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PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC) but is associated with renal toxicity. Sodium thiosulfate (ST) is used for nephroprotection for HIPEC with cisplatin, but standard HIPEC practices vary. METHODS: A prospective, nonrandomized, clinical trial evaluated safety outcomes of HIPEC with cisplatin 75 mg/m2 during cytoreductive surgery (CRS) in patients with EOC (n = 34) and endometrial cancer (n = 6). Twenty-one patients received no ST (nST), and 19 received ST. Adverse events (AEs) were reported according to CTCAE v.5.0. Serum creatinine (Cr) was collected preoperatively and postoperatively (Days 5-8). Progression-free survival (PFS) was followed. Normal peritoneum was biopsied before and after HIPEC for whole transcriptomic sequencing to identify RNAseq signatures correlating with AEs. RESULTS: Forty patients had HIPEC at the time of interval or secondary CRS. Renal toxicities in the nST group were 33% any grade AE and 9% grade 3 AEs. The ST group demonstrated no renal AEs. Median postoperative Cr in the nST group was 1.1 mg/dL and 0.5 mg/dL in the ST group (p = 0.0001). Median change in Cr from preoperative to postoperative levels were + 53% (nST) compared with - 9.6% (ST) (p = 0.003). PFS did not differ between the ST and nST groups in primary or recurrent EOC patients. Renal AEs were associated with downregulation of metabolic pathways and upregulation of immune pathways. CONCLUSIONS: ST significantly reduces acute renal toxicity associated with HIPEC with cisplatin in ovarian cancer patients. As nephrotoxicity is high in HIPEC with cisplatin, nephroprotective agents should be considered.
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Antineoplásicos , Hipertermia Induzida , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/uso terapêutico , Quimioterapia Intraperitoneal Hipertérmica , Antineoplásicos/uso terapêutico , Estudos Prospectivos , Hipertermia Induzida/efeitos adversos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia CombinadaRESUMO
The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.
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Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos da radiação , Tolerância a Radiação/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Neoplasias da Mama/fisiopatologia , Células Cultivadas , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Feminino , Expressão Gênica , Humanos , Glândulas Mamárias Humanas/citologia , Glândulas Mamárias Humanas/metabolismo , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.
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Guias de Prática Clínica como Assunto/normas , Sarcoma/diagnóstico , Sarcoma/terapia , HumanosRESUMO
PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) confers a survival benefit in epithelial ovarian cancer (EOC) and in preclinical models. However, the molecular changes induced by HIPEC have not been corroborated in humans. PATIENTS AND METHODS: A feasibility trial evaluated clinical and safety outcomes of HIPEC with cisplatin during optimal cytoreductive surgery (CRS) in patients with EOC diagnosed with stage III, IV, or recurrent EOC. Pre- and post-HIPEC biopsies were comprehensively profiled with genomic and transcriptomic sequencing to identify mutational and RNAseq signatures correlating with response; the tumor microenvironment was profiled to identify potential immune biomarkers; and transcriptional signatures of tumors and normal samples before and after HIPEC were compared to investigate HIPEC-induced acute transcriptional changes. RESULTS: Thirty-five patients had HIPEC at the time of optimal CRS; all patients had optimal CRS. The median progression-free survival (PFS) was 24.7 months for primary patients and 22.4 for recurrent patients. There were no grade 4 or 5 adverse events. Anemia was the most common grade 3 adverse event (43%). Hierarchical cluster analyses identified distinct transcriptomic signatures of good versus poor responders to HIPEC correlating with a PFS of 29.9 versus 7.3 months, respectively. Among good responders, significant HIPEC-induced molecular changes included immune pathway upregulation and DNA repair pathway downregulation. Within cancer islands, % programmed cell death protein 1 expression in CD8+ T cells significantly increased after HIPEC. An exceptional responder (PFS 58 months) demonstrated the highest programmed cell death protein 1 increase. Heat shock proteins comprised the top differentially upregulated genes in HIPEC-treated tumors. CONCLUSION: Distinct transcriptomic signatures identify responders to HIPEC, and preclinical model findings are confirmed for the first time in a human cohort.
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Carcinoma Epitelial do Ovário , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Estudos de Viabilidade , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Microambiente TumoralRESUMO
This study aimed to characterize chemotherapy-induced transient increase and surge of CA 19-9 level to treatment response in patients with advanced pancreatic ductal adenocarcinoma (PDAC). A retrospective case series was performed of advanced PDAC patients treated with first-line chemotherapy at City of Hope Comprehensive Cancer Center from Jan 2017 to May 2020. CA 19-9 surge was defined as an increase of >20% from baseline followed by a >20% drop in one or more subsequent CA 19-9 levels compared to baseline. Out of 106 advanced PDAC patients, 38 were evaluable for CA 19-9 surge. Fourteen (51.9%) patients treated with FOLFIRINOX and 3 (27.3%) patients treated with nab-P + Gem chemotherapy demonstrated an early transient rise in CA 19-9 level. A CA 19-9 surge was documented in 9 (23.7%) patients, all with duration of surge lasting < 16 weeks. Five out of 9 (55.6%) patients (4: FOLFIRINOX, 1: nab-P + Gem) with CA 19-9 surge demonstrated partial objective response rate on surveillance cross-sectional imaging. One patient (FOLFIRINOX) had stable disease, and 2 patients (1: FOLFIRINOX, 1: nab-P + Gem) were found to have disease progression after treatment interruption. The initial early rise of CA 19-9 levels during chemotherapy in patients with advanced PDAC may not indicate tumor progression. Rather, it may represent a chemotherapy-induced transient increase or surge phenomenon of the tumor marker in patients responding to treatment.
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Adenocarcinoma/tratamento farmacológico , Albuminas/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno CA-19-9/sangue , Desoxicitidina/análogos & derivados , Paclitaxel/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/sangue , Idoso , Desoxicitidina/efeitos adversos , Feminino , Fluoruracila/efeitos adversos , Humanos , Irinotecano/efeitos adversos , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/efeitos adversos , Neoplasias Pancreáticas/sangue , Estudos Retrospectivos , GencitabinaRESUMO
Papillary carcinoma of the breast represents approximately 0.5% of all newly diagnosed cases of breast cancer. The prevalence of both invasive and in situ papillary carcinoma seems to be greater in older postmenopausal women and, in relative terms, in males. Histologic features of the tumor include cellular proliferations surrounding fibrovascular cores, with or without invasion. In this review, characteristics of both in situ and invasive disease are outlined. Immunohistochemical analyses of papillary carcinoma suggest the utility of markers such as smooth muscle myosin heavy chain, calponin, p63, and high molecular weight keratins, which can characterize the myoepithelial cell layer. With respect to radiographic evaluation of papillary carcinoma, ultrasonography is the most extensively studied imaging modality, though magnetic resonance mammography has potential utility. Available data suggest improved outcome for papillary carcinoma as compared to invasive ductal carcinoma. Treatment-related information for patients with papillary carcinoma is limited, and patterns noted in available series suggest a variable approach to this disease. The scarcity of information underscores the need for further treatment- and outcome-related studies in papillary carcinoma of the breast.
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Neoplasias da Mama/diagnóstico , Carcinoma Papilar/diagnóstico , Neoplasias da Mama/terapia , Carcinoma Papilar/terapia , Feminino , HumanosRESUMO
BACKGROUND: There remains a lack of consensus regarding the optimal treatment for patients with curable adenocarcinoma of the anal canal (AAC). We sought to determine the role of definitive surgical resection and radiation in a large cohort of patients with AAC. MATERIALS AND METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) registry to identify all patients with nonmetastatic AAC from 1988 to 2004 and analyzed clinical factors, treatment modalities, and overall survival in this cohort. Kaplan-Meier survival curves were constructed to compare 5-year overall survival based on treatment groups: abdominal perineal resection (APR) only, APR and external beam radiation (APR and EBR), and EBR only. We performed a Cox regression analysis to determine factors predictive of outcome. RESULTS: A total of 165 patients were identified with nonmetastatic AAC. Of these, 30 patients were treated with an APR only, 42 patients with an APR and EBR, and 93 patients with EBR only. The 5-year survival for APR only, APR and EBR, and EBR only was 58%, 50%, and 30%, respectively. The difference in survival was statistically significant (APR vs. EBR, P = .02; APR and EBR vs. EBR, P = 0.04). Multivariate analysis completed on 86 patients in this cohort confirmed that factors accounting for the survival differences included age (P = 0.004), nodal stage (P = 0.001), and treatment groups (P = 0.03). The hazard ratio between EBR only compared with APR only was 2.78. CONCLUSIONS: Definitive surgical treatment in the form of an APR with or without EBR is associated with improved survival in patients with AAC.
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Adenocarcinoma/cirurgia , Neoplasias do Ânus/cirurgia , Colectomia/métodos , Adenocarcinoma/mortalidade , Neoplasias do Ânus/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Programa de SEER , Análise de SobrevidaRESUMO
UNLABELLED: The aim of this study was to determine the presence of high-risk HPV-16 in patients with HNSCC, assess the impact of HPV status on treatment response and survival in this select cohort treated with combined modality therapy and to identify the differences in HIF-1alpha and VEGF expression in HPV-positive and -negative tumors. PATIENTS AND METHODS: Patients had resectable, untreated stage III, IV HNSCC of the oral cavity, oropharynx, hyopharynx or larynx, and stage II cancer of the base of tongue, hypopharynx and larynx. HPV status was determined by conventional PCR in fresh frozen biopsy samples and by Taqman PCR assay on formalin-fixed, paraffin-embedded specimens. HIF-1alpha and VEGF expression were assessed by quantitative real-time PCR (RT-PCR). Multivariate Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) based on HPV status. RESULTS: HPV-16 was detected in 14 of 24 evaluable cases. There were no significant differences in response rates after neoadjuvant chemotherapy (86% vs. 90%) in HPV-positive and HPV-negative patients, respectively. There was a trend toward better progression-free (HR=0.15, 95% CI=0.002-12.54; p=0.06) and overall survival (HR=0.14, 95% CI=0.001-14.12; p=0.10) for HPV-positive patients. In a subset of 13 fresh frozen samples, RT-PCR revealed a significant increase in VEGF mRNA levels in HPV-positive tumors (p<0.01). No difference was seen for HIF-1alpha expression. CONCLUSION: HPV presence portended a better prognosis in patients with oropharyngeal SCC treated with a multimodality treatment in a prospective clinical trial. The level of VEGF mRNA was up-regulated in HPV-16-positive tumors possibly through an HIF-1 independent manner.
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Carcinoma de Células Escamosas/virologia , Papillomavirus Humano 16/isolamento & purificação , Neoplasias Orofaríngeas/virologia , Sequência de Bases , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Primers do DNA , Feminino , Papillomavirus Humano 16/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/terapia , Estudos Prospectivos , Análise de SobrevidaRESUMO
Pancreatic fistula is a major cause of morbidity after distal pancreatic resection. When resections are performed with linear stapling devices, the use of bioabsorbable staple line reinforcement has been suggested to decrease the rate of pancreatic fistula. Our objective was to investigate the incidence of pancreatic fistula when using the Gore Seamguard staple line reinforcement in stapled distal pancreatic resections. A retrospective review of 30 consecutive patients with stapled distal pancreatectomy was conducted. A broad definition of pancreatic fistula was used. Clinicopathologic factors and outcomes were compared between groups. Pancreatic fistula was diagnosed in 11 of 15 patients (73%) and three of 15 patients (20%) in the Seamguard and non-Seamguard groups, respectively (P = 0.002). Pancreatic parenchymal transection at the neck of the gland was associated with pancreatic fistula, whereas laparoscopic procedures, splenic preservation, or additional organ resection were not. On multivariate analysis, the association between Seamguard use and pancreatic fistula was significant (P = 0.005). In conclusion, after introduction of the Gore Seamguard bioabsorbable staple line reinforcement, we experienced a significant increase in the rate of pancreatic fistula. This experience raises concern about the efficacy of this device in limiting pancreatic fistula after stapled distal pancreatic resection.
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Implantes Absorvíveis/efeitos adversos , Dioxanos/efeitos adversos , Pancreatectomia , Fístula Pancreática/epidemiologia , Telas Cirúrgicas/efeitos adversos , Grampeamento Cirúrgico/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Grampeamento Cirúrgico/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To evaluate intraperitoneal (IP) nab-paclitaxel in patients with advanced malignancies that are primarily confined to the peritoneal cavity in a phase I trial. METHODS: Using a 3 + 3 dose escalation of IP nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle, we evaluated six dose levels (35-175 mg/m2/dose). Maximum tolerated dose (MTD) and pharmacokinetics (PK) of IP nab-paclitaxel were determined. RESULTS: There were no dose-limiting toxicities (DLTs) in cohorts 1-3. There was a DLT in one of six patients in cohort 4 (112.5 mg/m2) (grade 3 neutropenia causing treatment delay > 15 days) and a DLT in one of three patients in cohort 6 (175 mg/m2) (grade 4 neutropenia and grade 3 abdominal pain). A second patient in cohort 6 experienced a serious adverse event (cycle 1, grade 4 ANC ≤ 7 days, cycle 4, grade 2 left ventricular dysfunction). This dose level was determined to be above the MTD. No DLTs were seen in seven patients treated in cohort 5 (140 mg/m2). The MTD of IP nab-paclitaxel was established at 140 mg/m2 on days 1, 8, and 15 of a 28-day cycle. There was a PK advantage for IP nab-paclitaxel, with an IP plasma area under the concentration-time curve (AUC) ratio of 147-fold (range 50-403) and therapeutic range systemic drug levels. Eight of 27 enrolled patients had progression-free survival ≥ 6 months. One patient experienced complete response, and one patient experienced partial response. Six patients had stable disease. CONCLUSIONS: Weekly IP nab-paclitaxel has a favorable toxicity profile, a significant pharmacologic advantage, and promising clinical activity. CLINICAL TRIAL REGISTRATION: NCT00825201.
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Albuminas/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Neutropenia/epidemiologia , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Albuminas/farmacocinética , Antineoplásicos Fitogênicos/farmacocinética , Área Sob a Curva , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Infusões Parenterais , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Neutropenia/diagnóstico , Paclitaxel/farmacocinética , Neoplasias Peritoneais/patologia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
PURPOSE: To determine the maximally tolerated dose, toxicity, and pharmacokinetics of i.p. gemcitabine. EXPERIMENTAL DESIGN: Patients had peritoneal carcinomatosis. Gemcitabine (40, 80, 120, or 160 mg/m(2)) was administered into the peritoneal cavity in 2 L of warmed saline on days 1, 4, 8, and 12 of a 28-day cycle. RESULTS: Thirty patients received 63 (median, 2; range, 0-6) courses. Tumors included ovary (14), uterus (2), colon (6), pancreas (3), and others (5). Dose-limiting toxicity included nausea, vomiting, diarrhea, dyspnea, fatal respiratory failure, and grade 3 elevation of alanine aminotransferase in three patients. Hematologic toxicity and pain were =grade 2. Three patients had decreased or resolved ascites. Of 19 patients evaluable for response, 10 had stable disease (median, 3.5 courses) and 9 had progressive disease. The median peak peritoneal concentration was 1,116-fold (range, 456-1,886) higher than the peak plasma level. Plasma and peritoneal levels were undetectable within 8 to 12 h. At 120 mg/m(2), the median peritoneal area under the concentration versus time curve (AUC) was 82,612 ng/mL x h (range, 53,296-199,830) and the plasma AUC was 231 ng/mL x h (range, 47.6-259.5). The mean peritoneal advantage (AUC(peritoneal)/AUC(plasma)) was 847 (range, 356-1,385). CONCLUSIONS: I.p. administration of gemcitabine is tolerated within the tested dosage range. Technical problems with the Porta-Cath device and i.p. therapy per se may have been exacerbated by the enrollment of many patients with a variety of advanced i.p. diseases. Given the significant increase in local dose intensity and the documented activity of this drug, this agent may be an excellent candidate for i.p. therapy in optimally debulked ovarian cancer, either alone or in combination.
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Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Desoxicitidina/análogos & derivados , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/farmacocinética , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/farmacocinética , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , GencitabinaRESUMO
PURPOSE: Enhanced recovery after surgery (ERAS) protocols for gastric cancer patients have shown improved outcomes in Asia. However, data on gastric cancer ERAS (GC-ERAS) programs in the United States are sparse. The purpose of this study was to compare perioperative outcomes before and after implementation of an GC-ERAS protocol at a National Comprehensive Cancer Center in the United States. MATERIALS AND METHODS: We reviewed medical records of patients surgically treated for gastric cancer with curative intent from January 2012 to October 2016 and compared the GC-ERAS group (November 1, 2015-October 1, 2016) with the historical control (HC) group (January 1, 2012-October 31, 2015). Propensity score matching was used to adjust for age, sex, number of comorbidities, body mass index, stage of disease, and distal versus total gastrectomy. RESULTS: Of a total of 95 identified patients, matching analysis resulted in 20 and 40 patients in the GC-ERAS and HC groups, respectively. Lower rates of nasogastric tube (35% vs. 100%, P<0.001) and intraabdominal drain placement (25% vs. 85%, P<0.001), faster advancement of diet (P<0.001), and shorter length of hospital stay (5.5 vs. 7.8 days, P=0.01) were observed in the GC-ERAS group than in the HC group. The GC-ERAS group showed a trend toward increased use of minimally invasive surgery (P=0.06). There were similar complication and 30-day readmission rates between the two groups (P=0.57 and P=0.66, respectively). CONCLUSIONS: The implementation of a GC-ERAS protocol significantly improved perioperative outcomes in a western cancer center. This finding warrants further prospective investigation.
RESUMO
BACKGROUND: Laparoscopic total mesorectal excision for rectal cancer remains a difficult procedure with high conversion rates. We have sought to improve on some of the pitfalls of laparoscopy by using the DaVinci robotic system. Here we report our two-year experience with robotic-assisted laparoscopic surgery for primary rectal cancer. METHODS: A prospectively maintained database of all rectal cancer cases starting in November 2004 was created. A series of 39 consecutive unselected patients with primary rectal cancer was analyzed. Clinical and pathologic outcomes were reviewed retrospectively. RESULTS: 22 patients had low anterior, 11 intersphincteric and six abdominoperineal resections. Postoperative mortality and morbidity were % and 12.8%, respectively. The median operative time was 285 minutes (range 180-540 mins). The conversion rate was 2.6%. A total mesorectal excision with negative circumferential and distal margins was accomplished in all patients, and a median of 13 (range 7-28) lymph nodes was removed. The anastomotic leak rate was 12.1%. The median hospital stay was 4 days. There have been no local recurrences at a median follow-up of 13 months. CONCLUSIONS: Robotic-assisted surgery for rectal cancer can be carried out safely and according to oncological principles. This approach shows promising short-term outcomes and may facilitate the adoption of minimally invasive rectal surgery.
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Procedimentos Cirúrgicos do Sistema Digestório , Laparoscopia , Neoplasias Retais/cirurgia , Robótica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
Laparoscopic colectomy is a difficult procedure with a long learning curve. We describe in this study our technique for right- and left-sided laparoscopic medial-to-lateral colectomy. The medial approach involves division of the vascular pedicle first, followed by mobilization of the mesentery toward the abdominal wall, and finally freeing of the colon along the white line of Toldt. This approach allows immediate identification of the plane between the mesocolon and the retroperitoneum and renders the dissection fast and safe. Our series of 50 consecutive laparoscopic colectomies supports this concept. We believe that surgeons familiar with this technique will have an important tool in their armamentarium to circumvent some of the challenges of laparoscopic colectomy.
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Colectomia/métodos , Colo/irrigação sanguínea , Feminino , Humanos , Laparoscopia , MasculinoRESUMO
PURPOSE: The purpose of this Phase I study was to determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of i.p. docetaxel and to determine the peritoneal pharmacokinetics and pharmacological advantage of this agent. EXPERIMENTAL DESIGN: Twenty-one patients with peritoneal carcinomatosis received docetaxel administered via an implanted i.p. catheter at doses of 40, 80, 100, 125, or 156 mg/m2 every 3 weeks. DLTs on course 1 were used to define the maximum tolerated dose. RESULTS: Tumor types included gastric adenocarcinoma (n=7), ovarian cancer (n=4), other gastrointestinal primaries (n=3), and other cancers (n=7). Sixty cycles of i.p. docetaxel (median, 2; range, 1-11) were delivered. DLTs occurred in two patients at the 156 mg/m2 dose level; both developed an ileus, and one patient died of neutropenic sepsis. One of five evaluable patients treated with 125 mg/m2 docetaxel i.p. developed grade 4 neutropenic sepsis and stomatitis; another patient developed renal failure attributable to glomerulonephritis and grade 3 thrombocytopenia that was not judged to be dose-limiting. One of six patients receiving 100 mg/m2 D, the recommended Phase II dose, developed grade 4 neutropenia lasting <5 days. Other non-DLT treatment-related toxicities included dehydration requiring i.v. fluids, emesis, stomatitis, constipation, and abdominal pain. Best response on protocol therapy included 7 of 18 patients with stable disease for a median of 5 cycles (range, 2-11); 11 patients progressed by the first evaluation after a median of 2 cycles (range, 1-3). There were three patients inevaluable for response who received only one cycle of i.p. docetaxel (two because of patient preference and one because of adhesion formation). Pharmacokinetic evaluation revealed mean plasma areas under the curves (AUC) at 100 and 125 mg/m2 i.p. docetaxel of 3.14 and 6.33 microM.h (ranges, 1.02-5.88 and 3.97-12.70 microM. h), respectively; the mean peritoneal AUCs were 315 and 1063 microM.h (ranges, 250-373 and 239-2222 microM.h), respectively. The mean peak plasma concentrations at 100 and 125 mg/m2 i.p. docetaxel were 0.46 and 0.66 microM, and the mean peak peritoneal concentrations at those doses were 59 and 81 microM, respectively. The median and mean pharmacological advantage calculations (AUCperitoneal/AUCplasma) across all dose levels were 152 and 181, respectively (range, 18.8-367.4). The mean peritoneal 24- and 96-h concentrations were 0.9 microM (range, 0.2-1.6 microM) and <0.1 nM, respectively. The mean time that the concentration was >0.1 microM was 31.2 h (range, 27-36.5 h). CONCLUSIONS: i.p. docetaxel can be safely delivered at a dose of 100 mg/m2 i.p. every 3 weeks. This route of administration provides a significant peritoneal pharmacological advantage while delivering systemic concentrations consistent with the administration of standard i.v. doses.
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Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/toxicidade , Neoplasias Peritoneais/tratamento farmacológico , Taxoides/farmacocinética , Taxoides/toxicidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Docetaxel , Feminino , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Humanos , Infusões Parenterais , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Treatment summary and survivorship care plan studies are at the forefront of research priorities with precedence for ethnic minority inclusion. This preliminary study joined the advocacy, scientific, and medical communities to inform the development and evaluation of the Treatment Summary and Survivorship Care Plan (TSSCP-S) template targeted for Latino breast cancer patients (LCA). METHODS: The development of the TSSCP-S began as modifications to the American Society of Cancer Oncology (ASCO) (TSSCP-ASCO) template via a transcreation process informed by 12 LCA survivors/advocates, and evaluated by 10 survivor/advocates and health professionals. The TSSCP-S template development was guided by the Shared Care, Psychooncology Models, and Contextual Model of Health Related Quality of Life. RESULTS: The bilingual TSSCP-S was independently evaluated by bilingual, survivor/advocates, and health professionals (n = 10). Preliminary analyses indicate that the TSSCP-S template was rated more favorably than the TSSCP-ASCO on the following domains: content (p = 0.02), clarity (p = 0.02), utility (p = 0.04), cultural and linguistic responsiveness (p = 0.03), and socioecological responsiveness (p = 0.01). Evaluators noted that the TSSCP-S template was more patient-centered, and endorsed the acceptability as well as the potential utility and applicability of the bilingual TSSCP-S template to appropriately guide surveillance and follow-up care. CONCLUSIONS: Our findings indicate that the TSSCP-S achieved clinical, cultural, and linguistic responsiveness relevant to Latinos. Patient-centered TSSCP that are presented in a bilingual format are necessary to achieve the intended goals of TSSCP including appropriate patient information, education, and resources pertaining to their treatment, potential side effects, and recommended surveillance and follow-up care for English language limited patients. Additionally, our culturally responsive TSSCP-S development framework offers a model for TSSCP template development for targeted and underserved populations, including ethnic and linguistic minority cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: These data support the development and evaluation of a TSSCP targeted to an underserved, high-risk population, LCAs. Identifying methods to improve surveillance and follow-up guideline adherence may lead to improved clinical cancer outcomes and quality of life.
Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Hispânico ou Latino/etnologia , Multilinguismo , Feminino , Humanos , Idioma , Qualidade de Vida , Taxa de SobrevidaRESUMO
A patient/family-centered conference was conducted at an underserved community hospital to address Latinas' post-genetic cancer risk assessment (GCRA) medical information and psychosocial support needs, and determine the utility of the action research format. Latinas seen for GCRA were recruited to a half-day conference conducted in Spanish. Content was partly determined from follow-up survey feedback. Written surveys, interactive discussions, and Audience Response System (ARS) queries facilitated the participant-healthcare professional action research process. Analyses included descriptive statistics and thematic analysis. The 71 attendees (41 patients and 27 relatives/friends) were primarily non-US born Spanish-speaking females, mean age 43 years. Among patients, 73 % had a breast cancer history; 85 % had BRCA testing (49 % BRCA+). Nearly all (96 %) attendees completed the conference surveys and ARS queries; ≥48 % participated in interactive discussions. Most (95 %) agreed that the format met their personal interests and expectations and provided useful information and resources. Gaps/challenges identified in the GCRA process included pre-consult anxiety, uncertainty about reason for referral and expected outcomes, and psychosocial needs post-GCRA, such as absorbing and disseminating risk information to relatives and concurrently coping with a recent cancer diagnosis. The combined action research and educational conference format was innovative and effective for responding to continued patient information needs and addressing an important data gap about support needs of Latina patients and family members following genetic cancer risk assessment. Findings informed GCRA process improvements and provide a basis for theory-driven cancer control research.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Hispânico ou Latino/genética , Adolescente , Adulto , Idoso , Família , Feminino , Acessibilidade aos Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde , Pesquisa sobre Serviços de Saúde , Hispânico ou Latino/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Medição de Risco , Populações Vulneráveis , Adulto JovemAssuntos
Neoplasias da Mama/genética , Aconselhamento Genético , Cobertura do Seguro , Biópsia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Custos e Análise de Custo , Tomada de Decisões , Feminino , Aconselhamento Genético/economia , Humanos , Mastectomia , Planejamento de Assistência ao Paciente , Medição de Risco , Fatores de TempoRESUMO
The appropriate selection criteria for complete cytoreduction in patients with peritoneal surface malignancies have not been determined. We performed a retrospective analysis of all patients receiving cytoreductive surgery (CRS) during the study period of 2004 to 2008 to determine appropriate selection criteria for successful complete cytoreduction. During the study period, 38 patients underwent attempted CRS. Cytoreduction was scored complete, incomplete, or not reported in 53 per cent (n = 20), 37 per cent (n = 14), and 11 per cent (n = 4), respectively. Median overall survival for compete and incomplete cytoreduction was 56 months versus 5 months (P = 0.011), respectively. Compared with incomplete cytoreduction, patients receiving complete cytoreduction were more likely to have a lower Peritoneal Cancer Index (PCI) and not have received preoperative systemic chemotherapy (CT). Univariate analysis verified PCI greater than 20 (hazard ratio [HR], 0.048; CI, 0.004 to 0.515; P = 0.01) and CT (HR, 0.17; 0.004 to 0.77; P = 0.021) as predictors of incomplete cytoreduction. Small bowel (100%), periportal region (33%), and mesentery (27%) were the most common sites of residual disease. In conclusion, PCI less than 20 and the need for preoperative chemotherapy should be strongly considered when selecting patients with peritoneal surface malignancy for attempted cytoreduction. Early evaluation of the small bowel, mesentery, and periportal region for resectability prevents unnecessary surgery.
Assuntos
Seleção de Pacientes , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , California , Quimioterapia Adjuvante , Feminino , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Several publications reporting on health disparities document that ethnic minorities disproportionately experience delays in healthcare access, delivery, and treatment. However, few studies examine factors underlying access and receipt of healthcare among cancer survivors from the patient perspective. This study explores diagnostic and therapeutic care delays among a multiethnic sample of breast and cervical cancer survivors and examines contextual factors influencing diagnostic and therapeutic care delays. METHODS: Population-based sampling and a cross-sectional design were used to recruit 1377 survivors (breast cancer, n = 698; cervical cancer, n = 679). This multiethnic sample included 449 European American, 185 African American, 468 Latina American, and 275 Asian American survivors. RESULTS: Latina Americans were more likely to report diagnostic delays (P = .003), whereas African Americans were more likely to report therapeutic delays (P = .007). In terms of cancer type, cervical cancer survivors were more likely to report diagnostic (P = .004) and therapeutic delays (P = .000) compared with breast cancer survivors. "Fear of finding cancer" was the most frequently cited reason for diagnostic delays, and "medical reasons" were most frequently cited for therapeutic delays. CONCLUSIONS: Due in part to a higher proportion of diagnostic and therapeutic delays, ethnic minorities endure greater cancer burden, including poorer survival and survivorship outcomes. The medical community must recognize the impact of existing psychological and cultural dimensions on diagnostic care, as well as the personal and healthcare system level barriers that contribute to therapeutic delays.