Intraoperative Intraperitoneal Chemotherapy Research Articles

Intraperitoneal Chemotherapy as a Multimodal Treatment for Gastric Cancer Patients with Peritoneal Metastasis

Peritoneal metastasis of gastric cancer is mainly caused by the dispersion of free cancer cells from the serosal surface of the invaded stomach, from surgically transected lymphatic channels, and from tumor cell-containing blood from the primary lesion into the peritoneal cavity. Intraperitoneal chemotherapy (IPC) combined with surgery has performed for the prevention and treatment of peritoneal metastasis in gastric cancer. The efficacy of this technique is influenced by the pharmacokinetic advantage achievable with the anticancer drug, timing of administration, combination with hyperthermia, and tumor volume. The pharmacokinetic advantage for peritoneal cavity exposure relative to peripheral circulation by intraperitoneal delivery for drugs including cisplatin (10-fold advantage), mitomycin C (20- to 30-fold advantage), docetaxel (500-fold advantage), and paclitaxel (1000-fold advantage) has been confirmed. To avoid uneven drug distribution in the peritoneal cavity and the re-growth of residual tumor, it seems to be reasonable to perform IPC perioperatively; however, early perioperative intraperitoneal chemotherapy (EPIC) has a relatively high morbidity rate compared with intraoperative IPC. Hyperthermia has both cytotoxicity of itself and a synergistic effect with anticancer drugs, especially mitomycin C. In the adjuvant setting, patients with either hyperthermic intraperitoneal chemotherapy (HIPEC) or EPIC showed a significant improvement of survival compared to those with surgery alone. In addition, extensive intraoperative peritoneal lavage (EIPL) seems also to be a reasonable method to reduce free cancer cells in the peritoneal cavity. For the treatment of peritoneal metastasis, cytoreductive surgery which achieves R0 or R1 resection followed by IPC has demonstrated a survival benefit, whereas gross residual tumor (R2) treated by IPC has shown poor prognosis. Extensive cytoreductive surgery, such as peritonectomy, followed by IPC achieved long-term survival for selected patients, though this aggressive procedure led to high morbidity and mortality rates. It seems that combined chemotherapy (systemically and intraperitoneally) followed by conversion surgery can be expected to be a powerful procedure for the patients with gross peritoneal tumors.

Narrow-Band Imaging in Laparoscopic Management of Recurrent Platinum Sensitive Ovarian Cancer

The recurrence risk for advanced ovarian cancer managed using surgical cytoreduction and adjuvant chemotherapy is 60% to 70% [1]. The standard treatment of recurrent disease is still under debate and depends on patient history and characteristics of the tumor [1,2]. Recently, the role of cytoreductive surgery for platinum-sensitive cancer has been reassessed, and findings indicate that residual tumor is the most valuable determining factor for survival, even in recurrent disease [3]. Preliminary data seem to demonstrate that the addition of hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) could improve overall survival in these patients [4,5].

Palliative treatment of the advanced gastric cancer by means of surgery and HIPEC

We demonstrate a case report of the patient who suffered from advanced gastric cancer and was treated by means of surgery and HIPEC. Gastric cancer is a therapeutic challenge in the European countries due to late diagnosis, advanced stages of the disease in time of diagnosis and early recurrence in cases where a radical surgery is possible. The patient with an advanced gastric cancer (pT3N2M1 - peritoneal and ovarian metastases) was treated by means of radical surgery in combination with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC). Surgical treatment was followed by a standard chemotherapy. Due to recurrence, there was the second look surgery one year later again with HIPEC procedure. Patient survived 32 months after diagnosis and despite intraperitoneal recurrence she never developed clinically significant ascites and she never suffered from intestinal obstruction. This case demonstrate a potential benefit of new oncosurgical approach -radical surgery + HIPEC + EPIC in the treatment of gastric cancers (Tab. 2, Fig. 6, Graph 4, Ref. 18). Text in PDF www.elis.sk.

Peritoneal Dissemination of Hepatoid Carcinoma of the Ovary Treated with Cytoreductive Surgery and Hyperthermic Intraoperative Intraperitoneal Chemotherapy

Hepatoid carcinoma of the ovary (HCO) was first reported in 1987 in 5 cases of malignant ovarian tumors which were similar to hepatocarcinoma in the histological analysis. We report the first case in the literature of a patient diagnosed with HCO treated using HIPEC after extensive cytoreductive surgery, and we discuss the value of this therapeutical option in patients with HCO.

Akuter Sättigungsabfall nach Peritonektomie und hyperthermer intraperitonealer Chemotherapie

Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) may have a significant impact on physiological functions and is therefore a special challenge for anesthetists. In the presented case after opening the parietal pleura during subphrenical peritonectomy the HIPEC solution accidentally leaked into the right hemithorax with subsequent pleural effusion of more than 2,000ml. After extubation the patient presented with acute oxygen desaturation and orthopnea. Following pleural sonography and chest X-ray in the operating theatre and recovery area, a thorax drainage was inserted into the pleural space and ventilation support was provided by non-invasive continuous positive air pressure (CPAP) ventilation. With reference to recent publications the anesthesiological management of patients undergoing HIPEC is presented.

Comparison Different Methods of Intraoperative and Intraperitoneal Chemotherapy for Patients with Gastric Cancer: A Meta-analysis

To investigate the efficacy and safety of intraperitoneal chemotherapy (IPC) for patients with gastric cancer and to compare effects between different regimens of IPC. Randomized controlled trials comparing the effects of surgery plus intraperitoneal chemotherapy with surgery alone or comparing the efficacy between different regimens of intraperitoneal chemotherapy were searched for in Medline, Embase, Pubmed, the Cochrane Library and the Chinese BioMedical Disc and so on by two independent reviewers. After quality assessment and data extraction, data were pooled for meta-analysis using RevMan5.16 software. Tests of interaction were used to test for differences of effects among subgroups grouped according to different IPC regimens. Fifteen RCTs with a total of 1713 patients with gastric cancer were included for quality assessment and data extraction. Ten studies were judged to be of fair quality and entered into meta-analysis. Hyperthermic intraoperative intraperitoneal chemotherapy (HR=0.60, P<0.01), hyperthermic intraoperative intraperitoneal chemotherapy plus postoperative intraperitoneal chemotherapy (HR=0.47, P<0.01) and normothermic intraoperative intraperitoneal chemotherapy (HR=0.70, P=0.01) were associated with a significant improvement in overall survival. Tests of interaction showed that hyperthermia and additional postoperative intraperitoneal chemotherapy did not impact on its effect. Further analysis revealed that intraperitoneal chemotherapy remarkably decrease the rate of postoperative hepatic metastasis by 73% (OR=0.27, 95% CI=0.12 to 0.67, P<0.01). However, intraperitoneal chemotherapy increased risks of marrow depression (OR=5.74, P<0.01), fever (OR=3.67, P=0.02) and intra-abdominal abscess (OR=3.57, P<0.01). The present meta-analysis demonstrates that hyperthermic intraoperative intraperitoneal chemotherapy and normothermic intraoperative intraperitoneal chemotherapy should be recommended to treat patients with gastric cancer because of improvement in overall survival. However, it is noteworthy that intraperitoneal chemotherapy can increase the risks of marrow depression, intra-abdominal abscesses, and fever.

Cytoreductive surgery plus HIPEC in platinum-sensitive recurrent ovarian cancer patients: A case–control study on survival in patients with two year follow-up

ObjectivesTo compare survival data in platinum-sensitive recurrent ovarian cancer patients submitted to secondary cytoreduction (SCR) plus hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) (Cases) and a similar group of women not experiencing HIPEC (Controls). MethodsCase–control study, matching 30 Cases with 37 Controls, with at least 24months of follow-up. ResultsGroups were comparable for all characteristics, except for a higher proportion of patients with single-nodule relapses is the Controls (19 vs. 6; p=0.011). Median follow-up time was 46months in the Cases and 36months in the Controls. Twenty patients (66.6%) experienced secondary recurrence in the Cases and 37 women (100%) in the Controls (p=0.001). Moreover, 7 (23.3%) and 23 (62.2%) patients died of disease in the Cases and Controls respectively (p=0.003). The duration of secondary response was 26months in the Cases and 15months in the Controls (p=0.004). ConclusionsThe combination of SCR and HIPEC seems to improve survival rate in patients suffering from platinum-sensitive EOC recurrence with respect to no-HIPEC treatments. This result further supports the need of a randomized trial.

PP142-MON ASSESSMENT OF NUTRITIONAL AND MICRONUTRIENT STATUS IN HOSPITALIZED PATIENTS UNDERGOING CYTOREDUCTIVE SURGERY AND HYPERTHERMIC INTRAOPERATIVE INTRAPERITONEAL CHEMOTHERAPY

Rationale: The treatment of selected cases of peritoneal carcinomatosis with cytoreductive surgery for radical intent with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is a technique increasingly used. We assessed the nutritional and micronutrients status in patients undergoing HIPEC in a general surgery department of a university hospital. Methods: We studied 21 consecutive patients, 12 women (57%) and 9 men, mean age 53±11 years. We measured anthropometric parameters, BIA and the levels of visceral proteins and micronutrients before surgery and weekly thereafter. Statistical analysis was performed using the Student t-test to compare means and nonparametric tests. Results: The primary tumors were: ovary in 6 patients (29%), colon 5 (24%), appendiceal pseudomyxoma 4 (19%), mesothelioma 3 (14%), gastric 1 (5%), carcinoid 1 (5%), other 1 (5%). Twenty patients received parenteral nutrition for 10.9±10days. The average stay in hospital was 20±10days. The results of anthropometry, albumin and micronutrients before and after surgery are shown in the Table.

Hyperthermic intraperitoneal chemotherapy in ovarian cancer: rationale and clinical data

The outcome of ovarian cancer remains poor with conventional therapy. Intraperitoneal chemotherapy has some advantages over systemic chemotherapy, including favorable pharmacokinetics and optimal treatment timing. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) provides improved exposure of the entire seroperitoneal surface to the agent and utilizes the direct cytoxic and drug-enhancing effect of hyperthermia. While standard normothermic, nonintraoperative, intraperitoneal chemotherapy has been demonstrated to be beneficial in randomized trials and meta-analyses, there are no data from randomized HIPEC trials available yet. Cautious extrapolation of data from standard normothermic, nonintraoperative, intraperitoneal chemotherapy and data from Phase II and nonrandomized comparative studies suggest that HIPEC delivered at the time of surgery for ovarian cancer has definite potential. Data from ongoing randomized HIPEC trials to adequately answer the question of whether the addition of HIPEC actually prolongs survival in patients with peritoneal dissemination of primary and recurrent ovarian cancer are awaited in the near future.

In situ distribution of metallic platinum in tumor tissues after intraperitoneal platinum chemotherapy assessed by digital synchrotron-abetted x-ray fluorescence microscopy.

e13067 Background: Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and catheter-administered intraperitoneal chemotherapy (CAIPEC) are used to treat peritoneal surface-spreading malignancies, including Malignant Peritoneal Mesothelioma (MPM), to maximize local drug concentrations. Previous HIPEC studies showed tissue penetration of cisplatin ~5mm from the peritoneal surface; biodistribution of CAIPEC has not been reported. Methods: Our protocol for MPM includes initial debulking surgery with HIPEC (41°C over 1 hour, drug is then removed), 6 cycles of CAIPEC (room temperature, indefinite dwell-time), and a second debulking surgery with HIPEC. To compare tissue drug penetrations in HIPEC versus CAIPEC, on an IRB-approved protocol we collected peritoneal tissue from 6 MPM patients receiving HIPEC at initial (n=2; both cisplatin) or second surgery (n=4; 2 cisplatin and 2 oxaliplatin) for digital image localization of in situ Pt by synchrotron-abetted (Brookhaven National Laboratory, Upton NY) x-ray fluorescence microscopy at a resolution of 10 microns. Results: Overall Pt levels were highest at second surgery post-HIPEC (median=26.1ppm, range: 2.2-113.4), lowest at initial surgery post-HIPEC (median=5.2ppm, range=4.7-5.8), and intermediate at second surgery pre-HIPEC (median=16.0ppm, range=5.6-21.8). Every sample had higher Pt at the peritoneal surface; also highest at second surgery post-HIPEC (median=40.4ppm, range=4.4-219.7), lowest at initial surgery post-HIPEC (median=11.3ppm, range=8.4-14.2), and intermediate at second surgery pre-HIPEC (median=25.9ppm, range=8.4-29.9). At second surgery, each sample’s overall Pt level was higher than contemporaneous plasma Pt, pre-HIPEC (median=0.27ppm, range=0.08-0.33) and post-HIPEC (median=1.86ppm, range=0.84-2.87). Conclusions: Both CAIPEC and HIPEC effect tissue drug accumulation, greatest at the peritoneal surface. The proportion of peritoneal surface Pt was lowest in second surgery pre-HIPEC samples, suggesting more homogeneous and/or extensive drug distribution in CAIPEC than HIPEC, likely due to longer dwell-time.

Pharmacokinetic advantage of hyperthermic intraoperative intraperitoneal cisplatin and oxaliplatin.

e13066 Background: Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies in order to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage (PKA) of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) and intravenous fluid (IVF) administration, by affecting intravascular volume, would correlate with PKA. Methods: On an IRB-approved study, we collected blood and peritoneal perfusate from 13 patients undergoing HIPEC with a set dose of 100 mg cisplatin (n=4) or a BSA-based dose of 250 mg/m2 oxaliplatin (n=9), and measured Pt concentrations by Inductively Coupled Plasma Mass Spectrophotometry. Areas under concentration-time curves from 0-60 minutes (AUC0-60) were calculated by Trapezoidal Rule. PKA was calculated by (AUC0-60[peritoneal fluid]/AUC0-60[plasma]). Linear regression and Wilcoxon rank-sum test were performed using SAS. Results: Models with both BSA and IVF as predictors of PKA fit better than BSA alone for cisplatin (p=.022 vs. p=.076) but not for oxaliplatin (p=.119 vs. p=.037). The BSA and IVF model was a better fit for peritoneal cisplatin (p=.003) than for plasma cisplatin (p=.146). The BSA-only model was a better fit for plasma oxaliplatin (p=.013) than for peritoneal oxaliplatin (p=.778). There was no statistically-significant difference between the median PKA of cisplatin vs. oxaliplatin (p=.706). Conclusions: Our results suggest that BSA is a better PKA predictor than the compound’s diffusion properties. When a set drug dose is used, rather than a BSA-based dose, IVF is also an important predictor. This is likely due to HIPEC’s limited duration, thus the drug does not reach equilibrium between the peritoneal and vascular compartments. When monitoring the pharmacokinetic parameters of HIPEC administration, factors influencing intravascular volume, including BSA and IVF, should be considered. Maintaining intravascular volume repletion is a key strategy for maximizing PKA, and thereby minimizing systemic side effects due to HIPEC.

Effect of intraoperative intraperitoneal chemotherapy and postoperative nutritional support on intestinal permeability and cellular immune function in patients with advanced gastric cancer

To investigate the effect of hyperthermic intraoperative intraperitoneal chemotherapy(HIIC) and postoperative nutritional support on the intestinal permeability and the cellular immunity function in patients with advanced gastric cancer. All the patients diagnosed as advanced gastric cancer in the Gastric Tumor Diagnosis and Treatment Center of Jiangsu Cancer Hospital were randomly divided into three groups using random digit table:(1)EN group treated with enteral nutrition during postoperative period; (2)HIIC+EN group treated with HIIC combined with postoperative enteral nutrition;(3)HIIC+PN group treated with HIIC combined with postoperative parenteral nutrition. Index of lactulose/mannitol(L/M) ratio was used to evaluate the permeability of intestinal mucosa. The percentage of CD4(+), CD8(+) and NK cell, the ratio of CD4/CD8 T cell in peripheral blood were tested by flow cytometry. The time points of these measurements were the day before surgery, postoperative days (POD) 3, 7, and 12. Compared with the day before surgery(POD-1), the ratio of L/M on POD+3 increased significantly in all the three groups(0.1235±0.0611 vs. 0.0280±0.0183, 0.1648±0.0571 vs. 0.0305±0.0208, 0.1702±0.0628 vs. 0.0298±0.0229)(P<0.05) and then decreased gradually. The L/M ratio of EN(0.0278±0.0217) and HIIC+EN(0.0336±0.0235) groups recovered to the baseline on POD+12, however HIIC+PN group still had elevated L/M ratio(0.0616±0.0430). The percentage of CD4(+)T cell and the ratio of CD4/CD8 in HIIC+EN group and HIIC+PN group were significantly lower than those in EN group(P=0.033, P=0.002, respectively). Compared with the POD-1,the percentage of CD4(+)T cell and the ratio of CD4/CD8 in HIIC+EN group and EN group on POD+12 were increased significantly(P<0.05). HIIC may cause significant increase in intestinal permeability and inhibit cellular immunity in patients undergoing radical resection for advanced gastric cancer. Mucosal permeability can be reversed by enteral nutrition.

Cirugía del tracto urinario en pacientes con carcinomatosis peritoneal ovárica tratadas con citorreducción y quimioterapia intraperitoneal intraoperatoria hipertérmica

IntroductionThe objective of the present work is to describe our experience in the surgery of the ureter and bladder in patients with primary and recurrent ovarian cancer subjected to peritonectomy procedures and the administration of hyperthermic intraoperative intraperitoneal chemotherapy (HIIC). Patients and methodThose patients who required surgical procedures on the distal ureter or bladder, were selected from a prospective data base constructed at the beginning of the peritoneal carcinomatosis program in our centre. Seven patients fulfilled this requirement and were included in the study. A total of 81 patients diagnosed with primary or recurrent ovarian cancer from December 2007 to April 2011 were included for maximum effort cytoreduction and HIIC. ResultsIt was necessary to perform some surgical manoeuvre on the ureter or bladder in seven patients, with a median age of 46 years (40-71). Four patients were operated on due to recurrence of the ovarian disease and in the other 3 patients the indication was surgical rescue after non-optimal surgery in another centre. There was direct tumour involvement of the lower urinary tract in 4 of them. Three patients (42%) in the series developed at least one postoperative complication. ConclusionThe performing of peritonectomy procedures that include the eventual resection of the ureter or bladder, and the subsequent application of HIIC in a selected group of patients with peritoneal dissemination due to an ovarian carcinoma can be done with reasonable rates of postoperative morbidity. These surgical procedures may be necessary to achieve optimal surgery.

Tumor de Krukenberg secundario a carcinoma de colon durante el embarazo

Krukenberg tumor is defined as a metastatic uni- or bilateral ovarian tumor that contains significant amounts of signet ring cells and whose origin is mainly gastrointestinal. The incidence of metastatic tumors of the ovary is very small (1-5%), and that of the concurrence of an ovarian mass with metastatic malignant features and pregnancy is negligible.We report the case of a 19-year-old woman who, 18 months after diagnosis of a mucinous adenocarcinoma of the colon, was diagnosed with a Krukenberg tumor in the 29th week of pregnancy. Initially, cesarean section together with tumoral resection was performed. In a second stage, cytoreductive surgery was performed with hyperthermic intraoperative intraperitoneal chemotherapy. The patient is currently in clinical remission and is monitored by the oncology service.

Surgery for colorectal peritoneal carcinomatosis

Peritoneal carcinomatosis occurs in patients with advanced gastrointestinal and gynecological malignancies and also in patients who experience recurrence after treatment failure of the primary tumor. Malignant disease in the peritoneal cavity is a morbid and significant predictor of a diminished survival in a cancer patient. Systemic chemotherapy alone will not be adequate to palliate or treat patients with peritoneal carcinomatosis. Cytoreductive surgery is a new surgical technique that is performed using peritonectomy procedures to allow total eradication of peritoneal tumors. Intraperitoneal chemotherapy regimens such as intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) are effective adjuvant treatment to treat the minimal residual disease after cytoreductive surgery to reduce the risk of locoregional recurrence. A substantial body of evidence available in the current literature has documented the survival benefits of combining cytoreductive surgery and intraperitoneal chemotherapy to treat a previously fatal phase of malignancy. This review provides a summary of the developments in the understanding and treatment of peritoneal surface malignancy from colorectal cancer.

Intraoperative intraperitoneal chemotherapy with cisplatin in epithelial ovarian cancer

ObjectiveTo assess retrospectively the feasibility of intraoperative intraperitoneal (IP) chemotherapy with cisplatin in epithelial ovarian cancer.MethodsIP chemotherapy during optimal staging surgery was performed in 10 patients who were diagnosed with primary epithelial ovarian cancers between April 2008 and February 2011. Cisplatin (70 mg/m2 in 1 L normal saline solution) was administered in the abdominal cavity for 24 hours postoperatively and then adjuvant chemotherapy was started 2-4 weeks after surgery. Perioperative toxicity of the combined treatment was evaluated until the initiation of postoperative adjuvant chemotherapy.ResultsA total of 23 adverse events were observed in 9 of 10 patients (grade 1, 7; grade 2, 13; grade 3, 3; grade 4, 0). In descending order of frequency, adverse events affected the gastrointestinal system (n=14), hematologic system (n=6), pulmonary system (n=2), and genito-urinary system (n=1). The adverse events did not affect adjuvant systemic chemotherapy schedules. One patient experienced disease recurrence in the liver 16 months after surgery. The remaining 9 patients have been well controlled by chemotherapy and/or observation during the follow-up period of 4 to 39 months after surgery.ConclusionIntraoperative IP chemotherapy with cisplatin during surgical procedures is considered feasible for the treatment of primary epithelial ovarian cancer. Further studies, including long-term, prospective and comparative trials, are needed to validate the efficacy of this combined therapy.

Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Intraoperative Chemotherapy in the Treatment of Advanced Epithelial Ovarian Cancer

Background/Aims. Intraperitoneal intraoperative hyperthermic chemotherapy (HIPEC) has been used in the treatment of ovarian cancer. The purpose of the study is to determine the efficacy of HIPEC after cytoreductive surgery in advanced ovarian cancer. Patients/Methods. From 2006 to 2010 patients with advanced ovarian cancer were enrolled in a prospective nonrandomized study to undergo cytoreductive surgery combined with HIPEC. Clinical and histopathological variables were correlated to hospital mortality, morbidity, survival, and recurrences. Results. The mean age of 43 women was 59.9 ± 13.8 (16–82) years. The hospital mortality and morbidity rate were 4.7% and 51.2%, respectively. Complete cytoreduction was possible in 69.8%. The overall 5-year survival rate was 54%. The prognostic indicators of survival were the extent of prior surgery (P = 0.048) and the extent of peritoneal dissemination (P = 0.011). The recurrence rate was 30.2%. Conclusions. Maximal cytoreductive surgery combined with HIPEC is a well-tolerated, feasible, and promising method of treatment in advanced ovarian cancer.

Preliminary Results of Hyperthermic Intraperitoneal Intraoperative Chemotherapy as an Adjuvant in Resectable Pancreatic Cancer

Background and Aims. 5-year survival in patients with pancreatic cancer is poor. Surgical resection is the only potentially curative resection. The results of adjuvant treatment either with chemotherapy or with radiotherapy have been contradictory and the incidence of local-regional recurrence remains high. If local-regional recurrence is controlled survival may be expected to increase. Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) may be used in order to control local-regional recurrences. The purpose of the study is to identify the effect of HIPEC in patients with pancreatic cancer undergoing potentially resection. Patients and Methods. From 2007–2011, 21 patients, mean age 69.4 ± 9.5 (50–86) years, underwent tumor resection, and HIPEC with gemcitabine. The hospital mortality and morbidity rate was 9.5% and 33.3%, respectively. 5-year and median survival was 23% and 11 months, respectively. The recurrence rate was 50% but no patient developed local-regional recurrence. No patient was recorded with gemcitabine-induced toxicity. Conclusions. This clinical study of 21 patients is the first to combine an R0 pancreas cancer resection with HIPEC. Increased morbidity and mortality from intraoperative gemcitabine was not apparent. Patients with pancreatic cancer undergoing potentially curative resection in combination with HIPEC may be offered a survival benefit. Data suggested that local-regional recurrences may be greatly reduced. Further studies with greater number of patients are required to confirm these findings.

Laparoscopic Diagnosis and Laparoscopic Hyperthermic Intraoperative Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei Detected by CT Examination

Background. Patients with early stage of pseudomyxoma peritonei (PMP) are sometimes difficult to diagnose the primary sites and intraperitoneal spread of tumor and to perform a cytological study. Methods. Patients without a definitive diagnosis and with unknown extent of peritoneal spread of tumor underwent laparoscopy. Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) was administered as part of the same intervention. The results of treatment were evaluated at the time of second-look laparotomy (SLL) as a subsequent intervention. Results. Eleven patients were managed by diagnostic laparoscopy followed by laparoscopic HIPEC (LHIPEC). The operation time of laparoscopic examination and LHIPEC was 177 ± 26 min (range 124–261 min). No intraoperative complication was experienced. The peritoneal carcinomatosis index (PCI) score by laparoscopic observation was 16.5 ± 6.4 (range 0–30). One patient with localized pseudomyxoma peritonei (PMP) mucocele did not received LHIPEC; the other 10 patients with peritoneal metastases (PM) were treated with LHIPEC. After LHIPEC, ascites disappeared in 2 cases and decreased in the amount in the other 8 cases. Nine patients underwent SLL and cytoreductive surgery (CRS) combined with HIPEC. The duration between LHIPEC and SLL ranged from 40 to 207 days (97 ± 40 days). The PCI at the SLL ranged from 4 to 27 (12.9 ± 7.1). The PCI at the time of SLL decreased as compared to PCI at the time of diagnostic laparotomy in 7 of 9 patients. Median follow-up period is 22 months (range 7–35). All 11 patients are alive. Conclusion. The early results suggest that laparoscopic diagnosis combined with LHIPEC is useful to determine the surgical treatment plan and reduce the tumor burden before definitive CRS at SLL.

Adjuvant Bidirectional Chemotherapy with Intraperitoneal Pemetrexed Combined with Intravenous Cisplatin for Diffuse Malignant Peritoneal Mesothelioma

Cytoreductive surgery (CRS) with heated intraoperative intraperitoneal chemotherapy (HIPEC) has emerged as optimal treatment for diffuse malignant peritoneal mesothelioma (DMPM) showing median survivals of 36–92 months. However, recurrences occur frequently even in patients undergoing optimal cytreduction and are often confined to the abdomen. We initiated a Phase II study of adjuvant intraperitoneal pemetrexed combined with intravenous cisplatin for patients undergoing CRS and HIPEC for DMPM. The treatment consisted of pemetrexed 500 mg/m2 intraperitoneally and cisplatin 50 mg/m2 intravenously given simultaneously on day 1 of every 21 day cycle for 6 cycles. The primary endpoint of the study was treatment related toxicity. From July 2007 until July 2009 ten patients were enrolled. Nine of 10 completed all 6 cycles of adjuvant treatment per protocol. The most common toxicities were fatigue, nausea and abdominal pain grade 1 or 2. There was one grade 3 toxicity consisting of a catheter infection. The median survival for all 10 patients was 33.5 months. Pharmacokinetic analysis of intraperitoneal pemetrexed showed a peritoneal to plasma area under the curve ratio of 70. Our study shows that adjuvant intravenous cisplatin and intraperitoneal pemetrexed can be used following CRS and HIPEC for DMPM with low morbidity.