Aim Intra-operative fluorescence angiography (IOFA) with indocyanine green provides information on tissue perfusion that may help prevent an anastomotic leak (AL). The aim of this study was to assess the impact of IOFA on outcomes after left-sided colonic or low anterior resection with anastomosis for colorectal cancer. Methods All patients with left-sided colonic or rectal cancer, operated between June 2017 and December 2018, were prospectively included. IOFA has been routinely implemented since May 2018. Reproducibility of IOFA, after a 1:1 matching for relevant clinical risk factors of AL, was studied in patients with IOFA (IOFA+) and without IOFA (IOFAÀ). Outcomes were compared in terms of postoperative events such as clinically relevant AL as the primary end-point. Results In the IOFA+ group, changing of the initially planned colon transection due to inadequate perfusion occurred in five out of 46 patients (10.9%). Agreement between intra-operative assessment and postoperative blind review of IOFA was deemed strong (Cohen's kappa index 0.893, 95% CI 0.788-0.998, P < 0.001). Among 111 patients, 42 matched patients were included in each group. There was significantly more clinically relevant AL in the IOFAÀ group compared to the IOFA+ group (16.7% vs 2.4%, P = 0.026) involving significantly more anastomotic dehiscence which required re-intervention (19% vs 2.4%, P = 0.014). Additionally, more descending colon ischaemia/necrosis was observed in the IOFAÀ group compared with the IOFA+ group (9.5% vs 0%, P = 0.040). Conclusion In this prospective case-matched study, IOFA decreased the occurrence of clinically relevant AL due to necrosis of the descending colon or anastomosis. Upon blind review, perfusion assessment using IOFA was reproducible.

BackgroundPancreatic adenocarcinoma (PDAC) incidence is increasing worldwide. Several studies have shown that lymphopenia was correlated with a poor prognosis but the potential interest to measure lymphopenia in the pre and post-operative setting as well as its added value among conventional prognostic factors was never investigated.MethodsData from two independent cohorts in whom patients underwent resection for pancreatic carcinoma were retrospectively recorded. We examined the association between perioperative findings, pre and post-operative lymphocyte counts and overall survival (OS) in univariate and multivariate analyses. Performance assessment and internal validation of the final model were evaluated with Harrell’s C-index, calibration plot and bootstrap sample procedures.ResultsThree hundred ninety patients were included in the analysis between 2000 and 2011. Pre and post-operative lymphocyte counts were independent prognostic factors associated with OS in multivariate analysis (p = 0.0128 and p = 0.0764, respectively). The addition of lymphocyte count variable to the conventional parameters identified in multivariate analysis (metastatic lymph node ratio, veinous emboli and adjuvant chemotherapy) significantly improved the model discrimination capacity (bootstrap mean difference = 0.04; 95 % CI, 0.01–0.06). The use of a threshold and combining the categorical (≥1000; <1000) information in pre and post lymphocyte counts permitted the identification of 4 subgroups of patients with different prognosis (p < 0.0001). Finally, the description of patients in long-term remission showed that only 3 of 65 (4.6 %) patients with post-operative lymphocyte count under 1000/mm3 were alive 4 years after surgery contrary to 54 of 236 (22.8 %) patients with a post-operative lymphocyte count above 1000/mm3.ConclusionPre and post-operative lymphopenia are independent prognostic factors for OS and they have an additive value regarding conventional prognostic factors for death-risk stratification and to predict long-term survival. Lymphopenia should be included as stratification factors in future clinical trial assessing overall survival in pancreatic cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2860-6) contains supplementary material, which is available to authorized users.

Immune checkpoint blockade has proven its efficacy in hypermutated subtypes of metastatic colorectal cancers (mCRC). Immunogenic potential can also be observed with conventional chemotherapies, but this property has never been explored thoroughly in CRC patients. The CRC therapeutic arsenal includes oxaliplatin, a well-characterized platinum drug already described as immunogenic. Here, we investigated the impact of the oxaliplatin-based treatment on mCRC immunopeptidome. We demonstrated that oxaliplatin-resistant CRC cell lines overexpressed telomerase reverse transcriptase (TERT), colorectalassociated-tumor antigen-1 (COA-1) and mesothelin tumor-associated antigens. We identified new HLA class-II-restricted and promiscuous peptides derived from COA-1 and mesothelin. The two naturally processed peptides COA-1 331-345 and Meso 366-380 appear to be the most immunogenic in mCRC patients. A prospective cohort of 162 mCRC patients enabled us to explore the impact of oxaliplatin exposure on the antitumor-specific immune response. Interestingly, chemotherapy-naive mCRC patients present high immune CD4 T-cell responses directed against TERT, COA-1 and mesothelin-derived peptides. These antitumor Tcell responses were maintained after 3 months of oxaliplatin-based treatment. Altogether, these findings highlight the interest of immunostimulatory agents to improve the management of chemoresistant mCRC patients. Finally, the high frequency of immune responses targeting the new immunogenic peptides derived from COA-1 and mesothelin support their use in immunomonitoring strategies. C.T. and C.V. contributed equally to this work Additional Supporting Information may be found in the online version of this article.

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INTRODUCTIONGemcitabine is a chemotherapeutic agent frequently used by for the treatment of several malignancies both in the adjuvant and metastatic setting. Although myelosuppression is the most adverse event of this therapy, gemcitabine might induce severe pulmonary toxicities. We describe a case of pulmonary veno-occlusive disease (PVOD) related to gemcitabine.CASE PRESENTATIONThe patient was an 83-year-old man with a metastatic pancreatic cancer who was treated by gemcitabine as first-line therapy. He was in good health and received no other chemotherapy. A dose of 1000 mg/m2 of gemcitabine was administered over a 30-minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle. After a period of 6 months, a complete response was observed. Nevertheless, the patient developed a severe dyspnea, with arterial hypoxemia and very low lung diffusion for carbon monoxide. A CT scan showed diffuse ground glass opacities with septal lines, bilateral pleural effusion, and lymph node enlargement. On echocardiography, there was a suspicion of pulmonary hypertension with elevated systolic pulmonary artery pressure and normal left ventricular pressures. Right heart catheterization confirmed pulmonary hypertension and normal pulmonary artery occlusion pressure. Diagnosis of PVOD was made, and a gemcitabine-induced toxicity was suspected. A symptomatic treatment was started. At last follow-up, patient was in functional class I with near-normal of CT scan, arterial blood gases, and echocardiography. A gemcitabine-induced PVOD is the more likely diagnosis.

Objective: To survey the available literature regarding the use of auxiliary liver transplantation (ALT) in the setting of cirrhosis. Summary of background: ALT is a type of liver transplantation (LT) procedure in which part of the cirrhotic liver is resected and part of the liver graft is transplanted. The cirrhotic liver left in situ acts as an auxiliary liver until the graft has reached sufficient volume. Recently, a 2-stage concept named RAPID (Resection and Partial Liver segment 2/3 transplantation with Delayed total hepatectomy) was developed, which combines hypertrophy of the small graft followed by delayed removal of the native liver. Methods: A scoping review of the literature on ALT for cirrhosis was performed, focusing on the historical background of RAPID and the status of RAPID for this indication. The new comprehensive nomenclature for hepatectomy (''New World'' terminology) was used in this review. Results: A total of 72 cirrhotic patients underwent ALT [heterotopic (n ¼ 34), orthotopic (Auxiliary partial orthotopic liver transplantation, n ¼ 34 including 5 followed by resection of the native liver at the second stage) and RAPID (n ¼ 4)]. Among the 9 2-stage LTs (APOLT, n ¼ 5; RAPID, n ¼ 4), portal blood flow modulation was performed in 6 patients by deportalization of the native liver (n ¼ 4), portosystemic shunt creation (n ¼ 1), splenic artery ligation (n ¼ 3) or splenectomy (n ¼ 1). The delay between the first and second stages ranged from 18 to 90 days. This procedure led to an increase in the graft-torecipient weight ratio between 33% and 156%. Eight patients were alive at the last follow-up. Conclusions: Two-stage LT and, more recently, the RAPID procedure are viable options for increasing the number of transplantations for cirrhotic patients by using small grafts.

BackgroundThe positive role of CD8+ tumor-infiltrating lymphocytes (TIL) in patients with colorectal cancer (CRC) has been well described but the prognostic value of CD4 T cell subsets remained to be investigated. In this study, we expanded TIL from surgically resected liver metastases of patients with CRC and characterized the phenotype and the prognostic value of expanded-CD4 T cells.MethodsLiver metastases were surgically resected from 23 patients with CRC. Tumors were enzymatically digested and cultured in high dose of interleukin-2 for up to 5 weeks. T cell phenotype and reactivity of cultured-T cells were measured by flow cytometry and correlated with patients’ clinical outcomes.ResultsWe successfully expanded 21 over 23 TIL from liver metastases of patients with CRC. Interestingly, we distinguished two subsets of expanded T cells based on T cell immunoglobulin mucin domain-containing protein 3 (TIM-3) expression. Medians fold expansion of expanded T cells after rapid expansion protocol was higher in CD3+TIM-3low cultures. In an attempt to investigate the correlation between the phenotype of expanded CD4 T cells and clinical outcomes, we observed on one hand that the level of Tregs in culture as well as the expression of both PD1 and TIM-3 by expanded T cells was not correlated to the clinical outcomes. Interestingly, on the other hand, cultures containing high levels of Th17 cells were associated with a poor prognosis (p=0.0007).ConclusionsOur data confirmed the presence of Th17 cells in expanded T cells from liver metastases. Among CD4 T cell characteristics investigated, TIM-3 but not programmed cell death protein 1 predicted the expansion capacity of TIL while only the Th17 phenotype showed correlation with patients’ survival, suggesting a particular role of this T cell subset in CRC immune contexture.Trial registration numberNCT02817178.

To evaluate whether abdominal atherosclerosis was associated with poorer outcome in a single-centre cohort of patients suffering from nonocclusive mesenteric ischemia (NOMI). Methods: From January 2009 to December 2019, 121 consecutive patients from the critical care unit who underwent laparotomy for suspected NOMI and with available unenhanced and contrast-enhanced CT were included. Clinical and biological data at the time of the CT scan were retrospectively extracted from medical charts and reviewed by a single radiologist. Unenhanced CT acquisitions were used to calculate calcium scores of the abdominal aorta, celiac trunk, superior mesenteric artery (SMA) and common iliac arteries according to the Agatston method. Univariate and multivariate analysis were performed. Results: Among the 121 patients with NOMI and calcium score calculation, only 4 patients had no aortic calcifications (3 %) and 32 had no superior mesenteric artery calcification (26 %). 35 patients (29 %) died within 24 h after the abdominal CT scan. Univariate analysis showed that a total abdominal calcium score greater than 15 000 (last quartile) was significantly associated with death within 24 h (14 (40 %) vs 17 (20 %) patients, p = 0.035). By multivariate analysis, a total abdominal calcium score greater than 15 000 was an independent risk factor for death (HR = 1.94,, p = 0.044). Regarding separate calcium scores, only a SMA calcium score greater than 50 was a risk factor for death (HR 2.46,, p = 0.019). Conclusion:Our results show that abdominal atherosclerosis, especially in the SMA, is associated with poorer outcome in NOMI.