Marco Farsi

Helicobacter pylori secreted peptidyl prolyl cis, trans-isomerase drives Th17 inflammation in gastric adenocarcinoma.

Helicobacter pylori infection is characterized by an inflammatory infiltrate, consisting mainly of neutrophils and T cells. This study was undertaken to evaluate the type of gastric T cell response elicited by the secreted peptidyl prolyl cis, trans-isomerase of H. pylori (HP0175) in patients with distal gastric adenocarcinoma. The cytokine profile and the effector functions of gastric tumor-infiltrating lymphocytes (TILs) specific for HP0175 was investigated in 20 patients with distal gastric adenocarcinoma and H. pylori infection. The helper function of HP0175-specific TILs for monocyte MMP-2, MMP-9, and VEGF production was also investigated. TILs cells from H. pylori infected patients with distal gastric adenocarcinoma produced Interleukin (IL)-17 and IL-21 in response to HP0175. HP0175-specific TILs showed poor cytolytic activity while expressing helper activity for monocyte MMP-2, MMP-9 and VEGF production. These findings indicate that HP0175 is able to drive gastric Th17 response. Thus, HP0175, by promoting pro-inflammatory low cytotoxic TIL response, matrix degradation and pro-angiogenic pathways, may provide a link between H. pylori and gastric cancer.

Predictors of recurrence after laparoscopic ventral hernia repair.

Laparoscopic ventral hernia repair (LVHR) is widely used to manage ventral hernias, but predictors of hernia recurrence have been poorly investigated. This retrospective study investigated the influence of common risk factors on hernia recurrence. Data from 146 consecutive, unselected patients who underwent LVHR between 2000 and 2006 were collected. Demographic, clinical, and perioperative parameters were analyzed to identify predictable risk factors for hernia recurrence. Both univariate and multivariate Coxs regression analysis were employed. The overall recurrence rate was 8% (12 patients) after an average follow-up of 45 months. On univariate analysis, smoking (P=0.01) and earlier repair (P<0.00) were significantly different in recurred patients. However, only earlier repair was an independent predictor of multivariate Coxs regression analysis (hazard ratio 0.085, 95% confidence interval: 0.020-0.355; P=0.001). LVHR is a safe technique to repair ventral hernias. However, smokers with earlier failed repair attempts have a higher risk of recurrence.

Laparoscopic treatment of ventral hernias: prospective evaluation.

We describe 50 patients who recently underwent laparoscopic surgery. Early results, complications, and follow-up data were collected prospectively. Of 50 patients, 34 had an incisional hernia, whereas 16 had a primary defect. Three trocars were inserted. EndoShears or Ultracision was used for tissue manipulation. The prosthetic mesh used was an expanded polytetrafluoroethylene (ePTFE) mesh, inserted through the first trocar and fixed with a helicoidal stapler. Patients were followed-up in the outpatient clinic (mean, 14 months). Every operation was successfully completed, and mean operative time was 103 minutes. There were two small bowel injuries (4%) repaired by minilaparotomy. Postoperative pain was limited. Bowel movements, ambulation, and discharge were prompt. We noted 4 cases of urinary retention (8%), 8 seromas (16%), and 1 prolonged ileus, which resolved on day 5 spontaneously. Mean postoperative stay was 4 days. One patient was readmitted after 4 weeks because of incomplete obstruction, resolved conservatively. There has been only 1 recurrence (2%), 8 months after the operation. The technique appears safe and efficacious.

Modern approach to cholecysto-choledocholithiasis

Gallstones and common bile duct calculi are found to be associated in 8%-20% of patients, leading to possible life-threatening complications, such as acute biliary pancreatitis, jaundice and cholangitis. The gold standard of care for gallbladder calculi and isolated common bile duct stones is represented by laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography, respectively, while a debate still exists regarding how to treat the two diseases at the same time. Many therapeutic options are also available when the two conditions are associated, including many different types of treatment, which local professionals often administer. The need to limit maximum discomfort and risks for the patients, combined with the economic pressure of reducing costs and utilizing resources, favors single-step procedures. However, a multitude of data fail to strongly demonstrate the superiority of any technique (including a two or multi-step approach), while rigorous clinical trials that include so many different types of treatment are still lacking, and it is most likely unrealistic to conduct them in the future. Therefore, the choice of the best management is often led by the local presence of professional expertise and resources, rather than by a real superiority of one strategy over another.

Comparison of laparoscopic and open repair for primary ventral hernias.

We designed a retrospective clinical trial comparing laparoscopic primary ventral hernia repair (LPVHR) and open traditional repair (OPVHR). Demographics, perioperative data, results, and follow-up were examined to determine if there was any difference in the main outcomes. From January 2000 to December 2006, 28 consecutive, unselected patients, who successfully underwent LPVHR, were matched with 36 patients, who received OPVHR (with mesh) during the same period. The operating room records, clinical files, and outpatient sheets were examined. Patient demographics, results, and follow-up were compared in the 2 groups. Demographic characteristics, site of hernia, concomitant surgery, and defect size were comparable between the 2 groups, but the proportion of urgent procedures was higher in OPVHR patients (25% vs. 4%; P=0.03). The overall complication rates were similar, with some specific differences, whereas analgesic requirement and hospital stay were also comparable. The operative times were significantly longer for the LPVHR group (70 min vs. 35 min; P<0.000). Four recurrences were noted in both OPVHR and LPVHR patients, 11% versus 14%, respectively, with no significant difference (P=0.67). LPVHR seemed to be as safe as the OVHR in this study, although LPVHR increased operative time. The complications of each method should be taken into consideration before making the choice of the surgical approach.

Laparoscopic cholecystectomy: retrospective comparative evaluation of titanium versus absorbable clips.

We present a retrospective study of the use of titanium and absorbable clips during laparoscopic cholecystectomy. The aim was to determine any differences in outcome and costs. From January 1999 to February 2002, 690 patients who had successfully undergone a laparoscopic cholecystectomy were reviewed. According to the type of clip, we retrospectively identified two groups of patients: 199 in whom the surgeons had used absorbable clips (absorbable clip group, ACG) and 491 in whom the surgeons had used titanium nonabsorbable clips (titanium clip group, TCG). Data about demographics, operation, results, complications, and follow-up were collected and matched in the two groups. Demographics, concomitant surgery, and the American Society of Anesthesiologists (ASA) status were comparable between the two groups. Although the proportions of cases requiring urgent operation, intraoperative cholangiography, use of a fourth trocar, and use of drainage suction were similar, the difficulty score of the operation was lower (6.3 vs. 7.0, P =.03) and the operative time was shorter (44 vs. 61 minutes, P <.0001) in the ACG than in the TCG. Complications, hospital stay, and long-term results were satisfactory and comparable between the two groups. No correlation was found between clip type and the incidence of biliary tree injuries, bleeding, wound infection, or readmission. The cost of the two types of clips varied slightly (90 euros for each procedure). Despite the fact that absorbable clips are theoretically less likely to cause complications than metallic ones, we were not able to demonstrate any clinical advantage during laparoscopic cholecystectomy in this retrospective study. Furthermore, the results suggest that absorbable clips are preferred when the cholecystectomy presents fewer difficulties.

Minimally invasive surgical approach to pancreatic malignancies

Pancreatic surgery for malignancy is recognized as challenging for the surgeons and risky for the patients due to consistent perioperative morbidity and mortality. Furthermore, the oncological long-term results are largely disappointing, even for those patients who experience an uneventfully hospital stay. Nevertheless, surgery still remains the cornerstone of a multidisciplinary treatment for pancreatic cancer. In order to maximize the benefits of surgery, the advent of both laparoscopy and robotics has led many surgeons to treat pancreatic cancers with these new methodologies. The reduction of postoperative complications, length of hospital stay and pain, together with a shorter interval between surgery and the beginning of adjuvant chemotherapy, represent the potential advantages over conventional surgery. Lastly, a better cosmetic result, although not crucial in any cancerous patient, could also play a role by improving overall well-being and patient self-perception. The laparoscopic approach to pancreatic surgery is, however, difficult in inexperienced hands and requires a dedicated training in both advanced laparoscopy and pancreatic surgery. The recent large diffusion of the da Vinci(®) robotic platform seems to facilitate many of the technical maneuvers, such as anastomotic biliary and pancreatic reconstructions, accurate lymphadenectomy, and vascular sutures. The two main pancreatic operations, distal pancreatectomy and pancreaticoduodenectomy, are approachable by a minimally invasive path, but more limited interventions such as enucleation are also feasible. Nevertheless, a word of caution should be taken into account when considering the increasing costs of these newest technologies because the main concerns regarding these are the maintenance of all oncological standards and the lack of long-term follow-up. The purpose of this review is to examine the evidence for the use of minimally invasive surgery in pancreatic cancer (and less aggressive tumors), with particular attention to the oncological results and widespread reproducibility of each technique.

The CHOLEGAS study: multicentric randomized, blinded, controlled trial of gastrectomy plus prophylactic cholecystectomy versus gastrectomy only, in adults submitted to gastric cancer surgery with curative intent.

BackgroundThe incidence of gallstones and gallbladder sludge is known to be higher in patients after gastrectomy than in general population. This higher incidence is probably related to surgical dissection of the vagus nerve branches and the anatomical gastrointestinal reconstruction. Therefore, some surgeons perform routine concomitant cholecystectomy during standard surgery for gastric malignancies. However, not all the patients who are diagnosed to have cholelithiasis after gastric cancer surgery will develop symptoms or require additional surgical treatments and a standard laparoscopic cholecystectomy is feasible even in those patients who underwent previous gastric surgery. At the present, no randomized study has been published and the decision of gallbladder management is left to each surgeon preference.DesignThe study is a randomized controlled investigation. The study will be performed in the General and Oncologic Surgery, Department of Oncology – Azienda Ospedaliero-Universitaria Careggi – Florence – Italy, a large teaching institution, with the participation of all surgeons who accept to be involved in, together with other Italian Surgical Centers, on behalf of the GIRCG (Italian Research Group for Gastric Cancer).The patients will be randomized into two groups: in the first group the patient will be submitted to prophylactic cholecystectomy during standard surgery for curable gastric cancer (subtotal or total gastrectomy), while in the second group he/she will be submitted to standard gastric surgery only.Trial RegistrationClinicalTrials.gov ID. NCT00757640

Laparoscopic approach to gastrointestinal malignancies: Toward the future with caution

After the rapid acceptance of laparoscopy to manage multiple benign diseases arising from gastrointestinal districts, some surgeons started to treat malignancies by the same way. However, if the limits of laparoscopy for benign diseases are mainly represented by technical issues, oncologic outcomes remain the foundation of any procedures to cure malignancies. Cancerous patients represent an important group with peculiar aspects including reduced survival expectancy, worsened quality of life due to surgery itself and adjuvant therapies, and challenging psychological impact. All these issues could, potentially, receive a better management with a laparoscopic surgical approach. In order to confirm such aspects, similarly to testing the newest weapons (surgical or pharmacologic) against cancer, long-term follow-up is always recommendable to assess the real benefits in terms of overall survival, cancer-free survival and quality of life. Furthermore, it seems of crucial importance that surgeons will be correctly trained in specific oncologic principles of surgical oncology as well as in modern miniinvasive technologies. Therefore, laparoscopic treatment of gastrointestinal malignancies requires more caution and deep analysis of published evidences, as compared to those achieved for inflammatory bowel diseases, gastroesophageal reflux disease or diverticular disease. This review tries to examine the evidence available to date for the use of laparoscopy and robotics in malignancies arising from the gastrointestinal district.

The role of robotics in widening the range of application of minimally invasive surgery for pancreaticoduodenectomy.

Nearly two decades after its appearance, the use of minimallyinvasive techniques in pancreatic surgery is becoming more widespread, mostly due to the increased experience in this field and the availability of new technologies. However, if on one side minimally invasive surgery (MIS) has been associated with significant advantages over conventional open surgery in case of left sided pancreatectomies [1,2], pancreaticoduodenectomy (PD) is still considered a relative limitation to laparoscopic techniques [3e5]. About twenty years ago Gagner and Pomp from the University of Montr eal presented the first case of a laparoscopically performed pylorus-preserving PD for the treatment of chronic pancreatitis [6]. As a consequence, an increasing number of encouraging preliminary experiences coming from other centers followed, progressively expanding the indications from benign conditions to small malignancies of the pancreatic head [7]. Notwithstanding promising initial results and all the potential advantages connected with laparoscopy over conventional surgery, the intervening years have seen minimally invasive PD failing to obtain wide acceptance in real clinical practice worldwide [3,4]. Indeed, laparoscopic PD is regarded as a technically highdemanding procedure, mostly due to the deep, retroperitoneal location of the gland, its close relationship with major vascular structures and the complex reconstruction phase that requires at least three anastomoses. Several crucial maneuvers require angulated or curved lines of section and rigid laparoscopic instruments, with their restricted freedom of movement, can lead to significant technical difficulties [5,7]. In this regard, we do believe that PD represents one of the procedureswhichmay greatly benefit from robotics. A number of technical issues connected with conventional laparoscopy has been overcome, at least partially, by robotic platforms, which permit magnified 3-dimensional intraoperative view and enhanced surgical dexterity that, thanks to the endowristed maneuverability, affords optimal control on fine dissections. These features enable not only easier resecting and suturing, thus permitting more accurate anastomoses, but also facilitate the management of possible intraoperative complications such as major bleedings [8,9]. As a result, robot-assisted surgery has significantly increased the possibility of application of minimally invasive pancreatic surgery worldwide, particularly in the context of PD. This becomes evident if one notes the growing use of robotic surgery in PD over the last few years. By investigating the relevant scientific evidence, a significant difference of development and application of minimally invasive PD can be noted between the robotic and conventional