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.

A case of acute fulminant multiple sclerosis treated with alemtuzumab.

We describe the case of a woman who came to our attention for acute onset and very rapidly worsening left hemiplegia, vision loss and cognitive impairment. MRI, laboratory and clinical investigations were highly suggestive of an active inflammatory demyelinating disease. Following exclusion of other possible etiologies, a diagnosis of Marburg's variant multiple sclerosis was made. After repeated high-dose steroids and plasma-exchange, the patient was treated with a first course of alemtuzumab followed by improvement of the clinical and MRI picture. This is the first reported case of Marburg type multiple sclerosis treated with alemtuzumab.

Asthma and gender: The female lung.

Asthma is a common chronic disease that affects over 300 million people worldwide, resulting in a considerable socio-economic burden. Literature data suggest that asthma has a higher incidence in females, particularly at certain stages of pubertal development. Moreover, women seem to experience more asthma symptoms than men and to use more rescue medications, resulting in a reduced quality of life. Although several mechanisms have been proposed to explain these differences, there are not yet final data available in the literature on the role of gender in the pathogenesis of asthma and different behavior in females. Some study suggested a more prevalent hyper-responsiveness in women than in men. Nevertheless, in the literature definitive data on a possible different response to drugs used for asthma between males and females are not described. Understanding the mechanisms that underlie these gender differences in clinical history of asthma patients could give inspiration to new areas of research to obtain a more specific diagnostic and therapeutic approach gender-oriented.

Diagnostic work-up of inflammatory bowel disease in children: the role of calprotectin assay.

BACKGROUND: Some reports highlight the potential application of fecal calprotectin as a direct biomarker of intestinal inflammation and, therefore, as support in choosing candidates for endoscopy. The value of 100 µg/g was recently assumed as the best cutoff for this assay. The purpose of this study was to assess the diagnostic precision of the fecal calprotectin assay, compared to histology, as a stool-screening biomarker for inflammatory bowel disease (IBD) among a group of prospectively identified patients referred for recurrent abdominal pain and altered bowel habits. METHODS: Between 1999 and 2007 we prospectively evaluated the calprotectin assay in a cohort of patients with recurrent abdominal pain and altered bowel habits associated or not with other symptoms suggestive of IBD. All patients suspected of IBD, according to Rome and Porto criteria, provided stool specimens for the calprotectin assay and subsequently underwent endoscopic procedures. RESULTS: Compared to histology, the cutoff of 100 µg/g reached a sensitivity and specificity of 100% and 68%, respectively, and a likelihood ratio (LR) of 3.1. The cutoff value of 160 µg/g, however, in our series produced the best joint estimate of sensitivity and specificity: 100% and 80%, respectively, with an LR of 5. CONCLUSIONS: In pediatric patients with recurrent abdominal pain and changes in stool habits, a positive calprotectin assay is closely associated with IBD; its systematic employment, therefore, seems to improve the process of endoscopy referral. This test, simple and inexpensive, could be included in the first noninvasive phase of an IBD diagnostic work-up.

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.

Mild hepatitis at recommended doses of acetaminophen in patients with evidence of constitutionally enhanced cytochrome P450 system activity.

Acetaminophen (paracetamol) is used throughout the world for pain relief and antipyresis in both children and adults. In many countries, it can be purchased without a medical prescription and it is also a common component of a number of over-the-counter remedies for colds, influenza and the like. Fasting, malnutrition and use of alcohol and/or other drugs are thought to play causal roles in hepatotoxicity associated with recommended doses of acetaminophen although liver injury provoked by therapeutic doses has also been observed in the absence of these factors. We describe two patients who experienced subclinical hepatotoxic reactions after taking acetaminophen at therapeutic doses. The results of an antipyrine metabolism test suggest the presence of constitutional hyperactivity of the cytochrome P450-dependent mixed function oxidative system in both patients. We hypothesize that the latter contributed to the hepatotoxicity and that it may play a role in idiosyncratic reactions to this drug.

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.

Alcoholic and nonalcoholic forms of fatty liver disease.

Fatty liver (or steatosis) is an increasingly common finding in histolgical evaluation of liver biopsies. It is frequently associated with obesity, diabetes, metabolic syndromes, and/or alcohol abuse. When the steatosis is accompanied by inflammation and fibrosis, the risk of progression to severe liver disease is high. The aim of this paper is to review the clinical features, pathophysiology, natural history, and options for the treatment of nonalcoholic and alcoholic forms of fatty liver disease.

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.

Anticholinergic syndrome due to 'Devil's herb': when risks come from the ancient time.

We describe a case of Mandragora autumnalis poisoning which occurred in a 72-year-old female patient who had eaten the venenous M. Autumnalis, picked near her home, mistaking it for the edible Borago Officinalis. M. Autumnalis is a solanaceous plant, common in the Sicilian countryside, which contains a variable concentration of solanum alkaloids, causing gastrointestinal irritation, and tropane alkaloids, with anticholinergic properties. Unluckily, M. Autumnalis is often mistaken for the edible B. Officinalis, likewise widespread in Sicilian countryside. The diagnosis of Mandragora poisoning was made on the basis of clinical symptoms and signs of anticholinergic syndrome associated with a history of vegetable meal of uncontrolled origin, moreover analysing the vegetable obtained from gastric lavage. Decontamination and symptomatic treatment were useful in our patient to control acute poisoning.