Robotic platforms in gynaecological surgery: past, present, and future.

Background: More than two decades ago, the advent of robotic laparoscopic surgery marked a significant milestone, featuring the introduction of the AESOP robotic endoscope control system and the ZEUS robotic surgery system. The latter, equipped with distinct arms for the laparoscope and surgical instruments, was designed to accommodate remote connections, enabling the practice of remote telesurgery as early as 2001. Subsequent technological progress has given rise to a range of options in today's market, encompassing multi-port and single-port systems, both rigid and flexible, across various price points, with further growth anticipated. Objective: This article serves as an indispensable guide for gynaecological surgeons with an interest in embracing robotic surgery. Materials and methods: Drawing insights from the experience of the Strasbourg training centre for minimally invasive surgery (IRCAD), this article offers a comprehensive overview of existing robotic platforms in the market, as well as those in development. Results: Robotic surgical systems not only streamline established operative methods but also broaden the scope of procedures, including intra- and transluminal surgeries. As integral components of the digital surgery ecosystem, these robotic systems actively contribute to the increasing integration and adoption of advanced technologies, such as artificial intelligence-based data analysis and support systems. Conclusion: Robotic surgery is increasingly being adopted in clinical practice. With the growing number of systems available on the marketplace, the primary challenge lies in identifying the optimal platform for each specific procedure and patient. The seamless integration of robotic systems with artificial intelligence, image-guided surgery, and telesurgery presents undeniable advantages, enhancing the precision and effectiveness of surgical interventions. What is new?: This article provides a guide to the robotic platforms available on the market and those in development for gynaecologists interested in robotic surgery.

An update on atezolizumab for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a worldwide problem, with a high prevalence in nonindustrialized countries and a rising incidence in industrialized countries. Its close association with chronic liver diseases and liver cirrhosis represents a significant challenge in its treatment. Sorafenib, the first front-line systemic treatment for unresectable HCC cases, was approved only in 2007. The role of sorafenib remained largely unchallenged until very recently, with the sole exception of a trial demonstrating the noninferiority of lenvatinib, another tyrosine kinase inhibitor. The therapeutic scenario changed dramatically in 2020, when the combination of atezolizumab and bevacizumab proved to be significantly superior to sorafenib and, thus, establishing a new standard of care. In this monograph we provide an update about the safety and efficacy of atezolizumab reported in the clinical trials of HCC, as monotherapy or in combination with other agents.

Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma.

BACKGROUND: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. PATIENTS AND METHODS: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. RESULTS: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. CONCLUSIONS: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC.

Laparoscopic versus open extended radical left pancreatectomy for pancreatic ductal adenocarcinoma: an international propensity-score matched study.

BACKGROUND: A radical left pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC) may require extended, multivisceral resections. The role of a laparoscopic approach in extended radical left pancreatectomy (ERLP) is unclear since comparative studies are lacking. The aim of this study was to compare outcomes after laparoscopic vs open ERLP in patients with PDAC. METHODS: An international multicenter propensity-score matched study including patients who underwent either laparoscopic or open ERLP (L-ERLP; O-ERLP) for PDAC was performed (2007-2015). The ISGPS definition for extended resection was used. Primary outcomes were overall survival, margin negative rate (R0), and lymph node retrieval. RESULTS: Between 2007 and 2015, 320 patients underwent ERLP in 34 centers from 12 countries (65 L-ERLP vs. 255 O-ERLP). After propensity-score matching, 44 L-ERLP could be matched to 44 O-ERLP. In the matched cohort, the conversion rate in L-ERLP group was 35%. The L-ERLP R0 resection rate (matched cohort) was comparable to O-ERLP (67% vs 48%; P = 0.063) but the lymph node yield was lower for L-ERLP than O-ERLP (median 11 vs 19, P = 0.023). L-ERLP was associated with less delayed gastric emptying (0% vs 16%, P = 0.006) and shorter hospital stay (median 9 vs 13 days, P = 0.005), as compared to O-ERLP. Outcomes were comparable for additional organ resections, vascular resections (besides splenic vessels), Clavien-Dindo grade ≥ III complications, or 90-day mortality (2% vs 2%, P = 0.973). The median overall survival was comparable between both groups (19 vs 20 months, P = 0.571). Conversion did not worsen outcomes in L-ERLP. CONCLUSION: The laparoscopic approach may be used safely in selected patients requiring ERLP for PDAC, since morbidity, mortality, and overall survival seem comparable, as compared to O-ERLP. L-ERLP is associated with a high conversion rate and reduced lymph node yield but also with less delayed gastric emptying and a shorter hospital stay, as compared to O-ERLP.

A novel method for near-infrared fluorescence imaging of the urethra during perineal and transanal surgery: demonstration in a cadaveric model.

AIM: Transanal total mesorectal excision is a promising novel sphincter-saving procedure for low rectal cancer. However, the transanal bottom-up dissection is associated with increased rates of iatrogenic urethral injuries. Near-infrared fluorescence (NIRF) imaging, given its deeper tissue penetration, has been explored in a limited number of studies for enhanced intra-operative urethral visualization. In this study, we explored the feasibility of a novel, ultrabright, biocompatible fluorescent polymer to coat urinary catheters for the purpose of intra-operative urethral visualization. METHODS: In an ex vivo experiment, using a near-infrared laparoscope, the fluorescent signal of a coated catheter (near-infrared coating of equipment, NICE) was qualitatively and quantitatively compared to the signal of indocyanine green (ICG)/Instillagel® mixtures and ICG-filled catheters at several concentrations. Also, in three male human torsos, using fluorescent urinary catheters, NIRF-guided perineal dissections and a transanal total mesorectal excision were performed. Intra-operative NIRF-based urethral visualization was performed systematically. RESULTS: During the qualitative and quantitative fluorescence signal assessment, NICE-coated catheters were clearly superior to the ICG-based solutions. In the cadaveric experiments, enhanced urethral visualization was possible even at early stages of dissection, when the organ was covered by several tissue layers. CONCLUSIONS: NICE-coated catheters represent a promising potential to allow for NIRF-based intra-operative urethral visualization.

Natural Orifice Surgery: the next step in minimal invasiveness towards no scar surgery.

The possibility to operate into the abdominal cavity by means of flexible endoscopes introduced through natural orifices represents a major step forward in the continuous research for minimal invasive treatment attaining the unimaginable goal of no scar surgery. After several years of investigation in experimental settings, natural orifice surgery is becoming a valuable therapeutic option both as totally transluminal endoscopic approach or with the support of minimal transabdominal assistance. The promising operative results and the great interest determined among the patients always looking for effective treatment associated with less bodily trauma, postoperative pain and faster recovery, are pushing the development of dedicated technological solutions that will make natural orifice - no scar surgery more easy and reproducible to perform and applicable also to more advanced diseases. Natural orifice surgery has the potential to abolish the historical association of surgery to that of scar and pain representing a very appealing surgical option for the patients highly respectful of their body and psychological integrity.

Multimedia article. Combined sentinel node biopsy and localized sigmoid resection entirely by natural orifice transluminal endoscopic surgery: a new challenge to the old paradigm.

INTRODUCTION: We demonstrate localized sigmoidectomy with sentinel node biopsy performed entirely via natural orifice transluminal endoscopic surgery in a porcine model (see Video, Supplemental Digital Content 1, http://links.lww.com/A1170). METHODS: To perform transluminal endoscopic sentinel node biopsy in the sigmoid mesocolon, a conventional double-channel gastroscope created both the gastrotomy and pneumoperitoneum enabling peritoneoscopy. The sigmoid colon was exposed by an intracolonic magnet under extracorporeal control while intraluminal colonoscopy performed lymphatic mapping via submucosal injection of methylene blue dye. After searching the mesocolon for blue-stained lymph channels, the sentinel nodes were resected and retrieved by the intraperitoneal fiberscope. Immediate thereafter localized sigmoidectomy was performed via an additional transcolonic access just above the rectosigmoid junction. With the circular stapler anvil placed early into the proximal colon, mesenteric dissection and proximal transection were performed using conventional laparoscopic instruments worked through a long standard trocar passed transanally through the colotomy. The specimen was delivered per ano (pull-through technique) and the distal margin cross-stapled extracorporeally, including the colotomy within the specimen. Stapled intestinal anastomosis was fashioned by passing a circular stapler transanally (thus returning the rectal stump to its anatomic position) and mating it with the in situ anvil. The gastrotomy was closed as previously described. RESULTS: The operative duration was 31.4 minutes and technical success was readily achieved. Patency and integrity of the anastomosis was confirmed by sigmoidoscopy. CONCLUSION: Oncologically propitious surgery for germinal colonic neoplasia may be encompassed by natural orifice transluminal endoscopic surgery. This provocative proposal challenges the conventional treatment paradigm for early stage colonic neoplasia although much further validation of the concepts involved is required.

In vivo microrobots for natural orifice transluminal surgery. Current status and future perspectives.

The possibility to operate inside the peritoneal cavity through small holes performed in hollow organs that is presented by Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a major paradigm shift in general surgery. While this new approach seems very appealing from patients' perspectives because it eliminates completely abdominal wall aggression and promises to reduce postoperative pain, it is very challenging for surgeons because of the major constraints imposed by both the mode of access and the limited technology currently available. For this reason NOTES applications at the present time are performed by only a few surgeons and mainly to perform non-complex procedures. While new devices are under development, many of them are trying mainly to simply improve current endoscopic platforms and seem not to offer breakthrough solutions. The numerous challenges introduced by natural orifice approaches require a radical shift in the conception of new technologies in order to make this emerging operative access safe and reproducible. The convergence of several enabling technologies in the field of miniaturization, communication and micro-mechatronics brings the possibility to realize on a large scale the revolutionary concept of miniature in vivo co-operative robots. These robots provide vision and task assistance without the constraints of the entry incision and have been shown in experimental settings to possess many qualities that could be ideal to partner with Natural Orifice Surgery. This article explores the current status of microrobotics as well as presents potential future scenarios of their applications in NOTES.

Outcomes and survival after laparoscopic gastrectomy for adenocarcinoma. Analysis on 65 patients operated on by conventional or robot-assisted minimal access procedures.

AIMS: Despite laparoscopic surgery for gastric cancer has gained worldwide acceptance, long term results and survival are seldom reported. This study was designed to assess long term outcomes after laparoscopic gastrectomy with D2 dissection. The short term results of conventional and robot-assisted minimally invasive procedures were also examined. PATIENTS AND METHODS: The charts of 65 patients who underwent laparoscopic surgery for non-metastatic adenocarcinoma were reviewed retrospectively. This series included 35 patients with early gastric cancer (EGC) and 30 with advanced gastric cancer (AGC). A 4/5 laparoscopic subtotal gastrectomy (LSG) with D2 nodal clearance was the procedure of choice for distal cancers. Laparoscopic total gastrectomy (LTG) with modified D1 lymphadenectomy was performed for mid-proximal EGC. RESULTS: Sixty gastrectomies were carried out laparoscopically, 56 LSG and 4 LTG. Conversion to laparotomy was required in 5 patients with distal cancer. No intraoperative complication was registered. Morbidity included 2 duodenal leaks that healed conservatively. Two postoperative deaths were registered. An average number 31.3+/-8.8 lymph nodes were collected. The mean hospital stay was 10 days (range 7-24). The mean follow up was 30 months (range 2-86) and the cumulative overall 5 year survival rate was 78%. Survival at 5 years for EGC was 94% and survival at 4 years for AGC was 53% (57% for non-converted patients). CONCLUSIONS: Laparoscopic gastrectomy for cancer represents a valid alternative to open surgery with minimal morbidity and acceptable long term survival. Considering the risk of preoperative under diagnoses a D2 lymphadenectomy is suggested also for EGC. This study validated the effectiveness of minimally invasive technique in the management of gastric cancer.

Robot-assisted laparoscopic gastrectomy with D2 dissection for adenocarcinoma: initial experience with 17 patients.

Robot-assisted gastrectomy has been practised so far in very few centres in the world. The aims of this study were to assess the feasibility of robot-assisted gastrectomy for adenocarcinoma with D2 lymph nodal dissection and to analyze our preliminary results. Between January 2006 and August 2008, as many as 17 patients (11 females, 6 males) underwent laparoscopic robot-assisted surgery for non-metastatic adenocarcinoma of the stomach by a 3-armed da Vinci(®) Robotic Surgical System. The mean age of patients was 65.9 years. This series included eight patients with early gastric cancer (EGC) and nine with advanced gastric cancer (AGC). A 4/5 laparoscopic subtotal gastrectomy (LSG) with D2 nodal clearance was the procedure of choice for 16 distal cancers. Laparoscopic total gastrectomy (LTG) with D2 lymphadenectomy was performed for one AGC of the middle third of the stomach. No intraoperative complication was registered. Conversion to laparotomy was required in two patients with distal cancer. The mean operating time (excluding converted patients) was 352 min (348 for LSG). Morbidity consisted in one pancreatic leak that healed conservatively. One death occurred postoperatively for haemorragic stroke. On average, 25.5 ± 4 lymph nodes were collected (range 10-40). The resection margin was 6.4 ± 0.6 cm (range 4.2-8), and the margin was tumour free in all the specimens. The mean hospital stay of totally laparoscopic subtotal gastrectomy was 10 ± 1.2 days (range 8-13). The mean follow-up was 14 months (range 1-29) and three patients with AGC showed recurrence after LSG and died of disease. Robotics in gastrectomy for cancer is a feasible and safe procedure, yielding adequate D2 nodal clearance with respect of oncologic principles. Robotic techniques can represent a remarkable tool to improve laparoscopic surgeon's ability and precision in small surgical fields, i.e. during D2 dissection. This study demonstrated the feasibility of robot-assisted gastrectomy for cancer although further studies are required to validate our preliminary results, especially as far as patients' benefits are concerned.

The new 4DDome prosthesis: an original light and partially absorbable composite mesh for hernia repair.

INTRODUCTION: The use of non-absorbable meshes for the repair of inguinal hernias has become standard; however, these meshes have been associated with complications including long-term postoperative pain. To this end, a new partially absorbable composite mesh has been developed, and the aim of this study was to investigate its efficacy in animal and human trials. MATERIALS AND METHODS: Sixty male Wistar rats were used to evaluate the behavior of the newly designed composite mesh. Composite meshes were implanted in the extra-peritoneal plane for 2, 4 and 8 weeks and compared to a standard polypropylene mesh. Forty patients with symptomatic inguinal hernias were treated using a new 4DDome designed prosthesis. Follow-up was by clinical and ultrasound examination at 1, 6 and 12 months. RESULTS: The animal study demonstrated that the inflammatory reaction associated with the new composite mesh was significantly lower than a standard polypropylene mesh, characterized by a lower macrophage infiltrate (P < 0.001). The mesh did not shrink over the 8-week period, unlike the polypropylene mesh (P < 0.05). The human study showed that there were three minor postoperative complications, no recurrences and the mesh was well tolerated. Follow-up with serial ultrasound showed that at 10 days and 1 month the dome was clearly visible in position; however, by 6 months it had flattened out, been partially absorbed and become incorporated into the repair. CONCLUSION: These experimental and clinical studies have validated the concept of the new 4DDome composite mesh. It was well tolerated and was associated with good short-term results. The combination of the dome shape and the new composite mesh means that less polypropylene is required and represents a significant advance in anterior hernia repair.

Two-stage totally minimally invasive approach for acute complicated diverticulitis.

OBJECTIVES: Surgical options for acute diverticulitis with peritonitis include Hartmann's procedure or resection and primary anastomosis with or without a stoma. Initial laparoscopic lavage and drainage can control the acute intra-abdominal sepsis to allow for a delayed definitive procedure in nonemergency conditions. Potential advantages include the avoidance of a laparotomy, stoma and local infections at the origin of dehiscence and incisional hernias. We evaluated this approach in a selected group of patients. METHODS: Patients with intra-abdominal pus secondary to diverticular perforation requiring surgery were included in the study. Patients with localized pus amenable to computerized tomography (CT)-guided drainage, faecal peritonitis, severe generalized peritonitis, and those in which the perforation was spontaneously visible were excluded. Standard demographic data, CT findings, intra-operative findings and postoperative outcomes were analysed. RESULTS: Ten patients were suitable for the approach. Mean patient age was 60.2 years. Mean body mass index was 28.2 m2/kg. Mean postoperative stay was 8.5 days and uneventful in all patients. One patient re-presented after 3 weeks with acute peritonitis requiring open sigmoidectomy. Six patients successfully underwent laparoscopic sigmoidectomy with primary anastomosis 2-3 months later. Two patients were not re-operated because of comorbidity and one refused surgery. CONCLUSIONS: A two-stage totally minimally invasive approach may be a safe alternative strategy for selected cases of acute complicated diverticulitis.

Fatty liver and drugs.

Drug-induced liver diseases (DILD) are clinico-pathologic patterns of liver injury caused by drugs or other foreign compounds. Steatohepatitis is a rare form of DILD, and drugs account for fewer than 2% of non-alcoholic steatohepatitis (NASH). Drugs known to be capable of inducing steatosis and steatohepatitis can be divided into three broad groups: those that cause steatosis and steatohepatitis independently (e.g., amiodarone, perhexiline maleate); drugs which can precipitate latent NASH (e.g., tamoxifen); drugs whic duce sporadic events of steatosis/steatohepatitis (e.g., carbamazepine). Clinical DILD syndromes include acute viral hepatitis-like injury, acute liver failure, cholestatic hepatitis,liver disease with signs of hypersensitivity, autoimmune hepatitis-like injury, acute venous-Outflow obstruction, chronic cholestasis, ciirrhosis, steatosis and steatohepatitis. The clinical picture is by no means dependent on the mechanism of injury (direct hepatotoxicity, idiosyncratic reactions, hypersensitivity reactions). Reliable diagnosis of drug-induced liver disease requires demonstration of close correlation between the patient history and clinical, laboratory, and histological data.

Nutritional aspects in patients with non-alcoholic steatohepatitis (NASH).

BACKGROUND AND OBJECTIVES: Metabolic alterations are a common feature in patients affected by non-alcoholic steato-hepatitis (NASH). A strong correlation exists between overweight, in particular visceral fat accumulation, and prevalence of NASH, especially in men. Thus, diet-induced weight loss represents a fundamental tool in disease management of these patients. The aim of the present study was to evaluate body composition and nutrient utilisation in patients with NASH, comparing them with patients affected by chronic hepatitis related to hepatitis C virus (HCV) infection and with healthy subjects. MATERIALS AND METHODS: Twenty male outpatients with NASH (age: 41 +/- 11 yr; BMI: 26.2 +/- 2.1 kg/m2) and 14 HCV male patients (age 44.6 +/- 13 yr; BMI: 24.8 +/- 2.8 kg/m2) were enrolled in the study. A group of 20 healthy male subjects (age: 39 +/- 10 yr; BMI: 23.3 +/- 1.1 kg/m2) were studied as controls. Body composition was assessed by anthropometry and dual-energy X-ray absorptiometry; resting metabolic rate and nutrient oxidation by indirect calorimetry. A 7-day food diary was collected. The main biochemical parameters were measured using standardised laboratory techniques. RESULTS: Body weight was higher in NASH patients with respect to HCV patients and control subjects (respectively 75.2 +/- 8.9 vs 68.5 +/- 9.4 and vs 67.0 +/- 8.0 kg; P < 0.01) and this was essentially due to fat mass increase. Fat-free mass reduction was found in HCV patients with respect to both NASH and control subjects. Patients with NASH had a significantly higher waist circumference (P < 0.01) and a lower resting metabolic rate (RMR) with respect to HCV and control subjects. Energy intake was significantly higher in NASH patients (P < 0.01) compared to the other two groups. CONCLUSIONS: NASH patients showed an increase in body weight, fat mass and visceral fat accumulation with respect to HCV and control subjects. The reduction in RMR, coupled with increase energy intake may explain the body composition alterations found in these patients.

Nonalcoholic fatty liver disease: defining a common problem.

Non Alcoholic Fatty Liver Disease (NAFLD), with prevalence of 10-51% in general population involving all ages, is the major cause of elevation of ALT and a common finding by ultrasound screening and may range from simple steatosis, to Non Alcoholic Steatohepatitis (NASH) and its clinical consequences as cirrhosis and hepatocellular carcinoma. In this review will be analyse factors influencing the onset of the disease. NAFLD, primarly associated with insulin resistance, is in fact considered the hepatic manifestation of the metabolic syndrome: a cluster of disorder that includes obesity, diabetes mellitus, dyslipidaemia, arteriosclerosis and hypertension. The increased incidence and prevalence of obesity and diabetes may explain growing interest in NAFLD. Racial, ethnic, enviromental and behaviour models are also reviewed.

The natural history and risk factors for progression of non-alcoholic fatty liver disease and steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is a condition of increasing incidence in western Countries seldom associated to other diseases of high prevalence in general population (i.e. diabetes and obesity). NAFLD ranges from simple fatty liver to steatohepatitis (NASH), which may lead to cryptogenic cirrhosis and in some cases hepatocellular carcinoma (HCC). Natural history of NAFLD in humans is poorly understood and progression of liver disease seems to be due to interaction between hosting (i.e. genetic, gut flora, insulin resistance) and environmental factors (social and eating behaviours) that should be responsible of increased oxidative stress within hepatocytes. Even if we need non-invasive markers able to describe the progression of liver disease, only meaning of liver biopsy is useful to characterize the stigmata of worsening such as inflammation and fibrosis.

Influence of the surgical treatment on local recurrence of rectal cancer: a prospective study (1980-1992).

BACKGROUND AND OBJECTIVES: The incidence of locoregional recurrences (LR) following radical surgery of rectal cancer varies from 5% to 30% according to the literature. The purpose of this prospective study was to compare the outcome of the Abdomino-Perineal Excision (APE) vs. the Anterior Resection (AR) in a consecutive series of 188 patients who underwent surgery for cure from 1980 to the end of 1992 (81 APE and 107 AR), followed for 5 years, evaluating their influence on the incidence of the recurrences. METHODS: The patients were enrolled at random in the two surgical groups, provided that a radical excision of the tumour, with only two limits: the level of the lesion from the anal verge and the presence of a severe incontinence instrumentally proven. TNM, Dukes staging, grading, and tumour location were statistically evaluated. Further primary suture vs. packing of the perineal wound in APE and handsewn vs. stapled anastomosis in AR were compared in relation with the incidence of LR. RESULTS: The overall local recurrence rate was 19.2% (32/167), in details 19.7% for APE and 18.5% for AR. Similar recurrence rates were observed following both procedures, matching the patients according to the Dukes stage and different details of techniques. A slight statistically significant difference was found as far as the tumour location is concerned in the group treated with anterior resection (p = <0.05) because of the higher recurrence observed in AR performed for tumours of the lower third of the rectum in comparison with the more proximal level. CONCLUSIONS: The AA conclude that the choice of the right surgical procedure in the rectal carcinoma depends on the characteristics of the tumour and the conditions of the patients, provided that the oncologic indications were respected, because recurrence and survival rate are independent from the surgical approaches.

Pharmacotoxicological aspects of levosulpiride.

Levosulpiride is the levorotatory enantiomer of sulpiride, a substituted benzamide indicated as an antipsychotic, antidepressant, antiemetic and antidyspeptic drug, as well as for the treatment of somatoform disorders. In vivo sulpiride displays a number of neuroleptic properties which it shares with all typical neuroleptic drugs; however, it has also a number of divergent characteristics that set it apart as the principal compound of the so-called 'atypical neuroleptic agents'. The main mechanism of action of levosulpiride consists of blocking the D2 dopaminergic receptors, preferentially located on the presynaptic membranes in the dopaminergic pathways of the brain; this means that sulpiride is a selective autoreceptor blocker. The results of series of experimental trials conducted to evaluate the toxicologic characteristics of levosulpiride are presented. Both the acute, subacute, chronic and local toxicity trials, and the studies on reproduction toxicity, mutagenic potential and oncogenic/carcinogenic potential, demonstrate that levosulpiride is well tolerated by the animals tested (rats, mice, rabbits and dogs) at doses higher than those effective in human therapy. Moreover, the findings from the experimental studies on levosulpiride lead to exclude the toxicity from accumulation, tolerance, dependence or withdrawal syndrome. In conclusion, according to the evaluated preclinical studies, levosulpiride shows pharmacotoxicologic properties which make it suitable for the management of diseases for which the drug is indicated.