Michele De Simone

Hyperthermic intraperitoneal intraoperative chemotherapy after cytoreductive surgery for the treatment of abdominal sarcomatosis: clinical outcome and prognostic factors in 60 consecutive patients.

Abdominal sarcomatosis is a rare nosologic entity with a poor prognosis. After a Phase I study on cytoreductive surgery combined with hyperthermic intraperitoneal intraoperative chemotherapy (HIIC), the authors reported the results of the treatment of 60 patients using this novel multimodal approach.

Hyperthermic intraoperative intraperitoneal chemotherapy with cisplatin and doxorubicin in patients who undergo cytoreductive surgery for peritoneal carcinomatosis and sarcomatosis - Phase I study

Hyperthermic intraperitoneal intraoperative chemotherapy (HIIC) combined with cytoreductive surgery (CS) has been proposed as a new multimodal treatment mainly for carcinomatosis of gastrointestinal origin. To evaluate whether this regimen could be used for other tumor types, the authors conducted a Phase I study on HIIC with doxorubicin and cisplatin in patients with peritoneal carcinomatosis or sarcomatosis.

Irinotecan hepatic arterial infusion chemotherapy for hepatic metastases from colorectal cancer: A phase II clinical study

Aims and background The advantage of delivering chemotherapy by hepatic arterial infusion is the acquisition of a high concentration of the drug in the target. Irinotecan (CPT-11) is active for the treatment of advanced colorectal cancer. In phase I studies, doses of 20 mg/m2/d for 5 days given every 4 weeks as continuous infusion or 200 mg/m2 as a short 30-min infusion given every 3 weeks is recommended for phase II studies. Methods and study design Twelve patients with a median liver substitution of 30% (20-50%) were enrolled, 6 progressed after a FOLFOX-induced partial response and 6 progressed after 5-fluorouracil and folinic acid. All patients had a surgically (n = 6) or angiographically placed port (n = 6). They received hepatic arterial infusion chemotherapy with CPT-11 (200 mg/m2) on an outpatient basis, every 3 weeks as a short 30-min infusion for six cycles. Results Four partial responses were observed (33%) lasting 24, 15, 12 and 8+ weeks, 3 stable disease (25%) lasting more than 12 weeks, and 5 progressions (41%). Six patients (50%) presented a >30% reduction in CEA. Toxicity was G2 diarrhea in 5 patients (41%) and G2 myelosuppression in 6 (50%); one patient had abdominal right upper quadrant pain requiring analgesics. Conclusions CPT-11 is active as hepatic arterial infusion chemotherapy in liver metastases from colorectal cancer and can rescue systemically pretreated patients. Our schedule seems safe, feasible and well accepted on an outpatient basis.

Complete response of colorectal liver metastases after intra-arterial chemotherapy

AIMS AND BACKGROUND We demonstrated that colorectal liver metastases considered in complete response after intra-arterial floxuridine-based chemotherapy had recurred in situ. METHODS AND STUDY DESIGN One hundred and six colorectal liver metastases disappeared after intra-arterial chemotherapy. Persistent macroscopic disease was observed at surgery at the site of 52 of 106 liver metastases, even though computerized tomography scan and ultrasound showed a complete response. The sites of 35 initial liver metastases that were not visible at surgery were resected. Pathologic examination of these sites, considered in complete response, showed viable cancer cells in 22 of 35 cases. RESULTS After 1 year of follow-up, 33 of 106 liver metastases considered in complete response had recurred in situ. After 2 years of follow-up, persistent macroscopic or microscopic residual disease or recurrence was observed in 86 (81%) of the 106 liver metastases. CONCLUSIONS Nevertheless, 19% of the patients had a long-lasting response. This means that floxuridine given as intra-arterial hepatic chemotherapy can still be considered an interesting option of cure in the treatment of colorectal liver metastases. When feasible, the site of the lesion that disappeared after intra-arterial chemotherapy should be resected at surgery. The best palliative cure of liver metastases should be the combination of local-regional strategies like intra-arterial chemotherapy, surgery or radiofrequency ablation with the systemic approach.

Critical update and emerging trends in imatinib treatment for gastrointestinal stromal tumor.

The extraordinary success of imatinib in gastrointestinal stromal tumor (GIST) represents a model for molecularly targeted therapy of solid tumors. Research is currently going to identify the molecular basis of mechanisms of action and drug resistance. For the optimal management of the patients treated, a multidisciplinary approach, including medical oncologists, surgeons, pathologists, and radiologists is needed. In this article, we reviewed recent advances in the clinical management of GIST patients treated with imatinib, and in the knowledge of the molecular mechanisms that are basic to imatinib effects.

1st Evidence-based Italian consensus conference on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinosis from ovarian cancer

Ovarian cancer (OC) remains relatively rare, although it is among the top 4 causes of cancer death for women younger than 50. The aggressive nature of the disease and its often late diagnosis with peritoneal involvement have an impact on prognosis. The current scientific literature presents ambiguous or uncertain indications for management of peritoneal carcinosis (PC) from OC, both owing to the lack of sufficient scientific data and their heterogeneity or lack of consistency. Therefore, the Italian Society of Surgical Oncology (SICO), the Italian Society of Obstetrics and Gynaecology, the Italian Association of Hospital Obstetricians and Gynaecologists, and the Italian Association of Medical Oncology conducted a multidisciplinary consensus conference (CC) on management of advanced OC presenting with PC during the SICO annual meeting in Naples, Italy, on September 10-11, 2015. An expert committee developed questions on diagnosis and staging work-up, indications, and procedural aspects for peritonectomy, systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy for PC from OC. These questions were provided to 6 invited speakers who answered with an evidence-based report. Each report was submitted to a jury panel, representative of Italian experts in the fields of surgical oncology, gynecology, and medical oncology. The jury panel revised the reports before and after the open discussion during the CC. This article is the final document containing the clinical evidence reports and statements, revised and approved by all the authors before submission.

Treatment of Peritoneal Carcinomatosis from Colonic Cancer by Cytoreduction, Peritonectomy and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Experience of 12 Years

INTRODUCTION Peritoneal carcinomatosis (PC) is one of the routes of dissemination 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 with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). This approach is based on surgical cytoreduction of the primary tumour, peritonectomy (stripping of implants on the peritoneal surface) and HIPEC. The rationale of this treatment, after macroscopic disease removal, is to obtain an elevated and persistent drug concentration in the peritoneal cavity, with limited systemic effects. Many studies have reported encouraging results on overall survival (OS) and the disease-free interval in patients affected by PC. PATIENTS AND METHODS From October 1997 to November 2008, 411 operations for PC were performed in our institution; in 232 cases, cytoreduction plus HIPEC was carried out. Out of 72 operations for colonic cancer: 40 cytoreductions plus HIPEC, 12 cytoreductions+ EPIC (early postoperative intraperitoneal chemotherapy) and 16 debulking or explorative laparoscopies/laparotomies were performed. For the present study, the 40 patients who had undergone cytoreduction plus HIPEC for PC of colorectal cancer (CRC) were considered. RESULTS The complication rate was 55% (22/40) and mortality rate 2.5% (1/40). The specific features of both groups were considered for the survival curves and complication rates, with special reference to the peritoneal carcinomatosis index (PCI; range 0, absence of disease to 39) and completeness of cytoreduction score (CCR; 0, no residual tumor, to CCR 3, residual nodules greater than 25 mm). In Group A, patients operated on prior to 2002, the median survival time was 16.7 months compared to 24.6 months for Group B, those operated on after 2002. The poor survival of Group A seemed to be related to higher PCI and CCR scores. CONCLUSION Correct patient selection based on a maximum PCI of 16, associated with complete cytoreduction (CCR-0), produced encouraging results in our experience. To improve this encouraging survival outcome, it is very important to unify the surgical experience of expertise centres. Our results also suggest the need for an integrated approach to this condition to identify the correct aspect of the surgical domain and results that may be influencing the prognosis and the evolution of this patients.