ileostomía , Enfermedades Intestinales/cirugía , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Anciano , Femenino , Humanos , Enfermedades Intestinales/etiología , Persona de Mediana Edad , Neoplasias Ováricas/complicaciones , Estudios Retrospectivos , Neoplasias Uterinas/complicacionesRESUMEN
OBJECTIVE: To determine how anesthesia choice in women undergoing laparotomy for gynecologic malignancy affects pain control and narcotic use. METHODS: This is a retrospective study of women who underwent laparotomy for suspected gynecologic malignancy from May 2012 to January 2013. Patients were categorized into one of three groups: 1) patient controlled analgesia (PCA); 2) PCA+transversus abdominis plane block (TAP); and 3) patient-controlled epidural analgesia (PCEA). Mean narcotic use and patient reported pain scores were compared. RESULTS: The analysis includes 112 women (44 PCA, 30 TAP, 38 PCEA). Intraoperative factors were not different between groups with the exception of a significant difference in the rate of intra-operative complications (p=0.020), with lower rates in the PCEA group. The groups differed in intravenous narcotic use in each of the first three postoperative days (day 0: p=0.014; day 1: p<0.0001; day 2: p=0.048), with patients in the TAP group using the least on day 0 and those in the PCEA group using less on postoperative days 1 and 2. In addition, the PCEA group reported lower pain scores on postoperative days 1 and 2 (day 1: p=0.046; day 2: p=0.008). CONCLUSIONS: The use of patient controlled epidural anesthesia after laparotomy for gynecologic malignancy is associated with decreased IV and PO narcotic use and improved pain control without increasing complications or length of hospital stay. Further investigation with prospective randomized trials is warranted to elucidate the optimal post-operative pain management technique.