Survival outcomes in patients aged 75 years and over with peritoneal colorectal carcinomatosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC): multicenter study of the Spanish Group of Peritoneal Cancer Surgery (GECOP).

BACKGROUND: The attitude toward cytoreductive surgery with HIPEC in peritoneal carcinomatosis from colorectal cancer is unclear. The aim of this study is to report the perioperative outcomes after cytoreductive surgery with HIPEC in patients ≥ 75 years. METHODS: This retrospective multicenter study collected the data the Spanish Group of Peritoneal Cancer Surgery. Thirty-six patients with peritoneal carcinomatosis from colorectal cancer met the selection criteria for the study. Morbidity, mortality, disease-free and overall survival were analyzed. RESULTS: Morbidity (grade III-IV) was 17% and 2 patients died of complications related to the procedure (5.4%). Median disease-free survival (DFS) was 16 months. DFS at 1 and 3 years was 81% and 42%, respectively. Overall survival at 1 and 3 years was 96% and 75%. In the univariate analysis, preoperative comorbidities (p = 0.01), liver metastases (p = 0.02), blood transfusion (p = 0.001) and postoperative complications (p = 0.001); and in the multivariate analysis, perioperative blood transfusion (OR 2.56, 95% CI 1.95-6.24, p = 0.03) and postoperative complications (OR 3.25, 95% CI 2.35-7.56, p = 0.02) were associated with a lower overall survival. CONCLUSIONS: Age is not an absolute contraindication to perform cytoreduction surgery with HIPEC in highly selected elderly patients with colorectal peritoneal carcinomatosis.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei and appendix tumours in elderly patients: Is it justified?

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei and appendix tumours are widespread in the world. It is unclear what should be the attitude in elderly patients. METHODS: This retrospective multicenter study collected the database from ten Spanish centers from Spanish Group of Peritoneal Cancer Surgery. The study period was between November 2002 and March 2014. Seventeen patients with age greater than or equal to 75 years with peritoneal carcinomatosis from pseudomyxoma peritonei and appendix tumours met the selection criteria for the study. Outcomes in terms of morbidity and mortality such as disease-free and overall survival were analyzed. RESULTS: Median PCI was 16 (range 6-39). Ten postoperative adverse events were detected in nine patients (44.4%). 28% were grade I-II and 17% were grade III-IV. Disease-free survival at 1 and 3 years was 67 and 44%, respectively. Overall survival at 1 and 3 years was 100 and 88%, respectively. Only cytoreduction was related to worst disease free survival after univariate (p = 0.007) and multivariate (OR 11.639, 95% CI 1.24-109.74, p = 0.03) analyses. Cytoreduction was related to the worst overall survival after univariate analysis (p = 0.046). CONCLUSION: Cytoreductive surgery and HIPEC for pseudomyxoma peritonei and appendix tumours in elderly patients it is a procedure with feasible postoperative morbi-mortality and survival outcomes. TRIAL REGISTRATION: researchregistry1587 (retrospectively registered).

Morbidity and mortality outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients aged 75 years and over: Spanish group of peritoneal cancer surgery (GECOP) multicenter study.

BACKGROUND: The aim of this study is to report the perioperative outcomes of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in patients ≥75 years from a Spanish multi-institutional experience. METHODS: This multi-institutional retrospectively analyzed a prospectively collected clinical data from 10 Spanish hospitals that are part of the Spanish Group Peritoneal Cancer Surgery (GECOP). We assessed postoperative morbidity rates and performed univariate and multivariate analyses of factors associated with overall (grade I-IV) and major (grade III-IV) postoperative morbidity. RESULTS: A total of 85 patients aged ≥75 years were included. Forty six postoperative adverse events were detected in 37 patients (43.5%). Twenty five complications in 20 patients (23.5%) were mild (grade I-II) and 16 complications in 12 patients (14.1%) were moderate-severe (grade III-IV). Five patients died in the first 90 days after the procedure (5.9%). After multivariate analysis, independent factors associated with postoperative complications were: PCI> 12 (OR: 4.14, 95% CI 1.22-14.12, p = 0.043) and the need for perioperative blood transfusion (OR: 14.91, 95% CI 3.87-57.46, p < 0.001). Regarding grade III-IV complications, after multivariate analysis, the presence of preoperative albumin levels <3.5 mgr/dl (OR: 9.15, 95% CI 1.38-60.57, p = 0.017), need for diaphragmatic peritonectomy procedures (OR: 11.32, 95% CI 1.40-91.32, p = 0.023) and perioperative blood transfusion (OR: 8.58, 95% CI 1.44-51.16, p = 0.018) were independent factors. CONCLUSIONS: Cytoreductive surgery and performing HIPEC by experienced groups in selected patients aged ≥75 years can be performed with morbidity and mortality similar to that described in the literature.

"Assessment of RIFLE and AKIN criteria to define acute renal dysfunction for HIPEC procedures for ovarian and non ovarian peritoneal malignances".

BACKGROUND: The acute renal dysfunction (ARD) is a common complication in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Our aim is evaluate the ARD post-HIPEC procedures using the RIFLE and AKIN criteria. Evaluate the risk factors and analyze ARD's impact on postoperative course. METHODS: From 2011 to 2014, in a retrospective way using a prospective database were operated by HIPEC procedure. The ARD was analyzed by RIFLE and AKIN criteria. The perioperative features were analyzed and a multivariate analysis was performed to define the risk factors to develop the ARD. RESULTS: 141 patients were treated and analyzed. The ARD was detected in 30.5% (Injury 18.4% and Failure 12.1%) when RIFLE criteria were applied. The multivariate analysis detected that decrease of pH during HIPEC [OR = 29.39 (5.09-169.76)], PCI [OR = 1.07 (1.01-1.15)] and ureteral catheters [OR = 12.71 (1.44-111.85)] were associated to the development of acute renal injury (ARI) post-HIPEC. Decrease of Na during HIPEC [OR = 1.15 (1.01-1.30)], intraoperative inotrope use [OR = 3.83 (1.12-13.09)] and PCI [OR = 1.06 (1.0-1.14)] were associated to acute renal failure (ARF) post-HIPEC. The ARD was related to a higher length of stay hospital (17.2 ± 11 vs. 13.8 ± 8 days) (p = 0.05) but no impact in early survival was observed in ARD group. CONCLUSIONS: The widespread use of RIFLE criteria for ARD would have major benefits in terms of accurately diagnosing patients undergone HIPEC procedures. The ARD has a detrimental impact in length of stay hospital. The knowledge of risk factors helps us to prevent the ARD post-HIPEC by means of an aggressive and multidisciplinary perioperative management.

Peritonectomy procedures and HIPEC in the treatment of peritoneal carcinomatosis from ovarian cancer: Long-term outcomes and perspectives from a high-volume center.

BACKGROUND: Cytoreductive surgery with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) represents a radical therapeutic approach to achieve complete cytoreduction in ovarian peritoneal carcinomatosis. The aim of the present study was to analyze the outcomes obtained by the application of these procedures in a single center with extensive experience treating peritoneal carcinomatosis. PATIENTS AND METHODS: A series of 218 consecutive patients diagnosed with peritoneal carcinomatosis from primary or recurrent ovarian cancer (FIGO stage IIIC-IV) and treated with CRS + HIPEC between January 1996 and June 2012 were included in this observational study. RESULTS: Peritoneal carcinomatosis was treated primarily in 56% (124/218) of the cases and recurrently in 43% (94/218). A total of 42/218 patients (19%) presented with FIGO stage IV. Compared to recurrent cases, patients with primary ovarian carcinomatosis were older and presented higher Peritoneal Cancer Index (PCI) and percentage of FIGO stage IV; however, no significant differences in survival (5-year overall survival in patients with R0 cytoreduction, 63% and 56%, respectively) were observed. Cytoreduction score, PCI, lymphatic involvement and surgical morbidity ≥Grade III were statistically significant prognostic factors for survival in both univariate and multivariate analysis. CONCLUSIONS: CRS + HIPEC treating macroscopic and microscopic disease is currently an excellent surgical approach to achieve high rates of complete cytoreduction and improve survival in patients with peritoneal carcinomatosis from ovarian cancer. In order to minimize the high potential morbidity of these procedures, CRS + HIPEC should be performed in highly experienced centers.

Postoperative time course and utility of inflammatory markers in patients with ovarian peritoneal carcinomatosis treated with neoadjuvant chemotherapy, cytoreductive surgery, and HIPEC.

BACKGROUND: Inflammatory markers may help monitor postoperative evolution of surgical patients and detect complications. However, to date, the effect that neoadjuvant chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) may have in the postoperative kinetics of these parameters remains unknown. METHODS: Between July 2011 and June 2014, all patients who underwent neoadjuvant chemotherapy, cytoreductive surgery, and HIPEC for ovarian peritoneal carcinomatosis were studied. Patients were divided into four groups: no complications, noninfective complication, and infective complications during the first and second postoperative weeks. Retrospectively, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), white blood cell count, platelet-to-lymphocyte ratio, and prothrombin ratio were collected from postoperative days 1-14. Postoperative behavior of each parameter was carefully evaluated across groups. RESULTS: The study included 122 patients. Only CRP and NLR showed promising results. CRP presented a mean peak value at 48 h (186.1 mg/L), while NLR peaked at 24 h (10.21 mg/L). Both parameters rose with infective complications. Statistically significant differences were found at several time points compared with uncomplicated patients. A simple test comparing the peak value of CRP with the value when an infective complication was suspected accurately diagnosed these complications with sensitivity of 81 %, specificity of 91 %, and negative and positive predictive value of 93.1 and 76 %, respectively. This comparison presented lower diagnostic performance when NLR was used. CONCLUSIONS: Both CRP and NLR are useful in monitoring postoperative evolution in these patients; however, only CRP is useful for detecting infective complications.

Prediction model to discard a priori liver allografts.

BACKGROUND: The use of expanded criteria for donors to expand the donor pool has increased the number of discarded liver grafts in situ. The aim of our study was to elaborate a prediction model to reduce the percentage of liver grafts discarded before the procuring team is sent out. METHODS: We analyzed the donor factors of 244 evaluated candidates for liver donation. We performed a multiple logistic regression to evaluate the probability of liver grafts discarded (PD). RESULTS: The PD was determined by use of 3 variables: age, pathological ultrasonography, and body mass index >30. The area under curve was 82.7%, and, for a PD of 70%, the false-positive probability was 1.2%. CONCLUSIONS: We have created a useful clinical prediction model that could avoid up to 20% of discarded liver grafts.

LC-MS/MS quantitative analysis of paclitaxel and its major metabolites in serum, plasma and tissue from women with ovarian cancer after intraperitoneal chemotherapy.

A method for determination of the antineoplastic drug paclitaxel and its main metabolites (viz. 6α-hydroxypaclitaxel and p-3'-hydroxypaclitaxel) at the sub-ng/ml level is here presented. Sample preparation consisted of a liquid-liquid extraction step for cleanup and preconcentration of the target analytes prior to chromatographic analysis by tandem mass spectrometry detection (LC-ESI-MS/MS). The determination step was optimized by selected reaction monitoring (SRM) mode for highly selective identification and sensitive quantitation of paclitaxel and its metabolites in human serum, plasma and tissue. The detection limits were in the range 0.03-0.15ng/ml for serum and 0.07-0.62ng/g for tissue, with intra-day variability range from 0.5 to 2.7%, expressed as relative standard deviation. The method was applied to determine paclitaxel and its metabolites in serum and tissue from 13 women suffering from ovarian peritoneal carcinomatosis, after hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) treatment. The method reported here can be considered a suited tool to monitor the concentration of this drug in patients subjected to HIPEC as strategy to evaluate the toxicity and efficiency of this treatment.

Pseudomyxoma peritonei treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: results from a single centre

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare, slowly progressive disease whose prognosis depends primarily on the completeness of cytoreduction. The value of intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and of additional factors predicting long-term outcome and disease-free survival (DFS) remains poorly understood. This study aims to analyse survival rates and prognostic factors in patients undergoing maximal cytoreduction and HIPEC. METHODS: Thirty patients were selected from a prospective database of records for patients undergoing cytoreduction and HIPEC with mitomycin C or paclitaxel. Overall survival (OS), DFS, and the prognostic factors influencing them, were examined using multivariate analysis. RESULTS: Median follow-up was 44 months (range, 8-144). Histological classification of PMPs was DPAM in 6/30 of cases, PMCA-I in 10/30 and PMCA in 14/30. Complete cytoreduction (CC-0 and CC-1) was achieved in 28/30 of patients and CC-2 in 2/30. Median OS was 111 months (range 0-230) and five-year OS rate was 67%. Median DFS was 53.5 months (range 0-120) and 5-year DFS rate was 44%. Incomplete cytoreduction, lymph node involvement and PCI>20 were associated with poor prognosis for OS, while lymph node involvement, elevated CA-125 levels, unfavourable histology and previous chemotherapy were associated with poor outcomes for DFS. There was morbidity of Grade 3 or higher in 9/30. Post-operative mortality occurred in 1 case. CONCLUSION: Cytoreduction plus peritonectomy procedures combined with HIPEC is a safe treatment and could improve survival rates. Since the optimal cytoreduction is the primary prognostic factor, patients should be centralised under the care of experienced teams (AU)

Consolidation of enteric drainage for exocrine secretions in simultaneous pancreas-kidney transplant.

INTRODUCTION: Management of the exocrine drainage of the pancreatic graft in simultaneous pancreas kidney (SPK) transplantation has been a matter of debate for years. There is currently a trend toward a more physiological enteric drainage (ED). This study compared short- and long-term complications and graft survival in patients with enteric versus bladder exocrine secretion drainage. PATIENTS AND METHODS: Between January 1995 and November 2005, we performed 75 SPK transplants: 55 with ED and 20 with bladder drainage (BD). The rates of complications and graft survival were monitored over at least 36 months after transplantation. RESULTS: Mean posttransplant follow-up was 119.5 +/- 6.6 months. Urinary infection, hematuria, reflux pancreatitis, and repeat surgery rates were all significantly higher among the BD area. There was no intergroup difference in rejection rates or in the incidence of graft thrombosis, transplantectomy, anastomotic dehiscence, or intra-abdominal abscesses. Pancreas and kidney graft survival rates were similar in the two groups. CONCLUSIONS: In our experience, ED was more physiological than BD, and was associated with fewer complications.

The role of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinomatosis in recurrent ovarian cancer

BACKGROUND AND OBJECTIVES: Peritoneal carcinomatosis in women frequently has an ovarian origin. Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) along with radical surgery/peritonectomy could present a new therapeutic approach with curative intention. The purpose of this research is to evaluate the role of the administration of HIPEC. METHODS: A series of patients (N=26) diagnosed with peritoneal carcinomatosis for recurrent epithelial ovarian cancer (stage III) from January 1997 to December 2004 submitted to radical surgery/peritonectomy with optimal cytoreduction (R0-R1) were included in this study, 14 treated with HIPEC and 12 without HIPEC. RESULTS: The variables age, histologic type, peritonectomy procedures, peritoneal cancer index (PCI) and lymph node affectation were similar in both groups. The 5-year global survival was 58% and 17% (p=0.046), and 67% and 29% in patients with maximal cytoreduction (R0) (p=0.264), in the HIPEC- and non-HIPEC-treated patients, respectively. In patients with optimal cytoreduction and partial peritonectomy, 5-year global survival was also superior in the HIPEC group (75% vs. 11%, p=0.011). Average time free of disease was superior in the HIPEC group (48+/-42 vs. 24+/-21 months), with less reinterventions due to a new reappearance during the first three evolutionary years (2/14 vs. 4/12). Postoperative morbidity did not show substantial differences in both groups and there was no surgical mortality. CONCLUSIONS: HIPEC is a complement to radical surgery/ peritonectomy, which has been shown to be a surgical procedure with high tolerability, low morbimortality, enhanced survival and prolonged disease-free interval in patients with peritoneal carcinomatosis for recurrent ovarian cancer (AU)

No disponible

Tumores del estroma gastrointestinal (GIST): factores pronósticos de supervivencia tras citorreducción R0 / No disponible

Objetivo: analizar los posibles factores pronósticos de supervivenciaen tumores estromales gastrointestinales c-kit positivo(GIST), tras citorreducción óptima R0.Pacientes y método: estudio de 35 pacientes intervenidosen nuestra Unidad desde enero 2002 a febrero 2007, con tumoresdel estroma gastrointestinal CD117/c-kit positivo en los quese alcanzó citorreducción quirúrgica sin residuo tumoral macroscópico.Una base de datos prospectiva nos proporcionó las distintasvariables analizadas, de carácter demográfico, anatómico, clínico,histopatológico e inmunohistoquímico, entre otras. Elanálisis de la supervivencia actuarial se realizó según el método deKaplan-Meier y el análisis multivariante mediante el método de regresiónmúltiple de Cox.Resultados: la supervivencia global a 5 años fue del 77%,con una supervivencia media de 52 meses. El riesgo de malignidadsegún la clasificación de Fletcher y el tamaño tumoral mayorde 10 cm, influyeron significativamente de forma negativa sobrela supervivencia de los pacientes, tras el análisis univariante realizado(p < 0,05). La actividad proliferativa Ki-67 mayor del 50%fue la única covariable con significación estadística en el análisismultivariante. El 20% de los tumores recurrieron. Sólo 3 pacientesmetastáticos recibieron tratamiento adyuvante con mesilato deimatinib, todos ellos con Ki-67 > 50% y vivos en la actualidad.Conclusiones: el índice proliferativo Ki-67 podría representarun excelente marcador pronóstico de supervivencia en aquellospacientes con tumores del estroma gastrointestinal c-kit positivo.Su confirmación y el punto de corte adecuado deberían serobjeto de futuros estudios prospectivos, así como su posible utilidadpara seleccionar pacientes candidatos al tratamiento con mesilatode imatinib

Objective: to analyze the different factors predictive of survivalassociated with optimal R0-cytoreduction in c-kit-positivegastrointestinal stromal tumors.Methods: thirty-five patients were operated on in our OncologicalSurgery Department from January 2002 to February2007 because of CD117/c-kit-positive gastrointestinal stromal tumors,and an optimal surgical cytoreduction was obtained withoutmacroscopical residual disease. Demographic, anatomical, clinical,pathological, and immunohistochemical variables were analyzedfrom a specific database. Survival and multivariate analyseswere developed using Kaplan-Meier and multiple Cox regressionmodels, respectively.Results: five-year overall survival was 77% with a mean survivalof 52 months. Risk of malignant behaviour according toFletcher’s classification and tumor size higher than 10 cm had asignificantly negative influence on overall survival in the univariateanalysis (p < 0.05). Proliferative Ki-67 activity higher than 50%was the only statistically significant variable in the multivariateanalysis. Twenty percent of tumors recurred. Only 3 patients withmetastatic disease received adjuvant treatment with imatinib mesylate,all of them with Ki-67 > 50% and currently alive.Conclusions: the poliferative Ki-67 index could represent anexcellent predictive factor for survival in patients with c-kit-positivestromal gastrointestinal tumors. Confirmation and an adequatecut-off level should be the main objectives for futureprospective studies, mostly focused on the appropriate selectionof optimal candidates to imatinib-mesylate-based treatment

Treatment of peritoneal carcinomatosis from ovarian cancer. Present, future directions and proposals.

Peritoneal carcinomatosis, considered years ago as a final stage of unresectable cancer, can now be managed with curative intention by means of a radical cytoreductive surgical procedure with associated peritonectomy and intraperitoneal chemotherapy, as described by Sugarbaker. Malignant neoplasms such as mesothelioma and pseudomyxoma peritonei, ovarian and colon cancer nowadays are experiencing some new therapeutical approaches. Higher survival rates can be reached in ovarian cancer, which is commonly diagnosed in the presence of peritoneal carcinomatosis, using an optimal cytoreductive radical surgery with intraperitoneal chemotherapy. An actualised review of the treatment of advanced ovarian cancer and a proposal of a national multicentre protocol for the treatment of peritoneal carcinomatosis from ovarian cancer has been performed by a group of Spanish surgeons and oncologists dedicated to a therapeutical approach to this pathology.

Treatment of peritoneal carcinomatosis from ovarian cancer. Present, future directions and proposals

Peritoneal carcinomatosis, considered years ago as a final stage of unresectable cancer, can now be managed with curative intention by means of a radical cytoreductive surgical procedure with associated peritonectomy and intraperitoneal chemotherapy, as described by Sugarbaker. Malignant neoplasms such as mesothelioma and pseudomyxoma peritonei, ovarian and colon cancer nowadays are experiencing some new therapeutical approaches. Higher survival rates can be reached in ovarian cancer, which is commonly diagnosed in the presence of peritoneal carcinomatosis, using an optimal cytoreductive radical surgery with intraperitoneal chemotherapy. An actualised review of the treatment of advanced ovarian cancer and a proposal of a national multicentre protocol for the treatment of peritoneal carcinomatosis from ovarian cancer has been performed by a group of Spanish surgeons and oncologists dedicated to a therapeutical approach to this pathology (AU)

[Gastrointestinal stromal tumors (GIST): factors predictive of survival after R0-cytoreduction]. / Tumores del estroma gastrointestinal (GIST): factores pronósticos de supervivencia tras citorreducción R0.

OBJECTIVE: To analyze the different factors predictive of survival associated with optimal R0-cytoreduction in c-kit-positive gastrointestinal stromal tumors. METHODS: Thirty-five patients were operated on in our Oncological Surgery Department from January 2002 to February 2007 because of CD117/c-kit-positive gastrointestinal stromal tumors, and an optimal surgical cytoreduction was obtained without macroscopical residual disease. Demographic, anatomical, clinical, pathological, and immunohistochemical variables were analyzed from a specific database. Survival and multivariate analyses were developed using Kaplan-Meier and multiple Cox regression models, respectively. RESULTS: Five-year overall survival was 77% with a mean survival of 52 months. Risk of malignant behaviour according to Fletcher s classification and tumor size higher than 10 cm had a significantly negative influence on overall survival in the univariate analysis (p < 0.05). Proliferative Ki-67 activity higher than 50% was the only statistically significant variable in the multivariate analysis. Twenty percent of tumors recurred. Only 3 patients with metastatic disease received adjuvant treatment with imatinib mesylate, all of them with Ki-67 > 50% and currently alive. CONCLUSIONS: The poliferative Ki-67 index could represent an excellent predictive factor for survival in patients with c-kit-positive stromal gastrointestinal tumors. Confirmation and an adequate cut-off level should be the main objectives for future prospective studies, mostly focused on the appropriate selection of optimal candidates to imatinib-mesylate-based treatment.