RESUMO
BACKGROUND: Sacituzumab govitecan (SG), a novel antibody-drug conjugate (ADC) targeting TROP2, is approved for pre-treated metastatic triple-negative breast cancer (mTNBC). We conducted an investigator-initiated clinical trial evaluating neoadjuvant (NA) SG (NCT04230109), and report primary results. PATIENTS AND METHODS: Participants with early-stage TNBC received NA SG for four cycles. The primary objective was to assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) to SG. Secondary objectives included overall response rate (ORR), safety, event-free survival (EFS), and predictive biomarkers. A response-guided approach was utilized, and subsequent systemic therapy decisions were at the discretion of the treating physician. RESULTS: From July 2020 to August 2021, 50 participants were enrolled (median age = 48.5 years; 13 clinical stage I disease, 26 stage II, 11 stage III). Forty-nine (98%) completed four cycles of SG. Overall, the pCR rate with SG alone was 30% [n = 15, 95% confidence interval (CI) 18% to 45%]. The ORR per RECIST V1.1 after SG alone was 64% (n = 32/50, 95% CI 77% to 98%). Higher Ki-67 and tumor-infiltrating lymphocytes (TILs) were predictive of pCR to SG (P = 0.007 for Ki-67 and 0.002 for TILs), while baseline TROP2 expression was not (P = 0.440). Common adverse events were nausea (82%), fatigue (76%), alopecia (76%), neutropenia (44%), and rash (48%). With a median follow-up time of 18.9 months (95% CI 16.3-21.9 months), the 2-year EFS for all participants was 95%. Among participants with a pCR with SG (n = 15), the 2-year EFS was 100%. CONCLUSIONS: In the first NA trial with an ADC in localized TNBC, SG demonstrated single-agent efficacy and feasibility of response-guided escalation/de-escalation. Further research on optimal duration of SG as well as NA combination strategies, including immunotherapy, are needed.
Assuntos
Anticorpos Monoclonais Humanizados , Camptotecina/análogos & derivados , Imunoconjugados , Neoplasias de Mama Triplo Negativas , Humanos , Pessoa de Meia-Idade , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Terapia Neoadjuvante , Antígeno Ki-67 , Antígenos de Neoplasias/genética , Imunoconjugados/efeitos adversosRESUMO
BACKGROUND: The phase III MONALEESA trials tested the efficacy and safety of the cyclin-dependent kinase (CDK)4/6 inhibitor ribociclib with different endocrine therapy partners as first- or second-line treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). Using the largest pooled biomarker dataset of the CDK4/6 inhibitor ribociclib in ABC to date, we identified potential biomarkers of response to ribociclib. PATIENTS AND METHODS: Baseline circulating tumour DNA from patients in the MONALEESA trials was assessed using next-generation sequencing. An analysis of correlation between gene alteration status and progression-free survival (PFS) was carried out to identify potential biomarkers of response to ribociclib. RESULTS: Multiple frequently altered genes were identified. Alterations in ERBB2, FAT3, FRS2, MDM2, SFRP1, and ZNF217 were associated with a greater PFS benefit with ribociclib versus placebo. Patients with high tumour mutational burden (TMB) and with ANO1, CDKN2A/2B/2C, and RB1 alterations exhibited decreased sensitivity to ribociclib versus placebo. CONCLUSIONS: Although exploratory, these results provide insight into alterations associated with the improved response to ribociclib treatment and may inform treatment sequencing in patients with actionable alterations following progression on CDK4/6 inhibitors. Validation of potential biomarkers identified here and development of prospective trials testing their clinical utility are warranted. GOV IDENTIFIERS: NCT01958021, NCT02422615, NCT02278120.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Letrozol , Estudos Prospectivos , Aminopiridinas/uso terapêutico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a targetable subset of breast tumors, based on the evidence from clinical trials of novel anti-HER2 antibody-drug conjugates. This evolution has raised several biological and clinical questions, warranting the establishment of consensus to optimally treat patients with HER2-low breast tumors. Between 2022 and 2023, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process focused on HER2-low breast cancer. The consensus included a multidisciplinary panel of 32 leading experts in the management of breast cancer from nine different countries. The aim of the consensus was to develop statements on topics that are not covered in detail in the current ESMO Clinical Practice Guideline. The main topics identified for discussion were (i) biology of HER2-low breast cancer; (ii) pathologic diagnosis of HER2-low breast cancer; (iii) clinical management of HER2-low metastatic breast cancer; and (iv) clinical trial design for HER2-low breast cancer. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. A review of the relevant scientific literature was conducted in advance. Consensus statements were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This article presents the developed statements, including findings from the expert panel discussions, expert opinion, and a summary of evidence supporting each statement.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Consenso , OncologiaRESUMO
BACKGROUND: The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician's choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes. PATIENTS AND METHODS: Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline. RESULTS: Of 468 assessable patients, 290 had Trop-2 expression data [64% (n = 151 SG) versus 60% (n = 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n = 149 SG) versus 61% (n = 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations. CONCLUSIONS: SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup.
Assuntos
Imunoconjugados , Neoplasias de Mama Triplo Negativas , Anticorpos Monoclonais Humanizados , Biomarcadores , Camptotecina/análogos & derivados , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genéticaRESUMO
BACKGROUND: Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously. PATIENTS AND METHODS: Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer. RESULTS: In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). CONCLUSIONS: SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.
Assuntos
Imunoconjugados , Neoplasias Pulmonares , Anticorpos Monoclonais Humanizados , Camptotecina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Trophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor-positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy®) is an antibody-drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 at a high drug-to-antibody ratio via a unique hydrolyzable linker that delivers SN-38 intracellularly and in the tumor microenvironment. SG was granted accelerated FDA approval for metastatic triple-negative BC treatment in April 2020. PATIENTS AND METHODS: We analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2-) HR+/HER2- mBC from the phase I/II, single-arm trial (NCT01631552), who received intravenous SG (10 mg/kg) and whose disease progressed on endocrine-based therapy and at least one prior chemotherapy for mBC. End points included objective response rate (ORR; RECIST version 1.1) assessed locally, duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Fifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (33-79) years and all received at least two prior lines of therapy for mBC. At data cut-off (1 March 2019), 12 patients were still alive. Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%). Two patients discontinued treatment due to treatment-related adverse events. No treatment-related deaths occurred. At a median follow-up of 11.5 months, the ORR was 31.5% [95% confidence interval (CI), 19.5%-45.6%; 17 partial responses]; median DOR was 8.7 months (95% CI 3.7-12.7), median PFS was 5.5 months (95% CI 3.6-7.6), and median OS was 12 months (95% CI 9.0-18.2). CONCLUSIONS: SG shows encouraging activity in patients with pretreated HR+/HER2- mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339). TRIAL REGISTRATION: ClinicalTrials.gov NCT01631552; https://clinicaltrials.gov/ct2/show/NCT01631552.
Assuntos
Neoplasias da Mama , Imunoconjugados , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Camptotecina/análogos & derivados , Feminino , Hormônios , Humanos , Receptor ErbB-2 , Microambiente TumoralRESUMO
Background: While deregulation of the cyclin D1-CDK4/6-retinoblastoma pathway is common in hormone receptor positive (HR+) breast cancer, Rb is usually intact in HR+ breast cancer, and targeted CDK 4/6 inhibitors that act upstream of Rb, are routinely being utilized in clinical practice. However, factors that can lead to clinical resistance to CDK 4/6 inhibitors are not known. Patients and methods: We identified patients who had pre- and post-genotyping in tissue and peripheral blood samples after receiving CDK 4/6 inhibitors. Genotyping was carried out in tumor tissue or blood collected before start of CDK 4/6 inhibitor and after disease progression on CDK 4/6 inhibitor, covering more than 90% of the coding region in RB1. Results: We identified detectable acquired RB1 mutations in circulating tumor DNA (ctDNA) after exposure to CDK4/6 inhibitor (palbociclib, palbociclib, ribociclib) for 5, 8, and 13 months, respectively, in three patients. The RB1 mutations included substitution in donor splicing site of exon 8 of the RB1 gene in patient #1; substitution in donor splicing site of exon 22 of RB1 gene, exon 19 deletion, exon 3 insertion in patient #2; and RB1 exon 16 H483Y mutation in patient #3. None of these RB1 mutations were present in the pre-CDK 4/6 specimen highlighting these molecular alterations, which lead to functional loss of Rb1, likely emerged under selective pressure from the CDK4/6 inhibitor potentially confering therapeutic resistance. Conclusion: This is the first clinical report to describe the emergence of somatic RB1 mutations after exposure to palbociclib or ribociclib, in patients with metastatic breast cancer. Further research is needed to validate these findings, identify how these mutations temporally emerge under selective pressure of CDK 4/6 inhibitor, and develop rational therapeutic strategies.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Ligação a Retinoblastoma/efeitos dos fármacos , Proteínas de Ligação a Retinoblastoma/genética , Ubiquitina-Proteína Ligases/efeitos dos fármacos , Ubiquitina-Proteína Ligases/genética , Idoso , Aminopiridinas/uso terapêutico , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Purinas/uso terapêutico , Piridinas/uso terapêuticoRESUMO
OBJECTIVES: Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). This study assessed the biological activity of ribociclib (LEE011; CDK4/6 inhibitor) plus letrozole compared with single-agent letrozole in the presurgical setting. MATERIALS AND METHODS: Postmenopausal women (N = 14) with resectable, HR+, human epidermal growth factor receptor 2-negative (HER2-) early BC were randomized 1:1:1 to receive 2.5 mg/day letrozole alone (Arm 1), or with 400 or 600 mg/day ribociclib (Arm 2 or 3). Circulating tumor DNA and tumor biopsies were collected at baseline and, following 14 days of treatment, prior to or during surgery. The primary objective was to assess antiproliferative response per Ki67 levels in Arms 2 and 3 compared with Arm 1. Additional assessments included safety, pharmacokinetics, and genetic profiling. RESULTS: Mean decreases in the Ki67-positive cell fraction from baseline were: Arm 1 69% (range 38-100%; n = 2), Arm 2 96% (range 78-100%; n = 6), Arm 3 92% (range 75-100%; n = 3). Decreased phosphorylated Rb levels and CDK4, CDK6, CCND2, CCND3, and CCNE1 gene expression were observed following ribociclib treatment. Ribociclib and letrozole pharmacokinetic parameters were consistent with single-agent data. The ribociclib plus letrozole combination was well tolerated, with no Grade 3/4 adverse events over the treatment. CONCLUSION: The results suggest absence of a drug-drug interaction between ribociclib and letrozole and indicate ribociclib plus letrozole may reduce Ki67 expression in HR+, HER2- BC (NCT01919229).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , DNA de Neoplasias/sangue , Expressão Gênica/efeitos dos fármacos , Antígeno Ki-67/análise , Idoso , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Aminopiridinas/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias da Mama/química , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Ciclina D2/genética , Ciclina D3/genética , Ciclina E/genética , Quinase 4 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/genética , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Terapia Neoadjuvante , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Nitrilas/farmacocinética , Proteínas Oncogênicas/genética , Purinas/administração & dosagem , Purinas/efeitos adversos , Purinas/farmacocinética , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Proteína do Retinoblastoma/genética , Transdução de Sinais/genética , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Triazóis/farmacocinéticaRESUMO
The high prevalence of end-stage kidney diseases demands new treatment strategies. Decellularization approach may provide a viable option grow organs using a regenerative medicine approach. Goat kidney was decellularized by perfusion decellularization using detergents to produce an cellular construct for kidney scaffold. After pre-treatment with anticoagulant, the decellularized scaffold was analyzed for its intact three-dimensional natural architecture and vasculature. Perfusion of decellularized kidney preserved the structure and composition of renal extra-cellular matrix and vascular structures within the scaffold. No evidence of residual cellular components was found. This approach provides a model for understanding of whole organ regeneration.
RESUMO
BACKGROUND: Preclinical drug screens identified disulfiram as a potent in vitro inhibitor of prostate cancer (PCa) cell growth. Although many mechanisms for its anticancer activity have been proposed, tumor suppressor gene re-expression through promoter demethylation emerged as one of the more plausible. METHODS: We conducted an open-label, dose escalation trial of disulfiram in men with non-metastatic recurrent PCa after local therapy. Dose escalation occurred if a demethylating 'response' (that is, î¶10% decrease in peripheral blood mononuclear cell (PBMC) global 5-methyl cytosine (5(me)C) content) was observed in <3 patients in cohort 1. Cohorts 1 and 2 received disulfiram 250 mg and 500 mg daily, respectively. The primary end point was the proportion of subjects with a demethylation response. Secondary end points included the rate of PSA progression at 6 months, changes in PSA doubling time and safety/tolerability. RESULTS: Changes in global 5(me)C content were observed in two of nine patients (22.2%) in cohort 1 and 3 of 10 (30.0%) in cohort 2. Only five subjects were on trial for î¶6 months, all were in cohort 1 and all had PSA progression by 6 months. No changes in PSA kinetics were observed in either cohort. Disulfiram was poorly tolerated with six patients experiencing grade 3 adverse events (three per cohort). Three of the responders displayed pretreatment instability in their 5(me)C content. CONCLUSIONS: A minority of patients had transient global PBMC demethylation changes. Instability in 5(me)C may limit the reproducibility of these findings, limiting our ability to confirm our hypothesis. Given the toxicities and no clinical benefits, further development of disulfiram should not be pursued in this population.
Assuntos
Antineoplásicos/farmacocinética , Dissulfiram/farmacocinética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Idoso , Antineoplásicos/efeitos adversos , Ceruloplasmina/metabolismo , Metilação de DNA/efeitos dos fármacos , Dissulfiram/efeitos adversos , Epigênese Genética/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/genéticaRESUMO
OBJECTIVE: Metastatic involvement of inguinal lymph nodes (ILN) from rectal adenocarcinoma is unusual, particularly without signs of distant spread to other organ sites. By current convention, ILN involvement, including solitary involvement, is classified as metastatic disease (M). However, anecdotal reports suggest that such patients are a distinct entity and should be managed differently. The aim of this study was to gain further insight regarding this seemingly distinct patient subset. METHOD: This case series provides a descriptive report of patients with rectal adenocarcinoma and solitary inguinal lymph node metastasis (SILNM). RESULTS: Upon retrospective review of medical records from 4480 patients with rectal adenocarcinoma seen at Mayo Clinic Rochester from 1995 to 2004, six patients (0.13%) with SILNM were identified. Three had metachronous and three had synchronous SILNM (four left sided, one right sided, and one bilateral). The mean age at SILNM diagnosis was 61.3 years, and three patients had originally stage II (and three had stage III disease). Five patients received concurrent chemo-radiation therapy and one declined treatment. Among those with metachronous SILNM, the mean survival after diagnosis of rectal cancer was 42 months. By comparison, all three patients with synchronous SILNM were still alive after a mean duration of 40 months of follow up. CONCLUSION: Solitary involvement of ILNs might represent a distinct subset of patients with metastatic rectal adenocarcinoma who have a more favourable prognosis. If confirmed by larger studies, our data suggest that alternate management algorithms might be reasonable for such patients.
Assuntos
Adenocarcinoma/secundário , Canal Inguinal/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Retais/patologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
Lip reconstruction remains challenging. Accurate analysis of the defect and a thorough understanding of the anatomy and options for reconstruction will maintain the functional and aesthetic quality of this sensitive area.
Assuntos
Doenças Labiais/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Humanos , Técnicas de SuturaRESUMO
Intestinal obstruction from gallstones is a rare complication of gallstone disease. These ectopic gallstones can cause obstruction anywhere from the duodenum to the colon and are accompanied by a cholecystoduodenal/enteric/colic fistula. We report an 81-year-old male who presented with gallstone obstruction of the duodenum who underwent attempted endoscopic fragmentation and extraction that eventually led to small bowel obstruction from an impacted fragment of the stone. He underwent successful enterolithotomy and has been asymptomatic from the cholecystoduodenal fistula. Surgery is the gold standard for the treatment of this condition but the extent of the operation remains a matter of debate.
Assuntos
Obstrução Duodenal/etiologia , Endoscopia Gastrointestinal , Cálculos Biliares/complicações , Íleus/etiologia , Idoso de 80 Anos ou mais , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/cirurgia , Obstrução da Saída Gástrica/etiologia , Humanos , Masculino , Síndrome , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Stauffer syndrome, a very rare paraneoplastic syndrome, refers to reversible intrahepatic cholestasis in the setting of an abdominal malignancy. CASE: A 60-year-old female with a past medical history of uterine leiomyosarcoma status post radical hysterectomy, presented three months later with right upper quadrant abdominal pain. Laboratory evaluation revealed intrabdominal cholestasis and ultrasound of the abdomen showed an echogenic solid mass consistent with a metastatic leiomyosarcoma, and it was felt that her hyperbilirubinemia was due to Stauffer syndrome. However, three days later, blood culture grew gram negative bacilli, and CT scan of the abdomen revealed multiple mesenteric masses with air bubbles consistent with an abdominal abscess. The abscess was drained under CT-scan guidance and her cholestasis gradually came back to nearly normal. CONCLUSION: The case highlights the importance of considering infectious etiologies and Stauffer syndrome in the differential diagnosis of liver dysfunction in patients with intraabdominal malignancies.
Assuntos
Abscesso Abdominal/diagnóstico por imagem , Abscesso Abdominal/etiologia , Leiomiossarcoma/complicações , Neoplasias Uterinas/complicações , Dor Abdominal/etiologia , Colestase Intra-Hepática/diagnóstico por imagem , Colestase Intra-Hepática/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome , UltrassonografiaRESUMO
BACKGROUND: A declining sex ratio at birth has been documented during censuses in India. The decline is especially more in the northern states of Haryana and Punjab. We attempted to assess the role of society (preference for a male child, awareness and acceptability of the practice of sex determination), technology (availability and affordability) and government regulation in the adverse ratio for girls in the Ballabgarh block of Haryana in northern India. METHODS: The population (about 80 000) in the Ballabgarh block has been under constant demographic surveillance for the past 30 years and the data are stored electronically. This was used to determine the sex ratio at birth in the area since 1990. The data on availability of ultrasound machines was collected from the district authorities, as registration of these machines was made mandatory under the Prenatal Diagnostic Techniques Act, 1994. We interviewed 160 mothers and grandmothers to determine the awareness and acceptability of sex determination methods and practices. RESULTS: The demographic data for the past 10 years showed a declining sex ratio-from 881 in 1990-91 to 833 in 2000-01. The data support the view that in the initial part of this period, ultrasound was used for sex determination of all-order births but subsequently was used more in higher-order births. Our interviews with the mothers and grandmothers of the area showed that the practice of sex determination is prevalent and the attitude of the society is ambivalent. The increased availability of ultrasound machines in the area in the past 10 years corresponded to the decline in sex ratio. When the government made the practice illegal, the sex ratio improved only to fall again as the law was not implemented. Later years saw a more stringent implementation of the law and the sex ratio improved again. CONCLUSION: There is a 'demand' for sex determination technology and, therefore, this would continue to be 'supplied'. At most the 'supply' can be regulated. Social engineering efforts need to be targeted at reducing the demand if the sex ratio is to be improved.
Assuntos
Tecnologia Biomédica/legislação & jurisprudência , Regulamentação Governamental , Política Pública , Razão de Masculinidade , Aborto Eugênico/legislação & jurisprudência , Censos , Feminino , Humanos , Índia , Entrevistas como Assunto , Masculino , Análise para Determinação do Sexo/estatística & dados numéricosRESUMO
Se determinaron los títulos de Ca-125 en 27 pacientes normales, 11 pacientes con patología ginecológica benigna y 13 pacientes con cáncer ovárico en diferentes períodos de la evolución de su enfermedad. El análisis de los datos se hizo restrospectivamente. Considerando como normal un título de 65 U/ml, no hubo falsos positivos. Las pacientes con patologías ginecológicas benignas se comportan como las normales cuyos títulos no difieren de aquellas significativamente. Los títulos mayores a 65 U/ml correspondieron siempre a pacientes con cáncer ovárico. Hubo cuatro pacientes con título negativo y enfermedad reconocible clínica o quirúrgicamente. Los títulos positivos se correlacionaron con el tipo histológico y con el estadio quirúrgico de la enfermedad. En las pacientes con títulos seriados, la disminución del volumen tumoral se correlacionó con una disminución en los títulos. Estos datos surgieron que el Ca-125 se comporta en nuestra experiencia como en otras publicadas. Es de utilidad en el seguimiento, manejo y pronóstico de las pacientes con títulos positivos. Su negativización no garantiza curación y los títulos positivos aseguran la presencia de enfermedad. Tiene poco valor como método diagnóstico por su baja sensibilidad