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2.
Int J Surg Case Rep ; 63: 48-52, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31563663

RESUMO

INTRODUCTION: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-established procedure commonly employed in the management of peritoneal carcinomatosis (PC) from tumors of various specific origins. However, it is not traditionally used in the management of PC of pancreatic origin due to various reasons, including the aggressive nature of pancreatic tumors. CASE PRESENTATION: A 67-year-old female presented with a large amount of intractable malignant ascites. Computed tomography (CT) imaging showed a nodule in the right paracolic gutter. A diagnostic laparoscopy and omental biopsy showed a well-differentiated adenocarcinoma of pancreatic origin. She was initially not considered suitable for CRS and HIPEC due to apparent liver metastases on CT imaging and was arranged to undergo palliative chemotherapy; however, due to her large amount of refractory ascites and a suspected ruptured right krukenberg tumor, surgical intervention was offered. We performed CRS, bilateral salpingo-oophorectomy, and an omentectomy with a CC (completeness of cytoreduction) score of 1. HIPEC with mitomycin C was also administered. Notably, our patient remains clinically well at 48-months post CRS and HIPEC, with no signs or symptoms suggestive of tumor recurrence. CONCLUSION: Despite the current lack of evidence supporting the use of CRS and HIPEC in the curation of PC of pancreatic origin, this case report highlights the importance of patient selection in determining suitability for CRS. In the presence of positive prognostic factors and favorable tumor histology, CRS and HIPEC is a potential curative procedure that could be offered to highly selected patients presenting with PC from a primary pancreatic malignancy.

3.
Eur J Surg Oncol ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31444027

RESUMO

BACKGROUND: Most studies on the effects of intraoperative packed red blood cell transfusions (iPRBT) on patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown deleterious outcomes. It is unclear if this is a result of the transfusion itself or because iPRBTs serve as a surrogate of more advanced disease. METHODS: A retrospective analysis of 880 patients treated from 1996 to 2017. The effect of any exposure to iPRBT as well as the effect of peritoneal cancer index (PCI)-normalised iPRBT rates (ratio of iPRBT/PCI) on patients short- and long-term outcomes (recurrence-free (RFS) and overall survival (OS)) were assessed. Equally, the prognostic effect of postoperative PRBTs was analysed and adjusted for. RESULTS: Of the 880 patients included, only 26.4% had no iPRBT whereas 59.2% of patients had no postoperative PRBT. Patients with no iPRBTs had significantly lower PCIs, less high-grade complications, shorter ICU and hospital length of stay, as well as improved RFS and OS. Furthermore, high PCI-normalised iPRBTs resulted in worse perioperative and long-term outcomes, with a median OS of 41 months vs. 103 months (5-year survival rate 36.6% vs. 66.1%; p < 0.001) and median RFS of 13 months vs. 30 months (5-year RFS rate 18.3% vs. 37.6% p < 0.001) compared to those with a low iPRBT/PCI ratio. This independent effect was confirmed upon multivariable Cox regression analysis which corrected for important confounders including complexity of procedures and postoperative PRBTs (adjusted HR [aHR]2.04, 95%CI 1.36-3.04, p = 0.001 for OS; aHR 1.38, 95%CI 1.06-1.81, p = 0.017 for RFS). However, subgroup analysis (stratified by histopathologic disease entities) revealed that this independent prognostic effect was seen in high-grade mucinous appendiceal neoplasms, whereas PCI-normalised IPRBTs were not significantly prognostic in other histopathologic subgroups. CONCLUSION: iPRBTs significantly and independently impact perioperative and long-term outcomes of patients undergoing CRS/HIPEC. However, this effect mainly seems to occur in patients with high-grade mucinous neoplasms, whereas it may only be of borderline prognostic significance in other patient groups. The development of blood-sparing protocols may help improve outcomes of patients undergoing this complex oncologic procedure.

4.
Am J Surg ; 2019 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-31255258

RESUMO

OBJECTIVES: To assess the impact of short and long term outcomes of diaphragm resection and repair in cyto-reductive surgery (CRS) and intra-peritoneal chemotherapy (IPC). METHODS: 1230 consecutive CRS/IPC procedures were performed between 1996 and 2018 in Sydney, Australia. Among these, 652 underwent diaphragmatic intervention. The analysis was preformed according to histological subtype. First diaphragm interventions were compared to non-diaphragmatic CRS. Secondly, diaphragm resection was compared to diaphragm stripping. Overall survival and recurrence free survival was assessed based on histological diagnosis. RESULTS: There were no differences between the resection and stripping groups for the colorectal cohort. For mesothelioma, increased incidences of pleural effusions in the resection group were noted (63% vs.28%, p = 0.017). In HAMNs, the resection group was associated with increased reoperations (42% vs. 15%, p = 0.03) and in hospital death (16.7% vs. 0.6%, p = 0.012). Resection in LAMNs were linked with increased transfusion requirements (9 vs. 6, p = 0.01), reoperation (39% vs. 23%, p = 0.05) and prolonged length of stay (34 days vs. 25 days, p = 0.02). There were no differences in overall survival and recurrence free survival in colorectal cancer. Median overall survival was decreased in mesothelioma by 20 months. In LAMNs the median survival was significantly decreased for the resection group. Similarly, the resection group had a 4-month earlier recurrence. CONCLUSION: We conclude that diaphragm interventions are an essential part of CRS. They are associated with increased perioperative morbidity. This morbidity is not attributable to whether the patient underwent diaphragm stripping or resection. However in mesothelioma and LAMNs, requiring diaphragm resection is likely to be an indicator for tumor aggression.

5.
J Surg Oncol ; 120(4): 794-802, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31309588

RESUMO

BACKGROUND AND OBJECTIVES: To review long-term survival outcomes of patients with Peritoneal metastasis (PM) who underwent colorectal cancer (CRS) and intraperitoneal chemotherapy (PIC). METHODS: Patients that underwent CRS, with or without PIC, from January 1996 to March 2018 at the Peritonectomy Unit of St. George Hospital, Sydney were retrospectively analyzed from a prospectively maintained database. RESULTS: The study comprised of 1225 cases, including 687 females (56.1%) and 538 males (43.9%). Diagnoses included CRC (n = 363), followed by HAMN (n = 317), LAMN (n = 297), mesothelioma (n = 101), ovarian cancer (n = 55), and others including gastric, sarcoma, and neuroendocrine tumor (n = 92). The median OS, 5- and 10-year survivals for CRC were 35 months, 33% and 8%, respectively. Patients with LAMN, in relative to HAMN, experienced a higher median OS, 5- and 10-year survivals (248 months vs 63 months; 82% vs 52% and 59% vs 28%). The median OS for mesothelioma was 60 months with 5- and 10-year survivals of 48% and 19%, respectively. In ovarian cancer, the median OS was 30 months with 5- and 10-year survivals of 26% and 10%, respectively. For the remaining histological diagnoses, median OS and 5-year survival were 28 months and 27%, respectively. CONCLUSION: Our large-cohort data showed that CRS/PIC can provide long-term survival benefit to patients with PM of gastrointestinal and ovarian origin.


Assuntos
Neoplasias do Apêndice/mortalidade , Quimioterapia do Câncer por Perfusão Regional/mortalidade , Neoplasias Colorretais/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Neoplasias Pulmonares/mortalidade , Mesotelioma/mortalidade , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Injeções Intraperitoneais , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/patologia , Mesotelioma/terapia , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Assistência Perioperatória , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
6.
Ann Surg Oncol ; 26(11): 3627-3635, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31292804

RESUMO

OBJECTIVES: This study was designed to assess the short- and long-term outcomes of gastric resection in cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for lower gastrointestinal (GI) malignancies. METHODS: Patients with adenocarcinoma and appendiceal mucinous neoplasms were included. Redo and incomplete cytoreductions were excluded. A total of 756 patients were identified. Of these, 65 underwent gastric resection, 11 underwent wedge, 43 distal, and 11 subtotal and total gastrectomy. Preoperative differences were assessed for and addressed with matching. Perioperative outcomes, overall survival (OS), and risk-free survival (RFS) were assessed in two analyses: first all gastric resections were included and the second excluded wedge resections. Subgroup analysis according to diagnosis subtype was conducted. RESULTS: Demographic analysis revealed that markers of tumor aggression and poor nutrition were prevalent in the gastrectomy group. The matched analysis for gastric resections revealed higher rates of reoperation (38% vs. 22%, p = 0.028). After excluding wedge resections, increased rates of reoperation (40% vs. 22%, 0.019), grade 3/4 morbidity (76% vs. 59%, p = 0.036), and hospital stay (34 vs. 27 days, p = 0.012) were observed. For the unmatched cohort, OS (103 vs. 69 months, p = 0.501) and RFS (17 vs. 18 months, p = 0.181) for patients with CC = 0 were insignificantly different. In comparison for CC > 0, OS (31 vs. 83 months, p < 0.001) and RFS (9 vs. 20 months, p < 0.001) were significantly reduced in gastric resection. For the matched cohort, after excluding wedges, gastrectomy did not significantly decrease OS. However, RFS was decreased (11 vs. 20 months, p = 0.016). CONCLUSIONS: Despite high postoperative morbidity, when complete cytoreduction is achieved, the need for gastric resection is not associated with inferior long-term outcomes.

7.
Eur J Surg Oncol ; 2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31253546

RESUMO

INTRODUCTION: Early recurrence (ER) is defined as development of loco-regional peritoneal disease within 12-month of the initial CRS/PIC. Our aims were to identify overall survival (OS), recurrence-free survival (RFS) and independent prognostic factors associated with ER in PM of appendiceal neoplasm. MATERIALS AND METHODS: A prospectively-maintained database for patients with appendiceal neoplasm undergoing cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) from year 1996-2018 was retrospectively analysed. RESULTS: 208 female and 185 male patients were identified. With a median follow-up of 40-month, 40.2% of the patients developed ER. The median OS for ER was 24 months compared to late (LR) at 64 months. Median OS was not reached in non-recurrence (NR). 5-year survival for ER was less favourable compared to LR and NR (19.3%vs54.6%vs94%). No patients in ER group survived beyond 10-year. Independent negative predictors associated with ER on multivariate analysis were male patient (p = 0.013), blood transfusion of >8 units (p = 0.013), elevated preoperative CEA levels (>5 ng/ml; p = 0.002) and hard intraoperative tumour consistency (p < 0.001). Protective factor was a combination of CC1, hard tumour consistency and use of EPIC (p = 0.039). Independent prognostic factors that predicted recurrence of appendiceal PM were PCI >20 (p = 0.049), non-use of EPIC (p = 0.012), hard tumour consistency (p = 0.004) and use of previous chemotherapy (p = 0.023). CONCLUSION: ER following CRS and PIC of appendiceal PM is associated with reduced survival outcomes. Our data alludes to the importance of optimising the risk factors in order to delay loco-regional recurrence and improve long-term survival of these patients.

8.
Ann Surg Oncol ; 26(8): 2622-2630, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31123932

RESUMO

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex surgery to treat peritoneal surface malignancy (PSM). PSM and gastrointestinal (GI) resection from CRS can lead to significant GI symptoms and malnutrition. There is limited research into the nutrition status of this patient group and the impact of malnutrition on morbidity. OBJECTIVE: This study aims to determine if preoperative malnutrition, assessed using the Subjective Global Assessment (SGA), is associated with postoperative morbidity and increased length of stay (LOS) in patients undergoing CRS/HIPEC for PSM. METHODS: This study prospectively assessed the nutritional status of patients undergoing CRS/HIPEC using a validated nutrition assessment tool. Preoperative clinical symptoms, Peritoneal Cancer Index (PCI), intraoperative blood transfusions, operative time, GI resections, postoperative morbidity, and LOS, as well as pre- and postoperative nutritional interventions, were recorded. The impact of preoperative nutritional status was assessed in relation to postoperative complications and hospital LOS. RESULTS: The study included 102 participants; 34 patients (33%) were classified as malnourished (SGA = B or C). Preoperative weight loss (15% vs. 74%; p ≤ 0.001) and the presence of clinical symptoms (18% vs. 47%; p = 0.002) were significantly higher in malnourished patients. While PCI, intraoperative blood transfusions, and GI resections were independent predictors of morbidity, malnutrition was significantly associated with infectious complications and LOS. For each grade of worsening malnutrition, LOS increased by an average of 7.65 days. CONCLUSIONS: Preoperative malnutrition is prevalent in patients undergoing CRS/HIPEC and postoperative morbidity is common. Malnutrition is linked to LOS and plays a role in postoperative outcomes such as infection. Clear pre- and postoperative nutrition pathways are needed to optimize nutrition support and postoperative recovery.

9.
Nat Commun ; 10(1): 2164, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092820

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease, characterised by increased expression of type I interferon (IFN)-regulated genes and a striking sex imbalance towards females. Through combined genetic, in silico, in vitro, and ex vivo approaches, we define CXorf21, a gene of hitherto unknown function, which escapes X-chromosome inactivation, as a candidate underlying the Xp21.2 SLE association. We demonstrate that CXorf21 is an IFN-response gene and that the sexual dimorphism in expression is magnified by immunological challenge. Fine-mapping reveals a single haplotype as a potential causal cis-eQTL for CXorf21. We propose that expression is amplified through modification of promoter and 3'-UTR chromatin interactions. Finally, we show that the CXORF21 protein colocalises with TLR7, a pathway implicated in SLE pathogenesis. Our study reveals modulation in gene expression affected by the combination of two hallmarks of SLE: CXorf21 expression increases in a both an IFN-inducible and sex-specific manner.


Assuntos
Cromossomos Humanos X/genética , Genes Ligados ao Cromossomo X/genética , Interferon Tipo I/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lúpus Eritematoso Sistêmico/genética , Regiões 3' não Traduzidas/genética , Adulto , Fatores Etários , Estudos de Casos e Controles , Feminino , Genes Ligados ao Cromossomo X/imunologia , Predisposição Genética para Doença , Humanos , Interferon Tipo I/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Regiões Promotoras Genéticas/genética , Fatores Sexuais , Receptor 7 Toll-Like/genética
10.
Am J Surg ; 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30982572

RESUMO

BACKGROUND: Peritoneal cancer index (PCI) is an important prognostic factor in colorectal cancer peritoneal metastases (CRPM), however it fails to consider the time period over which disease burden develops. The volume-time index (VTI) is the ratio between PCI and time from primary tumour resection. METHODS: A retrospective cohort study of 182 patients managed from 1996 to 2017 was performed. RESULTS: As stratified by high vs low VTI groups, median overall survival (OS) was 23 months (95% 17-46) vs 44 months (95% 35-72) with a difference in 5-year OS of 20.3% (95%CI 10.2-40.4) vs 40.1% (95%CI 29.7-54.1), p = 0.002. No difference in 5-year recurrence free survival (RFS) exists. On multivariable analysis, an elevated VTI was independently associated with poorer OS (adjusted HR 3.20, 95%CI 1.64-6.23, p < 0.001) and RFS (adjusted HR 1.90, 95%CI 1.10-3.29, p = 0.02). CONCLUSION: VTI is an independent prognostic factor for OS and RFs in patients with CRPM undergoing CRS/IPC, behaving as a surrogate of tumour aggressiveness.

11.
Int J Surg Case Rep ; 57: 48-51, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30901569

RESUMO

INTRODUCTION: In modern surgical era, local haemostatic agents and blood components such as recombinant activated factor VII (rFVIIa) have expanded surgeons' armamentarium in controlling "surgical" and "nonsurgical bleeding". We report a case of intraoperative thrombosis and cardiac arrest involving use of local haemostatic agent in intraoperative cell salvage and rFVIIa administration in extended right hepatectomy. PRESENTATION OF CASE: A 46-year-old lady underwent extended right hepatectomy using cardiopulmonary bypass (CPB) and autotransfusion with ICS for metastatic gastrointestinal stromal tumour. She became extremely coagulopathic following weaning of CPB despite an array of fluid and blood products replacements. Decision to administer rFVIIa as a measure to arrest bleeding was unsuccessful. Extensive systemic thrombosis occurred which resulted in cardiac arrest and mortality. DISCUSSION: The thromboembolic event was unclear but likely multifactorial. Two important hypotheses were the administration of rFVIIa and use of local haemostatic agent in ICS. CONCLUSION: Reported incidence of thromboembolism with use of rFVIIa in refractory bleeding is variable. More randomised controlled trials are needed to ascertain the efficacy and safety profile of the haemostatic agent. At present, off-label use of rFVIIa should be guided by the risk:benefit profile on a case-to-case basis. The authors also feel strongly against the use of local haemostatic gel in conjunction with ICS due to potential systemic circulation of the thrombin.

12.
Am J Surg ; 217(4): 704-712, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30704669

RESUMO

BACKGROUND: This study examines the impact of intraoperative macroscopic tumour consistency on short-term and long-term outcomes after cytoreductive surgery (CRS) with intraperitoneal chemotherapy (IPC) for appendiceal adenocarcinoma with peritoneal metastases. METHODS: Macroscopic intraoperative tumour consistency was classified in three groups as soft (jelly-like geltatinous tumours), hard (hard tumour nodules without gelatinous features) and intermediate (both soft and hard features). In-hospital mortality, major morbidity, intensive care unit (ICU), high dependency unit (HDU) and total hospital stay, disease-free survival (DFS) and overall survival (OS) were compared. RESULTS: The three groups had similar perioperative short-term outcomes. Patients with soft, intermediate and hard tumours revealed differences in OS (p < 0.001) and DFS (p = 0.03). Multivariable analysis revealed a shorter OS for patients with hard versus soft tumours (HR for hard tumours = 4.43, 95%CI 2.19-9.00). CONCLUSIONS: Intraoperative macroscopic tumour consistency may be used as a prognostic marker for survival in patients with appendiceal adenocarcinoma with peritoneal metastases.

13.
Eur J Surg Oncol ; 45(4): 620-624, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30611566

RESUMO

OBJECTIVES: To assess the impact of short and long term outcomes of diaphragmatic interventions in cyto-reductive surgery (CRS) and intra-peritoneal chemotherapy (IPC). METHODS: 1230 consecutive CRS/IPC procedures were preformed between 1996 and 2018 in Sydney, Australia. Redo procedures and incomplete cyto-reductions were excluded. Among these, 599 underwent diaphragmatic intervention. Preoperative heterogeneity was assessed for in 6 parameters and addressed with propensity score matching. CRS/IPC requiring diaphragmatic interventions were compared to CRS/IPC without diaphragmatic involvement. Ten perioperative outcomes were measured. Overall survival was assessed based on diagnosis type. RESULTS: Intraoperative results revealed a significant increase in operative hours (7.85 vs. 7.28, p = 0.033). Transfusion requirements were insignificantly different. Postoperatively, increased grade III and IV complications (36% vs. 26%, p = 0.052) were noted. There was no difference with regards to intensive care stay, hospital length of stay, hospital death and return to theatre. In terms of respiratory specific complications, an increased incidence of pneumothorax (13% vs. 3%, p = 0.001) and pleural effusions (24% vs. 16%, p = 0.043) were noted, whilst the differences in pneumonia were insignificant. Overall survival revealed diaphragm interventions; did not affect survival outcomes in colorectal cancers (p = 0.750, RR = 1.077, CI 0.683-1.697) and increased relative risk in low-grade appendiceal mucinous neoplasms (p = 0.025, RR = 2.437, CI 1.121-5.298). CONCLUSION: After our three-tiered research strategy, we conclude that despite the marginal increase in short term morbidity; diaphragmatic interventions do not decrease survival in colorectal cancers and diaphragmatic disease in LAMNs maybe an independent prognosticator of disease aggression.


Assuntos
Neoplasias do Apêndice/patologia , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos de Citorredução , Diafragma/cirurgia , Mesotelioma/terapia , Neoplasias Císticas, Mucinosas e Serosas/terapia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/terapia , Complicações Pós-Operatórias/etiologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Feminino , Humanos , Infusões Parenterais , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Císticas, Mucinosas e Serosas/secundário , Duração da Cirurgia , Neoplasias Peritoneais/secundário , Derrame Pleural/etiologia , Pneumotórax/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
14.
J Surg Oncol ; 119(3): 336-346, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30554404

RESUMO

BACKGROUND AND OBJECTIVES: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival. METHODS: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases. RESULTS: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001). CONCLUSION: iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.


Assuntos
Quimioterapia do Câncer por Perfusão Regional/mortalidade , Neoplasias Colorretais/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Peritoneais/mortalidade , Adolescente , Adulto , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
15.
Anticancer Res ; 38(10): 5917-5921, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30275219

RESUMO

BACKGROUND/AIM: To assess the impact of short- and long-term outcomes of bilateral vs. unilateral diaphragm interventions in cyto-reductive surgery (CRS) and intra-peritoneal chemotherapy (IPC). PATIENTS AND METHODS: A total of 652 CRS/IPC procedures, between 1996 and 2018, required diaphragm interventions. Among these, 388 underwent bilateral intervention. Preoperative heterogeneity was assessed in 6 parameters and addressed with propensity score matching. The association of each respective analysis was assessed with 11 outcomes. Overall survival was assessed based on histology. RESULTS: CRS/IPC requiring bilateral diaphragmatic interventions illustrated significantly increased operative hours (9.6 vs. 8.6 hours, p<0.001). Postoperatively, there was significantly increased red blood cell (RBC) transfusion (6.37 units vs. 4.47 units, p=0.007) and grade III and IV complications (57.3% vs. 40.6%, p=0.004). No difference was noted in ICU stay, total length of stay, hospital death and return to OT. In terms of respiratory complications, an increased incidence of pneumothorax (16.5% vs. 6.2%, p<0.001) was noted whilst pleural effusions and pneumonia occurrences were non-significant. Overall survival, revealed bilateral interventions in low-grade appendiceal mucinous neoplasm conferred an increased relative risk (p=0.037, RR=2.230, 95%CI=1.052-4.730). They did not have an effect on OS in colorectal cancer and mesothelioma. CONCLUSION: Despite the increase in short-term morbidity, bilateral diaphragm interventions resulted in similar long-term survival to unilateral interventions.


Assuntos
Adenocarcinoma Mucinoso/mortalidade , Neoplasias do Apêndice/mortalidade , Quimioterapia do Câncer por Perfusão Regional/mortalidade , Neoplasias Colorretais/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Diafragma/cirurgia , Neoplasias Peritoneais/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Hipertermia Induzida , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
16.
Hum Mol Genet ; 27(21): 3813-3824, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085094

RESUMO

Genetic variation within the major histocompatibility complex (MHC) contributes substantial risk for systemic lupus erythematosus, but high gene density, extreme polymorphism and extensive linkage disequilibrium (LD) have made fine mapping challenging. To address the problem, we compared two association techniques in two ancestrally diverse populations, African Americans (AAs) and Europeans (EURs). We observed a greater number of Human Leucocyte Antigen (HLA) alleles in AA consistent with the elevated level of recombination in this population. In EUR we observed 50 different A-C-B-DRB1-DQA-DQB multilocus haplotype sequences per hundred individuals; in the AA sample, these multilocus haplotypes were twice as common compared to Europeans. We also observed a strong narrow class II signal in AA as opposed to the long-range LD observed in EUR that includes class I alleles. We performed a Bayesian model choice of the classical HLA alleles and a frequentist analysis that combined both single nucleotide polymorphisms (SNPs) and classical HLA alleles. Both analyses converged on a similar subset of risk HLA alleles: in EUR HLA- B*08:01 + B*18:01 + (DRB1*15:01 frequentist only) + DQA*01:02 + DQB*02:01 + DRB3*02 and in AA HLA-C*17:01 + B*08:01 + DRB1*15:03 + (DQA*01:02 frequentist only) + DQA*02:01 + DQA*05:01+ DQA*05:05 + DQB*03:19 + DQB*02:02. We observed two additional independent SNP associations in both populations: EUR rs146903072 and rs501480; AA rs389883 and rs114118665. The DR2 serotype was best explained by DRB1*15:03 + DQA*01:02 in AA and by DRB1*15:01 + DQA*01:02 in EUR. The DR3 serotype was best explained by DQA*05:01 in AA and by DQB*02:01 in EUR. Despite some differences in underlying HLA allele risk models in EUR and AA, SNP signals across the extended MHC showed remarkable similarity and significant concordance in direction of effect for risk-associated variants.

17.
Int J Hyperthermia ; : 1-7, 2018 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-30130987

RESUMO

BACKGROUND: It is believed that the oncologic behavior of mucinous colorectal adenocarcinoma (MC) is different from non-mucinous adenocarcinoma (NMC). The aim of the study is to compare long-term survivals between patients with MC and those with NMC following cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). METHODS: This was a retrospective study of prospectively collected data of patients with peritoneal metastases of colorectal origin following CRS and IPC. Group I included patients with MC which was defined as being composed of >50% extracellular mucin. Group II included those with NMC. Subgroup analysis was performed according to the location of primary tumor. RESULTS: A total of 213 patients were included in this study. The two groups had similar hospital mortality, high dependency unit stay. MC group had a significantly longer mean intensive care unit (ICU) stay (p = .037) and total hospital stay (p = .037). There was no significant difference in overall survival (OS) and disease-free survival (DFS) between two groups (p = .657 and p = .938, respectively). Multivariate analysis showed that the presence of mucin was not an independent negative prognostic factor for OS (p = .190). CONCLUSION: In summary, patients with MC had a similar long-term survival outcome with those with NMC following CRS and IPC.

18.
Ann Rheum Dis ; 77(7): 1078-1084, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29625966

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic component in its pathogenesis. Through genome-wide association studies (GWAS), we recently identified 10 novel loci associated with SLE and uncovered a number of suggestive loci requiring further validation. This study aimed to validate those loci in independent cohorts and evaluate the role of SLE genetics in drug repositioning. METHODS: We conducted GWAS and replication studies involving 12 280 SLE cases and 18 828 controls, and performed fine-mapping analyses to identify likely causal variants within the newly identified loci. We further scanned drug target databases to evaluate the role of SLE genetics in drug repositioning. RESULTS: We identified three novel loci that surpassed genome-wide significance, including ST3AGL4 (rs13238909, pmeta=4.40E-08), MFHAS1 (rs2428, pmeta=1.17E-08) and CSNK2A2 (rs2731783, pmeta=1.08E-09). We also confirmed the association of CD226 locus with SLE (rs763361, pmeta=2.45E-08). Fine-mapping and functional analyses indicated that the putative causal variants in CSNK2A2 locus reside in an enhancer and are associated with expression of CSNK2A2 in B-lymphocytes, suggesting a potential mechanism of association. In addition, we demonstrated that SLE risk genes were more likely to be interacting proteins with targets of approved SLE drugs (OR=2.41, p=1.50E-03) which supports the role of genetic studies to repurpose drugs approved for other diseases for the treatment of SLE. CONCLUSION: This study identified three novel loci associated with SLE and demonstrated the role of SLE GWAS findings in drug repositioning.

19.
Am J Clin Oncol ; 41(10): 943-948, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29624505

RESUMO

INTRODUCTION: The impact of concomitant urologic procedures (UPs) on perioperative and long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is uncertain. METHODS: In total, 935 consecutive CRS/HIPEC procedures were performed between 1996 and 2016 in Sydney, Australia. Among these, 73 (7.8%) involved concomitant UP. The association of concomitant UP with 21 perioperative outcomes and overall survival was assessed using univariate and multivariate analyses. RESULTS: In-hospital mortality was 1.8%. Patients requiring UP were more likely to require transfusion of ≥5 units of red blood cells (P=0.031) and have a complete cytoreduction (79% vs. 60%, P<0.001). On multivariate analysis, UP was not associated with in-hospital mortality (2.7% vs. 1.7%, P=0.407) or grade III/IV morbidity (52% vs. 41%, P=0.376). The incidence of ureteric fistula (4% vs. 1%, P=0.004), return to theater (26% vs. 14%, P=0.005) and digestive fistula (22% vs. 11%, P=0.005) was higher in the UP group. The addition of a UP did not significantly impact overall survival for appendiceal cancer (P=0.162), colorectal cancer (P=0.315), or pseudomyxoma peritonei (P=0.120). CONCLUSIONS: Addition of a UP was not associated with an increased risk of grade III/IV morbidity or poorer long-term survival after CRS/HIPEC.

20.
ANZ J Surg ; 88(10): 975-981, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29510456

RESUMO

Peritoneal metastasis (PM) following primary resection of colorectal cancer is common. The combined use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy has significantly improved the survival outcome of patients with colorectal PM (CRPM). Diagnosing and treating early PM is essential as its extent is correlated with poorer outcomes. There are two novel therapies - second-look surgery and synchronous hyperthermic intraperitoneal chemotherapy - that are proposed to prophylactically treat or intervene early in the disease process to reduce the incidence and adverse outcomes associated with PM. These strategies are limited to patients at high risk of developing CRPM, including those that had synchronous PM or ovarian metastases resected at primary tumour removal, or a perforated primary tumour. The data on advanced primary tumour (T4) as a prognostic factor for PM after primary resection suggest that T4a tumours are prognostically worse than T4b. This literature review outlines the evidence, feasibility and safety regarding the pre-emptive treatments, as well as the relevance of T4a tumours as a risk factor for metachronous CRPM.

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