A Prospective European Trial Comparing Laparotomy, Laparoscopy, Robotic-Assisted, and Transanal Total Mesorectal Excision Procedures in High-Risk Patients with Rectal Cancer: The RESET Trial.

OBJECTIVE: To compare total mesorectal excision (TME) techniques combined with sphincter-sparing procedure in high-risk patients (HRPs). BACKGROUND: TME is the standard treatment for rectal cancer, but can be challenging in HRPs. The available surgical approaches must be compared, especially in HRPs. METHODS: Prospective, observational, multicenter trial to compare laparotomy (OTME), laparoscopy (LTME), robotic-assisted surgery (RTME), and transanal surgery (TaTME) in HRPs. The composite primary outcome included circumferential radial margin (CRM) ≥1mm, TME grade II-III, and absence of Clavien-Dindo grade III-IV complications. Three propensity score analyses were performed (LTME vs. RTME, RTME vs. TaTME, LTME vs. TaTME). RESULTS: 1078 HRPs (75% of men, median body mass index of 27 kg/m2, 50% of tumors in the lower third of the rectum) underwent surgery. The RTME and TaTME groups included patients with more advanced and lower tumors and coloanal anastomosis (P<0.001). Operative time was longer for RTME surgery (P<0.001). Conversion rate was similar for minimally invasive procedures (4.5%). The global R0 resection rate was 96% without difference among techniques. The primary outcome rates were 82.4%, 64.3%, 74.7%, and 80.3% for LTME, OTME, RTME, and TaTME, respectively. None achieved the expected success rate (85%), and propensity score analyses found no differences. Operative results were similar between high- and low-volume inclusion centers only for RTME. CONCLUSIONS: The RESET trial yielded high-quality results despite focusing on HRPs. Minimally invasive procedures showed similar sphincter-sparing procedure outcomes, but LTME included patients with more favorable tumors. Oncologic and functional outcomes will be evaluated at 2 years (ClinicalTrials.gov, ID: NCT03574493).

Gastric neuroendocrine tumors: 20-Year experience in a reference center.

Few studies have been published on the long-term outcomes of patients with gastric neuroendocrine tumors (gNETs). We analyzed their management over a two-decade period, focusing on endoscopic and clinical outcomes. Clinical, laboratory, endoscopic, surgical, and histopathological data from Types 1 and 3 gNETs histologically diagnosed between March 2000 and December 2021 at the European Institute of Oncology (IEO, Milan) were retrospectively collected. Sixty-nine patients were included (60 Type 1, 9 Type 3): 53 (77%) were treated endoscopically, 6 (9%) surgically, and 10 (14%) did not receive any treatment. Overall, 293 lesions were removed endoscopically: 74% by forceps, 20% by endoscopic mucosal resection (EMR), and 5% by endoscopic submucosal dissection (ESD). No differences were observed between EMR and ESD in terms of complete resection rate (p value = .50) and complications rate (p value = .084). The median follow-up period was 5.8 years (range: 0.3-20.5), during which no gNET-related deaths were observed. Metachronous gNETs developed in 60% of patients with Type 1 gNET. Six patients with lymph node metastases (LNM) were younger (p value = .006) and had larger lesions (p value <.001) than patients without LNM. Most Type 1 gNETs were successfully excised using forceps, with EMR and ESD being equally effective. The presence of incomplete resection was not associated with a worse prognosis, which remains excellent in this highly recurrent disease. Younger age and a size ≥10 mm were associated with an increased risk of LNM. CLINICAL TRIAL REGISTRATION: Project code UID 2854.

Circulating tumor DNA in patients with locally advanced rectal cancer treated with multimodal treatment.

Background: The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy. Objectives: We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes. Design: Between November 2014 and November 2019, we conducted a monocentric prospective observational study enrolling consecutive patients with LARC managed with neoadjuvant standard CRT (capecitabine and concomitant pelvic long-course radiotherapy), followed by consolidation capecitabine in selected cases and surgery. Methods: Blood samples for ctDNA were obtained at pre-planned timepoints. We evaluated the correlation of baseline variant allele frequency (VAF) with pathologic complete response (pCR) down-staging, node regression (pN0), event-free survival (EFS), and overall survival (OS). Results: Among 112 screened patients, 61 were enrolled. In all, 38 (62%) had a positive ctDNA at baseline with VAF > 0 and 23 had negative ctDNA (VAF = 0). Among patients with negative ctDNA, 30% had a complete response, while only 13% of positive ctDNA patients had pCR [odds ratio (OR) 0.35 (95% confidence interval (CI): 0.10-1.26), p = 0.11]. Similarly, 96% and 74% of pN0 were observed among negative and positive ctDNA patients, respectively [OR 0.13 (95% CI: 0.02-1.07), p = 0.058]. The presence of a baseline VAF > 0 was associated with a trend toward a lower EFS compared with VAF = 0 patients [hazard ratio (HR) = 2.30, 95% CI: 0.63-8.36, p = 0.21]. Within the limitations of small sample size, no difference in OS was observed according to the baseline ctDNA status (HR = 1.18, 95% CI: 0.35-4.06, p = 0.79). Conclusion: Within the limitations of a reduced number of patients, patients with baseline negative ctDNA seem to show a higher probability of pN0 status and a trend toward improved EFS. Prospective translational studies are required to define the role of ctDNA analysis in the multimodal treatment of LARC.

Radio-Guided Surgery with a New-Generation ß-Probe for Radiolabeled Somatostatin Analog, in Patients with Small Intestinal Neuroendocrine Tumors.

BACKGROUND: Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to detect radiation emitted by radio-labeled somatostatin analogs. OBJECTIVE: We aimed to assess the sensitivity (SE) and SP of the intraoperative RGS approach using a ß-probe with a per-lesion analysis, while assessing safety and feasibility as secondary objectives. METHODS: This prospective, single-arm, single-center, phase II trial (NCT05448157) enrolled 20 patients diagnosed with small intestine NETs (SI-NETs) with positive lesions detected at 68Ga-DOTA-TOC positron emission tomography/computed tomography (PET/CT). Patients received an intravenous injection of 1.1 MBq/Kg of 68Ga-DOTA-TOC 10 min prior to surgery. In vivo measurements were conducted using a ß-probe. Receiver operating characteristic (ROC) analysis was performed, with the tumor-to-background ratio (TBR) as the independent variable and pathology result (cancer vs. non-cancer) as the dependent variable. The area under the curve (AUC), optimal TBR, and absorbed dose for the surgery staff were reported. RESULTS: The intraoperative RGS approach was feasible in all cases without adverse effects. Of 134 specimens, the AUC was 0.928, with a TBR cut-off of 1.35 yielding 89.3% SE and 86.4% SP. The median absorbed dose for the surgery staff was 30 µSv (range 12-41 µSv). CONCLUSION: This study reports optimal accuracy in detecting lesions of SI-NETs using the intraoperative RGS approach with a novel ß-probe. The method was found to be safe, feasible, and easily reproducible in daily clinical practice, with minimal radiation exposure for the staff. RGS might potentially improve radical resection rates in SI-NETs. CLINICAL TRIALS REGISTRATION: 68Ga-DOTATOC Radio-Guided Surgery with ß-Probe in GEP-NET (RGS GEP-NET) [NCT0544815; https://classic. CLINICALTRIALS: gov/ct2/show/NCT05448157 ].

Diagnosis and staging of small intestinal neuroendocrine tumors with CT enterography and PET with Gallium-68: preoperative risk stratification protocol.

PURPOSE: Pre-operative diagnosis and staging of small intestine neuroendocrine tumors (SI-NETs) remain sub-optimal, with open palpation during surgery still considered the gold standard. This limits a standardized implementation of minimally invasive surgery (MIS). The aim of this single-center retrospective study was to assess a tailored diagnostic work-up to identify candidates at low risk of undetected disease who may benefit from MIS. METHODS: Patients diagnosed with SI-NETs between 2013 and 2022 who underwent contrast-enhanced computed tomography enterography (CTE) and Ga68-DOTATOC-positron emission tomography-CT (68 Ga DOTATATE PET/CT) preoperatively and subsequently underwent open surgical resection were included. Imaging studies were reassessed by two radiologists. Combined use of CTE and 68 Ga DOTATATE PET/CT in determining primary lesion disease burden (number of lesions) and LN disease stage (distal and proximal relative to superior mesenteric vessels) was assessed, using surgical reports and pathology as gold standard. RESULTS: Overall, 56 patients were included. Sensitivity of CTE and 68 Ga DOTATATE PET/CT for at least one primary SI-NET was 100% and 94%, respectively. In the presence of concordance between studies, combined use of CTE and 68 Ga DOTATATE PET/CT for detection of single primary tumors improved specificity to 89% (n = 25/28) with a positive predictive value of 87.5% (n = 21/24). Distal LN disease was identified in 89.2% of cases (n = 33/37). The association of single lesion and distal LN disease was found pre-operatively in 32% of patients (n = 18). CONCLUSION: Combined use of CTE and 68 Ga DOTATATE PET/CT enables identifying low-risk surgical candidates (single SI-NET lesions with distal LN disease).

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database.

Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083).

Textbook outcome as indicator of surgical quality in a single Western center: results from 300 consecutive gastrectomies.

Textbook outcome (TO) has been proposed as a tool to evaluate surgical quality. Textbook oncological outcome (TOO) adds chemotherapeutic compliance to TO. This study was conducted to analyze the TO and TOO of patients with gastric adenocarcinoma who underwent surgery at our center. Data from a prospective database of patients operated on for gastric adenocarcinoma between September 2018 and September 2022 were analyzed. Postoperative management followed Enhanced Recovery After Surgery guidelines. The Dutch Upper Gastrointestinal Cancer Audit group defined TO as a multidimensional measure (10 items). TOO also considers guideline-accordant chemotherapeutic compliance. Three hundred patients underwent surgery during the study period (167 men, 133 women). One hundred seventy-six (58.7%) reached TO. Achieving TO was influenced by patients' comorbidities, calculated via the Charlson Comorbidity Score (3 vs. 4; p = 0.002) and surgery type (subtotal gastrectomy; p < 0.001), but not by the American Society of Anesthesiologists (ASA) score (p = 0.057) or surgical approach (laparoscopic vs. open; p = 0.208). The analysis of TOO included 213 patients. Of these, 71 (33%) underwent complete adequate systemic treatment. Compared with the non-TOO group, patients who achieved TOO had a lower median age (64 vs. 73 years; p < 0.001) and lower ASA score (p < 0.001) and more frequently underwent preoperative chemotherapy (p < 0.001). Our results represent the experience of a single team at a high-volume Western institute. Patients' comorbidities and surgery type influenced whether TO was achieved. Conversely, younger age, lower ASA score and preoperative chemotherapy were associated with TOO.

Tumour-specific mesorectal excision for rectal cancer: Systematic review and meta-analysis of oncological and functional outcomes.

BACKGROUND: Tumour-specific mesorectal excision (TSME) practice for rectal cancer only relies on small retrospective studies. This study aimed to perform a systematic review and meta-analysis to assess the oncological and functional outcomes of TSME practice. METHODS: A systematic review protocol was drawn to include all the studies that compared partial versus total mesorectal excision (PME vs TME) practised for rectal adenocarcinoma up to 16 cm from the anal verge. A systematic literature search was conducted on EMBASE-Medline, Pubmed and Cochrane Library. Reports were screened for the study's outcomes: oncological radicality, postoperative anastomotic leak risk and functional outcomes. Included studies were appraised for risk-of-bias and meta-analysed. Evidence was rated with the GRADE approach. RESULTS: Twenty-seven studies were included, consisting of 12325 patients (PME n = 4460, 36.2%; TME n = 7865, 63.8%). PME was performed for tumours higher than 10 cm from the anal verge in 54.5% of patients. There was no difference between PME and TME in circumferential resection margin positivity (OR 1.31, 95%CI 0.43-3.95, p = 0.64; I2 = 38%), and local recurrence risk (HR 1.05, 95%CI 0.52-2.10, p = 0.90; I2 = 40%). The postoperative leak risk (OR 0.42, 95%CI 0.27-0.67, p < 0.001; I2 = 60%) and the major low anterior resection syndrome risk (OR 0.34, 95%CI 0.28-0.40, p < 0.001; I2 = 0%) were lower after PME surgery. No difference was found in urinary incontinence (OR 0.68, 95%CI 0.13-3.67, p = 0.66) and urinary retention after early catheter removal (OR 2.00, 95%CI 0.24-16.51, p = 0.52). CONCLUSIONS: Evidence from this meta-analysis shows that TSME for rectal cancer has good oncological results and leads to the best-fitted functional results possible for the patient's condition.

Digestive MiNENs: Could histological classification and molecular characterization drive clinical outcome and therapeutic approach?

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are epithelial neoplasms in which neuroendocrine and non-neuroendocrine discrete components are combined, each of which constitutes ≥ 30% of the neoplasm. The finding of an additional neuroendocrine component seems to characterize the tumor's biological behavior. Few studies have proved MiNENs histogenetic and molecular characterization, and the development of molecular markers for more accurate classification of MiNENs represents a clinical need. However, a common origin of the neuroendocrine and non-neuroendocrine components from a pluripotent cancer stem cell could be suggested. The optimal clinical management of MiNENS is largely unknown. Whenever feasible, curative-intent resection should be performed for localized disease; in advanced disease, the treatment should be targeted to the component responsible for the metastatic spreading. This paper provides a revision of the current knowledge on MiNENs, focusing on available evidence about their molecular characterization to suggest a prognostic stratification of these rare forms.

First Live-Experience Session with PET/CT Specimen Imager: A Pilot Analysis in Prostate Cancer and Neuroendocrine Tumor.

OBJECTIVE: to evaluate the feasibility of the intra-operative application of a specimen PET/CT imager in a clinical setting. MATERIALS AND METHODS: this is a pilot analysis performed in three patients who received an intra-operative administration of 68Ga-PSMA-11 (n = 2) and 68Ga-DOTA-TOC (n = 1), respectively. Patients were administrated with PET radiopharmaceuticals to perform radio-guided surgery with a beta-probe detector during radical prostatectomy for prostate cancer (PCa) and salvage lymphadenectomy for recurrent neuroendocrine tumor (NET) of the ileum, respectively. All procedures have been performed within two ongoing clinical trials in our Institute (NCT05596851 and NCT05448157). Pathologic assessment with immunohistochemistry (PSMA-staining and SSA immunoreactivity) was considered as standard of truth. Specimen images were compared with baseline PET/CT images and histopathological analysis. RESULTS: Patients received 1 MBq/Kg of 68Ga-PSMA-11 (PCa) or 1.2 MBq/Kg of 68Ga-DOTA-TOC (NET) prior to surgery. Specimens were collected, positioned in the dedicated specimen container, and scanned to obtain high-resolution PET/CT images. In all cases, a perfect match was observed between the findings detected by the specimen imager and histopathology. Overall, the PET spatial resolution was sensibly higher for the specimen images compared to the baseline whole-body PET/CT images. Furthermore, the use of the PET/CT specimen imager did not significantly interfere with any procedures, and the overall length of the surgery was not affected using the PET/CT specimen imager. Finally, the radiation exposure of the operating theater staff was lower than 40 µSv per procedure (range 26-40 µSv). CONCLUSIONS: the image acquisition of specimens obtained by patients who received intra-surgery injections of 68Ga-PSMA-11 and 68Ga-DOTA-TOC was feasible and reliable also in a live-experience session and has been easily adapted to surgery daily practice. The high sensitivity, together with the evaluation of intra-lesion tumor heterogeneity, were the most relevant results since the data derived from specimen PET/CT imaging matched perfectly with the histopathological analysis.

Nodal Merkel Cell Carcinoma with Unknown Primary Site and No Distant Metastasis: A Single-Center Series.

Merkel cell carcinoma (MCC) is a very rare and aggressive neuroendocrine carcinoma originating from Merkel cells, typically with a skin nodule; however, it exceptionally presents with only a basin lymph node localization, with neither a cutaneous primary site nor distant metastases. From 1996 to 2020, among patients with histologically confirmed MCC managed at a neuroendocrine neoplasm-referral center, we selected those with an exclusive nodal basin, no distant metastasis, and an unknown primary site defined by cross-sectional and physical examination. A total of 55 out of 310 patients fulfilled the selection criteria. The median age was 64 years and the majority were males. Inguinal lymph-nodes were the most common anatomic site. With a median follow-up of 4.3 years, the 5-year relapse-free survival (RFS) rate was 56.6 (95% CI 42.0-68.8%) and the 5-year cancer specific survival (CSS) rate was 68.5 (95% CI 52.8-79.9%) for the whole population. The 36 patients (65.5%) undergoing lymphadenectomy (LND) + radiotherapy (RT) ± chemotherapy had a 5-year RFS rate of 87.2% (95% CI 65.5-95.7%) and a 5-year CSS rate of 90.5% (95% CI 67.0-97.5), which were better than those receiving LND alone. In a multivariable analysis, the survival benefit for LND + RT remained significant. Results from one of the largest single-center series of nMCC-UP suggest that a curative approach including RT can be effective, similar to what is observed for stage IIIB MCC. Multicentric studies with homogenous populations should be carried out in this controversial clinical entity, to minimize the risk of biases and provide robust data.

Predicting resectability of primary tumor and mesenteric lymph-node masses in patients with small-intestine neuroendocrine tumors.

BACKGROUND: Vascular infiltration may jeopardize resection of the primary tumor and mesenteric metastatic masses in small-intestine neuroendocrine tumors (SI-NETs). However, other factors may play a role in predicting resectability. METHODS: After computed tomography (CT) scan, three radiological parameters were considered: (1) degree of superior mesenteric artery involvement (SMA) according to a previous classification (2) degree of superior mesenteric venous involvement (SMV) as either absent, peripheral or proximal (3) presence or not of mesenteric fibrosis retraction (MF). Pre-surgical parameters were matched to surgical outcome. RESULTS: Forty-nine consecutive patients were submitted to laparotomy. Of them, 37 had complete primary tumor and mesenteric masses resection. SMA (p = 0.001), SMV (p = 0.008), metastasis site (p = 0.001) and MF (p < 0.001) were all significantly associated with the likelihood to receive resection at univariate analysis. All the five patients with infiltration of SMV proximal to middle colic vein were unresectable. At multivariable analysis excluding SMA stage, the absence of MF (HR 13.1, I.C. 1.44-119; p = 0.002) was the only factor associated with the likelihood to receive primary tumor and mesentery radical surgery. CONCLUSIONS: SMA stage 3-up and/or signs of MF, as well as infiltration of SMV proximal to middle colic vein at CT scan are predictive of operative failure in patients with SI-NETs. The assessment of such factors should be always considered in the decision-making process of such patients especially in those with asymptomatic disease with synchronous unresectable liver metastases.

Prognostic features of gastro-entero-pancreatic neuroendocrine neoplasms in primary and metastatic sites: Grade, mesenteric tumour deposits and emerging novelties.

Updates in classification of gastro-entero-pancreatic neuroendocrine neoplasms better reflect the biological characteristics of these tumours. In the present study, we analysed the characteristics of neuroendocrine tumours that could aid in a more precise stratification of risk groups. In addition, we have highlighted the importance of grade (re)assessment based on investigation of secondary tumour lesions. Two hundred and sixty-four cases of neuroendocrine tumours of gastro-entero-pancreatic origin from three centres were included in the study. Tumour morphology, mitotic count and Ki67 labelling index were evaluated in specimens of primary tumours, lymph node metastases and distant metastases. These variables were correlated with overall survival (OS) and relapse-free survival (RFS). Tumour stage, number of affected lymph nodes, presence of tumour deposits and synchronous/metachronous metastases were tested as possible prognostic features. Mitotic count, Ki-67 labelling index, primary tumour site, tumour stage, presence of tumour deposits and two or more affected lymph nodes were significant predictors of OS and RFS. At the same time, mitotic count and Ki-67 labelling index can be addressed as continuous variables determining prognosis. We observed a very high correlation between the measures of proliferative activity in primary and secondary tumour foci. The presence of isolated tumour deposits was identified as an important determinant of both RFS and OS for pancreatic (hazard ratio [HR] = 7.61, 95% confidence interval [CI] = 3.96-14.6, P < 0.0001 for RFS; HR = 3.28, 95% CI = 1.56-6.87, P = 0.0017 for OS) and ileal/jejunal neuroendocrine tumours (HR = 1.98, 95% CI = 1.25-3.13, P = 0.0036 for RFS and HR 2.59, 95% CI = 1.27-5.26, P = 0.009 for OS). The present study identifies the presence of mesenterial tumour deposits as an important prognostic factor for gastro-entero-pancreatic neuroendocrine tumours, provides evidence that proliferative parameters need to be treated as continuous variables and further supports the importance of grade determination in all available tumour foci.

First Ex Vivo Results of ß--Radioguided Surgery in Small Intestine Neuroendocrine Tumors with 90Y-DOTATOC.

Background: In neuroendocrine tumor (NET), complete surgery could better the prognosis. Radioguided surgery (RGS) with ß--radioisotopes is a novel approach focused on developing a new probe that, detecting electrons and operating with low background, provides a clearer delineation of the lesions with low radiation exposition for surgeons. As a first step to validate this procedure, ex vivo specimens of tumors expressing somatostatin receptors, as small intestine neuroendocrine tumor (SI-NET), were tested. Materials and Methods: SI-NET presents a high uptake of a beta-emitting radiotracer, 90Y-DOTATOC. Five SI-NET patients were enrolled after performing a 68Ga-DOTATOC positron emission tomography/computed tomography (CT) and a CT enterography; 24 h before surgery, they received 5 mCi of 90Y-DOTATOC. Results: Surgery was performed as routine. Tumors and surrounding tissue were sectioned in different samples and examined ex vivo with the beta-detecting probe. All the tumor samples showed high counts of radioactivity that was up to a factor of 18 times higher than the corresponding cutoff value, with a sensitivity of 96% and a specificity of 100%. Conclusions: These first ex vivo RGS tests showed that this probe can discriminate very effectively between tumor and healthy tissues by the administration of low activities of 90Y-DOTATOC, allowing more precise surgery.

Fluorescence-guided D3 lymphadenectomy in robotic right colectomy with complete mesocolic excision.

BACKGROUND: In robotic right hemicolectomy for cancer, appropriate lymphadenectomy is essential. Visualization of draining lymph nodes and blood flow with near-infrared (NIR) fluorescence DaVinci® imaging system is a recent development. We present the technique of robotic right colectomy with complete mesocolic excision (CME) and D3 lymphadenectomy using Indocyanine Green (ICG) endoscopic submucosal injection to intraoperatively identify tumour lymphatic basin. METHODS: The day before surgery, in patients scheduled for robotic right colectomy an endoscopic submucosal injection of 3 mg of ICG solution around the tumor is realized. Robotic right hemicolectomy is performed with suprapubic trocars layout and "bottom to up dissection", realizing a CME with central vessel ligation and D3 lymphadenectomy. Site of primary tumor and lymphatic basin are visible with the FireflyTM camera modality. RESULTS: From July 2016 to July 2020, 85 patients received a robotic right colectomy with CME and D3 lymphadenectomy. In 50 patients, ICG submucosal injection was performed: visualisation of the site of primary tumour and of LN in the D3 area was possible in all cases; in 17/50 patients (34%), LN out from anatomical lymphatic basin were identified. No side effects were observed. CONCLUSIONS: In this series, submucosal ICG injection showed to be feasible and safe. The accuracy in identification of D3 lymphatic basin was high, thus permitting an image-guided radical lymphadenectomy. Fluorescent technology represents an interesting innovation to ameliorate surgery of colon cancer.

Cisplatin plus capecitabine concomitant with intensity-modulated radiation therapy in non-metastatic anal squamous cell carcinoma: the experience of a single research cancer center.

BACKGROUND AND AIMS: The standard treatment of non-metastatic anal squamous cell carcinoma (ASCC) consists of chemotherapy with mitomycin (MMC) plus 5-fluorouracil (5FU) for 1-2 cycles concomitant with pelvic radiotherapy. Subsequent studies introduced cisplatin (CDDP) combined with 5FU, with unclear results. We evaluated the doublet capecitabine (C) and CDDP as a possible alternative to MMC-5FU regimen concomitant with intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: We carried out a retrospective study on 67 patients affected by stage I-III ASCC, treated with CDDP (60-70 mg/m2 every 21 days for two courses) plus C (825 mg/m2 twice daily for 5 days/week) chemotherapy concomitant with IMRT for curative intent. RESULTS: At a median follow up of 41 months, the clinical complete response calculated at the 6-month time-point (6-moCR), the 6-month objective response rate and the 6-month disease control rate were 93%, 94%, and 99%, respectively.Disease-free survival rates at 1, 2, and 3 years were 89%, 87%, and 85%, while the overall survival rates at 1 and 2 years were 100% and 95%. The colostomy-free survival rates were 90% at 1 year and 88% at 2 years. Grade 3-4 acute adverse events were reported in 61% of patients; predominantly skin toxicity (46%) and limited hematological toxicity (12%). CONCLUSION: In this retrospective study, chemotherapy with C plus CDDP concomitant with IMRT proved safe and effective, and may represent a possible alternative option to standard MMC-containing regimen for curative intent.

Histopathological and Immunophenotypic Changes of Pancreatic Neuroendocrine Tumors after Neoadjuvant Peptide Receptor Radionuclide Therapy (PRRT).

Peptide Receptor Radionuclide Therapy (PRRT) is an emerging therapeutic option for pancreatic neuroendocrine tumors (PanNETs). A possible role for PRRT as a neoadjuvant agent is still largely undetermined, explored only in case reports or small case series. Likewise, the histopathological and immunophenotypic changes induced by PRRT are poorly characterized. In the present study, 24 patients who underwent neoadjuvant PRRT on the basis of their disease's characteristics were retrospectively matched with 24 patients who underwent upfront surgery. A comprehensive morphological and immunohistochemical evaluation was conducted to identify the differences in the two groups. The most significant findings were that the total percentage of stroma increased significantly in patients who underwent PRRT (p < 0.0001) and the characteristics of the stroma were different in the two groups. The somatostatin receptors type 2A (SSTR2A) were retained in most patients (87%) after PRRT. The density of CD163+ M2-polarized macrophages was greater in the PRRT group (p = 0.022), and M2-polarized macrophages tended to assume an epithelioid morphology (p = 0.043). In the neoadjuvant PRRT group, none of the histological parameters considered were associated with progression-free survival (PFS). Neoadjuvant PRRT in PanNETs is associated with reduced tumor diameter, an increased percentage of stroma, preserved SSTR2A expression in most of the cases, and an increased CD163+ M2-polarized macrophages density.