Dynamic Profiling of the Immune Tumor Microenvironment in Locally Advanced Gastric Cancer Treated with Perioperative Chemotherapy.

INTRODUCTION: In locally advanced gastric cancer (GC), FLOT represents the standard perioperative regimen and combination with immunotherapy is under investigation. However, the role of immune tumor microenvironment (TME) is poorly recognized in this setting. We aimed to study TME characteristics and dynamics during FLOT. METHODS: Paired biopsy (PRE) and surgical (POST) samples of 25 patients treated with FLOT were prospectively analyzed. After collection of clinic-pathological data, NanoString analyses were performed. The primary objective of the study was to assess the changes induced by chemotherapy in POST compared to PRE samples. RESULTS: The unsupervised hierarchical method analysis clearly distinguished PRE and POST samples, even though some cases showed high immune gene expression at baseline. When POST samples were compared with PRE, a differential expression in hyper-expressed gene sets related to cytotoxicity, T-cell functions, complement system, tumor necrosis factor superfamily, cell cycle, and regulation was recognized. Downstaging of the primary tumor (T-regression, measured by pathologic compared to clinical T stage) was the covariate most frequently associated with these changes. Using the immune cell profiling, cases with T-regression reported a significant increase of T, CD8+ T and B cells and a decrease in mast cells, while nonresponders demonstrated an increase of T, B, cytotoxic, and mast cells. CONCLUSION: Our analysis shows that FLOT significantly influences immune TME of GC. While relevant modifications preferentially occur in tumors showing primary tumor regression, response to treatment seems to be associated with a specific immune profile.

Robotic Heller-Dor for Idiopathic Achalasia: the Pisa experience.

Achalasia is a rare motility disorder of the esophagus. According to the Chicago Classification criteria, there are three clinical types of Achalasia and the treatment is patient-tailored. Laparoscopic Heller-Dor is the gold-standard treatment for the most frequent types of Achalasia. However, robotic surgery is able to combine the clinical advantages of minimally invasive surgery with a powerful dexterity on complex anatomic structures. The aim of this study is to report the institutional experience developed in a referral center of esophageal surgery in the treatment of Achalasia by Robotic Heller-Dor. We retrospectively analyzed data of patients that consecutively underwent Robotic Heller-Dor at our institution between January 2012 and January 2020 using the Da Vinci® Surgical System. Sixty-nine patients underwent Robotic Heller-Dor. Among the patients, 35 (51%) were classified as type I, 29 (42%) as type II, and 5 (7%) as type III. The Da Vinci® SI HD Surgical System and the Da Vinci® XI HD Surgical System were used in 56 (81%) and 13 (19%) patients, respectively. No mucosal perforation was observed and post-operative mortality was absent. The mean follow-up was 23.3 months (6-84). Ten patients (14.5%) reported post-operative complaints. In our opinion, Robotic Heller-Dor is an effective tool in the treatment of Achalasia. Robotic Heller-Dor may be a suitable procedure for learning and teaching robotic surgery in the perspective of pursing more complex esophago-gastric surgical procedures.

Laparoscopic pancreaticoduodenectomy: a systematic literature review.

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is gaining momentum, but there is still uncertainty regarding its safety, reproducibility, and oncologic appropriateness. This review assesses the current status of LPD. METHODS: Our literature review was conducted in Pubmed. Articles written in English containing five or more LPD were selected. RESULTS: Twenty-five articles matched the review criteria. Out of a total of 746 LPD, 341 were reported between 1997 and 2011 and 405 (54.2 %) between 2012 and June 1, 2013. Pure laparoscopy (PL) was used in 386 patients (51.7 %), robotic assistance (RA) in 234 (31.3 %), laparoscopic assistance (LA) in 121 (16.2 %), and hand assistance in 5 (0.6 %). PL was associated with shorter operative time, reduced blood loss, and lower rate of pancreatic fistula (vs LA and RA). LA was associated with shorter operative time (vs RA), but with higher blood loss and increased incidence of pancreatic fistula (vs PL and RA). Conversion to open surgery was required in 64 LPD (9.1 %). Operative time averaged 464.3 min (338-710) and estimated blood 320.7 mL (74-642). Cumulative morbidity was 41.2 %, and pancreatic fistula was reported in 22.3 % of patients (4.5-52.3 %). Mean length of hospital stay was 13.6 days (7-23), showing geographic variability (21.9 days in Europe, 13.0 days in Asia, and 9.4 days in the US). Operative mortality was 1.9 %, including one intraoperative death. No difference was noted in conversion rate, incidence of pancreatic fistula, morbidity, and mortality when comparing results from larger (≥30 LPD) and smaller (≤29 LPD) series. Pathology demonstrated ductal adenocarcinoma in 30.6 % of the specimens, other malignant tumors in 51.7 %, and benign tumor/disease in 17.5 %. The mean number of lymph nodes examined was 14.4 (7-32), and the rate of microscopically positive tumor margin was 4.4 %. CONCLUSIONS: In selected patients, operated on by expert laparoscopic pancreatic surgeons, LPD is feasible and safe.

Robotic giant hiatal hernia repair: 3 year prospective evaluation and review of the literature.

BACKGROUND: While conventional laparoscopic repair for giant hiatal hernias is considered difficult, robotic technology is likely to result in an improved postoperative course. METHODS: We prospectively analysed patients with giant hiatal hernias who underwent robotic repair during a 3 year period. Preoperative data, operative variables, complications, clinical outcomes and anatomical recurrence after 1 year were evaluated. RESULTS: Six patients with giant hiatal hernias underwent robotic repair using the Da Vinci surgical system. The mean operative time was 182 min. The mean hospital stay was 6 days. No patients required reoperation for disease recurrence, and all claimed the absence of postoperative symptoms. CONCLUSIONS: Robotic approaches can minimize surgical trauma in patients with giant hiatal hernias and result in favourable outcomes in terms of anatomical recurrence and quality of life. With the availability of the da Vinci System, all patients with giant hiatal hernias can be offered a minimally invasive surgical option.

Laparoscopic robot-assisted versus open total pancreatectomy: a case-matched study.

BACKGROUND: The enhanced dexterity offered by robotic assistance could be excessive for distal pancreatectomy but not enough to improve the outcome of laparoscopic pancreaticoduodenectomy. Total pancreatectomy retains the challenges of uncinate process dissection and digestive reconstruction, but avoids the risk of pancreatic fistula, and could be a suitable operation to highlight the advantages of robotic assistance in pancreatic resections. METHODS: Eleven laparoscopic robot-assisted total pancreatectomies (LRATP) were compared to 11 case-matched open total pancreatectomies. All operations were performed by one surgeon during the same period of time. Robotic assistance was employed in half of the patients, based on robot availability at the time of surgery. Variables examined included age, sex, American Society of Anesthesiologists score, body mass index, estimated blood loss, need for blood transfusions, operative time, tumor type, tumor size, number of examined lymph nodes, margin status, post-operative complications, 90-day or in-hospital mortality, length of hospital stay, and readmission rate. RESULTS: No LRATP was converted to conventional laparoscopy, hand-assisted laparoscopy or open surgery despite two patients (18.1 %) required vein resection and reconstruction. LRATP was associated with longer mean operative time (600 vs. 469 min; p = 0.014) but decreased mean blood loss (220 vs. 705; p = 0.004) than open surgery. Post-operative complications occurred in similar percentages after LRATP and open surgery. Complications occurring in most patients (5/7) after LRATP were of mild severity (Clavien-Dindo grade I and II). One patient required repeat laparoscopic surgery after LRATP, to drain a fluid collection not amenable to percutaneous catheter drainage. One further patient from the open group required repeat surgery because of bleeding. No patient had margin positive resection, and the mean number of examined lymph nodes was 45 after LRATP and 36 after open surgery. CONCLUSIONS: LRATP is feasible in selected patients, but further experience is needed to draw final conclusions.