Supine bottom-up extralevator abdominoperineal excision for anorectal adenocarcinoma is not inferior to standard approach and may be thus safely performed.

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.

Hepatic haemophagocytosis in haematology patients with hepatic dysfunction: prognostic impact and contribution of liver biopsy combined with the haemophagocytic syndrome diagnostic score (HScore).

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.

Case-Matched Comparison of Functional and Quality of Life Outcomes of Local Excision and Total Mesorectal Excision Following Chemoradiotherapy for Rectal Cancer.

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 ).

Management of non-functional pancreatic neuroendocrine tumors by endoscopic ultrasound-guided radiofrequency ablation: Retrospective study in two tertiary centers.

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.

Outcomes of patients with initially locally advanced pancreatic adenocarcinoma who did not benefit from resection: a prospective cohort study.

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.

A single-center experience with pancreatic cystic neuroendocrine tumors.

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.

A multicenter randomized trial comparing a 25-gauge EUS fine-needle aspiration device with a 20-gauge EUS fine-needle biopsy device.

BACKGROUND AND AIMS: Several studies have compared EUS-guided FNA with fine-needle biopsy (FNB), but none have proven superiority. We performed a multicenter randomized controlled trial to compare the performance of a commonly used 25-gauge FNA needle with a newly designed 20-gauge FNB needle. METHODS: Consecutive patients with a solid lesion were randomized in this international multicenter study between a 25-gauge FNA (EchoTip Ultra) or a 20-gauge FNB needle (ProCore). The primary endpoint was diagnostic accuracy for malignancy and the Bethesda classification (non-diagnostic, benign, atypical, malignant). Technical success, safety, and sample quality were also assessed. Multivariable and supplementary analyses were performed to adjust for confounders. RESULTS: A total of 608 patients were allocated to FNA (n = 306) or FNB (n = 302); 312 pancreatic lesions (51%), 147 lymph nodes (24%), and 149 other lesions (25%). Technical success rate was 100% for the 25-gauge FNA and 99% for the 20-gauge FNB needle (P = .043), with no differences in adverse events. The 20-gauge FNB needle outperformed 25-gauge FNA in terms of histologic yield (77% vs 44%, P < .001), accuracy for malignancy (87% vs 78%, P = .002) and Bethesda classification (82% vs 72%, P = .002). This was robust when corrected for indication, lesion size, number of passes, and presence of an on-site pathologist (odds ratio, 3.53; 95% confidence interval, 1.55-8.56; P = .004), and did not differ among centers (P = .836). CONCLUSION: The 20-gauge FNB needle outperformed the 25-gauge FNA needle in terms of histologic yield and diagnostic accuracy. This benefit was irrespective of the indication and was consistent among participating centers, supporting the general applicability of our findings. (Clinical trial registration number: NCT02167074.).

Effect of clinical status on survival in patients with borderline or locally advanced pancreatic adenocarcinoma.

OBJECTIVE: To determine the effect of clinical status (weight variation and performance status [PS]) at diagnosis and during induction treatment on resectability and overall survival (OS) rates in patients with borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC). METHODS: From 2005 to 2017, 454 consecutive patients were diagnosed with LAPC or BRPC. We evaluated the PS (0-1 or 2-3), body mass index at diagnosis, and weight loss (WL) > 5% at initial staging and after induction treatment and separated continuous weight loss (CWL) from weight stabilization. RESULTS: A total of 294 patients (64.8%) presented with WL, and 57 patients (12.6%) presented with a PS of 2-3. At restaging, 60 patients (13.2%) presented with CWL. Independent factors that poorly influenced the OS were a PS of 2-3 at diagnosis (P < .01), CWL at restaging (P < .01), and absence of resection (P < .01). Factors independently impeding resection were LAPC (P < .01), PS > 1 at diagnosis (P < .01), and CWL (P = .01). In total, 142 patients (31.3%) underwent pancreatectomy. Independent factors that poorly influenced the OS in the resected group were PS > 0 at diagnosis (P = .01) and obesity (P < .01). For the 312 unresected cancer patients (68.7%), CWL (P < .01) was identified as an independent factor that poorly influenced the OS. CONCLUSION: Clinical parameters that are easy to measure and monitor are independent factors of poor prognosis. The variation of weight during the induction treatment, more than WL at diagnosis, significantly precluded resection and was an independent factor of shorter OS in unresected patients.

Agreement on endoscopic ultrasonography-guided tissue specimens: Comparing a 20-G fine-needle biopsy to a 25-G fine-needle aspiration needle among academic and non-academic pathologists.

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.

Prognostic Value of Resection Margin Involvement After Pancreaticoduodenectomy for Ductal Adenocarcinoma: Updates From a French Prospective Multicenter Study.

OBJECTIVE: The aim of the study was to assess the relevance of resection margin status for survival after resection of pancreatic-head ductal adenocarcinoma. SUMMARY BACKGROUND DATA: The definition and prognostic value of incomplete microscopic resection (R1) remain controversial. METHODS: Prognostic factors were analyzed in 147 patients included in a prospective multicenter study on the impact of tumor clearance evaluated using a standardized pathology protocol. RESULTS: Thirty patients received neoadjuvant treatment (NAT = 20%); 41 had venous resection (VR = 28%), and 70% received adjuvant chemotherapy. In-hospital mortality was 3% (5/147). Follow-up was 83 months. Tumor clearance was 0, <1.0, <1.5, and <2.0 mm in 35 (25%), 92 (65%), 95 (67%), and 109 (77%) patients, respectively. R0-resection rates decreased from 75% to 35% when changing the definition of R1 status from R1-direct invasion (0 mm) to R1 <1.0 mm. On univariate analysis, clearance <1.0 or <1.5 mm, pT stage, pN stage, LNR ≥0.2, tumor grade 3, and lymphovascular invasion were significantly associated with 5-year survival. On multivariate analysis, pN was the most powerful independent predictor (P = 0.004). Clearance <1.0 or <1.5 mm had borderline significance for the entire cohort, but was relevant in certain subgroups (upfront pancreatectomy (n = 117; P = 0.049); without VR or NAT (n = 87; P = 0.003); N+ without VR or NAT (n = 50; P = 0.004). No N0-patient had R1-0 mm. Additional independent risk predictors were (1) R1 <1.0 mm for the SMA-margin in specific subgroups (upfront pancreatectomy, N0 patients without NAT, N+ patients without NAT or VR; (2) R1-0 mm posterior-margin for the NAT group (P = 0.004). CONCLUSION: Tumor clearance <1.0 or <1.5 mm was an independent determinants of postresection survival in certain subgroups. To avoid misinterpretation, future trials should specify the clearance margin in millimeter. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00918853.

A 25-gene classifier predicts overall survival in resectable pancreatic cancer.

BACKGROUND: Pancreatic carcinoma is one of the most lethal human cancers. In patients with resectable tumors, surgery followed by adjuvant chemotherapy is the only curative treatment. However, the 5-year survival is 20%. Because of a strong metastatic propensity, neoadjuvant chemotherapy is being tested in randomized clinical trials. In this context, improving the selection of patients for immediate surgery or neoadjuvant chemotherapy is crucial, and high-throughput molecular analyses may help; the present study aims to address this. METHODS: Clinicopathological and gene expression data of 695 pancreatic carcinoma samples were collected from nine datasets and supervised analysis was applied to search for a gene expression signature predictive for overall survival (OS) in the 601 informative operated patients. The signature was identified in a learning set of patients and tested for its robustness in a large independent validation set. RESULTS: Supervised analysis identified 1400 genes differentially expressed between two selected patient groups in the learning set, namely 17 long-term survivors (LTS; ≥ 36 months after surgery) and 22 short-term survivors (STS; dead of disease between 2 and 6 months after surgery). From these, a 25-gene prognostic classifier was developed, which identified two classes ("STS-like" and "LTS-like") in the independent validation set (n = 562), with a 25% (95% CI 18-33) and 48% (95% CI 42-54) 2-year OS (P = 4.33 × 10-9), respectively. Importantly, the prognostic value of this classifier was independent from both clinicopathological prognostic features and molecular subtypes in multivariate analysis, and existed in each of the nine datasets separately. The generation of 100,000 random gene signatures by a resampling scheme showed the non-random nature of our prognostic classifier. CONCLUSION: This study, the largest prognostic study of gene expression profiles in pancreatic carcinoma, reports a 25-gene signature associated with post-operative OS independently of classical factors and molecular subtypes. This classifier may help select patients with resectable disease for either immediate surgery (the LTS-like class) or neoadjuvant chemotherapy (the STS-like class). Its assessment in the current prospective trials of adjuvant and neoadjuvant chemotherapy trials is warranted, as well as the functional analysis of the classifier genes, which may provide new therapeutic targets.

Endotherapy in case of relapse of neoplastic Barrett's esophagus after successful initial endoscopic resection.

BACKGROUND: Endotherapy in cases of neoplastic Barrett esophagus (BE) relapse after successful initial endoscopic management is commonly accepted, but few studies analyze this topic and also take into account the metachronous lesions. AIMS: To evaluate the efficiency of endotherapy in the case of neoplastic BE relapse after successful complete endoscopic eradication of neoplastic BE and metaplastic BE. METHODS: Retrospective review of medical records was collected in a computerized and prospective manner between 2000 and 2015, in a single tertiary care center. Recurrence was defined by histological presence of high-grade dysplasia or superficial adenocarcinoma at least 6 months after the end of successful initial endotherapy. RESULTS: Eighteen patients were assessed (1F/17 M). Delay between initial treatment and relapse was 16.6 months (range 6-33). Endotherapy for relapse obtained a sustained and complete remission for 8/18 (44%) patients, with an average endoscopic follow-up of 28 months. The complication rate of endotherapy was 6%. Surgical management was required in 33% (2 pT2N0M0, 2 pTisN0M0, 1 pTm2N0M0 and 1 pTm3N0M0) and salvage radiochemotherapy in 17% (3/18). One patient treated by 6 sessions of ER was considered as a failure given the multiple sessions of endotherapy. Multivariate analysis showed that length of BE (>5 cm), late stenosis adverse events and the quality of vertical margin during initial ER are predictive factors for disease-free survival (p value < 0.01, Hazard Ratio up to 0.076). CONCLUSION: Endotherapy could be a treatment for management of neoplastic BE relapse, but should be carefully used, with strict follow-up.

Transcriptomic analysis predicts survival and sensitivity to anticancer drugs of patients with a pancreatic adenocarcinoma.

A major impediment to the effective treatment of patients with pancreatic ductal adenocarcinoma (PDAC) is the molecular heterogeneity of this disease, which is reflected in an equally diverse pattern of clinical outcome and in responses to therapies. We developed an efficient strategy in which PDAC samples from 17 consecutive patients were collected by endoscopic ultrasound-guided fine-needle aspiration or surgery and were preserved as breathing tumors by xenografting and as a primary culture of epithelial cells. Transcriptomic analysis was performed from breathing tumors by an Affymetrix approach. We observed significant heterogeneity in the RNA expression profile of tumors. However, the bioinformatic analysis of these data was able to discriminate between patients with long- and short-term survival corresponding to patients with moderately or poorly differentiated PDAC tumors, respectively. Primary culture of cells allowed us to analyze their relative sensitivity to anticancer drugs in vitro using a chemogram, similar to the antibiogram for microorganisms, establishing an individual profile of drug sensitivity. As expected, the response was patient dependent. We also found that transcriptomic analysis predicts the sensitivity of cells to the five anticancer drugs most frequently used to treat patients with PDAC. In conclusion, using this approach, we found that transcriptomic analysis could predict the sensitivity to anticancer drugs and the clinical outcome of patients with PDAC.

Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy in solid pancreatic masses.

BACKGROUND AND STUDY AIMS: The differential diagnosis of solid pancreatic masses by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is currently suboptimal in centers that are not equipped with rapid on-site evaluation. Needle-based confocal laser endomicroscopy (nCLE) enables real-time in vivo microscopic imaging during endoscopy. This study aimed to describe nCLE interpretation criteria for the characterization of pancreatic masses, with histopathological correlation, and to perform the first validation of these criteria. PATIENTS AND METHODS: A total of 40 patients were evaluated by EUS-FNA combined with nCLE for the diagnosis of pancreatic masses. Final diagnosis was based on EUS-FNA histology and follow-up at 1 year. Five unblinded examiners defined nCLE criteria for adenocarcinoma, chronic pancreatitis, and neuroendocrine tumor (NET) using a set of video sequences from 14 patients with confirmed pathology (Step 1). These criteria were retrospectively validated by four independent, blinded examiners using sequences from 32 patients (Step 2). RESULTS: nCLE criteria were described for adenocarcinoma (dark cell aggregates, irregular vessels with leakages of fluorescein), chronic pancreatitis (residual regular glandular pancreatic structures), and NET (black cell aggregates surrounded by vessels and fibrotic areas). These criteria correlated with the histological features of the corresponding lesions. In the validation review, a conclusive nCLE result was obtained in 75 % of cases (96 % correct). Statistical evaluation provided promising results, with high specificity, and negative and positive predictive values for all types of pancreatic masses. CONCLUSION: Considering the low negative predictive value of EUS-FNA, nCLE could help to rule out malignancy after a previous inconclusive EUS-FNA. Larger studies are required to confirm these findings and to establish the role of nCLE in the diagnosis of pancreatic masses. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01563133).

Neoplastic Barrett's oesophagus and long-term follow-up after endoscopic therapy: complete histological eradication of Barrett associated with high-grade dysplasia significantly decreases neoplasia relapse.

BACKGROUND AND AIMS: Endotherapy (ET) has replaced surgery as the first-line treatment of high-grade dysplasia (HGD)/superficial ECA (ECAs) from Barrett's oesophagus (BO). However, long-term follow-up and predictive factors of relapse are not so well studied. The aim of the following study was to evaluate the efficiency of ET for treatment of HGD/ECAs and to determine factors of long-term efficiency. METHODS: ET procedures were manually reported and registered in a hospital data base from March 2000 to July 2010. Inclusion criteria were HGD/ECA on pre-resection biopsies, complete histological and sufficient oncological resection of HGD/ECAs, and complete macroscopic resection of metaplastic BO. Sixty patients (53 men, mean age = 65 years) were included. RESULTS: Median follow-up was 66 months [range 42-80]. Complete eradication of residual histological metaplastic BO occurred in 29 patients (48 %). Relapse rate at 36 months was 16.6 % (n = 10) and was unchanged at 60 months of follow-up. There was only one relapse (3.4 %) in case of complete eradication of metaplastic BO and 9 (31 %) in case of incomplete eradication. In univaried and multi-varied analysis, complete eradication of metaplastic BO (p < 0.05) and BO length <5 cm (p < 0.05) were predictive of neoplastic BO non relapse. The length of BO remained a prognostic factor for disease-free survival (DFS). When these preponderant data were cancelled out in multi-varied analysis, complete eradication of BO was a prognostic factor for DFS (p < 0.05). CONCLUSION: Complete histological eradication of BO by ET significantly decreases the rate of neoplasia relapse.

In vivo characterization of pancreatic cystic lesions by needle-based confocal laser endomicroscopy (nCLE): proposition of a comprehensive nCLE classification confirmed by an external retrospective evaluation.

BACKGROUND AND AIMS: The differential diagnosis of solitary pancreatic cystic lesions is sometimes difficult. Needle-based confocal laser endomicroscopy (nCLE) performed during endoscopic ultrasound-fine-needle aspiration (EUS-FNA) enables real-time imaging of the internal structure of such cysts. Criteria have already been described for serous cystadenoma and intraductal papillary mucinous neoplasm (IPMN). The aims of the study were to determine new nCLE criteria for the diagnosis of pancreatic cystic lesions, to propose a comprehensive nCLE classification for the characterization of those lesions, and to carry out a first external retrospective validation . METHODS: Thirty-three patients with a lone pancreatic cystic lesion were included (CONTACT 1 study). EUS-FNA was combined with nCLE. Diagnosis was based on either pathology result (Group 1, n = 20) or an adjudication committee consensus (Group 2, n = 13). Six investigators, unblinded, studied cases from Group 1 and identified nCLE criteria for mucinous cystic neoplasm (MCN), pseudocyst (PC), and cystic neuroendocrine neoplasm (NEN). Four external reviewers assessed, blinded, the yield and interobserver agreement for the newly identified (MCN, PC) and previously described (IPMN, SC) criteria in a subset of 31 cases. RESULTS: New nCLE criteria were described for MCN (thick gray line), PC (field of bright particles), and cystic NEN (black neoplastic cells clusters with white fibrous areas). These criteria correlated with the histological features of the corresponding lesions. In the retrospective validation, a conclusive nCLE result was obtained for 74 % of the cases (87 % "true" and 13 % "false" with respect to the final diagnosis). On this limited case series, the nCLE criteria showed a trend for high diagnostic specificity (>90 % for mucinous cysts, 100 % for non-mucinous cysts). CONCLUSIONS: Based on this newly completed atlas of interpretation criteria, nCLE could facilitate the diagnosis of pancreatic cystic lesion types.

[A solid variant of a serous cystadenocarcinoma of the pancreas]. / Un cystadénocarcinome séreux du pancréas dans une variante solide.

Cystic pancreatic neoplasms concern 1 to 2% of the pancreatic tumours. The serous ones are considered benign tumours but since 1989, several pancreatic serous cystadenocarcinomas (SCAC) cases have been reported. We report the case of a SCAC with a particular pattern. An 80-year-old female patient presented a 4-cm tumour in the neck of the pancreas associated with liver lesions evoking, on imagery exams, focal nodular hyperplasia nests. A cephalic duodenopancreatectomy and a resection of the liver lesions were carried out. The gross exam showed a tumour with a pattern mostly solid and an area made of cysts. The microscopic exam displayed two patterns: the solid one, predominant, made of mild atypical clear cells, and the cystic one. The liver lesions revealed solid pattern similar to the pancreatic tumour one. The tumoral cells were cytokeratin 7, AE1/AE3 and inhibin positives. The Periodic-acid Schiff showed cytoplasmic granulations, which were digested after diasatasis. Only the presence of metastases allows distinguishing a pancreatic serous cystadenoma from a SCAC. To date, thirty cases of pancreatic SCAC have been reported. Immunohistochemistry cannot confirm the malignancy nature of the lesion but it needs to be done in order to cross out the differential diagnosis, that is pancreatic metastatic clear cell renal carcinoma. Nevertheless, it remains a pathology with good prognosis. Only two cases have been reported but ours case a predominant solid pattern.

Evaluation of pCLE in the bile duct: final results of EMID study : pCLE: impact in the management of bile duct strictures.

INTRODUCTION: Pre-operative histology of bile duct stenosis is associated with low accuracy. Probe confocal laser endomicroscopy (pCLE) enables optical biopsy or in vivo histology. The definitive results of the EMID study are presented here, comparing optical biopsies with definitive histology. AIMS AND METHODS: Sixty one patients with a biliary stricture without any previous histology were included (July 2007-May 2012). An endoscopic ultrasound (EUS) had to be conducted before the ERCP procedure. pCLE was done using CholangioFlex during the ERCP procedure. Results were compared to those of definitive histology obtained by biopsy or surgery in case of malignant lesions, and by surgery or 1-year follow-up in case of benign lesions. RESULTS: Six patients were excluded because no definitive histology was available. There were 41 malignant lesions and 14 benign lesions. Sensitivity, specificity, PPV, NPV, and accuracy with combination of pCLE with endobiliary and EUS biopsies were 100, 71, 91, 100, and 93%, respectively (with a significant increase of accuracy compared with endobiliary and EUS biopsies without pCLE, p = 0.03). 19 patients had a biliary stricture without individualized mass (6 malignant lesions, 13 benign lesions). Sensitivity, specificity, PPV, NPV, and accuracy for pCLE were 83, 77, 62, 91, and 79%, respectively. Sensitivity, specificity, PPV, NPV, and accuracy for combination of pCLE with endobiliary and EUS biopsies were 100, 69, 60, 100, and 79%, respectively. CONCLUSION: The addition of a pCLE procedure in the diagnostic histologic examination of a biliary stricture permits a significant increase in diagnostic reliability and allows for a VPN of 100%.

[The RENAPE network: towards a new healthcare organization for the treatment of rare tumors of the peritoneum. Description of the network and role of the pathologists]. / Réseau RENAPE : vers une nouvelle organisation des soins pour le traitement des tumeurs rares du péritoine. Description du réseau et rôle des pathologistes.

As part of the national 2009-2013 Cancer Plan, and with the support of the National cancer Institute and the French ministry of health, the National network for the treatment of rare peritoneal malignancies (RENAPE) has been organized. Its main objective is to optimize the framework for the healthcare management and treatment of rare peritoneal malignancies. This specific organization covers the whole national territory including clinical expert and specialized structures and should lead to an appropriate treatment based on expertise and proximity. Within the RENAPE network, the RENA-PATH group gathers the pathologists actively involved in the management of rare peritoneal malignancies. The actions of RENA-PATH are focused primarily on the harmonization of pathological diagnostic criteria, reporting of new cases in the RENAPE registry and histology reviewing.

[Peritoneal pseudomyxoma: an overview emphasizing pathological assessment and therapeutic strategies]. / Mise au point sur le pseudomyxome péritonéal. Aspects anatomo-pathologiques, et implications thérapeutiques.

Pseudomyxoma peritonei is a clinical entity characterized by a gelatinous ascite associated with mucinous tumor deposits spreading on peritoneal surface and potentially invading abdominal organs. It is considered as a tumor process linked, in most of cases, to a mucinous appendiceal neoplasm. Pseudomyxoma peritonei may benefit from a therapeutic strategy combining cytoreductive surgery and intra-peritoneal chemotherapy, which has led to a major prognosis improvement. Different classifications are available and the last one corresponds to the WHO 2010 version, which individualizes pseudomyxoma peritonei in two classes: low grade and high grade mucinous carcinoma. The very low frequency of this entity and its specific therapeutic strategy need specific health care centres, as well as physicians and pathologists collaborating through dedicated networks. The aim of this article is to summarize the pathology, causes, mechanisms and therapeutic approaches of pseudomyxoma peritonei, as well as their interfaces with dedicated networks.