Medium levels of transcription and replication related chromosomal instability are associated with poor clinical outcome.

Genomic instability (GI) influences treatment efficacy and resistance, and an accurate measure of it is lacking. Current measures of GI are based on counts of specific structural variation (SV) and mutational signatures. Here, we present a holistic approach to measuring GI based on the quantification of the steady-state equilibrium between DNA damage and repair as assessed by the residual breakpoints (BP) remaining after repair, irrespective of SV type. We use the notion of Hscore, a BP "hotspotness" magnitude scale, to measure the propensity of genomic structural or functional DNA elements to break more than expected by chance. We then derived new measures of transcription- and replication-associated GI that we call iTRAC (transcription-associated chromosomal instability index) and iRACIN (replication-associated chromosomal instability index). We show that iTRAC and iRACIN are predictive of metastatic relapse in Leiomyosarcoma (LMS) and that they may be combined to form a new classifier called MAGIC (mixed transcription- and replication-associated genomic instability classifier). MAGIC outperforms the gold standards FNCLCC and CINSARC in stratifying metastatic risk in LMS. Furthermore, iTRAC stratifies chemotherapeutic response in LMS. We finally show that this approach is applicable to other cancers.

Risk factors for gastric perforation after cytoreductive surgery in patients with peritoneal carcinomatosis: Splenectomy and increased body mass index.

BACKGROUND: Gastric perforation after cytoreductive surgery (CRS) is an infrequent complication. There is lack of evidence regarding the risk factors for this postoperative complication. The aim of this study was to assess the prevalence of postoperative gastric perforation in patients undergoing CRS for peritoneal carcinomatosis (PC) and to evaluate risk factors predisposing to this complication. METHODS: We designed a unicentric retrospective study to identify all patients who underwent an open upfront or interval CRS after a primary diagnosis of PC of different origins between March 2007 and December 2018 at a French Comprehensive Cancer Center. The main outcome was the occurrence of postoperative gastric perforation. RESULTS: Five hundred thirty-three patients underwent a CRS for PC during the study period and 13 (2.4%) presented a postoperative gastric perforation with a mortality rate of 23% (3/13). Neoadjuvant chemotherapy was administered in 283 (53.1%) patients and 99 (18.6%) received hyperthermic intraperitoneal chemotherapy (HIPEC). In the univariate analysis, body mass index (BMI), peritoneal cancer index, splenectomy, distal pancreatectomy, and histology were significantly associated with postoperative gastric perforation. After multivariate analysis, BMI (OR [95%CI] = 1.13 [1.05-1.22], p = 0.002) and splenectomy (OR [95%CI] = 26.65 [1.39-509.67], p = 0.029) remained significantly related to the primary outcome. CONCLUSIONS: Gastric perforation after CRS is a rare event with a high rate of mortality. While splenectomy and increased BMI are risk factors associated with this complication, HIPEC does not seem to be related. Gastric perforation is probably an ischemic complication due to a multifactorial process. Preventive measures such as preservation of the gastroepiploic arcade and prophylactic suture of the greater gastric curvature require further assessment.

Frozen section examination of sentinel lymph nodes can be used as a decisional tool in the surgical management of early cervical cancer.

INTRODUCTION: Sentinel lymph node (SLN) detection has been shown to be accurate in detecting lymph node involvement in early-stage cervical cancer. The objective of this study was to evaluate the accuracy of frozen section examination in the assessment of SLN status, with the aim of adequately driving the intra-operative decision. METHODS: We designed a retrospective study including patients from two comprehensive cancer centers between January 2001 and December 2018 with early-stage cervical cancer (IA1-IB2 according to International Federation of Gynecology and Obstetrics (FIGO) 2018) undergoing SLN dissection. The SLN procedure was performed using a cervical injection with technetium-99m combined with blue dye or indocyanine green in most cases. RESULTS: A total of 176 patients fulfilled inclusion criteria. Bilateral mapping was detected in 153 (86.7%) of them. Nineteen of these patients (12.4%) had SLN involvement: 13 with macrometastases, three with micrometastases and three with isolated tumor cells (ITC). Macrometastatic disease was missed on frozen section in 3/13 FIGO 2018 stage IIIC patients. The three patients with ITC were also missed by frozen section examination.Considering only macrometastases as lymph node involvement, frozen section sensitivity was 76.9% (95% CI 49.7 to 91.8) and negative predictive value (NPV) was 97.9% (95% CI 94.0 to 99.3) in patients with bilateral detection. Including micrometastases, sensitivity was 81.2% (95% CI 57.0 to 93.4) and NPV remained at 97.9% (95% CI 93.9 to 99.3). CONCLUSIONS: With a prevalence of final-stage IIIC in patients with pre-operative early-stage cervical cancer of the order of 10% in this series, the NPV of frozen section examination of SLN is very high, with an inferior limit of the CI superior to 94%. Diagnostic accuracy remains acceptable even if micrometastases are considered. The impact of missed ITC has not been established. Frozen section examination can be incorporated in the intra-operative decision algorithm.

Magnetic resonance imaging after external beam radiotherapy and concurrent chemotherapy for locally advanced cervical cancer helps to identify patients at risk of recurrence.

OBJECTIVE: Tumor volume and regression after external beam radiotherapy have been shown to be accurate parameters to assess treatment response via magnetic resonance imaging (MRI). The aim of the study was to evaluate the prognostic value of tumor size reduction rate after external beam radiotherapy and chemotherapy prior to brachytherapy. METHODS: Patients with locally advanced cervical cancer treated at two French comprehensive cancer centers between 1998 and 2010 were included. Treatment was pelvic external beam radiotherapy with platinum based chemotherapy followed by brachytherapy. Records were reviewed for demographic, clinical, imaging, treatment, and follow-up data. Anonymized linked data were used to ascertain the association between pre-external and post-external beam radiotherapy MRI results, and survival data. RESULTS: 185 patients were included in the study. Median age at diagnosis was 45 years (range 26-72). 77 patients (41.6%) were International Federation of Gynecology and Obstetrics stage IB2-IIA disease and 108 patients (58.4%) were stage IIB-IVA. Median tumor size after external beam radiotherapy and chemotherapy was 2.0 cm (range 0.0-8.0) and median tumor size reduction rate was 62.4% (range 0.0-100.0%). Tumor size and tumor reduction rate at 45 Gy external beam radiotherapy MRI were significantly associated with local recurrence free survival (P<0.001), disease free survival, and overall survival (P<0.05). Tumor reduction rate ≥60% was significantly associated with a decreased risk of relapse and death (HR (95% CI) 0.21 (0.09 to 0.50), P=0.001 for local recurrence free survival; 0.48 (0.30 to 0.77) P=0.002 for disease free survival; and 0.51 (0.29 to 0.88), P=0.014 for overall survival). CONCLUSIONS: Tumor size reduction rate >60% between pre-therapeutic and post-therapeutic 45 Gy external beam radiotherapy with concurrent chemotherapy was associated with improved survival. Future studies may help to identify patients who may ultimately benefit from completion surgery, adjuvant chemotherapy, and closer follow-up.

Well-Differentiated Papillary Mesothelioma of the Peritoneum: A Retrospective Study from the RENAPE Observational Registry.

BACKGROUND: Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare entity. Questions regarding management are still being debated as no more than 50 cases have been reported in the literature. OBJECTIVE: We aimed to analyze the clinical, therapeutic, and prognostic data of patients with WDPMP from the RENAPE observational registry. PATIENTS AND METHODS: All patients diagnosed with WDPMP and prospectively included in the RENAPE national registry between 2010 and 2018 were also included in our study. Expert pathologists from the RENA-PATH group confirmed all cases. All clinical, therapeutic, postoperative, and prognostic data were extracted and analyzed. RESULTS: We report on 56 patients with a mean age of 52 years (range 21-74). WDPMP was incidentally diagnosed during imaging or surgery in 16% and 36% of patients, respectively, and an association with synchronous malignancy was found in 18% of patients. Nine lesions showed discrete signs of fatty invasion. The median Peritoneal Cancer Index was 11 (range 0-33). Eleven patients were treated with definitive excision, 4 were treated with cytoreductive surgery (CRS) only, 37 were treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), and 2 were treated with CRS plus HIPEC plus early postoperative intraperitoneal chemotherapy. CRS was considered to be complete in 90% of cases. One patient died postoperatively and 16 patients (31%) faced postoperative complications. The median disease-free survival was 144 months; Four patients relapsed, with a median period of 27 months. No prognostic factors could be identified. CONCLUSIONS: Our analysis confirms the favorable prognosis of WDPMP. CRS and HIPEC could be a therapeutic option for diffuse, symptomatic, and/or recurrent disease.

Laparoscopic hand-assisted Miami Pouch after pelvic exenteration in 10 steps.

BACKGROUND: Improvements in surgical technique of pelvic exenteration have mainly occurred in the reconstructive phase of the procedure. Quality of life seems to be improved when performing continent rather than non-continent urinary diversion [1]. Unfortunately, Miami continent urinary pouch is a surgical technique not frequently used among surgeons. METHODS: This video illustrates the creation of a laparoscopic hand-assisted Miami Pouch in 10 consecutive steps. We present the case of a patient with an isolated central pelvic recurrence of cervical cancer who underwent a laparoscopic anterior pelvic exenteration, which is not included in the film. The surgery was performed by an experienced oncological surgeon in a French comprehensive cancer center. RESULTS: We split the surgical technique in the 10 following steps: CONCLUSIONS: Miami Pouch is a urinary reconstructive procedure that can improve quality of life after pelvic exenteration. As it has been previously reported, this film illustrates the feasibility of laparoscopic hand-assisted Miami Pouch after laparoscopic anterior pelvic exenteration [2,3]. A step-by-step comprehensive standardization of surgical techniques shortens learning curve of training surgeons [4].

Impact of Combination Chemotherapy in Peritoneal Mesothelioma Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The RENAPE Study.

BACKGROUND: The introduction of cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improved the prognosis of selected patients with peritoneal mesothelioma (PM). OBJECTIVE: The objective of our study was to evaluate whether different HIPEC agents were associated with different outcomes in patients with PM. METHODS: From the RENAPE database, we selected all patients with histology-proven PM who underwent CRS + HIPEC from 1989 to 2014. Inclusion criteria were age ≤ 80 years, performance status ≤ 2, and no extraperitoneal metastases. RESULTS: Overall, 249 patients underwent CRS + HIPEC for PM. The HIPEC regimen included five chemotherapeutic agents (CAs), consisting of cisplatin, doxorubicin, mitomycin-C, oxaliplatin, and irinotecan. When considering all CAs (alone or in combination), there was no significant statistical difference in regard to postoperative overall survival (OS). However, OS was better when using two CAs (group 2 drugs) versus one CA (group 1 drug) (p = 0.03). The different CA regimens were equally distributed between the two groups. This association between OS and HIPEC agent, as well as a trend for better progression-free survival, were both observed in the two-drug group versus the one-drug group (p = 0.009) for patients undergoing complete cytoreductive surgery (CC-0) with an epithelioid subtype. CONCLUSIONS: This large study seems to show improved OS when combined CAs, especially with platinum-based regimens, are used for HIPEC in patients with PM, but needs to be confirmed by a randomized controlled trial.

Left Lateral Endosurgical Extraperitoneal Total Hysterectomy with Para-Aortic and Pelvic Lymphadenectomy: A Novel Approach for the Obese Patient with Endometrial Cancer.

STUDY OBJECTIVE: To describe the left lateral extraperitoneal approach to perform complete para-aortic and pelvic lymphadenectomy and transverse total hysterectomy from left to right as a novel approach to treat obese patients with endometrial cancer. Laparoscopic management of obese patients represents a challenge for the gynecologic surgeon. The extraperitoneal approach is technically easier in the obese patient because it naturally creates a bowel-free operative field. DESIGN: A prospective pilot bicentric and descriptive study (Canadian Task Force classification III) evaluating the feasibility and reproducibility of the transverse total hysterectomy and complete lymphadenectomy through left endoscopic extraperitoneal approach in obese patients with endometrial cancer. SETTING: A comprehensive cancer center in Toulouse and a teaching university hospital in Madrid. PATIENTS: Sixteen consecutive overweight or obese patients (body mass index > 25 kg/m2) with high-risk endometrial cancer. INTERVENTIONS: Currently, the left extraperitoneal approach is routinely used to perform complete para-aortic and pelvic lymphadenectomy. It provides direct access to the left ureter and uterine pedicle. This access can be extended to the right side when performing a transverse extrafascial hysterectomy from left to right. The procedure starts from the left extraperitoneal space, where the left uterine artery is sectioned and the vesicovaginal and rectovaginal septa are developed, without opening the peritoneum. Colpotomy is performed from the left to the right side. Once the right ureter is identified, the right uterine artery can be safely transected. Alternatively, the right uterine artery can be sealed and sectioned during the right pelvic lymphadenectomy. At the end of the procedure the peritoneum is opened to complete the surgery. MEASUREMENTS AND MAIN RESULTS: Between May 2015 and February 2016, 16 consecutive obese patients were successfully treated using this technique. Median patient age was 62 years (range, 44-78), and median body mass index was 32.5 kg/m2 (range, 26-42). In 3 cases the right uterine artery was sealed during the right pelvic lymphadenectomy, in 11 cases after completing vaginal opening, and in 2 cases after peritoneal opening. The median operative time was 137.5 minutes (range, 66-260). The median blood loss was 85 mL (range, 0-260), and no blood transfusion was required in any of our 16 patients. No significant complications occurred. CONCLUSION: The full extraperitoneal approach represents an interesting alternative strategy for the surgical treatment of obese patients with high-risk endometrial cancer.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis in the Elderly: A Case-Controlled, Multicenter Study.

OBJECTIVE: This study was designed to identify factors associated with morbidity and mortality in patients older than 70 years who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC). BACKGROUND: Major surgery is associated with higher morbidity and mortality in elderly patients. For PC, CRS and HIPEC is the only current potential curative therapy, but the risks inherent to this patient population have called its benefits into question. METHODS: We retrospectively analyzed a multi-center database from 1989 to 2015. All patients who underwent CRS and HIPEC for PC were selected and patients older than 70 years were matched 1:4 with a younger cohort according to cancer origin, peritoneal cancer index (PCI), and completeness of cytoreduction. Major morbidity and mortality were analyzed. RESULTS: Of 2328 patients, 188 patients older than aged 70 years were matched with 704 younger patients. Patients older than aged 70 years demonstrated a higher American Society of Anesthesiologist score (≥ASA III 10.8 vs. 6.6 %, p = 0.008). There was no difference in overall 90-day morbidity (≥70: 45.7 % vs. <70: 44.5 %; p = 0.171); however, patients older than 70 years had significantly more cardiovascular complications (13.8 vs. 9.2 %, p = 0.044). Differences between the older and younger cohorts failed to reach significance for 90-day mortality (5.4 and 2.7 %, respectively; p = 0.052), and failure-to-rescue (11.6 and 6.1 %, respectively; p = 0.078). In multivariate analysis, PCI > 7 (95 % CI 1.051-5.798, p = 0.038) and HIPEC duration (95 % CI 1.106-6.235, p = 0.028) were independent factors associated with morbidity in elderly patients. CONCLUSIONS: CRS and HIPEC appear feasible for selected patients older than aged 70 years, albeit with a higher risk of medical complications associated with increased mortality.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for First Relapse of Ovarian Cancer.

BACKGROUND: To assess impact of surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients treated for a first relapse of ovarian cancer (FROC). PATIENTS AND METHODS: Patients with a FROC treated with second-line chemotherapy, surgery and HIPEC were retrospectively included from 13 Institutions. Studied parameters were interval free between the end of initial treatment and the first relapse, second-line chemotherapy, peritoneal cancer index and completeness of surgery, HIPEC, mortality and morbidity, pathological results and survival. RESULTS: From 2001 to 2010, 314 patients were included. The main strategy was secondary chemotherapy followed by surgery and HIPEC (269/314-85.6%). Mortality and morbidity rates were respectively 1% and 30.9%. Median follow-up was 50 months, 5-year overall survival was 38.0%, with no difference between platinum-sensitive or -resistant patients and 5-year disease-free survival was 14%. CONCLUSION: HIPEC allows encouraging survival in the treatment of FROC, better in case of complete surgery, with acceptable mortality and morbidity rates.

Population pharmacokinetics of peritoneal, plasma ultrafiltrated and protein-bound oxaliplatin concentrations in patients with disseminated peritoneal cancer after intraperitoneal hyperthermic chemoperfusion of oxaliplatin following cytoreductive surgery: correlation between oxaliplatin exposure and thrombocytopenia.

PURPOSE: First, to evaluate the peritoneal (IP), plasma ultrafiltrated (UF) and protein-bound (B) pharmacokinetics (PK) of oxaliplatin after intraperitoneal hyperthermic chemoperfusion (HIPEC) following cytoreductive surgery. Second, to evaluate the relationship between oxaliplatin exposure and observed toxicity. METHODS: IP, UF, and B concentrations from 75 patients treated by 30-min oxaliplatin-based HIPEC procedures were analysed according to a pharmacokinetic modelling approach using NONMEM. Oxaliplatin was administered in a 5 % dextrose solution (2 L/m(2)) at 360 (n = 58) or 460 mg/m(2) (n = 17). The most frequently observed toxicities were related to the peritoneal, systemic exposures and to the parameters corresponding to the oxaliplatin absorption from peritoneal cavity into plasma. RESULTS: IP (n = 536), UF (n = 669) and B (n = 661) concentrations were simultaneously described according to a five-compartment PK model with irreversible nonlinear binding from UF to B according to a Michaelis-Menten equation. The mean (±SD) maximum fraction of dose absorbed and elimination half-life from the peritoneum was 53.7 % (±8.5) and 0.49 h (±0.1), respectively. The mean (±SD) ratio AUC(IP)/AUC(UF) was 5.3 (±2) confirming the pharmacokinetic advantage of the procedure. Haemoperitoneum (22.7 %), neuropathy (18.7 %), grade 3/4 thrombocytopenia (13.3 %) were the most frequently reported toxicities. AUC(UF) accounts for approximately 12 % of the variation in the maximum percentage of platelet decrease (r = 0.35, p = 0.002). Thrombocytopenia was correlated with higher AUCUF, partly dependent on the extent and rate of oxaliplatin absorption. CONCLUSIONS: Despite a common dose administered, variability in peritoneal and systemic oxaliplatin exposures are observed, leading to differences in haematological toxicity between patients.

Survival benefit of hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer: a multi-institutional case control study.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) and complete surgical removal of the tumor, in relapsing patients may provide a clinical benefit. There is no consensus considering the place of HIPEC for patients who had first ovarian cancer relapse. To assess for possible efficacy of HIPEC on overall survival (OS) rates in this situation, we performed a multi-institutional study. METHODS: The current study was a retrospective case control multi-institutional study comparing a group of patients treated with HIPEC to a group of patients treated without HIPEC. Inclusion criteria were first relapse of a serous ovarian carcinoma and >6 months after the end of initial treatment. Exclusion criteria were another pathological subtype of ovarian cancer, a relapse at <6 months after initial treatment, and a second relapse or more. We aimed to assess OS, morbidity, and mortality rates and prognostic factors. RESULTS: From June 1997-July 2011, 42 patients were included, 23 in the HIPEC group and 19 in the control group. Each patient from the two groups had a complete secondary surgery at the time of the first relapse. At 4 years OS was 75.6 % in the HIPEC group and 19.4 % in the control group (p = 0.013). In a multivariate analysis, HIPEC and interval-free before the end of initial treatment were both independent prognostic factors. CONCLUSION: When compared to the control group, complete secondary surgery and HIPEC appear to afford a better OS rate than complete secondary surgery alone, in case of first ovarian cancer relapse. Further randomized trials are warranted to confirm these results.

Oxaliplatin-based hyperthermic intraperitoneal chemotherapy in primary or recurrent epithelial ovarian cancer: A pilot study of 31 patients.

BACKGROUND: The feasibility and safety of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) associated with cytoreductive surgery (CRS) was assessed in patients with peritoneal carcinomatosis resulting from primary advanced or relapsing epithelial ovarian cancer (EOC). METHODS: Thirty-one patients received neoadjuvant platin-based chemotherapy followed by oxaliplatin-based HIPEC associated with CRS as consolidation of primary therapy (n = 19) or for relapsing disease (n = 12). Grade 3/4 complications were recorded according to National Cancer Institute definitions. RESULTS: Median peritoneal carcinomatosis index (PCI) was 2.7 after neoadjuvant chemotherapy. Mean duration of surgery was 352 min (range 105-614) and median hospital stay was 11 days (range 6-87). Grade 3 toxicity was observed in nine patients: five required repeat surgery, two an invasive procedure, four rehospitalization, and three a return to the ICU. No grade 4 toxicity occurred, excepted one hypokalemia. Median progression-free survival (PFS) for primary advanced EOC was 13.2 months and 1-year PFS was 59.3%. Median PFS for relapsing patients was 14.3 months and 1-year PFS was 54.4%. CONCLUSION: CRS with oxaliplatin-based HIPEC is feasible and relatively safe in recurrent and primary EOC. HIPEC after neoadjuvant chemotherapy reduces the PCI and decreases the number of surgical procedures and morbidity. Further evaluations of this procedure are required to assess the survival benefits.

[Importance of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer]. / Place de la chimio-hyperthermie intrapéritonéale (CHIP) dans le cancer de l'ovaire.

Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer. Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer. Literature review reveals a number of different experiences on feasibility of this technique, but scientific evidence of current studies remains poor. Much more research is still required to elucidate unanswered questions. Before this technique can be routinely used, some controversial aspects have to be defined: which drug is the best to deliver and at what temperature, is it necessary to use mono- or poly-chemotherapy regimens, which is the time-point for HIPEC in the natural history of ovarian cancer: at front-line therapy, at interval debulking following initial neo-adjuvant chemotherapy, at consolidation following front-line therapy, or at the time of recurrence. Nevertheless, we must not forget that the most important issue in ovarian cancer prognosis is maximal cytoreductive surgery, with no residual disease at completion of initial surgery.

Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin.

PURPOSE: To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis (PC) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated. The standard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period, but who had not benefited from HIPEC because the technique was unavailable in the center at that time. RESULTS: Forty-eight patients were retrospectively included in the standard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospectively. All characteristics were comparable except age and tumor differentiation. There was no difference in systemic chemotherapy, with a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard group versus 63 months in the HIPEC group. Two-year and 5-year overall survival rates were 81% and 51% for the HIPEC group, respectively, and 65% and 13% for the standard group, respectively. Median survival was 23.9 months in the standard group versus 62.7 months in the HIPEC group (P < .05, log-rank test). CONCLUSION: Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.

Cost-effectiveness of intraperitoneal chemohyperthermia in the treatment of peritoneal carcinomatosis from colorectal cancer.

OBJECTIVES: Our purpose was to assess the cost-effectiveness of intraperitoneal chemohyperthermia (IPCH) compared to palliative chemotherapy (STANDARD) against peritoneal carcinomatosis arising from colorectal cancer. METHODS: We performed a retrospective study of 96 patients whose peritoneal carcinomatosis had been diagnosed between January 1998 and December 2003 and treated either with IPCH or with palliative chemotherapy in French comprehensive cancer centers. Patients were followed up over a 3-year period. Effectiveness was measured by restricted mean survival at 3 years. The Bang and Tsiatis method was used to handle cost-censored data. The confidence limits of the mean cost per patient in each group and the mean incremental cost per life-year saved were computed using 1000 bootstrapreplicates. We also computed an acceptability curve for the incremental cost-effectiveness ratio (ICER). RESULTS: We found that IPCH improved survival and was more costly than STANDARD treatment. Over a 3-year observation period, IPCH yielded an average survival gain of 8.3 months at the additional cost of euro58,086 (95% confidence interval 35,893-112,839) per life-year saved. CONCLUSION: The ICER of IPCH is acceptable given the severity and burden of peritoneal carcinomatosis for which there is no alternative curative treatment.

Pharmacokinetics of oxaliplatin during open versus laparoscopically assisted heated intraoperative intraperitoneal chemotherapy (HIPEC): an experimental study.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is being evaluated for patients with minimal residual or no residual disease after primary surgery and chemotherapy for stage III ovarian carcinoma. The technical feasibility of the laparoscopic approach for HIPEC has been demonstrated in a previous study. An experimental study on the porcine model was carried out to compare oxaliplatin pharmacokinetics during a laparoscopic-assisted procedure versus the coliseum technique for HIPEC. METHODS: Adult pigs received an HIPEC procedure that was based on 460 mg/m(2) of oxaliplatin over 30 minutes with a perfusate heated at 41 degrees C to 43 degrees C. The HIPEC drains were placed in the upper and lower quadrants of the abdomen. Peritoneal fluid and blood samples were collected every 10 minutes during the procedure, and the pharmacokinetics of oxaliplatin was studied. RESULTS: Two groups of 10 adult pigs were studied. All the procedures were successfully completed with an adequate intra-abdominal temperature and distribution. No major technical problems were encountered. At the end of the HIPEC, 41.5% of the molecule was absorbed in the laparoscopic group compared with 33.4% in the laparotomy group (P = .0543). Peritoneal oxaliplatin half-life (T((1/2))) was significantly faster in the laparoscopic procedure (median, 37.5 vs. 59.3 minutes, P = .02). The area under the curve ratio of peritoneal to plasma reflects a more important oxaliplatin crossing through the peritoneal barrier in the laparoscopic procedure (ratio, 16.4 in the closed procedure vs. 28.1 in the open one; P = .03). CONCLUSIONS: This study confirms the technical feasibility and reliability of the laparoscopic approach for HIPEC, and it extends knowledge concerning peritoneal drug absorption. Oxaliplatin absorption is far higher with laparoscopy in terms of time course in peritoneal perfusion. Clinical application in selected patients may be expected after further experimental investigation designed to define the adequate drug dosage.

Feasibility of laparoscopic peritonectomy followed by intra-peritoneal chemohyperthermia: an experimental study.

OBJECTIVE: Hyperthermic intraperitoneal chemotherapy (HIPEC) is being evaluated for patients with minimal residual or no residual disease after primary surgery and chemotherapy for stage III ovarian carcinoma. The use of operative laparoscopy to perform peritonectomy and HIPEC is reported. METHODS: Five adult pigs were used. The placement of trocars in the four quadrants was planned in order to complete a total peritonectomy and then to place the HIPEC drains. The umbilical trocar was then replaced manually by the surgeon through a Lapdisc to manipulate the bowel loops. The abdominal cavity was filled with heated saline (43 degrees C), and the pumps were activated for 30 min. RESULTS: The procedure was successfully completed with an adequate intraabdominal temperature and distribution. CONCLUSION: These preliminary data suggest the technical feasibility of the laparoscopic approach for HIPEC, in an animal model without carcinomatosis. Our ongoing research is designed to gather pharmacokinetic data in an experimental controlled randomized fashion to compare a laparoscopic to a laparotomy approach on the same model.