Davide Cavaliere

Evaluation of extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced epithelial ovarian cancer.

Objective Although standard treatment for advanced epithelial ovarian cancer (EOC) consists of surgical debulking and intravenous platinum- and taxane-based chemotherapy, favorable oncological outcomes have been recently reported with the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of the study was to analyze feasibility and results of CRS and HIPEC in patients with advanced EOC. Materials/Methods This is an open, prospective phase 2 study including patients with primary or recurrent peritoneal carcinomatosis due to EOC. Thirty-nine patients with a mean (SD) age of 57.3 (9.7) years (range, 34–74 years) were included between September 2005 and December 2009. Thirty patients (77%) had recurrent EOC and 9 (23%) had primary EOC. Results For HIPEC, cisplatin and paclitaxel were used for 11 patients (28%), cisplatin and doxorubicin for 26 patients (66%), paclitaxel and doxorubicin for 1 patient (3%), and doxorubicin alone for 1 patient (3%). The median intra-abdominal outflow temperature was 41.5°C. The mean peritoneal cancer index (PCI) was 11.1 (range, 1–28); and according to the intraoperative tumor extent, the tumor volume was classified as low (PCI <15) or high (PCI ≥15) in 27 patients (69%) and 12 patients (31%), respectively. Microscopically complete cytoreduction was achieved for 35 patients (90%), macroscopic cytoreduction was achieved for 3 patients (7%), and a gross tumor debulking was performed for 1 patient (3%). Mean hospital stay was 23.8 days. Postoperative complications occurred in 7 patients (18%), and reoperations in 3 patients (8%). There was one postoperative death. Recurrence was seen in 23 patients (59%) with a mean recurrence time of 14.4 months (range, 1–49 months). Conclusions Hyperthermic intraperitoneal chemotherapy after extensive CRS for advanced EOC is feasible with acceptable morbidity and mortality. Complete cytoreduction may improve survival in highly selected patients. Additional follow-up and further studies are needed to determine the effects of HIPEC on survival.

Laparoscopic peritoneal lavage: a definitive treatment for diverticular peritonitis or a "bridge" to elective laparoscopic sigmoidectomy?: a systematic review.

AbstractTo this day, the treatment of generalized peritonitis secondary to diverticular perforation is still controversial. Recently, in patients with acute sigmoid diverticulitis, laparoscopic lavage and drainage has gained a wide interest as an alternative to resection. Based on this backdrop, we decided to perform a systematic review of the literature to evaluate the safety, feasibility, and efficacy of peritoneal lavage in perforated diverticular disease.A bibliographic search was performed in PubMed for case series and comparative studies published between January 1992 and February 2014 describing laparoscopic peritoneal lavage in patients with perforated diverticulitis.A total of 19 articles consisting of 10 cohort studies, 8 case series, and 1 controlled clinical trial met the inclusion criteria and were reviewed. In total these studies analyzed data from 871 patients. The mean follow-up time ranged from 1.5 to 96 months when reported. In 11 studies, the success rate of laparoscopic peritoneal lavage, defined as patients alive without surgical treatment for a recurrent episode of diverticulitis, was 24.3%. In patients with Hinchey stage III diverticulitis, the incidence of laparotomy conversion was 1%, whereas in patients with stage IV it was 45%. The 30-day postoperative mortality rate was 2.9%. The 30-day postoperative reintervention rate was 4.9%, whereas 2% of patients required a percutaneous drainage. Readmission rate after the first hospitalization for recurrent diverticulitis was 6%. Most patients who were readmitted (69%) required redo surgery. A 2-stage laparoscopic intervention was performed in 18.3% of patients.Laparoscopic peritoneal lavage should be considered an effective and safe option for the treatment of patients with sigmoid diverticulitis with Hinchey stage III peritonitis; it can also be consider as a “bridge” surgical step combined with a delayed and elective laparoscopic sigmoidectomy in order to avoid a Hartmann procedure. This minimally invasive staged approach should be considered for patients without systemic toxicity and in centers experienced in minimally invasive surgery techniques. Further evidence is needed, and the ongoing RCTs will better define the role of the laparoscopic peritoneal lavage/drainage in the treatment of patients with complicated diverticulitis.

Mast Cells Positive to Tryptase and c-Kit Receptor Expressing Cells Correlates with Angiogenesis in Gastric Cancer Patients Surgically Treated

Background. Angiogenesis is a complex process involved in both growth and progression of several human and animal tumours. Tryptase is a serin protease stored in mast cells granules, which plays a role in tumour angiogenesis. Mast cells (MCs) can release tryptase following c-Kit receptor (c-KitR) activation. Method. In a series of 25 gastric cancer patients with stage T3N2-3M0 (by AJCC for Gastric Cancer 7th Edition), immunohistochemistry and image analysis methods were employed to evaluate in the tumour tissue the correlation between the number of mast cells positive to tryptase (MCPT), c-KitR expressing cells (c-KitR-EC), and microvascular density (MVD). Results. Data demonstrated a positive correlation between MCPT, c-KitR-EC, and MVD to each other. In tumour tissue the mean number of MCPT was 15, the mean number of c-KitR-EC was 20, and the mean number of MVD was 20. The Pearson test correlating MCPT and MVD, c-KitR-EC and MVD was significantly (r = 0.64, P = 0.001; r = 0.66, P = 0.041, resp.). Conclusion. In this pilot study, we suggest that MCPT and c-KitR-EC play a role in gastric cancer angiogenesis, so we think that several c-KitR or tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new antiangiogenetic approach.

Surgical treatment of primitive gastro-intestinal lymphomas: a systematic review

Primitive Gastrointestinal Lymphomas (PGIL) are uncommon tumours, although time-trend analyses have demonstrated an increase. The role of surgery in the management of lymphoproliferative diseases has changed over the past 40 years. Nowadays their management is centred on systemic treatments as chemo-/radio- therapy. Surgery is restricted to very selected indications, always discussed in a multidisciplinary setting. The aim of this systematic review is to evaluate the actual role of surgery in the treatment of PGIL.A systematic review of literature was conducted according to the recommendations of The Cochrane Collaboration. Main outcomes analysed were overall survival (OS) and disease free survival (DFS).There are currently 1 RCT and 4 non-randomised prospective controlled studies comparing surgical versus medical treatment for PGIL. Seven hundred and one patients were analysed, divided into two groups: 318 who underwent to surgery alone or associated with chemotherapy and/or radiotherapy (surgical group) versus 383 who were treated with chemotherapy and/or radiotherapy (medical group).Despite the OS at 10 years between surgical and medical groups did not show relevant differences, the DFS was significantly better in the medical group (P = 0.00001). Accordingly a trend was noticed in the recurrence rate, which was lower in the medical group (6.06 vs. 8.57%); and an higher mortality was revealed in the surgical group (4.51% vs. 1.50%).The chemotherapy confirms its primary role in the management of PGIL as part of systemic treatment in the medical group. Surgery remains the treatment of choice in case of PGIL acutely complicated, although there is no evidence in literature regarding the utility of preventive surgery.

Efficacy of surgery and imatinib mesylate in the treatment of advanced gastrointestinal stromal tumor: a systematic review

AIMS AND BACKGROUND In patients with localized gastrointestinal stromal tumors, surgery remains the elective treatment. Nowadays, imatinib therapy has been standardized in advanced gastrointestinal stromal tumors, showing continuous improvements in progression-free and overall survival. A combination of imatinib therapy and surgery may also be effective in a subset of patients with metastatic or unresectable gastrointestinal stromal tumors. In this review, the authors analyzed the role of imatinib mesylate associated to surgery in unresectable and/or metastatic gastrointestinal stromal tumors. METHODS AND STUDY DESIGN We searched for all published and unpublished randomized controlled clinical trials and controlled clinical trials. We conducted the review according to the recommendations of The Cochrane Collaboration. We used Review Manager 5 software for the statistical analysis. RESULTS There are currently no randomized controlled clinical trials or controlled clinical trials on this issue. We performed a subgroup analysis in the patients preoperatively treated with imatinib mesylate. This subgroup revealed a minor incidence of recurrent or metastatic gastrointestinal stromal tumors and a greater incidence of locally unresectable gastrointestinal stromal tumors in the responsive disease group (P = 0.001). In this patient group, more complete resections were observed (P = 0.00001). Furthermore, in the same patient group we observed a more significant 12 and 24-month disease-free survival after imatinib treatment and complete resection (respectively P= 0.06 and P= 0.003) and also a better 24-month overall survival (P = 0.004). CONCLUSIONS There is actually only one ongoing European randomized study evaluating surgery of residual disease in patients with metastatic gastrointestinal stromal tumors responding to imatinib mesylate. Imatinib mesylate represents the standard treatment as preoperative supplement for locally unresectable and/or metastatic gastrointestinal stromal tumors, and a trial to compare the approach versus surgery alone is not necessary. For patients responding to imatinib or patients with prolonged stable disease, resection of residual disease should be considered. A phase III randomized study evaluating surgery of residual disease in patients with metastatic gastrointestinal stromal tumor responding to imatinib mesylate, EORTC 62063, has been opened. Moreover, surgery should be considered for patients at higher risk of complications during pharmacological debulking. In advanced gastrointestinal stromal tumors, the advantages of the integrated treatment are significant in the complete or partial response disease group in terms of more complete resections and better disease-free and overall survival.

New Trends in Acute Management of Colonic Diverticular Bleeding: A Systematic Review.

AbstractColonic diverticular disease is the most common cause of lower gastrointestinal bleeding. In the past, this condition was usually managed with urgent colectomy. Recently, the development of endoscopy and interventional radiology has led to a change in the management of colonic diverticular bleeding.The aim of this systematic review is to define the best treatment for colonic diverticular bleeding.A systematic bibliographic research was performed on the online databases for studies (randomized controlled trials [RCTs], observational trials, case series, and case reports) published between 2005 and 2014, concerning patients admitted with a diagnosis of diverticular bleeding according to the PRISMA methodology.The outcomes of interest were: diagnosis of diverticulosis as source of bleeding; incidence of self-limiting diverticular bleeding; management of non self-limiting bleeding (endoscopy, angiography, surgery); and recurrent diverticular bleeding.Fourteen studies were retrieved for analysis. No RCTs were found. Eleven non-randomized clinical controlled trials (NRCCTs) were included in this systematic review. In all studies, the definitive diagnosis of diverticular bleeding was always made by urgent colonoscopy. The colonic diverticular bleeding stopped spontaneously in over 80% of the patients, but a re-bleeding was not rare. Recently, interventional endoscopy and angiography became the first-line approach, thus relegating emergency colectomy to patients presenting with hemodynamic instability or as a second-line treatment after failure or complications of hemostasis with less invasive treatments.Colonoscopy is effective to diagnose diverticular bleeding. Nowadays, interventional endoscopy and angiographic treatment have gained a leading role and colectomy should only be entertained in case of failure of the former.

Laparoscopic lymph node biopsy in intra-abdominal lymphoma: high diagnostic accuracy achieved with a minimally invasive procedure.

Ultrasound or computed tomography-guided percutaneous lymph nodes biopsy often do not supply sufficient tissue for the histopathologic diagnosis of a lymphoma. Laparoscopic lymph node biopsy (LLB) has the advantage of obtaining the entire lymph node and avoiding the invasivity and all the possible complications of a laparotomy. The aim of the present study is to assess the safety and diagnostic accuracy of the LLB in intra-abdominal lymphoma. Between April 1999 and October 2005, 36 LLB were performed in 35 patients to rule out or to follow the progression of a lymphoma. The clinical outcome and the pathology reports were analyzed retrospectively. A conversion to laparotomy was necessary in 2 cases due to intraoperative difficulties (5.8%). No major postoperative complications or mortality occurred. Mean hospital stay was 2.1 days. In 9 patients, LLB was performed to follow a possible progression of the lymphoma, whereas in 26 patients it was used to establish a diagnosis. Two repeated LLB were necessary to achieve a correct diagnosis in 1 patient. Fourteen patients had non-Hodgkin lymphoma, 6 patients had Hodgkin lymphoma, 9 patients presented an infiltration by primitive or metastatic tumors, and 7 patients had benign lymphadenopathy. In 97% of the cases, LLB supplied the necessary information for the correct diagnosis, classification, and subsequent therapeutic decisions. In conclusion, LLB is a safe and effective procedure. Its diagnostic accuracy is superior to percutaneous techniques. LLB can be proposed as the procedure of choice to sample deep lymphatic tissues in patients with intra-abdominal lymphadenopathy at a very low morbidity rate and as an outpatient procedure in selected cases.

Role of Damage Control Surgery in the Treatment of Hinchey III and IV Sigmoid Diverticulitis: A Tailored Strategy

Abstract Many of the treatment strategies for sigmoid diverticulitis are actually focusing on nonoperative and minimally invasive approaches. The aim of this systematic review was to evaluate the actual role of damage control surgery (DCS) in the treatment of generalized peritonitis caused by perforated sigmoid diverticulitis. A literature search was performed in PubMed and Google Scholar for articles published from 1960 to July 2013. Comparative and noncomparative studies that included patients who underwent DCS for complicated diverticulitis were considered. Acute Physiology and Chronic Health Evaluation score, duration of open abdomen, intensive care unit length of stay, reoperation, bowel resection performed at first operation, fecal diversion, method, and timing of closure of abdominal wall were the main outcomes of interest. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses algorithm for the literature search and review, 10 studies were included in this systematic review. DCS was exclusively performed in diverticulitis patients with septic shock or requiring vasopressors intraoperatively. Two surgical different approaches were highlighted: limited resection of the diseased colonic segment with or without stoma or reconstruction in situ, and laparoscopic washing and drainage without colonic resection. Despite the heterogeneity of patient groups, clinical settings, and interventions included in this review, DCS appears to be a promising strategy for the treatment of Hinchey III and IV diverticulitis, complicated by septic shock. A tailored approach to each patient seems to be appropriate.

Ghost ileostomy after anterior resection for rectal cancer: a preliminary experience.

PurposeThe aim of this study was to describe and evaluate the feasibility and the eventual advantages of ghost ileostomy (GI) versus covering stoma (CS) in terms of complications, hospital stay and quality of life of patients and their caregivers after anterior resection for rectal cancer.MethodsIn this prospective study, we included patients who had rectal cancer treated with laparotomic anterior resection and confectioning a stoma (GI or CS), in the period comprised between January 2008 and January 2009. Short-term and long-term surgery-related mortality and morbidity after primary surgery (including that stoma-related and colorectal anastomosis-related) and consequent to the intervention of intestinal recanalization (CS group) and GI closure were evaluated. We evaluated hospital stay and quality of life of patients and their caregivers.ResultsStoma-related morbidity rate was higher in the CS group than in GI group (37% vs. 5.5%, respectively, P = 0.04). Morbidity rate after intestinal recanalization in the CS group was 25.9% and 0% after GI closure (P = 0.08). Overall stoma morbidity rate was significantly lower in the GI group with respect to CS group (5.5% vs. 40.7%, respectively, P = 0.03). CS group was characterized by a significantly longer recovery time (P = 0.0002). Caregivers and stoma-related quality of life were better in the GI group than in CS group (P < 0.0001 and P = 0.0005, respectively).ConclusionsGI is feasible, characterized by shorter recovery, lesser degree of total, as well as anastomosis-related morbidity and higher quality of life of patients and the caregivers in respect to CS. We suggest that GI (should be evaluated as an alternative to conventional ileostomy) could be indicated in selected patients that do not present risk factors, but require caution for anastomotic leakage for the low level of colorectal anastomosis.

Outcome of laparoscopic splenectomy for malignant hematologic diseases

Aim The role of laparoscopic splenectomy in the treatment of hematological diseases is still controversial. The aim of this study was to assess whether the benign or malignant nature of hematological diseases may influence the outcome of laparoscopic splenectomy. Patients and methods Between August 1997 and March 2002, 63 unselected patients with hematologic diseases underwent a laparoscopic splenectomy. Patients were divided into two groups according to the benign (Group A, 38 patients) or malignant (Group B, 25 patients) nature of the hematological diseases. Results Patients in group B were significantly (a) older, (b) had larger spleens that more frequently needed accessory incisions for specimen retrieval, (c) had greater transfusion requirements, and (d) were fed later than patients in group A. There were no statistically significant differences among the two groups in terms of (a) body-mass index, (b) operative time, (c) conversion rate, (d) blood loss, (e) pain medication requirements, and (f) hospital stay. Two postoperative deaths occurred among patients in group B, but none of them was related to surgery. Conclusions The results of the study showed that: a) the nature of the disease does not influence the outcome of laparoscopic splenectomy, b) the size of the spleen might increase the risk of conversion, but it is no longer a contraindication to laparoscopic splenectomy, and c) laparoscopic splenectomy can be effectively performed in the treatment of malignant hematologic diseases.