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Abstract Purpose To determine if improvement in imaging reduces the non-resection rate (NRR) among patients with pancreatic ductal adenocarcinoma (PDAC). Methods From 2000 to 2019, 751 consecutive patients with PDAC were considered eligible for a intention-to-treat pancreatectomy and entered the operating room. In April 2011, our institution acquired a dual energy spectral computed tomography (CT) scanner and liver diffusion weighted magnetic resonance imaging (DW-MRI) was included in the imaging workup. We consequently considered 2 periods of inclusion: period #1 (February 2000–March 2011) and period #2 (April 2011–August 2019). Results All patients underwent a preoperative CT scan with a median delay to surgery of 18 days. Liver DW-MRI was performed among 407 patients (54%). Median delay between CT and surgery decreased (21 days to 16 days, P

Patient-derived tumor organoids have emerged as a crucial tool for assessing the efficacy of chemotherapy and conducting preclinical drug screenings. However, the conventional histological investigation of these organoids necessitates their devitalization through fixation and slicing, limiting their utility to a single-time analysis. Here, we use stimulated Raman histology (SRH) to demonstrate non-destructive, label-free virtual staining of 3D organoids, while preserving their viability and growth. This novel approach provides contrast similar to conventional staining methods, allowing for the continuous monitoring of organoids over time. Our results demonstrate that SRH transforms organoids from one-time use products into repeatable models, facilitating the efficient selection of effective drug combinations. This advancement holds promise for personalized cancer treatment, allowing for the dynamic assessment and optimization of chemotherapy treatments in patient-specific contexts., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Background: Current guidelines consider observation a reasonable strategy for G1 or G2 nonfunctional pancreatic neuroendocrine tumors (nf pNETs) ≤2 cm. We aimed to characterize their natural behavior and confront the data with the outcomes of patients undergoing upfront surgery., Methods: Data from patients with histologically confirmed nf pNETs ≤2 cm, managed at a single tertiary referral center between 2002 and 2020, were retrospectively reviewed., Results: Thirty-nine patients (mean age 62.1 years, 56% male) with 43 lesions (mean size 12.7±3.9 mm; 32 grade 1 [G1] and 7 grade 2 lesions [G2]) were managed by careful surveillance. Progression was observed in 15 lesions (35%; mean follow up 47 months). Six patients (18%) underwent secondary surgery because of an increase in tumor size or dilation of the main pancreatic duct; 3 of them had lymph node metastasis in the resected specimen. Surgery was followed by pancreatic fistula in 2/6 patients, 1 of whom died. Fourteen patients (mean age 59 years, 64.3% female, mean size of lesions 11.4±3.1 mm) underwent pancreatic surgery immediately after diagnosis. The surgery-associated complication rate was 57.1% (8/14). Of the 14 patients, 13 remained recurrence free (mean follow up 67 months). Recurrent metastatic disease was observed 3 years after pancreaticoduodenectomy (R0, 15 mm G2 lesion, 0 N+/8 N) in 1 patient., Conclusions: The behavior of small nf pNETs is difficult to predict, as there is evidence for malignant behavior in a subgroup of patients, even after surgical treatment. Optimal management remains challenging, as pancreatic surgery is associated with significant morbidity., Competing Interests: Conflict of Interest: Mariola Marx: Fellowship in advanced endoscopy supported by Boston Scientific. The other authors have no conflicts of interest to declare., (Copyright: © Hellenic Society of Gastroenterology.)

No codified/systematic surveillance program exists for borderline/locally advanced pancreatic ductal carcinoma treated with neoadjuvant FOLFIRINOX and a secondary resection. This study aimed to determine the trend of recurrence in patients who were managed using such a treatment strategy. From 2010, 101 patients received FOLFIRINOX and underwent a pancreatectomy, in a minimum follow-up of 5 years. Seventy-one patients (70%, R group) were diagnosed with recurrence after a median follow-up of 11 months postsurgery. In the multivariable analysis, patients in the R-group had a higher rate of weight loss ( p = 0.018), higher carbohydrate antigen (CA 19-9) serum levels at diagnosis ( p = 0.012), T3/T4 stage ( p = 0.017), and positive lymph nodes ( p < 0.01) compared to patients who did not experience recurrence. The risk of recurrence in patients with T1/T2 N0 R0 was the lowest (19%), and all recurrences occurred during the first two postoperative years. The peak risk of recurrence for the entire population was observed during the first two postoperative years. The probability of survival decreased until the second year and rebounded to 100% permanently, after the ninth postoperative year. Close monitoring is needed at reduced intervals during the first 2 years following a pancreatectomy and should be extended to later than 5 years for those with unfavorable pathological results.

Background and Aims: Colorectal lesions measuring greater than 20 mm are unsuitable for en bloc endoscopic mucosal resection (EMR): piecemeal EMR (PM-EMR) and endoscopic submucosal dissection (ESD) are needed. The European Society of Gastrointestinal Endoscopy (ESGE) recommends ESD only for microinfiltrative lesions, although Japanese teams perform en bloc ESD for all lesions. We report the outcomes obtained in our endoscopy unit for these lesions and assess the hybrid "knife-assisted piecemeal EMR" (KAPM-EMR) technique. The main aim was to assess the short-term outcomes (C1). The secondary objectives were to evaluate the long-term results (C2), adverse event rate and management of recurrence., Methods: We retrospectively analyzed data from patients treated by PM-EMR, KAPM-EMR and ESD for a colorectal lesion measuring greater than 20 millimeters using prospective inclusion over four years., Results: Data from 167 patients (median age: 70) with a median follow-up of 15.1 months were analyzed after excluding 95 patients. A total of 131 lesions were removed by PM-EMR, 24 by KAPM-EMR and 12 by ESD; 146/167 (87.4%) patients were considered in remission at C1. Recurrence was treated by endoscopy in 20/21 patients (95%); 86/89 (96.6%) were in remission at C2. A total of 16/167 patients developed adverse events, all of whom except one were endoscopically managed. KAPM-EMR was associated with a higher perforation risk (p=0.037). No differences in postoperative bleeding were found among the three groups (p=0.576)., Conclusions: Piecemeal resection remains an effective and safe technique for large colorectal adenomas. KAPM-EMR may be useful but should be applied with caution due to the risk of perforation.

Purpose: To analyze clinical outcomes of high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) for the treatment of anal canal cancers (ACC)., Methods and Materials: A total of 78 patients with ACC were treated at our institution by ISBT. Local Control (LC), disease-free survival (DFS), overall survival (OS), colostomy-free survival (CFS) and toxicity rates were analyzed., Results: With a median followup (FU) of 59.8 months (95% CI [55.8-64.2]), six (7.7%) local recurrences with 2 patients (2.6%) having persistent disease at 3 months were observed. The 5-year rate of LC for the entire population was 92% [83-96%]. The 5-year DFS rate was 86% [76-93%]. The 5-year OS was 96% [88-99%]. In the univariate analysis, chemotherapy was significantly associated with morbidity grade ≥2. Late digestive toxicity grade ≥3 was reported in 8.9% patients, 1 patient underwent colostomy due to toxicity. The 5-year CFS rate was 88% [79-94%]., Conclusions: HDR interstitial brachytherapy boost provide excellent rates of tumor control and colostomy-free survival with a favorable profile of GI toxicity. Continence in anal cancer survivors is a challenge and the boost technique must be discussed in a multidisciplinary approach as part of de-escalation treatments., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Extralevator abdominoperineal excision (APE) for rectal carcinoma has been described in order to improve pathological and oncological results compared to standard APE. To obtain the same oncological advantages as extralevator APE, we have previously described a new procedure starting by a perineal approach: the supine bottom-up APE. Our objective is to compare oncological and surgical outcomes between the supine bottom-up APE and the standard APE., Methods: All patients with low rectal adenocarcinoma requiring APE were retrospectively included and divided into 2 groups: supine bottom-up APE (Group A) and standard APE (Group B)., Results: From 2008 to 2016, 61 patients were divided into Groups A (n = 30) and B (n = 31). Postoperative outcomes and median length of stay were similar between groups. Patients from Group A had a significantly longer distal margin (30 [8-120] vs. 20 [1.5-60] mm, p = 0.04) and higher number of harvested lymph nodes (14.5 [0-33] vs. 11 [5-25], p = 0.03) than those from Group B. Circumferential resection margin involvement was similar between groups (28 vs. 22%, p = 0.6), whereas tumors from Group A were significantly larger and more frequently classified as T4 than those from Group B. Operative time was significantly shorter in Group A (437.5 [285-655] minutes) than in Group B (537.5 [361-721] minutes, p = 0.0009). At the end of follow-up, local recurrence occurred in 7 and 16% of patients from Groups A and B (p = 0.68). Three-year overall and disease-free survival rates were similar between groups (87 vs. 90%, p = 0.62 and 61 vs. 63%, p = 0.88, respectively)., Conclusion: Our findings suggest that supine bottom-up APE doesn't impair surgical outcomes, pathological results, overall and disease-free survivals in comparison with standard APE. This new procedure may be thus safely performed and decrease the operative time. Further randomized multicentric studies are required to confirm these results., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

GLI1 encodes a transcription factor that targets cell cycle regulators affecting stem cell proliferation. GLI1 gene fusions were initially described in pericytomas with a t[7;12] translocation and more recently in gastric plexiform fibromyxomas and gastroblastomas. This study describes the clinicopathologic, immunohistochemical, and molecular features of three intestinal-based neoplasms harboring GLI1 gene fusions. We studied three unique mesenchymal small bowel tumors. Paraffin embedded tumor tissues from these cases and 62 additional tumor samples that included a plexiform fibromyxoma were sequenced using a targeted RNAseq method to detect fusion events. The study patients included two women and one man who were 52, 80, and 22 years of age at the time of diagnosis. The tumors involved the submucosa and muscularis propria of the duodenum, jejunum, and ileum. All 3 tumors contained a proliferation of monotonous oval or spindle cells with scattered, somewhat dilated vessels. Two cases showed epithelioid structures such as glands, tubules, or nests. Immunohistochemical analysis revealed cytokeratin expression in the epithelioid components of both tumors displaying these features, and variable numbers of mesenchymal cells. Diffuse CD56 positivity was seen in the mesenchymal component of 2 tumors and desmin and smooth muscle actin staining in the other tumor. Immunostains for S-100 protein, DOG-1, and CD117 were negative in all cases. GLI1 fusions with different partner genes were detected in all tumors, and in the plexiform fibromyxoma, used as a control. Validation by fluorescence in situ hybridization was performed. None of the tumors have recurred or metastasize after surgery. We describe novel GLI1 fusions in 3 mesenchymal neoplasms of the small intestine, including 2 with biphenotypic features. Thus far, all cases have pursued indolent clinical courses. We propose the term " GLI1 -rearranged enteric tumor" to encompass this group of unique neoplasms of the small intestine that harbor GLI1 gene fusions and expand the spectrum of gastrointestinal neoplasms with these alterations., Competing Interests: Conflicts of Interest and Source of Funding: Project support for this research was provided in part by the Center for Translational Pathology [Ruben Diaz, Mai Ho, Leticia Dizon, Bing He] at the Department of Pathology and Laboratory Medicine, Weill Cornell Medicine. This work was supported by the Englander Institute for Precision Medicine [EIPM] of Weill Cornell Medicine. The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Neoadjuvant chemoradiotherapy followed by radical surgery is the standard curative treatment for mid- to low-rectal cancer. However, the combination of these treatments may affect patients' GI and genitourinary functions and their quality of life. In the cases of good clinical response to neoadjuvant treatment, local excision is a rectal sparing strategy that would limit these side effects., Objective: The aim of this study is to compare the effects of local excision or conventional laparoscopic total mesorectal excision after chemoradiotherapy in patients with rectal cancer., Design: The design is a retrospective study., Setting: The setting used is a single tertiary center., Patients: Patients with mid- to low-rectal cancer treated with chemoradiotherapy and accessible via conservative surgery at our hospital between January 2010 and December 2018 were included. Patients undergoing local excision were matched 1 to 1 with the patients undergoing total mesorectal excision by age, sex, body mass index, tumor height, and year of surgery., Main Outcome Measures: Quality of life and digestive and genitourinary functions were measured using validated questionnaires. The socioeconomic impact was also assessed., Results: Forty-four patients undergoing local excision agreed to participate and were matched with 44 patients undergoing total mesorectal excision. Patients who underwent local excision reported a more favorable global health status ( p < 0.01), emotional function ( p = 0.035), social function ( p = 0.04), and body image ( p = 0.04). The low anterior resection syndrome score (rate of major syndrome, 23.8% vs 54.5%; p < 0.01) and the specific fecal incontinence subscale score ( p < 0.01) were more favorable in the local excision group. Sexual and urinary outcomes were comparable between the 2 groups. Local excision had a lower impact on the professional status (35.7% vs 76.5%; p = 0.03)., Limitations: The study limitations include its retrospective design and small sample size., Conclusions: When indicated, local excision improves the bowel function and quality of life of patients undergoing surgery for rectal cancer after chemoradiotherapy compared with total mesorectal excision. See Video Abstract at http://links.lww.com/DCR/B997 ., Comparacin De Casos Emparejados De Los Resultados Funcionales Y De Calidad De Vida De La Escisin Local Y La Escisin Total De Mesorecto Despus De Quimiorradioterapia En Cncer De Recto: ANTECEDENTES:La quimiorradioterapia neoadyuvante seguida de cirugía radical es el tratamiento curativo estándar para el cáncer de recto medio-bajo. Sin embargo, la combinación de estos tratamientos puede afectar las funciones gastrointestinales y genitourinarias de los pacientes y su calidad de vida. En casos de buena respuesta clínica al tratamiento neoadyuvante, la escisión local es una estrategia conservadora del recto que limitaría estos efectos secundarios.OBJETIVO:Este estudio comparó los efectos de la escisión local o escisión total de mesorecto laparoscópica convencional después de quimiorradioterapia en pacientes con cáncer de recto.DISEÑO:Estudio retrospectivo.ENTORNO CLINICO:Centro terciario único.PACIENTES:Se incluyeron pacientes con cáncer de recto medio-bajo tratados con quimiorradioterapia y accesibles mediante cirugía conservadora en nuestro hospital entre enero del 2010 y diciembre del 2018. Los pacientes sometidos a escisión local se emparejaron uno a uno con los sometidos a escisión total de mesorecto por edad, sexo, índice de masa corporal, altura del tumor y año de cirugía.PRINCIPALES MEDIDAS DE RESULTADO:La calidad de vida, las funciones digestivas y genitourinarias se midieron mediante cuestionarios validados. También se evaluó el impacto socioeconómico.RESULTADOS:Cuarenta y cuatro pacientes sometidos a escisión local aceptaron participar y fueron emparejados con 44 pacientes sometidos a escisión mesorrectal total. Los pacientes que se sometieron a escisión local informaron un estado de salud global más favorable ( p <0,01), función emocional ( p = 0,035), función social ( p = 0,04) e imagen corporal ( p = 0,04). La puntuación baja del síndrome de resección anterior (tasa de síndrome mayor: 23,8 % frente a 54,5 %; p <0,01) y la puntuación de la subescala de incontinencia fecal específica ( p <0,01) fueron más favorables en el grupo de escisión local. Los resultados sexuales y urinarios fueron comparables entre los dos grupos. La escisión local tuvo un menor impacto en el estatus profesional (35,7% vs 76,5%; p = 0,03).LIMITACIONES:Diseño retrospectivo, tamaño de muestra pequeño.CONCLUSIONES:Cuando está indicada, la escisión local mejora la función intestinal y la calidad de vida de los pacientes sometidos a cirugía por cáncer de recto después de quimiorradioterapia en comparación con escisión total de mesorecto. Consulte Video Resumen en http://links.lww.com/DCR/B997 . (Traducción-Dr. Francisco M. Abarca-Rendon )., (Copyright © The ASCRS 2022.)

Background: Pancreatic cancer is an aggressive malignancy and a leading cause of cancer death worldwide; its lethality is partly linked to the difficulty of early diagnosis. Modern devices for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) were recently developed to improve targeting and sampling of small lesions, but innovative technologies for microscopic assessment are still lacking. Ex vivo fluorescence confocal laser microscopy (FCM) is a new digital tool for real-time microscopic assessment of fresh unfixed biological specimens, avoiding conventional histological slide preparation and potentially being highly appealing for EUS-FNB specimens., Methods: This study evaluated the possible role of FCM for immediate evaluation of pancreatic specimens from EUS-FNB. It involved comparison of the interobserver agreement between the new method and standard histological analysis during international multicenter sharing of digital images. Digital images from 25 cases of EUS-FNB obtained with real-time FCM technology and 25 paired digital whole-slide images from permanent conventional paraffin sections were observed by 10 pathologists from different Institutions in Europe, Japan, and the United States, in a blinded manner. The study evaluated 500 observations regarding adequacy, morphological clues, diagnostic categories, and final diagnosis., Findings: Statistical analysis showed substantial equivalence in the interobserver agreement among pathologists using the two techniques. There was also good inter-test agreement in determining sample adequacy and when assigning a diagnostic category. Among morphological features, nuclear enlargement was the most reproducible clue, with very good inter-test agreement., Interpretation: Findings in this study are from international multicenter digital sharing and are published here for the first time. Considering the advantages of FCM digital diagnostics in terms of reduced time and unaltered sample maintenance, the ex vivo confocal laser microscopy may effectively improve traditional EUS-FNB diagnostics, with significant implications for planning modern diagnostic workflow for pancreatic tumors., Funding: This study was not supported by any funding source., Competing Interests: Declaration of interests AC and CT are co-authors of a patent issued owned by 50% UCS Diagnostics srl (Italy) and 50% University Campus Bio-Medico (Rome, Italy). The other authors declare no competing interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Hepatic dysfunction (HD) is common in patients with haematological malignancies. Hepatic haemophagocytosis (HH) was detected in >50% of liver biopsies taken when HD remained unresolved after standard examination. We aimed to explore the contribution of liver biopsy in patients with both haematological malignancies and HD, describe the population of patients with HH, assess the prognostic impact of HH, and investigate haemophagocytic syndrome diagnostic score (HScore) utility in patients with HH. Between 2016 and 2019, 116 consecutive liver biopsies (76 transjugular, 40 percutaneous) were taken in 110 patients with haematological malignancy and HD (hyperbilirubinaemia, elevated transaminases, and/or cholestasis) and without a clear diagnosis. Liver biopsies were safe and diagnostically efficient. Predominant diagnoses included: HH (56%), graft-versus-host disease (55%), associated infections (24%), sinusoidal obstruction syndrome (15%), and tumoral infiltration (8%). Of patients, 35% were critically ill and 74% were allogeneic haematopoietic stem cell transplantation recipients, while 1-year overall survival (OS) was 35% with HH versus 58% without HH (p = 0.026). The 1-year OS was 24% with a HScore of ≥169 versus 50% with a HScore of <169 (p = 0.019). Liver biopsies are feasible in and contribute significantly to haematology patients with HD. HH occurred frequently and was associated with a poor prognosis. Combined with liver biopsy, the HScore may be helpful in refining haemophagocytic syndrome diagnosis., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Recently, there has been growing interest in investigating endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) for the management of small non-functional pancreatic neuroendocrine tumors (nf pNETs)., Patients and Methods: A bicentric retrospective study was performed that included patients with histologically confirmed nf pNETs who were consecutively treated by EUS-RFA between December 2015 and March 2021 at two tertiary referral centers., Results: In 27 patients (mean age 65.0 years, 52% male), EUS-RFA was successfully performed. All patients had sporadic G1 lesions (mean size 14.0 ± 4.6 mm, 7% uncinated process, 22% head, 11% body, 19% body/tail junction, and 41% tail). Overall, 9/27 lesions (33%) were cystic. The mean hospital stay was 3.2 days. Complete treatment response was confirmed in 25/27 patients (93%) on cross-sectional imaging (mean follow-up 15.7 ± 12.2 months, range 2-41 months). Two patients had two EUS-RFA sessions until complete necrosis was observed. Periprocedural acute pancreatitis occurred in 4/27 (14.8%), three of them were treated by endoscopic cystogastrostomy (11.1%). One patient underwent secondary surgery. The histopathology of the resected specimen revealed 3 mm of residual tumor tissue., Conclusion: EUS-RFA seems to be a promising treatment strategy for the management of small nf pNETs with excellent efficacy. Further evidence focusing on long-term survival, safety profile and recurrence is needed., (© 2021 Japan Gastroenterological Endoscopy Society.)

Background and study aims  The histologic diagnosis of submucosal tumors (SMTs) < 20 mm is challenging. Monitoring is the main option offered, but compliance is debatable. Endoscopic resection (ER) of malignant SMTs or those with an uncertain diagnosis is an alternative that has already been reported about and proposed in our center. The aims of this study were to confirm the safety of this resection strategy and to perform long-term follow-up of malignant SMTs after resection. Patients and methods  All patients who underwent ER for SMTs < 2 cm in a single center between 2007 and 2019 were included retrospectively. Patients were classified into two groups according to the need for postresection follow-up: benign SMTs (B-SMTs) and follow-up SMTs (FU-SMTs). Results  One hundred and one patients were included. The mean tumor size was 16.7 mm. In total, 92 of 101 SMTs had an uncertain diagnosis. Macroscopic resection was completed for 95 SMTs (93.1 %), with en bloc resection in 94 (92.1%). The morbidity rate was 3 %, with no mortality. A total of 84 of 101 SMTs (84 %) were B-SMTs and did not need monitoring, and 17 SMTs (19.7 %) were FU-SMTs (8 gastrointestinal stromal tumors, 6 neuroendocrine tumors, and 3 others). No relapse was reported in the FU-SMT group, with a median follow-up duration of 33 months [4-127] (61 months [17-127] for the gastrointestinal stroma tumor group). Conclusions  The study results suggest ER is a potentially reliable and effective strategy for upper gastrointestinal tract SMTs < 20 mm. Although the strategy needs further validation in advanced care units, it could eliminate the need for long-term monitoring, therefore targeting such follow-up efforts to patients with FU-SMTs., Competing Interests: Competing interests Marc Giovannini is a consultant for Cook medical and Pentax. Fabrice Caillol received honorary from Ambu., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: High-grade dysplasia (HGD) and intramucosal carcinoma (IMC) in Barrett's esophagus (BE) are now well-established indications for endoscopic resection (ER). Radiofrequency ablation (RFA) can be combined with ER in case of flat or long-segment BE ablation. We report here our experience of complementary RFA after widespread ER of neoplastic BE in daily practice., Method: We retrospectively reviewed data of 89 patients, treated between 2006 and 2013 by ER alone (group 1) or by ER combined with RFA (group 2)., Results: Fifty-five patients in group 1 (7F/48M, mean age 68 years) underwent widespread ER with eradication of residual non-dysplastic BE. Complete eradication of HGD/IMC and intestinal metaplasia (IM) was achieved in 32/32 (100%) and 48/55 (87.3%) patients, respectively. Thirty-four patients in group 2 (3F/31M, mean age 67 years) had a multimodal treatment strategy, with widespread ER followed by RFA. Mean Prague classification of BE in this group was significantly longer (C4.4M6.6 vs. C2.7M4.5, P<0.001). Complete eradication of HGD/IMC and non-dysplastic BE was confirmed in 26/27 (96.3%) and 20/34 (58.8%) patients, respectively. There was no significant difference between groups concerning adverse events (16.4% vs. 23.5%, P=0.58) or recurrence rate of HGD/IMC (9.1% vs. 14.7%, P=0.42). The mismatch rate between preoperative and final histological diagnosis was high in both groups, at 45.5% and 26.5%., Conclusions: A combination of ER and RFA can treat significantly longer neoplastic BE than ER alone, with the same efficiency and safety. Widespread ER, in contrast, is the only method of obtaining a reliable histological diagnosis., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Purpose: Using a standardized specimen protocol analysis, this study aimed to evaluate the resection margin status of patients who underwent resection for either distal cholangiocarcinoma (DC) or pancreatic ductal adenocarcinoma (PDAC). This allowed a precise millimetric analysis of each inked margin., Methods: From 2010 to 2018, 355 consecutively inked specimens from patients with PDAC ( n = 288) or DC ( n = 67) were prospectively assessed. We assessed relationships between the tumor and the following margins: transection of the pancreatic neck, bile duct, posterior surface, margin toward superior mesenteric artery, and the surface of superior mesenteric vein/portal vein groove. Resection margins were evaluated using a predefined cut-off value of 1 mm; however, clearances of 0 and 1.5 mm were also evaluated., Results: Patients with DC were mostly men (64% vs. 49%, p = 0.028), of older age (68 yo vs. 65, p = 0.033), required biliary stenting more frequently (93% vs. 77%, p < 0.01), and received less neoadjuvant treatment ( p < 0.001) than patients with PDAC. The venous resection rate was higher among patients with PDAC ( p = 0.028). Postoperative and 90-day mortality rates were comparable. Patients with PDAC had greater tumor size (28.6 vs. 24 mm, p = 0.01) than those with DC. The R1 resection rate was comparable between the two groups, regardless of the clearance margin. Among the three types of resection margins, a venous groove was the most frequent in both entities. In multivariate analysis, the R1 resection margin did not influence patient survival in either PDAC or DC., Conclusion: Our standardized specimen protocol analysis showed that the R1 resection rate was comparable in PDAC and DC.

Background: The benefit of precision medicine based on relatively limited gene sets and often-archived samples remains unproven. PERMED-01 (NCT02342158) was a prospective monocentric clinical trial assessing, in adults with advanced solid cancer, the feasibility and impact of extensive molecular profiling applied to newly biopsied tumor sample and based on targeted NGS (t-NGS) of the largest gene panel to date and whole-genome array-comparative genomic hybridization (aCGH) with assessment of single-gene alterations and clinically relevant genomic scores., Methods: Eligible patients with refractory cancer had one tumor lesion accessible to biopsy. Extracted tumor DNA was profiled by t-NGS and aCGH. We assessed alterations of 802 "candidate cancer" genes and global genomic scores, such as homologous recombination deficiency (HRD) score and tumor mutational burden. The primary endpoint was the number of patients with actionable genetic alterations (AGAs). Secondary endpoints herein reported included a description of patients with AGA who received a "matched therapy" and their clinical outcome, and a comparison of AGA identification with t-NGS and aCGH versus whole-exome sequencing (WES)., Results: Between November 2014 and September 2019, we enrolled 550 patients heavily pretreated. An exploitable complete molecular profile was obtained in 441/550 patients (80%). At least one AGA, defined in real time by our molecular tumor board, was found in 393/550 patients (71%, two-sided 90%CI 68-75%). Only 94/550 patients (17%, 95%CI 14-21) received an "AGA-matched therapy" on progression. The most frequent AGAs leading to "matched therapy" included PIK3CA mutations, KRAS mutations/amplifications, PTEN deletions/mutations, ERBB2 amplifications/mutations, and BRCA1/2 mutations. Such "matched therapy" improved by at least 1.3-fold the progression-free survival on matched therapy (PFS2) compared to PFS on prior therapy (PFS1) in 36% of cases, representing 6% of the enrolled patients. Within patients with AGA treated on progression, the use of "matched therapy" was the sole variable associated with an improved PFS2/PFS1 ratio. Objective responses were observed in 19% of patients treated with "matched therapy," and 6-month overall survival (OS) was 62% (95%CI 52-73). In a subset of 112 metastatic breast cancers, WES did not provide benefit in term of AGA identification when compared with t-NGS/aCGH., Conclusions: Extensive molecular profiling of a newly biopsied tumor sample identified AGA in most of cases, leading to delivery of a "matched therapy" in 17% of screened patients, of which 36% derived clinical benefit. WES did not seem to improve these results., Trial Registration: ID-RCB identifier: 2014-A00966-41; ClinicalTrials.gov identifier: NCT02342158 .

At numerous locations of the body, transition zones are localized at the crossroad between two types of epithelium and are frequently associated with neoplasia involving both type of tissues. These transition zones contain cells expressing markers of adult stem cells that can be the target of early transformation. The mere fact that transition zone cells can merge different architecture with separate functions implies for a unique plasticity that these cells must display in steady state. However, their roles during tissue regeneration in normal and injured state remain unknown. Here, by using in vivo lineage tracing, single-cell transcriptomics, computational modeling and a three-dimensional organoid culture system of transition zone cells, we identify a population of Krt17+ basal cells with multipotent properties at the squamo-columnar anorectal junction that maintain a squamous epithelium during normal homeostasis and can participate in the repair of a glandular epithelium following tissue injury.

Background/aim: FOLFOX (5-Fluorouracile and oxaliplatin) exhibits promising activity in advanced well-differentiated neuroendocrine tumors (NETs). This retrospective study aimed to analyze the outcome of metastatic enteropancreatic NETs patients treated with FOLFOX., Patients and Methods: We retrospectively identified patients treated with FOLFOX for NETs of enteropancreatic or unknown origin among those referred to our Regional Multidisciplinary Tumor Board., Results: Among 48 patients, most often pancreatic NETs (n=33, 68.8%), the median Ki67 index was 10%. The median number cycle of FOLFOX was 6 and median follow-up was 34.8 months. Disease control rate (DCR) was 83.3%. Median PFS and OS were 12.6 and 29.4 months respectively. Median chemotherapy break was 14.1 months. No significant difference was observed between PFS and the following criteria: Ki67 index, primary tumor site, alkaline phosphatase levels, primary tumor surgery and 18 F-FDG PET positivity., Conclusion: FOLFOX exhibits a high DCR and a short duration of treatment with a relative long chemotherapy break in patients with metastatic enteropancreatic NETs., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Although there is evidence of a significant rise of neuroendocrine neoplasms (NENs) incidence, current treatments are largely insufficient due to somewhat poor knowledge of these tumours. Despite showing differentiated features, NENs exhibit therapeutic resistance to most common treatments, similar to other cancers in many instances. Molecular mechanisms responsible for this resistance phenomenon are badly understood. We aimed at identifying signalling partners responsible of acquired resistance to treatments in order to develop novel therapeutic strategies. We engineered QGP-1 cells resistant to current leading treatments, the chemotherapeutic agent oxaliplatin and the mTor inhibitor everolimus. Cells were chronically exposed to the drugs and assessed for acquired resistance by viability assay. We used microarray-based kinomics to obtain highthroughput kinase activity profiles from drug sensitive vs resistant cells and identified 'hit' kinases hyperactivated in drug-resistant cells, including kinases from FGFR family, cyclin-dependant kinases and PKCs in oxaliplatin-resistant (R-Ox) QGP-1 cells. We then validated these 'hit' kinases and observed that ERK signalling is specifically enhanced in QGP-1 R-Ox cells. Finally, we assessed drug-resistant cells sensitivity to pharmacological inhibition of 'hit' kinases or their signalling partners. We found that FGFR inhibition markedly decreased ERK signalling and cell viability in QGP-1 R-Ox cells. These results suggest that the FGFR/ERK axis is hyperactivated in response to oxaliplatin-based chemotherapeutic strategy. Thus, this sensitive approach, based on the study of kinome activity, allows identifying potential candidates involved in drug resistance in NENs and may be used to broadly investigate markers of NENs therapeutic response.

Background and Aims: The use of endoscopic treatment for early colorectal cancer (ECC) is increasing. The European guidelines suggest performing piecemeal endoscopic resection (pmR) for benign lesions and en bloc resection for ECC, especially for patients with favorable lymph node involvement risk evaluations. However, en bloc resections for lesions larger than two centimeters require invasive endoscopic techniques. Our retrospective single-center study aimed to determine the clinical impact of performing pmR for ECC rather than traditional en bloc resection., Methods: A single-center study was performed between January 2012 and September 2017. All ECC patients were included. The main objective was to evaluate the number of patients who potentially underwent unnecessary surgery due to piecemeal resection. The secondary endpoints were as follows: disease-free survival (DFS), defined as the time from pmR to endoscopic failure (local recurrence not treatable by endoscopy), complication rate, number of patients who did not undergo surgery by default, and factors predictive of outcomes and complications., Results: One hundred and forty-six ECC endoscopically treated patients were included. In total, 85 patients were excluded (71 who underwent en bloc resection, 14 with pending follow-up). Data from 61 patients (33 women and 28 men) were analyzed. Two patients underwent potentially unnecessary surgery [3.28% (0.9%- 11.2%)]. The DFS rate was 87% (75%-93%) at 6 months and 85% [72%-92%] at 12 months. The median follow- up time was 16.5 months (12.4-20.9). Three patients (4.9%) had complications. One patient did not undergo surgery by default. A Paris classification of 0-2c (HR=9.3 (2.4-35.9), p<0.001) and Vienna classification of 5 [HR=16.3 (3.3-80.4), p<0.001] were factors associated with poor DFS., Conclusion: Performing pmR in place of en bloc resection for ECC had a limited impact on patients. If the pathology (especially deep margins) is analyzable, careful monitoring could be acceptable in ECC patients who undergo pmR.

Background: Pancreatic neuroendocrine tumors (PNET) are rare, with a significant malignant potential. This study aimed to determine outcomes of patients with resected PNETs according to the cystic component and confirm the accuracy of preoperative staging., Methods: From 1997 to 2016, 106 patients underwent resection of PNETs, including 73 purely solid (S-PNETs, 69%), 21 mixed (M-PNETs, 20%), and 12 purely cystic lesions (C-PNETs, 11%). To ensure consistent comparisons of overall (OS) and disease-free (DFS) survival outcomes between the 3 groups, the patients were matched according to the World Health Organization (WHO) grade and tumor height., Results: Overall, the rate of correlation between the preoperative and pathological diagnoses was low in the C-PNET group (33%, P = 0.03). None of the 24 patients (23%) with metastatic disease at the time of surgery were in the C-PNET group. Furthermore, significantly more parenchyma-sparing resections (P = 0.039) and fewer enlarged resections (P = 0.019) were achieved in the C-PNET group. C-PNET group had a significantly lower node invasion rate than the S-PNET and M-PNET groups (8% vs. 41% and 24%, P = 0.004). Although median OS was comparable in all 3 groups before (P = 0.3) and after (P = 0.18) matching, higher median DFS was observed in the C-PNET group than in the other groups after matching (P = 0.038)., Conclusion: C-PNET was associated with a better prognosis than PNET with a solid component. The results support a wait-and-see policy in cases wherein a reliable preoperative diagnosis remains challenging.

Purpose: To determine if improvement in imaging reduces the non-resection rate (NRR) among patients with pancreatic ductal adenocarcinoma (PDAC)., Methods: From 2000 to 2019, 751 consecutive patients with PDAC were considered eligible for a intention-to-treat pancreatectomy and entered the operating room. In April 2011, our institution acquired a dual energy spectral computed tomography (CT) scanner and liver diffusion weighted magnetic resonance imaging (DW-MRI) was included in the imaging workup. We consequently considered 2 periods of inclusion: period #1 (February 2000-March 2011) and period #2 (April 2011-August 2019)., Results: All patients underwent a preoperative CT scan with a median delay to surgery of 18 days. Liver DW-MRI was performed among 407 patients (54%). Median delay between CT and surgery decreased (21 days to 16 days, P < .01), and liver DW-MRI was significantly most prescribed during period #2 (14% vs 75%, P < .01). According to the intraoperative findings, the overall NRR was 24.5%, and remained stable over the two periods (25% vs 24%, respectively). While vascular invasion, liver metastasis, and carcinomatosis rates remained stable, para-aortic lymph nodes invasion rate (0.4% vs 4.6%; P < 0.001) significantly increased over the 2 periods. The mean size of the bigger extra pancreatic tumor significantly decrease (7.9 mm vs 6.4 mm (P < .01), respectively) when the resection was not done. In multivariate analysis, CA 19-9 < 500 U/mL (P < .01), and liver DW-MRI prescription (P < .01) favoured the resection., Conclusions: Due to changes in our therapeutic strategies, the NRR did not decrease during two decades despite imaging improvement.

Introduction: This study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice., Material and Methods: From 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment., Results: The 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3-16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P < 0.001). In resected patients, the ASA 3 score (P < 0.01), venous resection (P < 0.01), hemorrhage (P < 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P < 0.001)., Conclusions: Neoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Ltd.)

This case aims to report a video of a pancreaticoduodenectomy that required both portal vein and Michels type 9 hepatic artery reconstruction using the inverted splenic artery technique in a patient with a rare condition., (© 2020 Royal Australasian College of Surgeons.)

Background: A significant gap in pancreatic ductal adenocarcinoma (PDAC) patient's care is the lack of molecular parameters characterizing tumours and allowing a personalized treatment., Methods: Patient-derived xenografts (PDX) were obtained from 76 consecutive PDAC and classified according to their histology into five groups. A PDAC molecular gradient (PAMG) was constructed from PDX transcriptomes recapitulating the five histological groups along a continuous gradient. The prognostic and predictive value for PMAG was evaluated in: i/ two independent series (n = 598) of resected tumours; ii/ 60 advanced tumours obtained by diagnostic EUS-guided biopsy needle flushing and iii/ on 28 biopsies from mFOLFIRINOX treated metastatic tumours., Findings: A unique transcriptomic signature (PAGM) was generated with significant and independent prognostic value. PAMG significantly improves the characterization of PDAC heterogeneity compared to non-overlapping classifications as validated in 4 independent series of tumours (e.g. 308 consecutive resected PDAC, uHR=0.321 95% CI [0.207-0.5] and 60 locally-advanced or metastatic PDAC, uHR=0.308 95% CI [0.113-0.836]). The PAMG signature is also associated with progression under mFOLFIRINOX treatment (Pearson correlation to tumour response: -0.67, p-value < 0.001)., Interpretation: PAMG unify all PDAC pre-existing classifications inducing a shift in the actual paradigm of binary classifications towards a better characterization in a gradient., Funding: Project funding was provided by INCa (Grants number 2018-078 and 2018-079, BACAP BCB INCa&#95;6294), Canceropole PACA, DGOS (labellisation SIRIC), Amidex Foundation, Fondation de France, INSERM and Ligue Contre le Cancer., Competing Interests: Conflicts of interest The authors declare no competing financial interests, (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings., Methods: Between 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan-Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method., Results: FOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR) = 1.2, 95% confidence interval: 0.86-1.6, P = .03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0-1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR = 1.38, 95% confidence interval: 1-1.9, P < .01) and limited short-term treatment-related toxicity., Conclusions: The median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.

Background/objective: We evaluated the usefulness of the 2017 definition of borderline pancreatic ductal adenocarcinoma (BR-PDAC) in fit patients (performance status 0-1) based on anatomical (A) and biological dimensions (B)., Methods: From 2011 to 2018, 139 resected patients with BR-PDAC according to the 2017 definition were included: 18 patients underwent upfront pancreatectomy (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; BR-B group), and 121 received FOLFIRINOX (FX) induction chemotherapy and were divided into BR-A (CA 19-9 < 500 U/mL, no regional lymph node metastasis; n = 68) and BR-AB (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; n = 53) groups., Results: The 3 groups were comparable according to patient characteristics (except for back pain (P < .01) and CA 19-9 (P < .01)), intraoperative data, and postoperative courses. BR-AB patients required more venous resections (P < .01). The 3 groups were comparable on pathologic findings, except that BR-B patients had more lymph node invasions (P = .02). Median overall survival (OS) of the 121 patients was 45 months. In multivariate analysis, venous resection (P = .039) and R1 resection (P = .012) were poorly linked with OS, whereas BR-A classification (P < .01) independently favored OS. Median survival times of BR-A, BR-AB, and BR-B groups were undetermined, 27 months, and 20 months (P < .001), respectively., Conclusions: The 2017 definition was relevant for sub-classifying patients with BR-PDAC. The anatomical dimension (BR-A) was a favorable prognostic factor, whereas the biological dimension (BR-AB and BR-B) poorly impacted survival., Competing Interests: Declaration of competing interest None., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: Acinar cell carcinoma is a rare tumor of the pancreas. Our current series aimed to assess the clinical and morphological features of pancreatic acinar cell carcinoma and to evaluate the treatment strategies and prognosis., Methods: This retrospective study was conducted in 3 French referral centers. Clinical data were obtained from medical records, and data about survival were then calculated and compared using statistical analysis., Results: Forty-four patients were included (men, 81.8%; median age, 65.5 years; range, 21-85). Tumors were localized, locally advanced, or metastatic in 48.8%, 14.0%, and 37.2% of cases, respectively. Twenty-nine patients (65.9%) underwent a curative-intent resection (R0, 79.2%). First-line chemotherapy in metastatic patients was heterogeneous but mainly consisted in 5-fluorouracil-based or gemcitabine plus oxaliplatin combinations. Median disease-free survival was 12 months (range, 0-82 months). Median overall survival was 55.5 months; it was 40 months in patients with metastatic tumor compared with 106.5 months (P = 0.1058) in those with a nonmetastatic one. Age older than 60 years and a proliferation index greater than 30% were poor prognostic factors., Conclusions: In this large series of patients with pancreatic acinar cell carcinoma, the rate of R0 resection and the prognosis of patients appeared to be much better than that of classic ductal adenocarcinomas.

Background and Aim: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists., Methods: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens., Results: Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P < 0.001) and classification according to Bethesda (ĸ = 0.45 vs ĸ = 0.61, P < 0.001). This equally applied for expert academic and non-academic pathologists and for pancreatic and lymph node specimens. Sample quality was also rated higher for FNB, but agreement ranged from poor (ĸ = 0.04) to fair (ĸ = 0.55). Histology provided better agreement than cytology, but only when a core specimen was obtained with FNB (P = 0.004 vs P = 0.432)., Conclusion: This study shows that the 20-G FNB outperforms the 25-G FNA needle in terms of diagnostic agreement, independent of the background and experience of the pathologist. This endorses use of the 20-G FNB needle in both expert and lower volume EUS centers., (© 2019 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Purpose: The purpose of this study was to analyze and compare clinical outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after EBRT or radio chemotherapy for the treatment of anal canal cancers., Methods and Materials: One hundred patients with anal canal cancers were treated at our institution by ISBT [LDR (n = 50); HDR (n = 50)]. Chronic toxicity rates, local control, disease-free survival, overall survival, and colostomy-free survival of the two different dose-rate brachytherapy modalities were analyzed and compared., Results: With a median followup of 42.2 months (95% CI, [34.5-48.8]), 9 (9% [4.8-16.2%]) local recurrences were observed, 4 (8% [3.2-18.8%]) in LDR vs. 5 (10% [4.4-21.4%]) in HDR group (odds ratio [OR] = 1.28 [0.32-5.07], p = 0.73). The 5-year rate of local control for the entire population was 90% [81-95%], 93% [79-98%] vs. 86% [69-94%] for LDR and HDR, respectively (p = 0.38). The 5-year disease-free survival rate for all patients was 82% [71-90%], 88% [73-95%] vs. 72% [44-88%] for LDR and HDR, respectively (p = 0.21). The 5-year overall survival rate for global population was 94% [84-98%], with no significant differences between LDR (97% [79-100%]) and HDR (93% [80-98%]) (p = 0.27). The 5-year colostomy-free survival rate was 92% [83-96%], respectively, 95% [83-99%] vs. 86% [69-94%] for LDR and HDR (p = 0.21). Significant differences were found in terms of chronic toxicity rates, with 28 (56% [42.3-68.8%]) patients concerned in low-dose-rate brachytherapy vs. 17 (34% [22.4-47.9%]) in high-dose-rate brachytherapy (OR = 0.40 [0.18-0.91], p = 0.03)., Conclusions: Local recurrence rates were comparable between both groups; HDR brachytherapy seem to have a better toxicity profile. Our data confirmed the finding that HDR can be used to safely administer ISBT without increasing chronic toxicity., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Introduction: A new neoadjuvant regimen, together with more aggressive surgeries, appears to have increased the resectability rate in patients with pancreatic ductal adenocarcinoma (PDAC). Our study aimed to evaluate the outcomes of patients who underwent venous resection (VR) during pancreatectomies for PDAC., Materials and Methods: Between 2005 and 2017, 130 patients underwent pancreatectomies with type 3 or 4 (i.e., segmental resection without or with graft interposition, respectively) VR for PDAC. Patients' characteristics, surgical techniques, perioperative management, pathological findings, and outcomes were recorded and compared during 2 inclusion periods: the landmark year for the introduction of the FOLFIRINOX regimen and the hyperspecialization of our pancreatic-surgery team was 2010., Results: Performance of pancreatectomies with VR steadily increased through the 2 inclusion periods. In the overall series (n = 130), the median overall survival time and the 5-year survival proportion were 26.3 months and 21%, respectively. Upon multivariate analysis, ASA score 3 (P = 0.01) and R1 resection margins (P < 0.01) were found to be negative independent factors influencing survival. Patients who underwent upfront VR (n = 47) had survival rates similar to those of patients who received neoadjuvant treatment (n = 83). After 2010, more complex VR were performed; however, no difference was found between the 2 periods with respect to postoperative courses, pathologic findings, or survival after a matching process based on patients' characteristics and tumor stages., Conclusion: Over the last 2 decades, VR during pancreatectomy has been confirmed as a safe procedure despite the increase in technical complexity. Disappointingly, we did not observe any dramatic survival improvement., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

We present for the first time one-to-one correspondence between standard hematoxylin/eosin (H&E) stained tissue sections and stimulated Raman histology (SRH) - a label-free technique in which stimulated Raman scattering (SRS) and second harmonic generation (SHG) are combined to generate virtual H&E images. Experiments were performed on both human thin cryogenic slides from the gastrointestinal tract (GI) and thick freshly excised biopsies from endoscopic surgery. Results on cryogenic slides evidenced an excellent agreement between SRH and H&E images while the ones on biopsies established the relevance of SRH for rapid intraoperative histology to assist in surgical decision making., Competing Interests: The authors declare that there are no conflicts of interest related to this article. All tissue sections were collected in the context of Institut Paoli-Calmettes approved protocol from patients who provided informed consent. Tissues in excess of what was needed for diagnosis were eligible for imaging. All methods were performed in accordance with the European Union guidelines and regulations Commission Directive 2006/17/EC of 8 February 2006 as regards technical requirements for the donation, procurement and testing of human tissues and cells., (© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Conventional haematoxylin, eosin and saffron (HES) histopathology, currently the 'gold-standard' for pathological diagnosis of cancer, requires extensive sample preparations that are achieved within time scales that are not compatible with intra-operative situations where quick decisions must be taken. Providing to pathologists a close to real-time technology revealing tissue structures at the cellular level with HES histologic quality would provide an invaluable tool for surgery guidance with evident clinical benefit. Here, we specifically develop a stimulated Raman imaging based framework that demonstrates gastro-intestinal (GI) cancer detection of unprocessed human surgical specimens. The generated stimulated Raman histology (SRH) images combine chemical and collagen information to mimic conventional HES histopathology staining. We report excellent agreements between SRH and HES images acquire on the same patients for healthy, pre-cancerous and cancerous colon and pancreas tissue sections. We also develop a novel fast SRH imaging modality that captures at the pixel level all the information necessary to provide instantaneous SRH images. These developments pave the way for instantaneous label free GI histology in an intra-operative context.