Long-term outcomes in ypT0 rectal cancers: An international multi-centric investigation on behalf of Italian Society of Surgical Oncology Young Board (YSICO).

AIM: To investigate the outcome and pattern of survivals of rectal cancer patients presenting a complete or nearly complete tumor response after neo-adjuvant treatment. METHODS: Young surgeons <40 years old affiliated to the Italian Society of Surgical Oncology (YSICO) from 13 referral centers for colorectal cancer treatment, were invited to participate a retrospective study. Records from patients treated from 2005 to 2015 with a pathological diagnosis of ypT0/ypTis were retrieved and pooled in a common data-base for statistical purposes. All clinical and pathological variables were reviewed. Univariate and multivariate analyses were conducted with the end-point of survivals. RESULTS: Two hundreds and sixty-one patients were analyzed including 237 ypT0 and 24 ypTis. Nodal positive patients were 8.7%. More than sixty-six percent of the patients did not perform adjuvant chemotherapy, with a statistical difference comparing N0 versus N+ patients (66.8% vs 40.9%, p 0.02). Mean follow-up was of 47.6 months. Twenty-two relapses were observed, 91.6% at a distant site. The mean time to recurrence was of 35.3 months. On univariate analysis, the use of adjuvant chemotherapy correlated with better OS exclusively in ypT0N + patients and not in ypT0N0. Univariate and multivariate analyses documented nodal positivity as the only prognostic factor correlated with a worse OS. CONCLUSION: Recurrences were mostly diagnosed at a distant site and within the third year of follow-up. Nodal positivity was the only variable independently correlated with a worse OS. Univariate analysis documented a benefit for the use of adjuvant chemotherapy treatment exclusively in ypT0N + rectal cancers.

Irreversible electroporation as treatment of locally advanced and as margin accentuation in borderline resectable pancreatic adenocarcinoma.

In recent years, many local ablation technologies based on thermal damage have been used in the treatment of locally advanced pancreatic carcinoma (LAPC) and borderline resectable pancreatic carcinoma (BLRPC). However, they are associated with major complications because of possible vascular and ductal damage. Irreversible electroporation (IRE) is a nonthermal ablation technology that seems safe near vital vascular and ductal structures. IRE could be used as exclusive treatment of LAPC (en situ to IRE) after induction chemotherapy In BLRPC, surgery is not really radical in 6% of patients (microscopic residual) and local recurrences occur in 11-42% of apparent radical resections. IRE could be used as margin accentuation to increase posterior margin during radical surgery in BLRPC. Our outcomes are safety, time to progression. Secondary outcomes are overall survival, pain control and quality of life. We are performing a prospective evaluation of patients undergoing IRE for LAPC or BLRPC since July 2014. We have included patients with non-metastatic LAPC with maximum size ≤4 cm (en situ to IRE) and patients with BLRPC (complementary IRE). We have performed induction chemotherapy in both groups. After treatment, patients were evaluated on days 1, 2, 4, 7, 14, 21, 30, 60 and 90 with amylase and lipase serum and abdominal drainage test. Based on Ethics Committee's request, follow-up imaging was performed at the 10th day for safety evaluation, at 30, 60 and 90 days for response evaluation and then every 3 months. Seven patients (two women and five men) underwent IRE. Two patients had LAPC and received en situ to IRE. In five patients affected by BLRPC we performed IRE and pancreatic head resection. In all patients, intraoperative imaging confirmed that the treatment of the whole tumor volume was complete. All seven patients demonstrated nonclinically relevant elevation of their amylase and lipase, which returned normal at 5 days postprocedure. No patient showed evidence of clinical pancreatitis or fistula. No major complications were recorded. Patients with LAPC died of distant metastases 6 month after treatment. At 3- and 6-month follow-up, all patients with BLPRC were alive and disease free. Only one patient has already reached 9-month follow-up and is alive and disease free. Our results are only preliminary. However, IRE ablation of LAPC and BLRPC seems a safe and feasible treatment.

Transanal total mesorectal excision (taTME) for cancer located in the lower rectum: short- and mid-term results.

BACKGROUND: Laparoscopic trans-abdominal total mesorectal excision is technically demanding. Transanal Total Mesorectal Excision (taTME) is a new technique which seems to provide technical advantages. This study describes the results of taTME in a consecutive series of patients with low rectal cancer. METHODS: From January 2012 to December 2013, a consecutive series of 26 patients with low rectal cancer underwent laparoscopic taTME with coloanal anastomosis. cT4 or Type II-III rectal cancer (according to Rullier's classification) were contraindications to taTME. After anal sleeve mucosectomy, the rectal wall was transected at the ano-rectal junction. A single-access multichannel port was inserted in the anal canal. taTME was performed from down to up until the sacral promontory posteriorly and the Pouch of Douglas anteriorly were reached. A laparoscopic trans-abdominal approach was used to complete the left colon mobilization. RESULTS: Sixteen patients (61.5%) were male. The mean distance of the rectal cancer from the anal verge was 4.4 cm (range 3-6). Nineteen patients (73.1%) received long-course neoadjuvant radiotherapy. At final pathology, resection margins were negative in all the patients: the mean distal and radial resection margins were 19 mm and 11.2 mm, respectively. TME was complete in 23 patients (88.5%) and nearly complete in three. Postoperative mortality was 3.8%. The overall morbidity rate was 26.9% (7 patients): two patients (7.7%) had an anastomotic leakage (Dindo I-d). After a mean follow up of 23 months, no patients have developed a local recurrence. CONCLUSIONS: laparoscopic taTME allow wide resection margins and good quality TME.

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.

Low rates of loco-regional recurrence following extended lymph node dissection for gastric cancer.

AIM: The study by MacDonald et al. [Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725-30] has reported low loco-regional recurrence rates (19%) after gastric cancer resection and adjuvant radiotherapy. However, the lymph node dissection was often "inadequate". The aim of this retrospective study is to analyse if an extended lymph node dissection (D2) without adjuvant radiotherapy may achieve comparable loco-regional recurrence rates. METHODS: A prospective database of 200 patients who underwent a curative resection for gastric carcinoma from January 2000 to December 2006 was analysed. D2 lymph node dissection was standard. Recurrences were categorized as loco-regional, peritoneal, or distant. No patients received neoadjuvant or adjuvant radiotherapy. RESULTS: The in-hospital mortality rate was 1% (2 patients). The mean number of dissected lymph nodes was 25.9. Overall and disease-free survival at 5years were 60.7% and 61.2% respectively. During the follow-up, 60 patients (30%) have recurred at 76 sites: 38 (50%) distant metastases, 25 (32.9%) peritoneal metastases, and 13 (17.1%) loco-regional recurrences. The loco-regional recurrence was isolated in 6 patients and associated with peritoneal or distant metastases in 7 patients. The mean time to the first recurrence was 18.9 (95% confidence interval: 15.0-21.9) months. CONCLUSIONS: Extended lymph node dissection is safe and warrants low loco-regional recurrence rates.