Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Lynch syndrome-associated endometrial cancer patient with a rare novel germline likely pathogenic variant of MSH2 gene: A case report.

The Lynch syndrome (LS) is an autosomal dominant condition usually characterized by germline pathogenic variants in DNA mismatch repair (MMR) genes. Despite the guidelines now available, determining the pathogenicity of rare variants remains challenging, as the clinical significance of a genetic variant could be uncertain, but it may represent a disease-associated variation in the aforementioned genes. In this case report we will describe the case of a 47 years-old female affected by endometrial cancer (EC) with an extremely rare germline heterozygous variant in the MSH2 gene (c.562G > T p. (Glu188Ter), exon 3) that is likely pathogenic, and a family history consistent with LS.

Secondary cytoreductive surgery, hyperthermic intraperitoneal intraoperative chemotherapy, and chemotherapy alone: a retrospective comparison of alternative approaches in relapsed platinum sensitive ovarian cancer.

INTRODUCTION: The best treatment for relapsed platinum sensitive epithelial ovarian cancer (EOC) is controversial. The aim of the study was to compare progression-free survival (PFS) and overall survival (OS) in platinum-sensitive EOC patients treated with chemotherapy alone (CTA), secondary cytoreductive surgery (SCR) or SCR plus hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC). MATERIALS AND METHODS: Retrospective analysis of the clinical outcome of 46 EOC patients with at least 30 months of follow-up. RESULTS: Median follow-up time was 32 months for the CTA group, 30 months for the SCR group, and 45 months for the SCR + HIPEC group. Fifteen recurrences were observed in the CTA group, seven in the SCR group, and 16 in the SCR + HIPEC group. The median time elapsed between first and second recurrence (PFI-2) was significantly higher among patients treated with SCR + HIPEC, in comparison with patients treated with CTA (p = 0.012 andp = 0.017, respectively). On the contrary, PFI-2 did not significantly differ between the SCR and SCR + HIPEC groups (p = 0.877). A statistically significant difference in OS favouring SCR + HIPEC in comparison with CTA (p = 0.04) was observed. CONCLUSIONS: SCR HIPEC compared with CTA improves PFI-2 in patients with platinum-sensitive EOC recurrence. SCR + HIPEC might also improve OS in comparison with CTA. No improvement in favor of SCR + HIPEC vs SCR was observed,. These results further support the need of a randomized trial comparing chemotherapy with SCR ± HIPEC in this setting.

Contamination risk for operators performing semi-closed HIPEC procedure using cisplatin.

AIMS: Aim of this study was to assess operators' safety while performing a semi-closed HIPEC procedure for peritoneal carcinomatosis using cisplatin drugs. METHODS: Environmental air, theater personnel urine, operators' gloves and hand skin contamination were assessed during two non-consecutive working days. Six operating surgeons, two anesthesiologists and two theater nurses were included in the study. Glove samples were collected from the inner surface of the external glove and from the external surface of the inner glove from operating surgeons wearing a double pair of gloves. Personnel urine samples were collected before, after and 24 h from the procedure. RESULTS: Air and urine samples permanently resulted below detectable levels for cisplatin presence on all the tested sources and sessions. Cisplatin contamination was detected on the inner surface of the external gloves and on the outer surface of the inner gloves, but in a lower concentration for the latter. Skin wipe samples were below detectable levels for platinum presence. CONCLUSION: The results suggest that two pairs of gloves are adequate to protect the skin from antiblastic drugs. No sign of direct contact or systemic absorption of drugs was ever detected from the inspected samples. Semi-closed HIPEC technique appears to be a safe procedure for operators.

Treatment of diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery and HIPEC.

AIM: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally aggressive tumor with poor prognosis, related in most cases to asbestos exposure. It is increasing in frequency, but currently no standard therapy is available. The biology of this disease is still poorly understood. Several highly specialized centers have recently reported improved survival by means of an innovative local-regional approach. The purpose of this article is to evaluate the survival benefit and the morbidity rate of patients affected by DMPM treated at our institution by cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC). METHODS: This study includes 42 patients affected by DMPM treated by an uniform approach consisting of cytoreductive surgery associated with HIPEC using cisplatin and doxorubicin. The primary end point was overall survival and morbidity rate. The secondary end point was evaluation of prognostic variables for overall survival. RESULTS: The median follow-up period was 72 months (range 1-235 months). Thirty-five patients (83.3%) presented epithelial tumors and 7 were affected by multicystic mesothelioma. The mean peritoneal cancer index (PCI) was 13. Thirty-eight patients (90.4%) had complete cytoreduction (CC-0/1). The overall morbidity rate was 35.7% associated to a perioperative mortality of 7.1%. Median overall survival rate was 65 months with a 1- and 5-year survival rates of 63% and 44%, respectively. CONCLUSION: The treatment of DMPM by CRS+HIPEC in selected patients is a feasible technique that allows to achieve encouraging results in terms of overall survival rate, with an acceptable morbidity rate. Further investigations are needed to clarify the role and the timing of this promising technique.

Treatment of peritoneal carcinomatosis from ovarian cancer by surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC).

AIM: Ovarian cancer may be considered as an "intraperitoneal disease" by itself. When surgical removal associated with systemic chemotherapy fails, usually, the history of the patients is characterized by poor prognosis. Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this article was to evaluate the survival benefit and the morbidity of patients with ovarian cancer treated at our institution by cytoreductive surgery associated with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC). METHODS: Between October 1995 and December 2012 more than 600 operations for PC were performed; in 308 cases surgical cytoreduction associated with HIPEC was carried out. Eighty-five patients treated by cytoreduction associated with HIPEC were affected by recurrent epithelial ovarian cancer (EOC). Statistical analysis was performed on 70 patients (last 15 patients were too recent for evaluation). Two trials were applied: 1) patients presenting first peritoneal relapse after surgery and systemic chemotherapy (CT), 6 months later from last CT administration; 2) multiple relapse patients. RESULTS: On 70 patients, morbidity and mortality rates were 35.7% and 7.1%, respectively. Overall median survival was 42.0 months, but in primary EOC was 48.0 months and in recurrent EOC was 28 months (P=0.12). Statistical analysis revealed that the completeness of cytoreduction was the most statistically significant factor related to survival: in completely citoreduced patients, overall survival was 48 months. CONCLUSION: Citoreductive surgery associated to platinum compounds HIPEC is feasible and relatively safe in recurrent and primary PC from ovarian cancer. Better selection of patients and second-look surgery in high risk-patients have to be investigated to improve those encouraging results.

Treatment of peritoneal carcinomatosis from colonic cancer by cytoreduction, peritonectomy and HIPEC: preliminary results in highly selected patients.

AIM: Peritoneal carcinomatosis (PC) is one of the routes of spread of abdominal neoplasms and is generally considered a lethal disease, with a poor prognosis by conventional chemotherapeutic treatments. While systemic chemotherapy has little impact on the treatment of peritoneal disease, some centers have reported encouraging results on overall survival (OS) and disease-free survival (DFS) with surgical cytoreduction associated with hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this article is to evaluate the survival benefit and the morbidity in patients affected by colorectal PC treated at our institution by cytoreductive surgery associated with HIPEC. METHODS: In our institution, from October 1995 to June 2012, about 550 operations for PC were performed; in 300 cases cytoreduction plus HIPEC was carried out. Out of 90 operations for colonic cancer: 50 cytoreduction plus HIPEC, 12 cytoreduction and EPIC (early postoperative intraperitoneal chemotherapy) and 28 debulking or explorative laparoscopies/laparotomies were performed. For the present study, 50 patients who had undergone cytoreduction and HIPEC for PC of colorectal cancer origin (CRC) were considered. RESULTS: The morbidity and mortality rates were 34% (17/50) and 2% (1/50), respectively. The patients were divided in two groups according to PCI (peritoneal cancer index, range 0-39) and CC score (completeness of cytoreduction): in Group A (23 patients, PCI>16, CC-2) the median survival time was 15 months compared to 48.1 months for Group B (27 patients, PCI≤16, CC-0/1). The poor survival of Group A seemed to be related to higher PCI and CC score. CONCLUSION: Patient selection based on a maximum PCI of 16 associated with a complete cytoreduction (CC-0) produced encouraging results.

Treatment of pseudomyxoma peritonei with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC): a single center experience.

AIM: Pseudomyxoma peritonei (PMP) is a rare form of peritoneal carcinomatosis characterized by abnormal quantity of extracellular mucinous material. It almost originates from a primary appendiceal tumor with different malignancy degrees. The purpose of this study was to evaluate outcome and long-term survival on 80 patients affected by PMP after cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: From October 1995 to June 2012, about 550 operations for PC were performed; in 300 cases surgical cytoreduction in association with HIPEC was carried out. Regarding PMP, 80 procedures of CRS and HIPEC were performed. This approach is based on surgical removal of the primitive cancer, peritonectomy (stripping of implants on the peritoneal surface) and HIPEC performed with cisplatinum and C mytomicin. The rationale of this treatment is to obtain, after macroscopic disease removal, an elevated and persistent drug concentration in the peritoneal cavity, with limited systemic effects. RESULTS: The complication rate was 52.5% (42/80) with no postoperative deaths. The median overall and progression-free survival were 144 and 88 months, respectively. Not complete cytoreductive surgery (P<0.001), tumor histology (P=0.02) and previous systemic chemotherapy (p = 0.03) were identified in the univariate analysis as independent predictors for a poorer long-term survival. In the multivariate analysis, the completeness of cytoreduction was the only significant variable influencing the outcome. Incomplete cytoreduction (P<0.01) resulted the only statistically significant variable associated with a higher incidence of postoperative complications. CONCLUSION: PMP can be treated with curative intent in a large percentage of cases by cytoreductive surgery associated with HIPEC. This new approach could be performed safely with acceptable morbidity and mortality in selected patients treated in specialized centers. Completeness of cytoreduction allows to achieve the best results.

Prognostic factors and oncologic outcome in 146 patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: Italian multicenter study S.I.T.I.L.O.

AIM: The present study was specifically designed to assess the major clinical and pathological variables of patients with colorectal peritoneal carcinomatosis in order to investigate whether currently used criteria appropriately select candidates for peritonectomy procedures (cytoreductive surgery) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: Preoperative, operative and follow-up data on 146 consecutive patients presenting with peritoneal carcinomatosis of colorectal origin and treated by surgical cytoreduction combined with HIPEC in 5 Italian Hospital and University Centers were prospectively entered in a common database. Univariate and multivariate analyses were used to assess the prognostic value of clinical and pathologic factors. RESULTS: Over a minimum 24-month follow-up, the overall morbidity rate was 27.4% (mortality rate: 2.7%) and was directly related to the extent of surgery. Peritoneal cancer index (PCI), unfavorable peritoneal sites, synchronous or previously resected liver metastasis and the completeness of cytoreduction, all emerged as independent prognostic factors correlated with survival. CONCLUSIONS: Until research provides more effective criteria for selecting patients based upon the biomolecular features of carcinomatosis, patients should be selected according to the existing independent prognostic variables.

Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

AIM: This retrospective multi-institutional study addresses the role of surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of multicystic peritoneal mesothelioma (MCPM). MCPM is an uncommon tumour with uncertain malignant potential and no current standard therapy. Additionally, poorly defined pathological and biological features of this disease were investigated. METHODS: Twelve patients with MCPM underwent 14 procedures of cytoreduction and HIPEC in two Italian referral centres. Nine patients had recurrent disease after previous debulking (one operation in six patients, two in two, four in one). Biological markers related to mesothelioma origin and clinical features were assessed by immunohistochemical studies. RESULTS: Median follow-up was 64 months (range 5-148). Optimal cytoreduction (residual tumour nodules ≤2.5 mm) was performed in all the procedures. One grade IV postoperative complication (NCI/CTCAE v.3.0) and no operative death occurred. All the patients are presently alive with no evidence of disease, including two patients who underwent the procedure twice, due to locoregional disease recurrence. Five- and ten-year progression-free survival was 90% and 72%, accounting for a. statistically significant difference (P = 0.0001) with progression-free survival following previous debulking surgery (median 11 months; range 2-31). All cases showed low proliferative activity assessed by mitotic rate and Ki-67 expression. CONCLUSIONS: MCPM is a borderline tumour with a high propensity to local-regional recurrence. Definitive tumour eradication by means of cytoreduction and HIPEC seems more effective than debulking surgery in preventing disease relapse. Low mitotic rate and poor Ki-67 expression might be related to the peculiar behaviour of MCMP.

Alkaloids in bufonid toads (melanophryniscus): temporal and geographic determinants for two argentinian species.

Bufonid toads of the genus Melanophryniscus represent one of several lineages of anurans with the ability to sequester alkaloids from dietary arthropods for chemical defense. The alkaloid profile for Melanophryniscus stelzneri from a location in the province of Córdoba, Argentina, changed significantly over a 10-year period, probably indicating changes in availability of alkaloid-containing arthropods. A total of 29 alkaloids were identified in two collections of this population. Eight alkaloids were identified in M. stelzneri from another location in the province of Córdoba. The alkaloid profiles of Melanophryniscus rubriventris collected from four locations in the provinces of Salta and Jujuy, Argentina, contained 44 compounds and differed considerably between locations. Furthermore, alkaloid profiles of M. stelzneri and M. rubriventris strongly differed, probably reflecting differences in the ecosystem and hence in availability of alkaloid-containing arthropods.

Ten years experience in the treatment of pseudomyxoma peritonei by cytoreduction, peritonectomy and semi-closed hyperthermic antiblastic peritoneal perfusion.

BACKGROUND: In the literature good results have been reported for the treatment of Pseudomyxoma peritonei (PMP) by cytoreduction, peritonectomy and hyperthermic antiblastic peritoneal perfusion (H.A.P.P.). Forty-eight patients affected by PMP have been treated with this technique over the past ten years. PATIENTS AND METHODS: Peritoneal perfusion has been performed with the original semiclosed tecnique after complete surgical cytoreduction in 188 patients affected by peritoneal carcinomatosis. In 48 of the cases the patients were affected from PMP. Aggressive surgical cytoreduction was performed with multiple visceral resections and peritonectomies. RESULTS: Seventeen patients (38%) presented major perioperative complications, and in five cases the reoperation of the patient was required. In spite of this high complication rate, there was no perioperative mortality. The results of the Kaplan-Meier 5- and 10-year survival analysis, were 94% and 82%, respectively, with a disease-free survival of 80% at 5 years and 70% at 10 years. Thirty-nine patients (81.2%) had no evidence of disease at follow-up (range 1-120 months). DISCUSSION: Up to date, the most effective treatment for PMP has been aggressive cytoreduction plus H.A.P.P.

120 peritoneal carcinomatoses from colorectal cancer treated with peritonectomy and intra-abdominal chemohyperthermia: a S.I.T.I.L.O. multicentric study.

A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.

Solid-state study of mepivacaine hydrochloride.

Different crystalline forms of the local anaesthetic mepivacaine hydrochloride (MH) were revealed by Fourier transform infrared spectroscopy (FT-IR), not by conventional differential scanning calorimetry (DSC). The existence of two polymorphic anhydrous modifications was discovered and further characterized by X-ray powder diffraction and thermal analysis: Form II, the commercial one, and the more stable Form I, obtained by re-crystallization from Form II. Two pseudopolymorphs were also obtained: Form III, a solvate crystallized from ethanol and Form IV, a solvate crystallized from methanol. Single crystal X-ray diffraction data for both solvates were collected and their structures were determined. Form II, metastable and monotropically related to Form I, generates through desolvation of Form III, very often present in industrial processing, where crystallization from ethanol solution is a common practice. For the sake of clarity, the presence of polymorphic forms should be reported in the drug master files of MH. However, since MH is readily water soluble, the observed polymorphism has no relevance to its typical clinical use as aqueous solutions.

[Complications of cytoreductive surgery associated with intraperitoneal chemohyperthermia: prevention and treatment]. / Complicanze della chirurgia citoriduttiva associata a chemioipertermia intraperitoneale (CIIP) prevenzione e trattamento.

New approach to peritoneal carcinomatosis combining cytoreductive surgery and hypertermic intraperitoneal chemotherapy suggest improved survival when it is possible to achieve a complete cytoreduction. In this study we consider the major complications related to this procedure and purpose our approach for their prevention and treatment.

[Cytoreduction and intraoperative peritoneal chemohyperthermia in carcinomatosis from colonic carcinoma and in peritoneal pseudomyxoma]. / Citoriduzione e chemioipertermia intraoperatoria peritoneale (CIIP) nella carcinosi da carcinoma del colon e nello pseudomixoma peritonei.

New approach in treatment of peritoneal carcinomatosis combining cytoreductive surgery and intraperitoneal chemotherapy suggests improved survival when it is possible to achieve a complete cytoreduction. In this study we consider the carcinomatosis from colorectal and appendiceal adenocarcinoma. In all cases, patients in whom cytoreductive surgery was complete had a median survival much longer compared with patients in whom was not possible and, as perfusion works on minimal residual disease, peritonectomy is the only surgical technique that aim at total removal of parietal and visceral peritoneal lesions.

Intra-arterial hepatic chemoembolization in liver metastases from neuroendocrine tumors: a phase II study.

Neuroendocrine tumors, particularly those of gastrointestinal tract origin, have a predisposition for metastasizing to the liver, causing parenchymal substitution and paraneoplastic syndrome. Lipiodol embolization combined with anticancer drugs is a recent tool in regional therapy. It has been proven that chemoembolization reduces tumor bulk and hormone levels, and that it palliates the symptoms of many patients with liver-dominant neuroendocrine metastases. Beginning in December 1988, ten patients with unresectable and chemotherapy-refractory liver metastatic neuroendocrine tumors were treated with chemoembolization based on a mixture of lipiodol, mitomycin, cisplatin, epirubicin, followed by gelfoam powder and contrast media. Toxicity encountered included: upper right quadrant pain requiring narcotics, elevation of lactate dehydrogenase, alkaline phosphatase, and transaminases. One patient had liver abscess and persistent fever for 2 weeks. We obtained two complete remissions lasting 12 and 34 months and 5 partial remissions. The median survival was 22 months. Four patients had urinary elevation of 5-hydroxyindolacetic acid (5-HIAA). They showed more than a 75% decrease in urinary secretion after treatment. In a patient with transplanted liver we noticed a partial response lasting 7 months. We conclude that chemoembolization will improve the clinical condition of a significant percentage of patients with liver metastases, that future therapy of carcinoid tumors will be based on specific tumor biology and that treatment will be customized for each individual patient combining the use of cytoreductive procedures including radiofrequency ablation, laser treatment and chemoembolization.

[Indications for integrated surgical treatment of peritoneal carcinomatosis of colorectal origin: experience of the Italian Society of Locoregional Integrated Therapy in Oncology]. / Indicazioni al trattamento chirurgico integrato delle carcinosi peritoneali di origine colorettale: esperienza della società Italiana di terapie integrate locoregionali in oncologia.

A multicentric prospective study has been carried on 69 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intraoperative hyperthermic chemoperfusion. CC 0-1 has been achieved in 82%. Major morbidity and mortality was respectively 21.7% and 2.9%. Three years overall survival was 26.7% for all series. Difference in survival evaluating CC 0-1 vs CC 2 patients and PCI < or = 10 vs > 10 was statistically significant. Evaluating only patients CC 0-1 and PCI < or = 10 overall survival rised up to 44.7% at 4 years. A smaller subgroup of patients with a disease-free interval to peritoneal carcinomatosis > or = 2-year showed a 50% disease-free survival at 5 years. In conclusion PCI < or = 10, complete or optimal cytoreduction feasibility and disease-free interval have to be considered for the patients selection to the integrate treatment.

[Treatment of peritoneal mesothelioma using cytoreduction and intraperitoneal hyperthermic chemotherapy]. / Trattamento del mesotelioma peritoneale mediante citoriduzione e chemioipertermia intraperitoneale (CIIP).

UNLABELLED: Malignant mesothelioma of the peritoneum is a rare tumor for which the therapeutic approach has not yet been standardized. Cytoreductive surgery and hyperthermic antiblastic peritoneal perfusion (HAPP) may be effective in the treatment of this neoplasm. From 1995 to March 2003, we operated 24 patients with malignant peritoneal mesothelioma. Nineteen times we were able to perform radical surgery and HAPP: 6 CC-0, 10 CC-1 and 3 CC-2 (nodules smaller than 1 cm). HAPP was performed by the original "semi-closed" technique, using MMC+ CDDP in 3 patients, CDDP + doxorubicin in 15 patients, only doxorubicin in 1 patient). RESULTS: Operating mortality was 11% and postoperative morbidity was 26%. 4 patients are DOD (40, 20, and 2 at 2 months); 5 patients are AWD (72, 34, 25, and 2 at 15 months); 8 patients are NED (81, 47, 2 at 20 months, 16, 13, 12 months, 1 patient recently operated). The median survival is 40 months. The high rate of morbidity and mortality is due to the presence of postoperative paraneoplastic syndromes, with alterations of coagulation and onset of ARDS. Therefore the good survival results make the methodic one of the best options in the treatment of the disease.

[Treatment of pseudomyxoma peritonei using cytoreduction and intraperitoneal hyperthermic chemotherapy]. / Il trattamento dello pseudomixoma peritonei (PMP) mediante citoriduzione e chemioipertermia intraperitoneale (CIIP).

Pseudomixoma peritonei (PMP) is a rare neoplasia with a low grade of clinical malignity. Generally, the main treatment of this tumor is the surgical debulking. Best results are obtained combining surgery and hyperthermic antiblastic peritoneal perfusion (HAPP) with CDDP and MMC. From April '97 to March 2003, we operated on 132 patients, 8 times with a palliative intent. In 27 times we achieved a complete cytoreduction (17 CC0 and 10 CC1) followed by HAPP. As regards results, no post-operative mortality was reported and 19% of major morbidity was observed. 26 patients are NED at maximum follow-up of 6 years and 1 patient had recurrence 6 months after primary resection. We believe that cytoreduction and HAPP is the golden standard of PMP therapy when it is possible to achieve a complete cytoreduction. Most of the times, the disease is not radically treated and therefore, after diagnosis, patients should be only referred to specialized centers.