Alessio Pigazzi

Robotic-assisted laparoscopic low anterior resection with total mesorectal excision for rectal cancer

BackgroundWith advanced stereoscopic vision, lack of tremor, and the ability to rotate the instruments surgeons find that robotic systems are ideal laparoscopic tools. Because of its high operating cost, however, robotic surgery should be reserved to procedures in which the technology can be of maximum benefit, usually when precise dissections in confined spaces are required. Because conventional laparoscopic total mesorectal excision is a challenging procedure, we have sought to assess the utility of the DaVinci robotic system in laparoscopic low anterior resections for cancer of the rectum.MethodsBetween November 2004 and May 2005 robotic-assisted low anterior resection with total mesorectal excision was performed on six consecutive patients with rectal cancer. These cases were compared with six consecutive low anterior resections performed with conventional laparoscopic techniques by the same surgeon.ResultsThere were no conversions in either group. Operative and pathological data, complications, and hospital stay were similar in the two groups. Robotic operations appeared to cause less strain for the surgeon.ConclusionsRobotic-assisted laparoscopic low anterior resection for rectal cancer is feasible in experienced hands. This technique may facilitate minimally invasive radical rectal surgery.

Short-Term Outcomes After Robotic-Assisted Total Mesorectal Excision for Rectal Cancer

BackgroundLaparoscopic total mesorectal excision for rectal cancer remains a difficult procedure with high conversion rates. We have sought to improve on some of the pitfalls of laparoscopy by using the DaVinci robotic system. Here we report our two-year experience with robotic-assisted laparoscopic surgery for primary rectal cancer.MethodsA prospectively maintained database of all rectal cancer cases starting in November 2004 was created. A series of 39 consecutive unselected patients with primary rectal cancer was analyzed. Clinical and pathologic outcomes were reviewed retrospectively.Results22 patients had low anterior, 11 intersphincteric and six abdominoperineal resections. Postoperative mortality and morbidity were % and 12.8%, respectively. The median operative time was 285 minutes (range 180–540 mins). The conversion rate was 2.6%. A total mesorectal excision with negative circumferential and distal margins was accomplished in all patients, and a median of 13 (range 7–28) lymph nodes was removed. The anastomotic leak rate was 12.1%. The median hospital stay was 4 days. There have been no local recurrences at a median follow-up of 13 months.ConclusionsRobotic-assisted surgery for rectal cancer can be carried out safely and according to oncological principles. This approach shows promising short-term outcomes and may facilitate the adoption of minimally invasive rectal surgery.

Risk Factors for Anastomotic Leakage After Anterior Resection for Rectal Cancer

BACKGROUND The risk factors for anastomotic leak (AL) after anterior resection have been evaluated in several studies and remain controversial as the findings are often inconsistent or inconclusive. OBJECTIVE To analyze the risk factors for AL after anterior resection in patients with rectal cancer. DESIGN Retrospective analysis. SETTING The Nationwide Inpatient Sample 2006 to 2009. PATIENTS A total of 72 055 patients with rectal cancer who underwent elective anterior resection. MAIN OUTCOME MEASURES To build a predictive model for AL using demographic characteristics and preadmission comorbidities, the lasso algorithm for logistic regression was used to select variables most predictive of AL. RESULTS The AL rate was 13.68%. The AL group had higher mortality vs the non-AL group (1.78% vs 0.74%). Hospital length of stay and cost were significantly higher in the AL group. Laparoscopic and open resections with a diverting stoma had a higher incidence of AL than those without a stoma (15.97% vs 13.25%). Multivariate analysis revealed that weight loss and malnutrition, fluid and electrolyte disorders, male sex, and stoma placement were associated with a higher risk of AL. The use of laparoscopy was associated with a lower risk of AL. Postoperative ileus, wound infection, respiratory/renal failure, urinary tract infection, pneumonia, deep vein thrombosis, and myocardial infarction were independently associated with AL. CONCLUSIONS Anastomotic leak after anterior resection increased mortality rates and health care costs. Weight loss and malnutrition, fluid and electrolyte disorders, male sex, and stoma placement independently increased the risk of leak. Laparoscopy independently decreased the risk of leak. Further studies are needed to delineate the significance of these findings.

Oncologic outcomes of robotic-assisted total mesorectal excision for the treatment of rectal cancer.

Objective:To evaluate local recurrence and survival after robotic-assisted total mesorectal excision (RTME) for primary rectal cancer. Summary Background Data:RTME is a novel approach for the treatment of rectal cancer and has been shown to be safe and effective. However, the oncologic results of this approach have not been reported in terms of local recurrence and survival rate. Methods:Sixty-four consecutive rectal cancer patients with stage I–III disease treated between November 2004 and June 2008 were analyzed prospectively. Results:All patients underwent RTME: 34 had colorectal anastomosis, 18 underwent coloanal anastomosis, and 12 received abdominoperineal resection. Operative mortality rate was 0%. The median operative time was 270 min and median blood loss was 200 mL. The conversion rate was 9.4%. Anastomotic leakage occurred in 4 of 52 (7.7%) patients with anastomosis. Median number of harvested lymph nodes was 14.5. Median distal margin of tumor was 3.4 cm. The circumferential resection margin was negative in all surgical specimens. No port-site recurrence occurred in any patient. Six patients developed recurrence: 2 combined local and distant, and 4 distal alone (mean follow-up of 20.2 months; range, 1.7–52.5). None of the patients developed isolated local recurrence. The mean time to local recurrence was 23 months. The 3-year overall and disease-free survival rates were 96.2% and 73.7%, respectively. Conclusions:RTME can be carried out safely and effectively in terms of recurrence and survival rates. Further prospective randomized trials are necessary to better define the absolute benefits and limitations of robotic rectal surgery.

Stimulation of endothelial nitric oxide production by homocyst(e)ine

Hyperhomocyst(e)inemia, characterized by accelerated atherosclerosis, is believed to induce endothelial cell injury and promote atherothrombosis by supporting the generation of hydrogen peroxide. Earlier observations in our laboratory demonstrated that in vitro nitrosation of homocyst(e)ine (HCY) prevents the generation of hydrogen peroxide. We, therefore, hypothesized that stimulating the production of nitric oxide (NO) by endothelial cells would detoxify HCY by forming the corresponding S-nitrosothiol, S-nitroso-homocysteine. In an attempt to prove this hypothesis, media containing 1 mM L-arginine, 1 microM bradykinin, a known NO agonist, and one of the biologically relevant thiols (HCY, cysteine, or glutathione) at concentrations of 0, 0.05, 0.5 and 5.0 mM were incubated with bovine aortic endothelial cells (BAEC) for 0.5, 1 and 4 h. S-nitrosothiol (RSNO) concentrations were measured by photolysis-chemiluminescence. Nitric oxide synthase (eNOS or isoform 3) activity and Nos 3 steady-state mRNA levels were determined by the conversion of [3H]L-arginine to [3H]L-citrulline and Northern analysis, respectively. Results demonstrate that increasing concentrations of HCY, and not cysteine or glutathione, in the presence of bradykinin at 0.5, 1, and 4 h led to significant (P < 0.05 by ANOVA) time- and dose-dependent increases in RSNO produced by BAEC. Cells exposed to 1 microM calcium ionophore A23187 in the presence of 5.0 mM HCY also produced a time-dependent increase in RSNO compared to control (P < 0.05 by ANOVA). In an attempt to determine if de novo synthesis was occurring, BAEC were treated with bradykinin following a 4 h pretreatment with HCY. Pretreatment with HCY followed by stimulation also led to a time- and dose-dependent increase in RSNO production (P < 0.05 by ANOVA). Using high performance liquid chromatography with electrochemical detection, S-nitroso-homocysteine was identified following treatment of BAEC with HCY and bradykinin. The increase in RSNO production in the presence of bradykinin and HCY at 4 h occurred concomitantly with a 78% increase in eNOS activity and a 58% increase in steady-state Nos 3 mRNA, with no change in Nos 3 mRNA half-life, compared to control. A partial explanation for HCYs unique ability to support an increase in NO production was demonstrated by showing that the t1/2 of HCY in media was greater than that of cysteine or glutathione. These data show that, in the presence of an NO agonist, HCY increases RSNO production in a time- and dose-dependent fashion that is reflected by an increase in eNOS activity and Nos 3 transcription. These results suggest that stimulation of endogenous NO, or provision of an exogenous NO donor, may ameliorate endothelial cell injury and thereby decrease the atherothrombotic risk of hyperhomocyst(e)inemic states.

Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial

Summary Background Local excision is an organ-preserving treatment alternative for patients with stage I rectal cancer. However, local excision alone is associated with a high risk of local recurrence and inferior survival compared to transabdominal rectal resection. Here we investigate the oncologic and functional outcomes of neoadjuvant chemoradiotherapy and local excision for T2N0 rectal cancer. Methods This was a prospective, multi-institutional, single arm phase 2 trial for patients with clinically-staged T2N0 distal rectal cancer, treated with neoadjuvant chemoradiotherapy consisting of capecitabine (original dose 825mg/m2, twice daily, on days 1-14 and 22-35) , oxaliplatin (50mg/m2 weeks 1, 2, 4, 5), and radiation (5 days/week at 1.8 Gy/day for 5 weeks to a dose of 45 Gy, then a boost, for a total dose of 54 Gy) followed by local excision. Due to adverse events during chemoradiotherapy, the dose of capecitabine was reduced to 725 mg /m2, twice daily, 5 days/week, for 5 weeks, and the total dose of radiation to 50.4 Gy. Patients were followed at scheduled intervals and evaluated for recurrence and survival. Anorectal function (ARF) and quality of life (QOL) were assessed at baseline and one year after surgery, using validated instruments. The primary endpoint was 3-year disease-free survival for all eligible patients and for patients who completed chemotherapy and radiation, and had ypT0, ypT1, or ypT2 tumors, and negative resection margins. This trial is registered with ClinicalTrials.gov, number NCT00114231. Findings Seventy-nine eligible patients were accrued to the trial, and started nCRT. Three patients did not complete nCRT or LE per-protocol. Four additional patients completed protocol treatment, but one had a positive margin and three had ypT3 tumours. Median follow-up was 56 months. Of the 79 patients, five (6%) developed distant recurrence, and three (4%) recurred locally. All but two underwent salvage surgery. Three-year disease-free survival and overall survival for the entire group were 88% (0.88 (95% CI: 0.81, 0.96) and 95% (95% CI: 0.90, 1.00), respectively. Overall 14 (29%) of 79 patients had grade 3-4 gastrointestinal adverse events, 12 (16%) of 79 patients had grade 3-4 pain as an adverse event, 12 (16%) of 79 patients had grade 3-4 hematological adverse events, and 9 (11%) of 79 patients had grade 3 dermatologic adverse events during chemoradiation. Six (8%) of the 77 patients who had surgery had grade 3 pain, 3(4%) of 77 patients had grade 3-4 hemorrhage, 3 (4%) of 77 patients had gastrointestinal adverse events, 2 (3%) of 77 patients had infectious/febrile neutropenia, 2 (3%) of 77 patients had hematological adverse events, and one (1%) had neurological adverse events. The rectum was preserved in 72 of the 79 (91%) patients. ARF and QOL were unchanged one year after surgery compared to baseline. Interpretation Most patients with T2N0 rectal cancer treated with nCRT and LE achieved organ preservation without deterioration of their quality of life. The estimated 3-year DFS rate was within the defined margin of efficacy. Our data suggest that nCRT followed by LE may be considered as an organ-preserving alternative in carefully selected patients with clinically-staged T2N0 tumours who refuse, or are not candidates for, transabdominal resection.

Totally Robotic Low Anterior Resection with Total Mesorectal Excision and Splenic Flexure Mobilization

Some limitations of conventional laparoscopy have been overcome by the enhanced dexterity of the robotic da Vinci system, and its use in gastrointestinal procedures is evolving. However, difficulties accessing multiple quadrants of the abdomen with the first robotic system led to a rather slow introduction of the da Vinci into the field of abdominal surgery compared with its success with urologic and cardiac procedures. The new da Vinci S HD system offers improved range of motion that allows for easier access to a wider surgical field. The authors developed a new “one-step” setup to perform a low anterior resection with total mesorectal excision and splenic flexure mobilization for rectal cancer using a completely robotic approach. This technical report describes all the major aspects for successful performance of this complex minimally invasive procedure.

Oncologic outcomes of laparoscopic surgery for rectal cancer: A systematic review and meta-analysis of the literature

AIM To review and compare the oncologic outcomes in patients with rectal cancer undergoing laparoscopic vs. open rectal surgery. METHODS An electronic literature search was performed for trials reporting oncologic outcomes for laparoscopic rectal resections. Variables of interest were survival, recurrence rates, margin status and nodal retrieval. Trials were excluded if variables were not specifically analysed for rectal resections. A meta-analysis was performed to assess the difference in oncologic outcomes between the two treatment approaches. RESULTS Data on a total of 1403 laparoscopic (LG) and 1755 open (OG) rectal resections were gathered from 24 publications. Overall survival at 3 years (LG=76%, OG=69%) was not statistically different between the two treatment groups. The mean local recurrence rates were 7% for laparoscopic and 8% for open procedures (NS). There was no difference in radial margin positivity, 5% of patients undergoing laparoscopic surgery compared to 8% for open surgery. Laparoscopic procedures harvested a mean of 10 nodes as compared to 12 for open procedures, p=0.001. CONCLUSIONS Data gathered in this meta-analysis indicate that there are no oncologic differences between laparoscopic and open resections for treatment of primary rectal cancer.

Nitric Oxide Inhibits Thrombin Receptor-activating Peptide-induced Phosphoinositide 3-Kinase Activity in Human Platelets

Although nitric oxide (NO) has potent antiplatelet actions, the signaling pathways affected by NO in the platelet are poorly understood. Since NO can induce platelet disaggregation and phosphoinositide 3-kinase (PI3-kinase) activation renders aggregation irreversible, we tested the hypothesis that NO exerts its antiplatelet effects at least in part by inhibiting PI3-kinase. The results demonstrate that the NO donorS-nitrosoglutathione (S-NO-glutathione) inhibits the stimulation of PI3-kinase associated with tyrosine-phosphorylated proteins and of p85/PI3-kinase associated with the SRC family kinase member LYN following the exposure of platelets to thrombin receptor-activating peptide. The activation of LYN-associated PI3-kinase was unrelated to changes in the amount of PI3-kinase physically associated with LYN signaling complexes but did require the activation of LYN and other tyrosine kinases. The cyclic GMP-dependent kinase activator 8-bromo-cyclic GMP had similar effects on PI3-kinase activity, consistent with a model in which the cyclic nucleotide mediates the effects of NO. Additional studies showed that wortmannin and S-NO-glutathione have additive inhibitory effects on thrombin receptor-activating peptide-induced platelet aggregation and the surface expression of platelet activation markers. These data provide evidence of a distinct and novel mechanism for the inhibitory effects of NO on platelet function.

Pilot series of robot-assisted laparoscopic subtotal gastrectomy with extended lymphadenectomy for gastric cancer.

BackgroundRobotic surgery is evolving as a therapeutic tool for thoracic and urologic applications; however, its use in gastric cancer surgery has not been extensively reported. The objective of this pilot series was to assess the feasibility of using robotic surgery in performing an extended lymphadenectomy for gastric cancer.MethodsBetween June 2005 and July 2006, seven patients (3 female, 4 male) underwent combined laparoscopic subtotal gastrectomy with omentectomy and robot-assisted extended lymphadenectomy using the da Vinci® Surgical System for early distal gastric tumors. The mean age of the patients was 64 years. Tumor staging ranged from 0 to II. Six patients had adenocarcinoma and one patient had a high-grade dysplastic adenoma.ResultsAll procedures were completed successfully without conversion. The median operating time was 420 min. There was one intraoperative complication requiring a colon resection for a devascularized segment. The median number of nodes harvested was 24 (range = 17–30). Resection margins were negative in all specimens. Patients were hospitalized a median of 4 days (range = 3–9). Thirty-day mortality was 0%. Patients resumed a solid diet a median of 4 days postoperatively. Median followup was 9 (range = 0–10) months. There have been no tumor recurrences to date.ConclusionExtended lymphadenectomy for gastric cancer using robotic surgery is safe and allows for an adequate lymph node retrieval. Our preliminary results suggest that this novel technique offers short hospital stays and low morbidity for patients undergoing surgical resection of distal gastric malignancies. Future studies will be necessary to better define the role of robotic surgery in gastric cancer treatment.