Peritoneal metastasis of advanced epithelial ovarian carcinoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective international multicentric data analysis.

INTRODUCTION: The purpose of our study was to evaluate outcome data after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis originating from advanced epithelial ovarian carcinoma (PMOC). PATIENTS AND METHODS: A retrospective international multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group. RESULTS: One thousand four hundred and ninety-one patients from 11 specialized units underwent CRS and HIPEC that of those 326 (21.9%) upfront surgeries, 504 (33.8%) interval surgery, and 661(44.3%) recurrent cases. Complete Cytoreduction(CC0/1) was achieved in 1213 patients (81.3%). Treatment -related mortality was 0.8%, major operative complications (Grades 3-5) was 25.1%. Factors associated with major operative complications include prior surgical score (PSS for recurrent cases; RC) PSS>2,p = 0.000), PCI(≤15, >15 cut-off level; p ≤ 0.000), completeness of cytoreduction (CC, p=0.000), high CA125 levels (>25 mg/dl), presence of ascites, high CRP (>5 mg/dl) levels and low albumin levels (below to 2.5 mg/dl) (p ≤ 0.05). The median survival was 58 months in upfront surgery(UFS), 60 months in interval surgery(IS), and 42 months in RC. The overall survival for five years was 45% for UFS, 37% for IS, 28% for RC cases. CCscore (p = 0.000), CA125, CRP and albumin levels (p ≤ 0.05) were predictors for progression free survival. PCI(p ≤ 0.000), major postoperative complications (p = 0.004), incomplete CRS(CC2/3)(p < 0.001), prior chemotherapy (hazard ratio [HR], 3-8; p < 0.001) and PSS>2 for RC were independent predictors of poor overall survival. CONCLUSION: The combined treatment strategy for PMOC may be performed safely with acceptable morbidity and mortality in the specialized units.

Prognostic Factors of Malignant Peritoneal Mesothelioma Experienced in Japanese Peritoneal Metastasis Center.

BACKGROUND AND OBJECTIVES: The current standard of treatment for malignant peritoneal mesothelioma(MPM)is cytoreductive surgery(CRS)plus perioperative intraperitoneal or systemic chemotherapy(comprehensive treatment), The present study was performed to clarify the prognostic factors of PMP after comprehensive treatment. METHODS: Among 63 patients with MPM, male and female patients were 34 and 29. CRSwas performed in 47 patients and complete cytoreduction(CC-0) was performed in 14(22%)patients. Mean numbers of resected peritoneal sectors and organs were 5.2(1-13), and 2.9(0- 9), respectively. Hyperthermic intraperitoneal chemoperfusion(HIPEC)was performed in 27 patients. Grade 1/2, Grade 3, and Grade 4 complications were experienced in 5, 6, and 3 patients, respectively. One patient died of sepsis, and the mortality rate was 2.3%. Independent prognostic factors for favorable prognosis were performance of HIPEC, peritoneal cancer index (PCI)score C12, no distant metastasis and histologic epithelial type. Relative risk of no HIPEC, PCI score B13, presence of distant metastasis and non epithelial type were 7.69, 22.1, 3.6 and 3.9, respectively. CONCLUSIONS: Risk factors for death after comprehensive treatment were no HIPEC, PCI score B13, and non epithelial type. However, only 11(17%)patients showed PCI score C12. Accordingly, PCI score should be reducedC12 before CRSby neoadjuvant chemotherapy.

Cytoreductive surgery under aminolevulinic acid-mediated photodynamic diagnosis plus hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis from ovarian cancer and primary peritoneal carcinoma: results of a phase I trial.

BACKGROUND: We conducted a phase I clinical trial to evaluate the sensitivity, specificity, and safety of cytoreductive surgery (CRS) under aminolevulinic acid-mediated photodynamic diagnosis (ALA-PDD) plus hyperthermic intraperitoneal chemotherapy (HIPEC) on 20 patients with peritoneal carcinomatosis (PC) from ovarian cancer and primary peritoneal carcinoma (PPC). PATIENTS AND METHODS: Patients took 5-aminolevulinic acid (5-ALA) at a dose of 20 mg/kg orally with 50 mL of water 2 h before surgery. During surgery, the abdominal cavity was observed under blue light (wavelength of 440 nm) before and after CRS plus HIPEC. Specimens were excised and submitted for pathological examination to evaluate the specificity of ALA-PDD. Postoperative course was closely monitored and detailed information was recorded. RESULTS: CRS under ALA-PDD plus HIPEC was performed 21 times in 20 patients with PC (16 ovarian cancer, 4 PPC) between June 2011 and October 2013. With the exception of 1 (5 %) patient, strong red fluorescence was detected in 19 patients with ovarian cancer, with a sensitivity of 95 %. All specimens from red fluorescent lesions were invaded by cancer cells, with a specificity of 100 %. No severe adverse events occurred during the perioperative period, with the exception of some abnormal laboratory results and mild complications. All patients were alive until the last follow-up. CONCLUSION: ALA-PDD provided a high sensitivity and specificity in detecting peritoneal metastasis in patients with PC from ovarian serous carcinoma and PPC. CRS under ALA-PDD plus HIPEC was a feasible and safe treatment option for patients with PC from ovarian cancer and PPC.

Peritoneal cancer treatment.

INTRODUCTION: In the past, peritoneal surface malignancy (PSM) was considered as a final stage of cancer, and patients were offered the best supportive care. Recently, a new therapeutic alternative approach based on the combination of surgery with chemotherapy was developed. In this curative intent, the macroscopic disease was treated with cytoreductive surgery (CRS) combined with perioperative chemotherapy, including neoadjuvant chemotherapy, hyperthermic intraoperative intraperitoneal chemotherapy, extensive intraoperative peritoneal lavage and early postoperative intraperitoneal chemotherapy AREAS COVERED: This article reviews the mechanisms of the formation of PSM, quantitative estimation of PSM and residual disease, multimodal treatment, value of laparoscopy, prognostic factors and patients' selection for the multimodal therapy. EXPERT OPINION: Recent studies show that CRS plus intraperitoneal chemotherapy applications confer prolonged survival in patients with PSM from colorectal, gastric, ovarian, appendiceal mucinous carcinoma and diffuse malignant peritoneal mesothelioma. The comprehensive treatment is now justified as state-of-the-art for patients with peritoneal metastasis.

Outcome data of patients with peritoneal carcinomatosis from gastric origin treated by a strategy of bidirectional chemotherapy prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a single specialized center in Japan.

BACKGROUND: Management of peritoneal disseminated gastric cancer (GC) remains a challenging problem. The purpose of our study was to evaluate the outcome of bidirectional induction chemotherapy [bidirectional intraperitoneal and systemic induction chemotherapy (BIPSC)] in patients with peritoneal carcinomatosis (PC) arising from GC who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: Overall, 194 patients with PC arising from GC were treated with BIPSC comprising intraperitoneal docetaxel at a dose of 20 mg/m(2) and cisplatin at a dose of 30 mg/m(2) followed by four cycles of oral S-1 at a dose of 60 mg/m(2). CRS and HIPEC were performed in responders to BIPSC. RESULTS: Of these 194 patients, 152 (78.3 %) underwent CRS and HIPEC between January 2005 and December 2012. Treatment-related mortality was 3.9 %, and major complications occurred in 23.6 % of patients. The median survival rate was 15.8 months, with 1-, 2-, and 5-year survival rates of 66, 32 and 10.7 %, respectively, in the patients treated with combined treatment. Multivariate analysis identified pathologic response to BIPSC (p = 0.001), low tumor burden [peritoneal cancer index (PCI) ≤ 6] (p = 0.001), and completeness of CRS (CC-0, CC-1) (p = 0.001) as independent predictors for a better prognosis. CONCLUSION: As a viable option, BIPSC with CRS and HIPEC for patients with PC arising from GC may be performed safely, with acceptable morbidity and mortality, in a specialized unit. Response to BIPSC, optimal CRS and limited peritoneal dissemination seem to be essential to achieve the best outcomes in these patients.

Pharmacokinetics of docetaxel during hyperthermic intraperitoneal chemotherapy for peritoneal metastasis.

UNLABELLED: The purpose of this manuscript is to report the pharmacokinetics of docetaxel during hyperthermic intraperitoneal chemotherapy (HIPEC) after peritonectomy. MATERIALS AND METHODS: Eleven patients with peritoneal metastasis (PM) underwent peritonectomies combined with 40 min of HIPEC with 40 mg/body of docetaxel. The pharmacokinetics of docetaxel were studied by using high-performance liquid chromatography. RESULTS: The docetaxel concentration at the start of HIPEC (0 min) was 9.084 ± 0.972 mg/L. The concentration gradually decreased to 5.599 ± 0.458 mg/L 40 min after HIPEC. In contrast, serum docetaxel levels increased during HIPEC, reaching a maximum level of 0.1334 ± 0.0726 mg/L at 40 min. The clearance (CLp) was 3.164 ± 1.383 L/hr, and the area under the curve (AUC) ratio was 95.12 ± 87.32. The AUC ratio of less-extensive peritonectomies was significantly higher than that of extended peritonectomies. The docetaxel concentration in the tumor tissue increased at 40 min (4.45 mg/gr). The apparent permeability (Papp, 40 min) was 1.47 ± 0.67 mm/40 min. No severe adverse effects were observed after HIPEC. CONCLUSION: From these results, 40 mg is a safe dose for docetaxel combined with HIPEC, and the locoregional intensity of docetaxel is enough to control PM less than 1.47 mm in diameter.

Preoperative carcinoembryonic antigen level predicts prognosis in patients with pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Even though management of pseudomyxoma peritonei (PMP) was improved with cytoreductive surgery (CRS) and hyperthermic chemotherapy (HIPEC), several aspects of PMP still need to be optimized, including patient selection for surgery and prognostic factors. We assessed the role of preoperative carcinoembryonic antigen (CEA) levels in PMP patients treated with CRS and HIPEC. METHODS: A total of 449 PMP patients with documented preoperative CEA levels referred to our center between 2005 and 2011 underwent CRS and HIPEC. The association between CEA levels and characteristics of patients with PMP was assessed with χ (2) test, linear correlation, and logistic regression analyses. Survival analysis was performed with Cox proportional hazard model. RESULTS: Median age was 55 (range 19-84) years. There were 245 (54.5 %) females and 204 (45.5 %) males. Preoperative CEA levels were elevated in 328 (73 %, sensitivity) patients with PMP. Preoperative CEA levels were also related to peritoneal cancer index (P < 0.0001), cytoreductive surgery scores (P < 0.0001), progress free survival (P < 0.001) and overall survival (P < 0.001) in patients with PMP. CONCLUSIONS: Our results indicated that preoperative CEA levels are useful in predicting the extent of disease and surgical success as well as progress-free and overall survival in patients with PMP treated with cytoreductive surgery and HIPEC.

Solitary rectal ulcer syndrome: exploring possible management options.

Solitary rectal ulcer syndrome (SRUS) is a rare condition with various causes that results in ischemic injury. The aim of this study was to assess the clinical findings, diagnosis, and outcomes of treatment in patients with SRUS. Between 1992 and 2006, a retrospective review was undertaken for all patients diagnosed with SRUS. Fifty-eight patients were diagnosed with SRUS. Among patients with paradoxic rectal spasm (PRS), lesions disappeared in 1 of 3 given applied biofeedback treatment, and in 2 of 4 injected with Botulinum toxin (Botox). Twenty-three patients underwent appropriate surgical treatment. Overall, postoperative improvement was seen in 18 patients (78.2%). In conclusion, every patient with SRUS must be assessed for causative disease. Treatment should include conservative approaches such as Botox injection; in patients with pelvic floor disorders, surgical treatment should be considered.