Roberto Tozzi

Neo-adjuvant chemotherapy does not increase the rate of complete resection and does not significantly reduce the morbidity of Visceral–Peritoneal Debulking (VPD) in patients with stage IIIC–IV ovarian cancer

OBJECTIVE To measure the efficacy and the safety of Visceral-Peritoneal Debulking (VPD) in patients with stage IIIC-IV ovarian cancer and to compare the outcomes before and after chemotherapy. METHODS Between 2008 and 2013, 200 consecutive patients were offered VPD for stage IIIC/IV ovarian cancer. Exclusion criteria were: metastases in the lungs or 3 liver segments at CT review and/or disease on small bowel serosa or encasing the porta hepatis at explorative laparoscopy. The endpoints were efficacy (rate of complete resection, CR) and safety (morbidity and mortality). The results were compared between patients in group 1 (upfront surgery) and group 2 (during or after chemotherapy). RESULTS Ninety-eight patients were in group 1 and 102 in group 2. Twenty out of 200 patients (10%) did not have VPD, 180 out of 200 patients (90%) had VPD and CR: 90.8% in group 1, 89.8% in group 2. The mortality (1%) and intra-operative complication rate (3.3%) were similar. Post-operative complications rate was 34.8% in group 1 vs. 30.7% in group 2 (P=0.669). The difference in grade III (15.7% vs. 5.5%, P=0.053) and grade IIIb complications (13.4% vs. 4.4%, P=0.062) approached statistical significance. All other outcomes were not significantly different in the 2 groups. CONCLUSION VPD achieved CR in 90% of the patients. Neo-adjuvant chemotherapy did not increase the rate of CR and did not significantly decrease the morbidity or the complexity of the surgery.

Laparoscopic debulking of bulky lymph nodes in women with cervical cancer : indication and surgical outcomes

Objective  To describe the technique and the surgical outcome of laparoscopic resection of bulky lymph nodes before adjuvant treatment.

Diaphragmatic peritonectomy vs. full thickness resection with pleurectomy during Visceral-Peritoneal Debulking (VPD) in 100 consecutive patients with stage IIIC–IV ovarian cancer: A surgical-histological analysis

OBJECTIVE To compare the surgical and histological outcomes of diaphragmatic peritonectomy vs. full thickness resection with pleurectomy during Visceral-Peritoneal Debulking. METHODS Service evaluation protocol (Trust number 3265). All patients with stage IIIC-IV ovarian cancer who had diaphragmatic surgery between April 2009 and November 2013 were included. Clinical notes and histology reports were reviewed. Additional histology sections were undertaken. Patients were divided in Groups 1 (peritonectomy) and 2 (pleurectomy). The outcomes of interest were: surgical (intra- and post-operative morbidity, pulmonary morbidity, mortality, rate of complete resection) and histological (rate of diaphragmatic peritoneum, muscle and pleural involvement, rate of microscopic diaphragmatic free margins). RESULTS Sixty four patients had diaphragmatic peritonectomy (Group 1), 36 patients full thickness diaphragmatic resection with pleurectomy (Group 2). There was no significant difference in the rate of mortality (3% in both groups), overall intra- and post-operative morbidity (32.8% vs. 38.8%), pulmonary morbidity (9.3% vs. 19%, P=0.14). Histology showed tumor invasion in the diaphragmatic peritoneum (96%), muscle (28%) and pleura (19.4%). Microscopic free margins were seen in 86% vs. 92% in Groups 1 and 2. CONCLUSIONS Our study demonstrated that, in patients with ovarian cancer, diaphragmatic involvement extends to the muscle in almost 30% and to the pleura in 20% of the patients. Overall and specific morbidity was not significantly different when comparing peritonectomy vs. pleurectomy.

Chemokines mRNA expression in relation to the Macrophage Migration Inhibitory Factor (MIF) mRNA and Vascular Endothelial Growth Factor (VEGF) mRNA expression in the microenvironment of endometrial cancer tissue and normal endometrium: A pilot study

Tumor microenvironment inflammatory cells play a major role in cancer progression. Among these, the Tumor Associated Macrophages (TAMs) infiltration depends on the kind of chemokine, cytokines and growth factors secreted by the tumor cells and by the stroma in response to the cancer invasion. TAMs have been found to promote anti-tumor response in early stages and to stimulate neovascularization and metastases in advanced disease. In the microenvironment chemo-attractants of many human cancers, MIF and VEGF correlate with an increased TAMs recruitment. In addition, MIF enhances tumor cells metastases by modulating the immune responses and by promoting the angiogenesis related to VEGF. On the contrary the inhibition of MIF can lead to cell cycle arrest and apoptosis. Some chemokines (e.g. CXCL12, CXCL11, CXCL8) and their receptors, thanks to their ability to modulate migration and proliferation, are involved in the angiogenetic process. In this study we compared the expression of MIF mRNA with VEGF mRNA expression and with mRNA expression of other chemokines related to neo-angiogenesis, such as CXCL12, CXCL11, CXCL8 and CXCR4, in human endometrial cancer tissue (EC) and normal endometrium (NE). Fresh samples of EC tissue and NE were extracted from 15 patients with FIGO stage I-III undergoing primary surgery. Some of the tissue was sent for histology and part of it was treated with RNA later and stored at -80°C. Four patients dropped out. A significant up-regulation of MIF mRNA in EC tissue versus NE samples (P=0.01) was observed in all 11 patients. The MIF mRNA over-expression was coincident with a VEGF mRNA overexpression in 54% of patients (P=NS). MIF mRNA was inversely related to CXCL12 mRNA expression (P=0.01). MIF over-expression was significantly related to low grading G1-2 (P=0.01), endometrial type I (P=0.05), no lymphovascular spaces invasion (P=0.01) and 3years DFS (P=0.01). As reported in previous studies on patients with breast cancer, our data suggest that the up-regulation of MIF in patients with endometrial cancer might be related to the inhibition of distant and lymphatic spread.

Porta hepatis peritonectomy and hepato–celiac lymphadenectomy in patients with stage IIIC–IV ovarian cancer: Diagnostic pathway, surgical technique and outcomes

OBJECTIVE To report the surgical technique of ovarian cancer resection at the porta hepatis (PH) and hepato-celiac lymph nodes (HCL). To assess surgical and survival outcomes. Define the accuracy of an integrated diagnostic pathway. METHODS Patients with FIGO stage IIIC-IV ovarian cancer that underwent Visceral-Peritoneal Debulking (VPD). Data of patients with disease at the PH/HCL during VPD were extracted from our database. The CT scan findings were compared with the exploratory laparoscopy. Accuracy of CT scan, intra- and post-operative morbidity, rate of complete resection (CR), disease free and overall survival are reported. RESULTS Thirty one patients out of 216 (14.3%) had tumor at the PH and/or HCL. In 8 patients out of 31 (25.8%) it was only found with the aid of the exploratory laparoscopy. CR was achieved in 28 patients out of 31 (90.3%). Pathology confirmed disease in the PH/HCL specimens of all but one patient. Overall morbidity relating to the VPD was 29.2%. No complication was specifically related to the PH/HCL. Median disease free survival was 19months and median overall survival was 42months. CONCLUSION PH/HCL surgery was required in 15% of patients with FIGO stage IIIC-IV. The surgery was feasible, safe and significantly contributed to CR. CT scan failed to identify the disease in 31% of the patients. CT and laparoscopy correctly identified all patients.

Interval Laparoscopic En-Bloc Resection of the Pelvis (L-EnBRP) in patients with stage IIIC-IV ovarian cancer: Description of the technique and surgical outcomes

OBJECTIVE To describe the technique and evaluate the feasibility, efficacy and morbidity of the Laparoscopic En-Bloc Resection of the Pelvis (L-EnBRP) during Visceral-Peritoneal Debulking (VPD) at time of interval surgery. METHODS This report is part of a prospective non randomized study (service evaluation protocol) on the feasibility and safety of laparoscopy in patients with stage IIIC-IV ovarian cancer and gross residual disease following neoadjuvant chemotherapy. Primary endpoints of this part of the study were the feasibility (rate of patients in whom the surgery could be completed by laparoscopy), efficacy (rate of patients ended with a complete resection) and morbidity (number of patients that suffered complications specifically associated to the procedure) of L-EnBRP. The results were compared between patients in group 1 (L-EnBRP+L-VPD), group 2 (L-EnBRP+VPD) and group 3 (VPD). RESULTS Eighteen patients were in group 1, 8 in group 2 and 32 in group 3. Feasibility of L-EnBRP was 45% (26 patients out of 58), efficacy was 100% of the pelvic disease (94.4% overall disease) and morbidity was 5.5%. Main cause for conversion to laparotomy was high tumor load on diaphragm and/or mesentery. All but one patient had a complete resection (CR) of the disease. Group 1 patients had significantly earlier hospital discharge, lower blood loss and reduced overall morbidity than group 2 and 3. CONCLUSION L-EnBRP was feasible in almost half of the patients. In these patients a CR was achieved with a low morbidity rate. The latter was significantly decreased when compared to the patients who had a laparotomy.

Morbidity and reversal rate of ileostomy after bowel resection during Visceral-Peritoneal Debulking (VPD) in patients with stage IIIC-IV ovarian cancer

OBJECTIVE To investigate the morbidity of diverting loop ileostomy (DLI) performed during Visceral Peritoneal Debulking (VPD) for stage IIIC-IV ovarian cancer and to report the rate, timing, and morbidity of DLI reversal. METHODS We retrieved the data of all consecutive patients who underwent sigmoid-rectum resection (SRR) followed by DLI. Morbidity was defined as any surgical/medical complications clearly correlated to the DLI. The reversal rate of DLI was defined as the number of patients who had the continuity of the gastrointestinal tract restored in the study period. Finally, we recorded the timing and the morbidity of the reversal surgery. Factors associated with non-reversal of DLI were reported. RESULTS In the study period (01/2010-09/2016), complete data were available for 47 patients. Stoma-related complications occurred in 22 patients (46.8%). Eight patients (17.0%) were readmitted within 30days from surgery. Thirty-two patients (68.1%) had their stoma reversed. The primary cause of non-reversal was tumor recurrence/progression (7/15, 46.7%). Patients age, length of hospitalization, complications after VPD were associated with non-reversal of DLI. The mean time from DLI formation to stoma reversal was 6months (±1.7). Post-reversal related complications occurred in 37.1% of the patients. CONCLUSIONS In our series, 31.9% of the patients with FIGO stage IIIC-IV ovarian cancer who underwent SRR and DLI did not have stoma reversal. Overall they had approximately 45% risk of stoma-related morbidity and 37% risk of morbidity related to the stoma reversal. This information should be part of the consulting process when preparing for debulking surgery, particularly in patients who are likely to need a bowel resection.

En-bloc resection of the pelvis (EnBRP) in patients with stage IIIC–IV ovarian cancer: A 10 steps standardised technique. Surgical and survival outcomes of primary vs. interval surgery

OBJECTIVE In this study we describe the technique of the En-bloc resection of the pelvis (EnBRP) in 10 standardised and reproducible steps, whereby all pelvic organs, except the bladder, are removed together with the peritoneum. In addition, we compare the surgical and survival outcomes of patients who underwent upfront vs. interval surgery. METHODS Retrospective analysis of patients with FIGO Stage IIIC-IV ovarian cancer treated with Visceral Peritoneal Debulking (VPD) who had EnBRP. The study population was divided into Group 1 (up-front VPD) and group 2 (VPD after neo-adjuvant chemotherapy). The aim was to assess the incidence of EnBRP. We also assessed rate of complete resection (CR), procedure-specific and overall morbidity, disease free and overall survival. Results were compared between group 1 and 2. RESULTS Overall 92 out of 200 patients (46%) needed an EnBRP during the VPD. Forty-eight patients were in Group 1 and 44 patients in Group 2. CR was achieved in all patients. No intra-operative procedure specific morbidity was recorded. Dehiscence of bowel anastomosis was the only procedure specific morbidity. Rate was 2%, with 1 episode recorded in each group. Both patients were managed and settled with formation of a bowel diversion. The overall morbidity rate was 33%, 35% in group 1 and 31% in group 2. The mortality rate was 1%. Median disease free survival was 20months, 25 in group 1 vs. 15 in group 2 (P=0.009). CONCLUSIONS EnBRP is a safe and effective technique to tackle the pelvic disease of patients with advanced ovarian cancer. The reduced blood loss, the high rate of clear margins and CR of the disease are accompanied by a low rate of surgical morbidity. These features are particularly suitable for patients who are due to start or re-start chemotherapy. The standardization of the technique will make it more reproducible and easier to be taught. In addition, it will facilitate comparison of results and the inclusion of this technique in the portfolio of procedures as part of debulking surgery.

Concomitant Laparoscopic and Thoracoscopic Resection of Recurrent High-Grade Ovarian Cancer

STUDY OBJECTIVE To describe the first case of combined endoscopic management of a thoracic and abdominal recurrence of ovarian cancer. DESIGN An instructive video showing the combined thoracic and abdominal surgical procedure. SETTING Department of Gynecological Oncology, Churchill Hospital, Oxford University, UK. PATIENTS A 64-year-old woman undergoing endoscopic treatment for a third recurrence of ovarian cancer after a full surgical staging in 2007. The disease-free interval from the last recurrence was 31 months. INTERVENTION The operation was performed by a multidisciplinary team of thoracic and gynecologic oncologist surgeons. Surgery started with thoracoscopic resection of a right enlarged paracardiac lymph node of 24 mm and a small wedge of the right lung, which was attached to the lymph node. At laparoscopy, 2 nodules of 3 and 5 mm were excised from the mesosigmoid and 1 nodule of 20 mm was resected from the right hemidiaphragm. MEASUREMENTS AND MAIN RESULTS The total operative time was 251 minutes, and no intraoperative complication occurred. No conversion to open surgery was necessary. The estimated blood loss was 50 mL. There was no visible residual disease at the end of the surgery. The patient was discharged 4 days after surgery. The final pathology report confirmed the presence of endometrioid adenocarcinoma in all specimens removed. Adjuvant chemotherapy with carboplatin/paclitaxel was started 2 weeks later. At the 60-day follow-up, no complications were recorded. A computed tomographic scan performed after 6 cycles of chemotherapy did not reveal any evidence of relapse. CONCLUSIONS The combined endoscopic approach might be feasible in selected patients.

Uterine Scar Healing After Cesarean Section: Managing an Old Surgery in an Evidence-Based Environment

Cesarean section is one of the most commonly undertaken operations worldwide, and its rate is constantly increasing in recent years both in middleand highincome countries, despite several scientific societies developing informative campaigns to support vaginal delivery whenever it is possible in order to avoid complications in future pregnancies. Among the most important pieces of evidence about this point, more than 10 years ago the World Health Organization performed a global survey on maternal and perinatal health in Latin America, one of the areas with the highest rate of cesarean section worldwide;1 this multistage stratified sample comprised 24 geographic regions in eight countries, collecting data from 97,095 deliveries. According to this large cohort analysis, rate of cesarean delivery was positively associated with severe maternal morbidity and mortality, even after adjustment for risk factors; in addition, it was positively associated with a significant increase in fetal mortality rates and higher numbers of babies admitted to intensive care for 7 days or longer, even after adjustment for preterm delivery. Although cesarean section may be considered as a standardized technique, several different approaches may underlie different outcomes; in 2014, the Cochrane Collaboration published the updates of two interesting systematic reviews and meta-analyses,2,3 trying to shed new lights about the topic. The first report investigated the effects of nonclosure as an alternative to closure of the peritoneum on intraoperative and immediateand long-term postoperative outcomes,