Robotic Ultrasound-Guided Central Pancreatectomy with Main Pancreatic Duct Endoscopy Evaluation for High-Risk, Mixed-Type Intraductal Papillary Mucinous Neoplasm.

BACKGROUND: Central pancreatectomy (CP) is a parenchymal-sparing technique indicated for the resection of selected lesions of the neck or proximal body of the pancreas.1,2 The risk of postoperative complications is theoretically doubled because the surgeon has to manage two cut surfaces of the pancreas. The video shows a fully robotic CP to treat a 62-year-old male patient with a mixed-type intraductal papillary mucinous neoplasm (IPMN) of the pancreatic neck, using ultrasound (US) and Wirsung endoscopic evaluation to guide the pancreatic resection and ensure optimal resection margins. MATERIALS AND METHODS: A US-guided robotic CP was carried out, and an intraoperative endoscopic evaluation of the MPD was performed to determine the distal transection level. A transmesocolic, end-to-side, robot-sewn Wirsung-jejunostomy with internal MPD stenting was then created. The procedure was completed with a side-to-side jejunojejunostomy. RESULTS: The operative time was 290 min, with negligible blood loss. During the postoperative course, the patient experienced bleeding from a branch of the gastroduodenal artery with subsequent fluid collection, which was successfully treated with angioembolization and percutaneous drainage. He was discharged home on postoperative day 22. Final pathology revealed a non-invasive IPMN with low-grade dysplasia and free surgical margins. At 12 months of follow-up, the patient was doing well, with no evidence of local recurrence and endocrine or exocrine pancreatic insufficiency. CONCLUSIONS: The combination of robotic surgery with intraoperative US and Wirsungoscopy may offer distinct technical advantages for challenging pancreatectomies that follow the principles of parenchymal-sparing surgery.

Robotic Distal Pancreatectomy: A Novel Standard of Care? Benchmark Values for Surgical Outcomes From 16 International Expert Centers.

BACKGROUND AND OBJECTIVE: Robotic distal pancreatectomy (DP) is an emerging attractive approach, but its role compared with laparoscopic or open surgery remains unclear. Benchmark values are novel and objective tools for such comparisons. The aim of this study was to identify benchmark cutoffs for many outcome parameters for DP with or without splenectomy beyond the learning curve. METHODS: This study analyzed outcomes from international expert centers from patients undergoing robotic DP for malignant or benign lesions. After excluding the first 10 cases in each center to reduce the effect of the learning curve, consecutive patients were included from the start of robotic DP up to June 2020. Benchmark patients had no significant comorbidities. Benchmark cutoff values were derived from the 75th or the 25th percentile of the median values of all benchmark centers. Benchmark values were compared with a laparoscopic control group from 4 high-volume centers and published open DP landmark series. RESULTS: Sixteen centers contributed 755 cases, whereof 345 benchmark patients (46%) were included the analysis. Benchmark cutoffs included: operation time ≤300 minutes, conversion rate ≤3%, clinically relevant postoperative pancreatic fistula ≤32%, 3 months major complication rate ≤26.7%, and lymph node retrieval ≥9. The comprehensive complication index at 3 months was ≤8.7 without deterioration thereafter. Compared with robotic DP, laparoscopy had significantly higher conversion rates (5×) and overall complications, while open DP was associated with more blood loss and longer hospital stay. CONCLUSION: This first benchmark study demonstrates that robotic DP provides superior postoperative outcomes compared with laparoscopic and open DP. Robotic DP may be expected to become the approach of choice in minimally invasive DP.

Review on Perioperative and Oncological Outcomes of Robotic Gastrectomy for Cancer.

BACKGROUND: Minimally invasive gastrectomy is currently considered a valid option to treat gastric cancer and is gaining increasing acceptance. Recent reports have suggested that the application of robots may confer some advantages over conventional laparoscopy, but the role of robotic surgery in clinical practice is still uncertain. We aimed to critically review the relevant evidence comparing robotic to standard laparoscopic surgery in performing radical gastrectomy. METHODS: The Pubmed/Medline electronic databases were searched through February 2021. Paper conference and the English language was the only restriction applied to our search strategy. RESULTS: According to the existing data, robotic gastrectomy seems to provide some benefits in terms of blood loss, rate of conversion, procedure-specific postoperative morbidity, and length of hospital stay. Robotic gastrectomy is also associated with a longer duration of surgery and a higher economic burden as compared to its laparoscopic counterpart. No significant differences have been disclosed in terms of long-term survivals, while the number of lymph nodes retrieved with robotic gastrectomy is generally higher than that of laparoscopy. CONCLUSIONS: The current literature suggests that robotic radical gastrectomy appears as competent as the conventional laparoscopic procedure and may provide some clinical advantages. However, due to the relative paucity of high-level evidence, it is not possible to draw definitive conclusions.

Familial aggregation of gastric cancer with microsatellite instability.

BACKGROUND: Microsatellite instability (MSI) is currently a new molecular subtype of gastric cancer (GC). About 90% of GC cases appear sporadically. MSI seems to be responsible for both sporadic and familial GC. The aim of this study was to analyze the frequency of MSI in GC with familial history of GC. METHODS: The MSI analysis was conducted using five quasi-monomorphic mononucleotide repeats: BAT-26, BAT-25, NR-24, NR-21 and NR-27. From our database, we analyzed 457 patients in terms of cancer history across family members, particularly focusing on GC. RESULTS: MSI status in patients without familial history of GC was present in 22.1% of the cases, whereas in the patients with familial history of GC it was present in 28% of the cases (p = 0.220). For 1st or 2nd degree family members with GC, MSI was observed in 27.6% and in 30.8%, respectively (p = 0.812). MSI was observed in hereditary gastric cancer (HGC) in 33.3% and in familial gastric cancer (FGC) in 30%. No difference in survival rates was observed between the analyzed groups. CONCLUSIONS: In our publication, we could not find any link between familial background and the MSI status in GC patients. More detailed molecular and genetic analysis of subgroups of these patients is required.

Prognostic Value of Perineural Invasion in Resected Gastric Cancer Patients According to Lauren Histotype.

The purpose of this study is to investigate perineural invasion (PNI) as a prognostic factor in gastric cancer patients. 455 patients submitted to extended (D2 or more) lymphadenectomy (median number of 39 retrieved lymph nodes, range: 15-140) between 1995 and 2012 were retrospectively studied. Patients were categorized in two groups according to the PNI status, and PNI positivity was assessed in presence of cancer cells in the perinerium or the neural fascicles using hematoxylin and eosin staining. Median follow-up for surviving patients was 80.3 months. Survival analysis was performed by univariate and multivariate analysis, using a Cox proportional hazards model. 162 patients (33.9%) had positive PNI; this was strongly associated with advanced stages of disease, residual tumor, lymphovascular invasion, Lauren diffuse-mixed histotype and tumor size. Five-year cancer-related survival was 65,7% and 20,6% in PNI negative vs. positive groups, respectively (p < 0.001). The prognostic impact of PNI at univariate analysis was particularly evident in patients submitted to R0 surgery, early as well as advanced stage, advanced nodal stage and T status. At multivariate analysis, PNI did not result statistically significant in the overall series, but emerged as an independent prognostic factor in the group of patients with Lauren intestinal histotype (p = 0.005, hazard ratio: 1.99, 95% confidence interval 1.24-3.19). PNI is related to advanced stage and poor long-term survival in gastric cancer, and may serve as an adjunctive prognostic factor in the intestinal histotype.

Robot-assisted laparoscopic vs open gastrectomy for gastric cancer: Systematic review and meta-analysis.

AIM: To evaluate the potential effectiveness of robot-assisted gastrectomy (RAG) in comparison to open gastrectomy (OG) for gastric cancer patients. METHODS: A comprehensive systematic literature search using PubMed, EMBASE, and the Cochrane Library was carried out to identify studies comparing RAG and OG in gastric cancer. Participants of any age and sex were considered for inclusion in comparative studies of the two techniques independently from type of gastrectomy. A meta-analysis of short-term perioperative outcomes was performed to evaluate whether RAG is equivalent to OG. The primary outcome measures were set for estimated blood loss, operative time, conversion rate, morbidity, and hospital stay. Secondary among postoperative complications, wound infection, bleeding and anastomotic leakage were also analysed. RESULTS: A total of 6 articles, 5 retrospective and 1 randomized controlled study, involving 6123 patients overall, with 689 (11.3%) cases submitted to RAG and 5434 (88.7%) to OG, satisfied the eligibility criteria and were included in the meta-analysis. RAG was associated with longer operation time than OG (weighted mean difference 72.20 min; P < 0.001), but with reduction in blood loss and shorter hospital stay (weighted mean difference -166.83 mL and -1.97 d respectively; P < 0.001). No differences were found with respect to overall postoperative complications (P = 0.65), wound infection (P = 0.35), bleeding (P = 0.65), and anastomotic leakage (P = 0.06). The postoperative mortality rates were similar between the two groups. With respect to oncological outcomes, no statistical differences among the number of harvested lymph nodes were found (weighted mean difference -1.12; P = 0.10). CONCLUSION: RAG seems to be a technically valid alternative to OG for performing radical gastrectomy in gastric cancer resulting in safe complications.

Incidence and Prognostic Value of Metastases to "Posterior" and Para-aortic Lymph Nodes in Resectable Gastric Cancer.

BACKGROUND: The purpose of this retrospective study was to evaluate the incidence and prognostic value of metastases to "posterior" (8p, 12b/p, 13) and para-aortic lymph nodes in a large cohort of Western patients submitted to D2 plus lymphadenectomy. METHODS: Removal of "posterior" nodes was performed in 743 patients, and para-aortic lymphadenectomy in a subgroup of 390 patients. After lymph node mapping and retrieval on the fresh specimen, a median number of 41 total lymph nodes were analyzed. The median follow-up period was 37 months for the entire series and 68 months for survivors. RESULTS: Of 743 included patients, 23 (3.1%) had metastases in station 8p, 12 (1.6%) in station 12b/p, and 19 (2.6%) in station 13. On the whole, 47 of 743 patients (6.3%) had positive "posterior" nodes. Para-aortic metastases were present in 42 of 390 patients (10.8%). Metastases to "posterior" stations were significantly related to depth of invasion, number of positive nodes, and surgical radicality. Distal tumors showed higher trend to metastasize to "posterior" nodes than upper third, whereas for para-aortic metastases it was the reverse. 5-year survival in patients with positivity to "posterior" nodes was 17%, with no significant difference according to 8p, 12b/p, and 13 stations; long-term outcome was overlapping to pN3b stage. 5-year survival in para-aortic positive cases was 11%, and a trend to better outcome was observed in proximal tumors. CONCLUSIONS: Although metastases to "posterior" and para-aortic nodes are expression of an advanced nodal stage, not negligible survival rates are observed in subgroups of patients.

Lymphadenectomy: state of the art.

The extent of lymphadenectomy in gastric cancer (GC) surgery has been for long time a matter of debate. Randomized trials performed in the West reported worse results of D2 dissection, in terms of postoperative complications and long-term survival benefit, than Eastern series and observational studies from specialized Western centers. However, long-term re-evaluation of such trials and in depth-analysis of other experiences demonstrated the potential benefit of D2 in reducing the probability of cancer-related death and the safety of this procedure when avoiding unnecessary spleno-pancreatectomy and in centers with ad adequate surgical volume. Nowadays, the D2 is considered the standard treatment in most guidelines all over the world. More limited procedures (D1, D1 plus) may be adequate in selected cases, and more extended dissections (D2 plus) could be indicated in advanced forms with high risk of metastases to distant nodes, but in specialized centers or in the setting of clinical studies. The integration with neoadjuvant therapies and multimodality approach could offer a chance of cure in groups of patients with poor results when approached with standard treatment.

Risk factor analysis for involvement of resection margins in gastric and esophagogastric junction cancer: an Italian multicenter study.

BACKGROUND: Resection margin (RM) involvement is associated with negative prognosis after gastrectomy. Intraoperative frozen section (IFS) analysis allows radical resection to be achieved in a single operation but is time-consuming and resource-consuming. The aim of this study was to assess risk factors associated with RM involvement to identify patients who would benefit from IFS analysis. METHODS: We retrospectively analyzed patients who underwent gastrectomy with curative intent for gastric or esophagogastric junction (EGJ) cancer from 2000 to 2014 in six Italian hospitals. RM status was assessed by IFS analysis and/or definitive histopathology examination. A set of 21 potential risk factors were compared in a multivariate analysis between patients with positive RMs on IFS analysis or definitive histopathology examination and a control cohort of similar patients with negative RMs, with the samples stratified into three subgroups (T1, T2-T4 Lauren intestinal pattern, T2-T4 Lauren diffuse/mixed pattern). RESULTS: One hundred forty-five patients had positive RMs. Survival was significantly worse in positive RM patients than in negative RM patients (89.5 months vs 28.9 months). Multivariate analysis showed that in T1 cancers a margin distance of less than 2 cm is a risk factor for RM involvement (odds ratio 15.7), in T2-T4 intestinal pattern cancers, serosa invasion (odds ratio 6.0), EGJ location (odds ratio 4.1), and a margin distance of less than 3 cm (odds ratio 4.0) are independent risk factors, and in T2-T4 diffuse/mixed pattern cancers, lymphatic infiltration (odds ratio 4.2), tumor diameter greater than 4 cm (odds ratio 3.5), EGJ location (odds ratio 2.8), and serosa invasion (odds ratio 2.2) are independent risk factors. CONCLUSIONS: Survival after gastrectomy is negatively affected by positive RMs. IFS analysis should be routinely used in patients with a high risk of positive RMs, especially in diffuse pattern cancers.

Laparoscopic and robot-assisted gastrectomy for gastric cancer: Current considerations.

Radical gastrectomy with an adequate lymphadenectomy is the main procedure which makes it possible to cure patients with resectable gastric cancer (GC). A number of randomized controlled trials and meta-analysis provide phase III evidence that laparoscopic gastrectomy is technically safe and that it yields better short-term outcomes than conventional open gastrectomy for early-stage GC. While laparoscopic gastrectomy has become standard therapy for early-stage GC, especially in Asian countries such as Japan and South Korea, the use of minimally invasive techniques is still controversial for the treatment of more advanced tumours, principally due to existing concerns about its oncological adequacy and capacity to carry out an adequately extended lymphadenectomy. Some intrinsic drawbacks of the conventional laparoscopic technique have prevented the worldwide spread of laparoscopic gastrectomy for cancer and, despite technological advances in recent year, it remains a technically challenging procedure. The introduction of robotic surgery over the last ten years has implied a notable mutation of certain minimally invasive procedures, making it possible to overcome some limitations of the traditional laparoscopic technique. Robot-assisted gastric resection with D2 lymph node dissection has been shown to be safe and feasible in prospective and retrospective studies. However, to date there are no high quality comparative studies investigating the advantages of a robotic approach to GC over traditional laparoscopic and open gastrectomy. On the basis of the literature review here presented, robot-assisted surgery seems to fulfill oncologic criteria for D2 dissection and has a comparable oncologic outcome to traditional laparoscopic and open procedure. Robot-assisted gastrectomy was associated with the trend toward a shorter hospital stay with a comparable morbidity of conventional laparoscopic and open gastrectomy, but randomized clinical trials and longer follow-ups are needed to evaluate the possible influence of robot gastrectomy on GC patient survival.

Evolution and emerging future of cytoreducxtive surgery and hyperthermic intraperitoneal chemoperfusion in gastric cancer: From treating the incurable to preventing recurrence.

The number of new gastric cancer (GC) cases is decreasing, and these patients have longer survival thanks to new oncological treatments. In advanced GC a common evolution of this neoplasm is peritoneal metastases (PM). In the past this finding meant no chance for cure. However, today, using high quality operations and HIPEC, we are able to increase the number of patients treated with curative intention. New options in the diagnosis of PM, tumour susceptibility for different drugs, importance of quality of life, usage in ascites treatment, diagnostic tools in image-guided surgery, new targeted therapies and analysis of currently ongoing trials are presented together with today's knowledge of HIPEC efficacy in order to evaluate gastric PM. HIPEC is an effective tool in the treatment of selected patients with PM from GC. Together with new diagnostic options such as targeted therapies, HIPEC may improve the prognosis of these patients, not only by treating clinically manifest carcinomatosis, but also in the prophylactic setting, addressing occult peritoneal seeding.

Strong Prognostic Value of Microsatellite Instability in Intestinal Type Non-cardia Gastric Cancer.

BACKGROUND: The clinical role of microsatellite instability (MSI) in gastric cancer (GC) is controversial. A large series of patients submitted to respective surgery for primary GC with a long follow-up time was evaluated. METHODS: 472 patients with prospectively collected frozen samples of normal mucosa and tumor tissue stored in a biological tissue bank were included. Microsatellite analysis was evaluated using 5 quasi monomorphic mononucleotide repeats (BAT-26, BAT-25, NR-24, NR-21, and NR-27). The presence of MSI in 2 or more loci was classified as MSI-H, whereas all other cases were included in the microsatellite-stable (MSS) group. RESULTS: MSI-H phenotype was found in 111 of 472 patients (23.5%). MSI-H status was related significantly with older age, female gender, non-cardia location, WHO histotype, non-cardia Lauren intestinal type, and less advanced stages. Cancer-related 5-year survival was significantly higher in MSI-H versus MSS group (67.6% vs. 35%, p < 0.001). Stratified analysis revealed a significant impact of MSI on prognosis in non-cardia tumors of intestinal type or tubular/poorly differentiated histology, particularly in stages II and III; multivariate Cox regression analysis confirmed MSS status as a strong predictor of poor prognosis (hazard ratio 2.65, 95% CI 1.56-4.51, p < 0.001) in non-cardia intestinal type. No prognostic value of MSI in the diffuse-mixed type and signet-ring cell/mucinous histotypes was observed. CONCLUSIONS: MSI was confirmed as a significant predictor of long term outcome in a large series of GC with a long follow-up time, but the prognostic value is limited to selected histotypes of non-cardia tumors.

Monoclonal antibodies-based treatment in gastric cancer: current status and future perspectives.

Gastric cancer (GC) is the second leading cause of cancer-related death, and despite having improved treatment modalities over the last decade, for most patients, only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and the related signaling pathways offers, from the clinical point of view, promising advances for selected groups of patients. In the past, targeted therapies have significantly impacted the treatment strategy of several common solid tumors such as breast, colorectal, and lung cancers. Unfortunately, translational and clinical research shows fewer encouraging targeted treatments with regards to the GC. To date, only two monoclonal antibodies (mAb), named trastuzumab and ramucirumab, are approved for the treatment of advanced GC, suggesting that in GC, maybe more than in other cancers, effective targeted therapy requires patient selection based on precise predictive molecular biomarkers. The aim of this review is to summarize the available data on the clinical advantages offered by the use of mAbs in the treatment of advanced/metastatic GC. Future perspective is also discussed.

Robotic single docking total colectomy for ulcerative colitis: First experience with a novel technique.

INTRODUCTION: We describe a novel technique that could aid the surgeon to perform a total proctocolectomy with a single docking position of the da Vinci Si HD System. METHODS: Patients were positioned in 20° Trendelenburg lithotomy split legs position. A 12-mm trocar was for camera and 3 more trocars were placed: two robotics on left and right flanks and one laparoscopic in left iliac fossa. The robot was docked between the legs of the patients. RESULTS: Four proctocolectomies were performed. Mean operative time was 235 min (range 215-255); mean blood loss was 100 cc (range 50-200). Median post-operative stay was 6 days. Overall morbidity was 75%, whereas major complications occurred in 25%. Post-operative mortality was null. CONCLUSIONS: The robotic single docking approach to perform total proctocolectomy for ulcerative colitis is a time-saving technique respect to the multiple docking approach.

Clinical and Oncological Value of Preoperative BMI in Gastric Cancer Patients: A Single Center Experience.

Introduction. The impact of preoperative BMI on surgical outcomes and long-term survival of gastric cancer patients was investigated in various reports with contrasting results. Materials & Methods. A total of 378 patients who underwent a surgical resection for primary gastric cancer between 1994 and 2011 were retrospectively studied. Patients were stratified according to BMI into a normal group (<25, group A), an overweight group (25-30, group B), and an obesity group (≥30, group C). These 3 groups were compared according to clinical-pathological characteristics, surgical treatment, and long-term survival. Results. No significant correlations between BMI and TNM (2010), UICC stage (2010), Lauren's histological type, surgical results, lymph node dissection, and postoperative morbidity and mortality were observed. Factors related to higher BMI were male gender (P < 0.05), diabetes (P < 0.001), and serum blood proteins (P < 0.01). A trend to fewer lymph nodes retrieved during gastrectomy with lymphadenectomy in overweight patients (B and C groups) was observed, although not statistically significant. There was no difference in overall survival or disease-specific survival between the three groups. Conclusion. According to our data, BMI should not be considered a significant predictor of postoperative complications or long-term result in gastric cancer patients.

"Clinical significance of multifocal and multicentric breast cancers and choice of surgical treatment: a retrospective study on a series of 1158 cases".

BACKGROUND: The biological and clinical significance of multifocal and multicentric (MF/MC) breast cancers and the choice of appropriate surgical treatment for these tumors are still debated. METHODS: 1158 women operated on for a stage I-III breast cancer were included in this retrospective study; clinical and pathological data were obtained from the institutional database of the Department of Oncology of the University of Siena, Italy. The impact of MF/MC breast cancers on patterns of recurrence and breast cancer specific survival (BCSS) was investigated in relation to the type of surgical treatment. RESULTS: MF and MC cancers were present in 131 cases (11.3%) and 60 cases (5.2%) respectively and were more frequently treated with mastectomy (55 MF and 60 MC cancers, 81.2%) than with breast conserving surgery (36 MF cancers, 18.9%; p < 0.001). MF and MC breast cancers were associated with a worse prognosis with a BCSS of 154 months compared to 204 months of unicentric cancers (p < 0.001). In multivariate analysis, MF/MC cancers were independent prognostic factors for BCSS together with higher number of metastatic axillary nodes, absence of estrogen receptors and high proliferative activity. MF and MC cancers were related to a significantly shorter BCSS in patients submitted to mastectomy as well as those submitted to breast conserving surgery. Relapse at any site was higher in the subgroup of MF and MC cancers but the incidence of loco-regional and distant recurrences did not differ between patients treated with mastectomy or breast conserving surgery. CONCLUSIONS: Our results indicate that MF/MC cancers have a negative impact on prognosis and are related to higher loregional and distant relapse independently from the type of surgery performed. Adjuvant therapies did not modify the poorer outcome, but in patients receiving adjuvant anthacyclines, the differences with unicentric tumors were reduced. Our data support the hypothesis that MF/MC tumors may have a worse biological behavior and that the presence of multiple foci should be considered in planning adjuvant treatments.

Malignant rhabdoid tumor of the small intestine in adults: a brief review of the literature and report of a case.

A malignant rhabdoid tumor was first described as a subtype of Wilms tumor in 1978. The most frequent location of these tumors is the kidney, and they are common in childhood. The extrarenal localization of these tumors has been described mainly in the central nervous system (called atypical teratoid-rhabdoid tumors), liver, soft tissues and colon. Localization in the small intestine is uncommon and since the 1990s, only a few cases of malignant rhabdoid tumors in the small intestine have been reported. This tumor is very aggressive and the prognosis is poor. We herein present our personal experience with a rhabdoid tumor of the jejunum in a 76-year-old male, and also provide an analysis of the cases of malignant rhabdoid tumor of the small intestine previously described in the literature as for a brief review. We also compared the previous reports and our present case to try to identify prognostic factors.