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Sodium manganese hexacyanoferrate (NaMnHCF) is an attractive candidate as a cathode material for sodium-ion batteries due to its low cost and high energy density. However, its practical application is hindered by poor electrochemical stability caused by the Jahn-Teller effect of Mn and the unstable structure of NaMnHCF. Here, this paper aims to address this issue by introducing highly stable AMnHCF (where A = K, Rb, or Cs) through a facile method to composite with NaMnHCF. The findings reveal that all AMnHCFs have a "pillar effect" on the crystal structure of NaMnHCF. It is observed that the degree of pillar effect varies depending on the specific AMnHCF used. The less electrochemically inactive the alkaline ion is and the greater the degree of compositing with NaMnHCF, the more dramatic the pillar effect. KMnHCF shows limited pillar effect due to its rough composition with NaMnHCF and the loss of K+ upon (de)intercalation. RbMnHCF has lower electrochemical activity and can be better composited with NaMnHCF. On the other hand, CsMnHCF exhibits the strongest pillar effect due to the inactivation of Cs+ and the excellent coherent structure formed by CsMnHCF and NaMnHCF. This research provides a new perspective on stabilizing NaMnHCF with other alkaline elements.
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Lithium-ion batteries (LIBs) are promising energy storage devices for integrating renewable resources and high power applications, owing to their high energy density, light weight, high flexibility, slow self-discharge rate, high rate charging capability, and long battery life. LIBs work efficiently at ambient temperatures, however, at high-temperatures, they cause serious issues due to the thermal fluctuation inside batteries during operation. The separator is a key component of batteries and is crucial for the sustainability of LIBs at high-temperatures. The high thermal stability with minimum thermal shrinkage and robust mechanical strength are the prime requirements along with high porosity, ionic conductivity, and electrolyte uptake for highly efficient high-temperature LIBs. This Review deals with the recent studies and developments in separator technologies for high-temperature LIBs with respect to their structural layered formation. The recent progress in monolayer and multilayer separators along with the developed preparation methodologies is discussed in detail. Future challenges and directions toward the advancement in separator technology are also discussed for achieving remarkable performance of separators in a high-temperature environment.
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Purpose To assess the diagnostic accuracy of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with diagnostic contrast material-enhanced computed tomography (CT) in detecting lymph node (LN) metastasis in high-risk endometrial cancer. Materials and Methods This prospective multicenter HIPAA-compliant study had institutional review board approval, and all participants gave written informed consent. Data were accrued between January 2010 and June 2013. Patients underwent PET/CT and pelvic and abdominal lymphadenectomy. Two hundred seven of 215 enrolled patients had PET/CT and pathologic examination results for the abdomen and pelvis. Mean patient age was 62.7 years ± 9.6 (standard deviation). Data in all 23 patients with a positive abdominal examination and in 26 randomly selected patients with a negative abdominal examination were used for this central reader study. Seven independent blinded readers reviewed diagnostic CT and PET/CT results in different sessions 1 month apart. Accuracy was calculated at the participant level, correlating abdominal (right and left para-aortic and common iliac) and pelvic (right and left external iliac and obturator) LN regions with pathologic results, respecting laterality. Reader-average sensitivities, specificities, and areas under the receiver operating characteristic curve (AUCs) of PET/CT and diagnostic CT were compared. Power calculation was for sensitivity and specificity in the abdomen. Results Sensitivities of PET/CT versus diagnostic CT for the detection of LN metastasis were 0.65 (95% confidence interval [CI]: 0.57, 0.72) versus 0.50 (95% CI: 0.43, 0.58) (P = .01) in the abdomen and 0.65 (95% CI: 0.57, 0.72) versus 0.48 (95% CI: 0.41, 0.56) (P = .004) in the pelvis. Corresponding specificities were 0.88 (95% CI: 0.83, 0.92) versus 0.93 (95% CI: 0.89, 0.96) (P = .11) and 0.93 (95% CI: 0.86, 0.96) versus 0.89 (95% CI: 0.82, 0.94) (P = .27), and AUCs were 0.78 (95% CI: 0.66, 0.89) versus 0.74 (95% CI: 0.63, 0.86) (P = .39) and 0.82 (95% CI: 0.71, 0.92) versus 0.73 (95% CI: 0.63, 0.84) (P = .02). Conclusion FDG PET/CT has satisfactory diagnostic accuracy in the detection of abdominal LN metastasis in high-risk endometrial cancer. Compared with diagnostic CT alone, addition of PET to diagnostic CT significantly increased sensitivity in both the abdomen and pelvis while maintaining high specificity. © RSNA, 2017 Online supplemental material is available for this article.
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Neoplasias Endometriales/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/secundario , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fluorodesoxiglucosa F18 , Humanos , Metástasis Linfática , Persona de Mediana Edad , Radiofármacos , Reproducibilidad de los Resultados , Medición de Riesgo , Sensibilidad y EspecificidadRESUMEN
PURPOSE: Activating FGFR2 mutations have been identified in ~10% of endometrioid endometrial cancers (ECs). We have previously reported that mutations in FGFR2 are associated with shorter disease free survival (DFS) in stage I/II EC patients. Here we sought to validate the prognostic importance of FGFR2 mutations in a large, multi-institutional patient cohort. METHODS: Tumors were collected as part of the GOG 210 clinical trial "Molecular Staging of Endometrial Cancer" where samples underwent rigorous pathological review and had more than three years of detailed clinical follow-up. DNA was extracted and four exons encompassing the FGFR2 mutation hotspots were amplified and sequenced. RESULTS: Mutations were identified in 144 of the 973 endometrioid ECs, of which 125 were classified as known activating mutations and were included in the statistical analyses. Consistent with FGFR2 having an association with more aggressive disease, FGFR2 mutations were more common in patients initially diagnosed with stage III/IV EC (29/170;17%) versus stage I/II EC (96/803; 12%; p=0.07, Chi-square test). Additionally, incidence of progression (progressed, recurred or died from disease) was significantly more prevalent (32/125, 26%) among patients with FGFR2 mutation versus wild type (120/848, 14%; p<0.001, Chi-square test). Using Cox regression analysis adjusting for known prognostic factors, patients with FGFR2 mutation had significantly (p<0.025) shorter progression-free survival (PFS; HR 1.903; 95% CI 1.177-3.076) and endometrial cancer specific survival (ECS; HR 2.013; 95% CI 1.096-3.696). CONCLUSION: In summary, our findings suggest that clinical trials testing the efficacy of FGFR inhibitors in the adjuvant setting to prevent recurrence and death are warranted.
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Carcinoma Endometrioide/genética , Neoplasias Endometriales/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Anciano , Carcinoma Endometrioide/patología , Estudios de Cohortes , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , Neoplasias Endometriales/patología , Exones , Femenino , Humanos , Estimación de Kaplan-Meier , Estadificación de NeoplasiasRESUMEN
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.
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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
OBJECTIVE: The aim of this study was to evaluate the efficacy of adding bevacizumab to paclitaxel and carboplatin and as maintenance in a larger cohort of patients with advanced or recurrent endometrial carcinoma. METHODS: We retrospectively identified endometrial cancer patients treated with paclitaxel (175 mg/m per 3 hours), carboplatin (area under the curve, 5) and bevacizumab (15 mg/kg) and maintenance bevacizumab treated in a post-protocol treatment cohort and evaluated them with our previously published phase 2 trial of this regimen. RESULTS: Twenty-seven additional patients were identified; 19 received the regimen as first-line therapy, and 8 received the regimen as second-line therapy after prior paclitaxel and carboplatin. The 19 patients who received first-line therapy were analyzed alone and with the 15 patients enrolled on protocol. The 2 cohorts were similar with respect to risk factors. Overall survival curves were not statistically different between the protocol and the postprotocol patients (log-rank test; P > 0.1). Collectively, a total of 266 courses (median, 6 courses; range, 1-20 courses) of carboplatin, paclitaxel, and bevacizumab combination therapy and 305 courses (median, 16 courses; range, 0-45courses) of bevacizumab maintenance therapy were administered as first-line therapy. Collectively, the median progression-free survival was 20 months, and median overall survival was 56 months. Among 29 patients with measurable disease, the response rate was 82.8% (95% confidence interval, 69.0%-96.5%; 15 complete responses and 9 partial responses). Among the 8 patients who received paclitaxel and carboplatin and bevacizumab as second-line therapy after paclitaxel and carboplatin, the response rate was 87.5% (6 complete responses, 1 partial response). Their median progression-free survival and median overall survival were not reached after a median follow-up of 23.5 months. CONCLUSIONS: Although there are inherent limitations to small retrospective studies, this second analysis confirms the high response rate, progression-free survival, and overall survival in the bevacizumab, paclitaxel, and carboplatin regimen as first-line therapy in advanced and recurrent endometrial carcinoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Endometriales/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Bevacizumab/administración & dosificación , Carboplatino/administración & dosificación , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Estudios RetrospectivosRESUMEN
OBJECTIVE: To assess if FDG PET combined with diagnostic CT improves diagnostic CT accuracy to detect lymph node (LN) metastasis in advanced cervical cancer. METHODS: A prospective HIPAA compliant ACRIN/GOG multicenter trial was conducted. Patients underwent concurrent diagnostic contrast-enhanced CT (DCT) and PET and pelvic/abdominal lymphadenectomy. Seven independent blinded readers reviewed PET-DCT and DCT one-month apart. Reference standard was surgically removed LN pathology. Accuracy values were calculated at participant level, correlating abdominal (right and left para-aortic/common iliac) and pelvic (right and left external iliac/obturator) LN regions with pathology, respecting laterality. Reader average sensitivities/specificities of PET-DCT vs. DCT were compared with generalized linear mixed models, and AUCs with Obuchowski's method. RESULTS: One hundred fifty-three patients had PET-DCT and pathology. Forty-three of 153 patients had metastasis to abdominal LNs. Sample size calculation required review of the first 40 abdominal positive and 40 randomly selected abdominal negative studies. Patients were 24 to 74years (48.9±10.6) old. Mean sensitivities of PET-DCT/DCT for detection of LN metastasis in abdomen were 0.50 (CI: 0.44, 0.56) and 0.42 (CI: 0.36, 0.48) (p=0.052) and in pelvis 0.83 (CI: 0.78, 0.87) and 0.79 (CI: 0.73, 0.83) (p=0.15). Corresponding specificities were 0.85 (CI: 0.80, 0.89) and 0.89 (CI: 0.84, 0.92) (p=0.21) and 0.63 (CI: 0.54, 0.70) and 0.62 (CI: 0.53, 0.69) (p=0.83). Mean AUC values were 0.70 (CI: 0.61, 0.79) and 0.68 (CI: 0.59, 0.77) (p=0.43) and 0.80 (CI: 0.71, 0.88) and 0.76 (CI: 0.67, 0.85) (p=0.21) respectively. CONCLUSION: Addition of PET to DCT resulted in statistically borderline increase in sensitivity to detect LN metastasis in abdomen in advanced cervical cancer.
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Ganglios Linfáticos/diagnóstico por imagen , Neoplasias del Cuello Uterino/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/diagnóstico por imagen , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Espacio Retroperitoneal/diagnóstico por imagen , Espacio Retroperitoneal/patología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Adulto JovenRESUMEN
OBJECTIVE: The aim of the study was to determine the differential expression patterns of the wingless-type (Wnt) pathway inhibitors Dkk3 (Dickkopf 3), SFRP1 (secreted frizzled-related protein 1), and SFRP4 in normal müllerian tissue and endometrial endometrioid adenocarcinoma specimens. METHODS: Messenger RNA (mRNA) and protein levels of the Wnt pathway inhibitors Dkk3, SFRP1, and SFRP4 were evaluated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. A total of 87 human tissue specimens were obtained from 60 women who participated in Gynecologic Oncology Group protocol 210. Twenty-seven normal müllerian tissues, 32 early-stage, and 28 advanced-stage endometrial endometrioid cancer specimens were analyzed. RESULTS: Median age for this cohort was 60 years, with median body mass index of 32 kg/m. There was a difference in Dkk3 protein expression between normal müllerian tissues and primary endometrial endometrioid adenocarcinoma samples (P = 0.05). There was down-regulation of Dkk3, SFRP1, and SFRP4 mRNA expression in patients with high-grade disease (P = 0.08, 0.06, and 0.05, respectfully). Furthermore, a decrease in SFRP1 and SFPR4 mRNA expression was noted in patients with a diagnosis of locoregional and distant disease recurrence. Lastly, a trend toward decreased progression-free survival in patients with low Dkk3, SFRP1, and SFRP4 mRNA expression levels was noted. CONCLUSIONS: Wnt pathway inhibitor (Dkk3, sFRP1, and/or sFRP4) expression was down-regulated in patients with high-grade disease and was associated with locoregional and distant disease recurrence. Despite sample size (power) limitations, these results support previous preclinical studies and may suggest a therapeutic role for Wnt signaling in endometrial cancer.
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Biomarcadores de Tumor/metabolismo , Carcinoma Endometrioide/genética , Neoplasias Endometriales/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Proteínas de la Membrana/genética , Recurrencia Local de Neoplasia/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Adaptadoras Transductoras de Señales , Anciano , Biomarcadores de Tumor/genética , Western Blotting , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patología , Quimiocinas , Estudios de Cohortes , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Femenino , Estudios de Seguimiento , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Proteínas Proto-Oncogénicas/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Células Tumorales Cultivadas , Vía de Señalización WntRESUMEN
OBJECTIVE: We sought to validate the clinicopathologic implications and prognostic significance of ATR (ataxia telangiectasia mutated and Rad3-related) mutation in patients with endometrioid endometrial cancer and defective DNA mismatch repair enrolled in a cooperative group molecular staging study of endometrial cancer. METHODS: After pathology review, only endometrioid tumors with high neoplastic cellularity (≥70%) and high quality DNA for molecular analyses were included. MSI (microsatellite instability) typing was performed and the target sequence in exon 10 of ATR was evaluated by direct sequencing in all MSI-high tumors. Associations between ATR mutations and clinicopathologic variables were assessed using contingency table tests. Differences in overall survival (OS) and disease-free survival (DFS) were evaluated by univariate analyses and multivariable Cox proportional hazard models. RESULTS: A total of 475 eligible cases were identified. Of 368 MSI+ cases, the sequence of interest could be successfully genotyped in 357 cases. ATR mutations were exclusively identified in 46 tumors with high level microsatellite instability (MSI+) (12.9%, p<0.001) and were associated with higher tumor grade (p=0.001). ATR mutations were not associated with OS (HR 1.16; 95% CI, 0.58-2.32; p=0.68) or DFS (HR 0.61; 95% CI, 0.25-1.50; p=0.28). CONCLUSION: Truncating mutations in exon 10 of ATR occur exclusively in tumors with evidence of defective DNA mismatch repair. We were not able to confirm the prognostic value of these mutations in patients with endometrioid endometrial cancer.
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Biomarcadores de Tumor/genética , Carcinoma Endometrioide/genética , Neoplasias Endometriales/genética , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de la Ataxia Telangiectasia Mutada/genética , Carcinoma Endometrioide/patología , Estudios de Cohortes , Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales/patología , Femenino , Humanos , Inestabilidad de Microsatélites , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: Few studies have analyzed relationships between risk factors for endometrial cancer, especially with regard to aggressive (non-endometrioid) histologic subtypes, and prognosis. We examined these relationships in the prospective NRG Oncology/Gynecologic Oncology Group 210 trial. METHODS: Prior to surgery, participants completed a questionnaire assessing risk factors for gynecologic cancers. Pathology data were derived from clinical reports and central review. We used the Fine and Gray subdistribution hazards model to estimate subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations between etiologic factors and cause-specific subhazards in the presence of competing risks. These models were stratified by tumor subtype and adjusted for stage and socioeconomic status indicators. RESULTS: Median follow-up was 60months after enrollment (range: 1day-118months). Among 4609 participants, a total of 854 deaths occurred, of which, 582 deaths were attributed to endometrial carcinoma. Among low-grade endometrioid cases, endometrial carcinoma-specific subhazards were significantly associated with age at diagnosis (HR=1.04, 95% CI=1.01-1.06 per year, P-trend) and BMI (class II obesity vs. normal BMI: HR=2.29, 95% CI=1.06-4.98, P-trend=0.01). Among high-grade endometrioid cases, endometrial carcinoma-specific subhazards were associated with age at diagnosis (HR=1.05, 95% CI=1.02-1.07 per year, P-trend<0.001). Among non-endometrioid cases, endometrial carcinoma-specific subhazards were associated with parity relative to nulliparity among serous (HR=0.55, 95% CI=0.36-0.82) and carcinosarcoma cases (HR=2.01, 95% CI=1.00-4.05). DISCUSSION: Several endometrial carcinoma risk factors are associated with prognosis, which occurs in a tumor-subtype specific context. If confirmed, these results would suggest that factors beyond histopathologic features and stage are related to prognosis. ClinicalTrials.gov Identifier: NCT00340808.
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Neoplasias Endometriales/etiología , Neoplasias Endometriales/mortalidad , Factores de Edad , Carcinoma Endometrioide/etiología , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/patología , Neoplasias Endometriales/patología , Femenino , Humanos , Obesidad/complicaciones , Obesidad/epidemiologíaRESUMEN
BACKGROUND: Ventilator associated pneumonia (VAP) is an important and common complication of mechanically ventilated patients. It is the leading cause of morbidity and mortality in Intensive Care Units (ICU) worldwide. The aim of study was to determine the pattern of bacteria involved in VAP in intensive care unit of Jinnah hospital Lahore. METHODS: It was descriptive case series study, conducted over a period of one year on mechanically ventilated 50 patients. American Thoracic Society (ATS) guidelines recommend quantitative/semi-quantitative culture of endotracheal aspirates (ETA) or bronchoscopic aspirates/washing from the infected lung segments for the diagnosis of VAP. Hence this study was conducted to identify the types of bacteria involved in VAP in our ICU. Patients enrolled were clinically and radiologically suspected VAP, admitted in the ICU of Jinnah Hospital/Allama Iqbal Medical College (AIMC) Lahore. Bronchial washings were taken with the help of Fiber optic bronchoscope. Wherever bronchoscopy was not possible, subglottic secretions were collected with the help of sterilized catheter and sucker. Collected samples were sent to the Pathology laboratory of AIMC for aerobic culture and sensitivity. RESULTS: Major pathogenic bacteria isolated were Gram negative (74%). Among this group E. coli, Pseudomonas, Klebsiella and Acinetobacter were the commonest organisms. Gram positive bacteria were 20%, Staphylococcus aureus (MRSA) and beta-haemolyticus streptococci were the major isolate. In 4% cases mixed growth and in 2% cases no growth was reported. CONCLUSION: Major pathogenic organisms of VAP in our ICU are Gram negative bacteria. The Bacteriological culture of endobroncheal aspirates is helpful in the diagnosis and management of VAP. Emperic antibiotic therapy for VAP should cover Gram negative organisms.
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Bacterias/aislamiento & purificación , Contaminación de Equipos/estadística & datos numéricos , Unidades de Cuidados Intensivos , Neumonía Asociada al Ventilador/microbiología , Respiración Artificial/efectos adversos , Adulto , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Pakistán/epidemiología , Neumonía Asociada al Ventilador/epidemiología , Estudios RetrospectivosRESUMEN
OBJECTIVE: To determine which patients with near midline lesions may safely undergo unilateral groin dissection based on clinical exam and lymphoscintigraphy (LSG) results. METHODS: Patients participating in GOG-173 underwent sentinel lymph node (SLN) localization with blue dye, and radiocolloid with optional LSG before definitive inguinal-femoral lymphadenectomy (LND). This analysis interrogates the reliability of LSG alone relative to primary tumor location in those patients who had an interpretable LSG and at least one SLN identified. Primary tumor location was categorized as lateral (>2cm from midline), midline, or lateral ambiguous (LA) if located within 2cm, but not involving the midline. RESULTS: Two-hundred-thirty-four patients met eligibility criteria. Sixty-four had lateral lesions, and underwent unilateral LND. All patients with LA (N=65) and midline (N=105) tumors underwent bilateral LND. Bilateral drainage by LSG was identified in 14/64 (22%) patients with lateral tumors, 38/65 (58%) with LA tumors and in 73/105 (70%) with midline tumors. At mapping, no SLNs were found in contralateral groins among those patients with LA and midline tumors who had unilateral-only LSGs. However, in these patients groin metastases were found in 4/32 patients with midline tumors undergoing contralateral dissection; none were found in 27 patients with LA tumors. CONCLUSION: The likelihood of detectable bilateral drainage using preoperative LSG decreases as a function of distance from midline. Patients with LA primaries and unilateral drainage on LSG may safely undergo unilateral SLN.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/cirugía , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Neoplasias de la Vulva/diagnóstico por imagen , Neoplasias de la Vulva/cirugía , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Linfocintigrafia/métodos , Estudios Prospectivos , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias de la Vulva/patologíaRESUMEN
OBJECTIVES: To determine the efficacy and toxicity of radiation therapy and concurrent weekly cisplatin chemotherapy in achieving a complete clinical and pathologic response when used for the primary treatment of locally-advanced vulvar carcinoma. METHODS: Patients with locally-advanced (T3 or T4 tumors not amenable to surgical resection via radical vulvectomy), previously untreated squamous cell carcinoma of the vulva were treated with radiation (1.8 Gy daily × 32 fractions=57.6 Gy) plus weekly cisplatin (40 mg/m(2)) followed by surgical resection of residual tumor (or biopsy to confirm complete clinical response). Management of the groin lymph nodes was standardized and was not a statistical endpoint. Primary endpoints were complete clinical and pathologic response rates of the primary vulvar tumor. RESULTS: A planned interim analysis indicated sufficient activity to reopen the study to a second stage of accrual. Among 58 evaluable patients, there were 40 (69%) who completed study treatment. Reasons for prematurely discontinuing treatment included: patient refusal (N=4), toxicity (N=9), death (N=2), other (N=3). There were 37 patients with a complete clinical response (37/58; 64%). Among these women there were 34 who underwent surgical biopsy and 29 (78%) who also had a complete pathological response. Common adverse effects included leukopenia, pain, radiation dermatitis, pain, or metabolic changes. CONCLUSIONS: This combination of radiation therapy plus weekly cisplatin successfully yielded high complete clinical and pathologic response rates with acceptable toxicity.
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Antineoplásicos/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administración & dosificación , Neoplasias de la Vulva/tratamiento farmacológico , Neoplasias de la Vulva/radioterapia , Adulto , Anciano , Antineoplásicos/efectos adversos , Carcinoma de Células Escamosas/cirugía , Cisplatino/efectos adversos , Terapia Combinada , Fraccionamiento de la Dosis de Radiación , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Radioterapia/efectos adversos , Radioterapia/métodos , Neoplasias de la Vulva/cirugíaRESUMEN
Background Typhoid is a serious public health concern with increasing antibiotic resistance. Early suspicion and choice of susceptible antibiotics are key to avoiding the morbidity and mortality associated with this disease. We have carried out this study to assess the antibiotic sensitivity of typhoidal salmonellae in Kharian, Pakistan. Materials and methods This cross-sectional study was carried out at Combined Military Hospital, Kharian, Pakistan, from January 2019 to September 2020. Blood culture specimens from patients clinically suspected of enteric fever were tested through the BacT/ALERT 3D automated blood culture system. Positive microbial growth was further identified by colony morphology, appropriate staining, biochemical testing, and Salmonella-specific grouping sera. Salmonella typhi and Salmonella paratyphi A-C were further analyzed for antimicrobial susceptibility using agar disc diffusion testing by the modified Kirby-Bauer technique. The Clinical and Laboratory Standards Institute (CLSI) guidelines (2018-2020) document M-100 was followed for antibiotic selection and assigning the sensitivity status of the isolates. Meropenem and azithromycin were additionally tested keeping in view the possibility of encountering isolates with extensive antimicrobial resistance. Results A total of 315 blood culture samples were received during the study period. Of these, 239 (75.9%) reported negative and 76 (24.1%) were positive. The mean age was 22.37 ± 12.39 years. There were 41 (53.9%) males and 35 (46.1%) females. Salmonella enterica (combined Salmonella typhi and Salmonella paratyphi A) was 100% sensitive to azithromycin, meropenem, and imipenem. Ampicillin and chloramphenicol have 28.9% sensitivity each. Ceftriaxone, co-trimoxazole, and ciprofloxacin revealed 64.5%, 23.7%, and 11.8% sensitivity, respectively. Among them, 11.84% of the isolates were pan-sensitive, 35.5% of the cultures were multidrug-resistant (MDR), and 35.5% of the cultures were extensively drug-resistant (XDR). Conclusion The study demonstrates that polyresistant typhoidal salmonellae are no more confined to a couple of outbreaks in large cities of Pakistan. It is the tip of the iceberg, and the balance has tilted toward difficult-to-treat typhoid and paratyphoid fevers all across the country owing to significant resistance to the commonly used antityphoid antibiotics (cephalosporins and fluoroquinolones). Azithromycin and carbapenems are offering the last line of defense against the rampant Salmonella typhi and Salmonella paratyphi.
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OBJECTIVES: To evaluate the outcome of stage IVA cervical cancer treated with radiation and concurrent cisplatin-based chemotherapy. METHODS: We conducted a retrospective study of stage IVA cervical cancer patients from four trials (Gynecologic Oncology Group protocols 56, 85, 120, and 165) treated with radiotherapy with or without concurrent cisplatin-based chemotherapy. Patient records were reviewed for demographic and tumor features, treatment, and progression-free survival (PFS) and overall survival (OS). Stage IVA patients were compared to stage IIIB patients from these same studies. RESULTS: Among the 51 stage IVA patients studied, 92% were stage IVA on the basis of bladder involvement. The median PFS was 10.1 months (95% CI=6.3-14.5 months) and median OS was 21.2 months (95% CI=13.3-30.5 months). The 3 year survival was 32%. On univariate analysis, only advanced age was associated with OS (p=0.0115) but age had only marginal effect on PFS (p=0.083). Pathologic proven pelvic nodal metastasis was of marginal significance for both PFS and OS, p=0.059 and 0.064, respectively. Despite similar patient characteristics, the use of cisplatin-based chemotherapy had no impact on PFS or OS but was underpowered to address this question. When compared to stage IIIB patients, stage IVA patients had a poorer performance status (p=0.0231), larger tumor size (p=0.0302), and more frequent bilateral parametrial involvement (0.0063). CONCLUSION: Patients with stage IVA disease had poor median survival of only 21 months with only 32% 3 year survival. Stage IVA patients have larger tumor size, more bilateral parametrial involvement, and poorer survival when compared to stage IIIB patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia , Anciano , Braquiterapia , Cisplatino/administración & dosificación , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Hidroxiurea/administración & dosificación , Persona de Mediana Edad , Misonidazol/administración & dosificación , Estadificación de Neoplasias , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVES: To estimate the significance of hydronephrosis and impact of ureteral obstruction relief on outcome in patients with stage IIIB cervical cancer treated with radiation and concurrent chemotherapy. METHODS: We retrospectively studied stage IIIB cervical cancer patients treated on GOG trials 56, 85, 120 and 165 evaluating radiation and concurrent chemotherapy. Eligible patient records were reviewed to assess the presence of hydronephrosis and treatment of ureteral obstruction. Patients were classified into three groups; no hydronephrosis, hydronephrosis relieved from ureteral obstruction via stent or percutaneous nephrostomy and hydronephrosis without treatment of ureteral obstruction. RESULTS: 539 stage IIIB patients were studied. Hydronephrosis was present in 238 (44.2%). Patient age, race, and tumor characteristics (size, histology and grade) were not significantly different between patients with or without hydronephrosis. Patients with hydronephrosis received similar doses of radiation and cisplatin-based chemotherapy. Both overall and progression-free survival were worse with hydronephrosis (log-rank test p value=0.0189 and 0.0186, respectively). Univariable analysis identified five prognostic factors; pelvic nodal metastasis (p=0.0001), tumor diameter (p=0.0007), cisplatin-based concurrent chemoradiation (p=0.0031), hydronephrosis (p=0.0189), and performance status (p=0.0359). Hydronephrosis was associated with worse performance status (p<0.001). On multivariable analysis hydronephrosis was not a significant prognostic factor. Ureteral obstruction relief occurred for 88% of patients and was associated with improved survival. CONCLUSION: In patients with stage IIIB cervical cancer restricted to the pelvis, hydronephrosis at presentation is a significant but not independent prognostic factor associated with poor performance status and poorer survival. Relief of ureteral obstruction is correlated with improved outcome.
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Hidronefrosis/fisiopatología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Tasa de Supervivencia , Resultado del Tratamiento , Obstrucción Ureteral/fisiopatología , Obstrucción Ureteral/cirugía , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVE: The objective of the study was to study posttherapy chemoradiation hysterectomy histology with long-term survival in bulky stage 1(B) cervical cancer patients. STUDY DESIGN: Gynecologic Oncology Group protocols 71 and 123 enrolled 464 patients randomly allocated to pelvic radiation (75 Gy, n = 291) plus hysterectomy (RTH) or to pelvic radiation (75 Gy) and cisplatin (40 mg/m(2), n = 176) plus hysterectomy (RTCH). Risk of progression and death were evaluated by posttherapy hysterectomy response (good: <10% viable; poor: ≥10% viable). RESULTS: Median survivor follow-up was 112 months. Relative risks of disease progression and death were 0.656 (95% confidence interval, 0.472-0.912) and 0.638 (95% confidence interval, 0.449-0.908), favoring RTCH. Good response patients (345; 74%) had similar 10 year overall survival (OS) and progression-free survival (PFS) after RTH or RTCH (P > .47). Poor response patients after RTCH had superior OS (P = .046) and PFS (P = .084). Extrapelvic recurrences occurred more often in poor response patients. CONCLUSION: Posttherapy viable residual disease less than 10% was associated with reduced risk of progression and cancer-related death.
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Carcinoma/mortalidad , Carcinoma/terapia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Carcinoma/patología , Quimioterapia Adyuvante , Cisplatino/uso terapéutico , Progresión de la Enfermedad , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasia Residual , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVE: To determine if low node count from superficial groin dissection correlated with first recurrence in the groin for patients with early vulvar cancer. METHODS: The Gynecologic Oncology Group (GOG) conducted a trial for patients with early stage squamous vulvar cancer, lesions <2 cm in size and <5 mm in depth. All fatty tissue below the inguinal ligament, medial to the sartorious and lateral to the adductor longus was removed. Incision of the fascia and skeletonizing the femoral vessels were not required. For this secondary analysis, we reviewed the records of all patients to assess node counts. RESULTS: Of the 113 patients eligible for the study, 104 patients (with 117 dissected groins) did not have a first recurrence in the groin. The median number of negative nodes was 9 (range: 1-26). Nine patients (with 9 dissected groins) suffered a first recurrence in the groin. The median number of negative nodes removed per groin was 7 (range: 4-22). There were no significant differences between patients with first recurrence in the groin and those without (p value=0.7475). There was a broad overlap of the confidence intervals. CONCLUSIONS: We were unable to show that groin failure after superficial lymphadenectomy was a result of low lymph node count. The small number of recurrences made firm conclusions impossible. Variations in anatomy and other factors may make node counting an unreliable measure of surgical quality.
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Ganglios Linfáticos/patología , Recurrencia Local de Neoplasia/patología , Neoplasias de la Vulva/patología , Femenino , Humanos , Conducto Inguinal/patología , Conducto Inguinal/cirugía , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática , Persona de Mediana Edad , Factores de Riesgo , Neoplasias de la Vulva/cirugíaRESUMEN
PURPOSE: To investigate eight previously unreported Pakistani families with genetically undefined OCA for mutations in TYR. METHODS: Sanger sequencing of TYR has been performed in eight families with OCA phenotype. Mutation analysis was performed to establish the pathogenic role of novel mutation. Bioinformatics analysis was performed to predict the structural and functional impacts on protein due to the mutation. RESULTS: In this study, we identified six likely pathogenic variants of TYR (c.272 G>A, c.308 G>A, c.346C>T, c.715 C>T, c.832 C>T and c.1255 G>A), including one novel variant (c.308 G>A; p.Cys103Tyr), segregating as appropriate in each family. Cys103 lies in the highly conserved region of the tyrosinase enzyme, and p.Cys103Tyr is predicted to disturb enzymatic function via alteration of the configurational orientation of TYR leading to a more rigid polypeptide structure. We have also reviewed the mutation spectrum of TYR in Pakistani ethnicity. Published data on OCA families proposed that ~40% have been associated with genetic variations in the TYR gene. The mutations reported in this study have now been described with varying frequencies in Pakistani families, including very rare/unique mutations. CONCLUSION: A literature review of TYR gene mutations in Pakistani populations, combined with our genetic data, identified a number of gene mutations likely to represent regional ancestral founder mutations of relevance to Pakistani populations, in addition to sporadic and recurrent 'hotspot' mutations present repeatedly in other regions worldwide.
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Albinismo Oculocutáneo/genética , ADN/genética , Etnicidad , Predisposición Genética a la Enfermedad , Monofenol Monooxigenasa/genética , Mutación , Albinismo Oculocutáneo/etnología , Albinismo Oculocutáneo/metabolismo , Análisis Mutacional de ADN , Humanos , Monofenol Monooxigenasa/metabolismo , Pakistán , Linaje , FenotipoRESUMEN
PURPOSE: To determine whether maintaining HGB levels > or = 12.0 g/dL with recombinant human erythropoietin (R-HUEPO) compared to "standard" treatment (transfusion for HGB < or = 10.0 g/dL) improves progression-free survival (PFS), overall survival (OS) and local control (LC) in women receiving concurrent weekly cisplatin and radiation (CT/RT) for carcinoma of the cervix. In addition, to determine whether platinum-DNA adducts were associated with clinical characteristics or outcome. METHODS: Patients with stage IIB-IVA cervical cancer and HGB < 14.0 g/dL were randomly assigned to CT/RT+/-R-HUEPO (40,000 units s.c. weekly). R-HUEPO was stopped if HGB > 14.0 g/dL. Endpoints were PFS, OS and LC. Platinum-DNA adducts were quantified using immunocytochemistry assay in buccal cells. RESULTS: Between 08/01 and 09/03, 109 of 114 patients accrued were eligible. Fifty-two received CT/RT and 57 CT/RT+R-HUEPO. The study closed prematurely, with less than 25% of the planned accrual, due to potential concerns for thromboembolic event (TE) with R-HUEPO. Median follow-up was 37 months (range 9.8-50.4 months). PFS and OS at 3 years should be 65% and 75% for CT/RT and 58% and 61% for CT/RT+R-HUEPO, respectively. TE occurred in 4/52 receiving CT/RT and 11/57 with CT/RT+R-HUEPO, not all considered treatment related. No deaths occurred from TE. High-platinum adducts were associated with inferior PFS and LC. CONCLUSION: TE is common in cervical cancer patients receiving CT/RT. Difference in TE rate between the two treatments was not statistically significant. The impact of maintaining HGB level > 12.0 g/dL on PFS, OS and LC remains undetermined.