Management of cancer-related thrombosis in the era of direct oral anticoagulants: A comprehensive review of the 2019 ITAC-CME clinical practice guidelines. On behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

Venous thromboembolism (VTE) is a common disease complication in cancer patients and the second cause of death after cancer progression. VTE management and prophylaxis are critical in cancer patients, but effective therapy can be challenging because these patients are at higher risk of VTE recurrence and bleeding under anticoagulant treatment. Numerous published studies report inconsistent implementation of existing evidence-based clinical practice guidelines (CPG), including underutilization of thromboprophylaxis, and wide variability in clinical practice patterns across different countries and various practitioners. This review aims to summarize the 2019 ITAC-CME evidence-based CPGs for treatment and prophylaxis of cancer-related VTE, which include recommendations on the use of direct oral anticoagulants specifically in cancer patients. The guidelines underscore the gravity of developing VTE in cancer and recommend the best approaches for treating and preventing cancer-associated VTE, while minimizing unnecessary or over-treatment. Greater adherence to the 2019 ITAC guidelines could substantially decrease the burden of VTE and improve survival of cancer patients.

[Venous thromboembolism and pancreatic cancer]. / Maladie thromboembolique veineuse et cancer du pancréas.

Pancreatic cancer (PC) is a devastating malignancy with an overall 5-year survival of 8% for all stages combined. Most of the PC patients diagnosed have an advanced disease (40%) or metastatic stage (40%), which eliminates surgery as a potentially curative treatment. The disease course is often complicated by venous thromboembolism (VTE) events, which per se account for significant morbidity and mortality, with significantly worsen survival. PC is associated with the highest risk of VTE among all cancer patients. We review the literature data to address the incidence and clinical outcomes of VTE in PC patients. VTE incidence varies from 5 to 41% according to epidemiological studies and is as high as 57% in postmortem series. Since 2013, international clinical practice guidelines recommend primary thromboprophylaxis with a grade 1B level of evidence as an adjuvant therapy in advanced PC. A recent meta-analysis of randomized controlled trials investigating the benefit and risk of low-molecular-weight heparins (LMWH) in ambulatory advanced PC patients under chemotherapy showed that the incidence of VTE was 2.1% in patients treated with LMWH and 11.2% in controls (risk ratio, 0.18; 95% CI, 0.083-0.39; P<0.0001). In conclusion, improved earlier diagnosis and effective management of VTE, a frequent and life-threatening complication in PC, is warranted to improve PC patient outcomes.

Use of routine CT-SCANS to detect severe postoperative complications after pancreato-duodenectomy.

BACKGROUND: To evaluate the performance of CT-scans performed one week after pancreato-duodenectomy (PD) to detect severe postoperative complications requiring an invasive treatment. PATIENTS AND METHODS: This monocentric retrospective study was conducted on data collected between 2005 and 2013. Patients undergoing PD underwent CT-scan with IV contrast at the end of the first postoperative week. The results of the CT-scans were analyzed to evaluate the usefulness of this procedure. The main assessment criterion was the occurrence of type-III complication (or greater) according to the Dindo-Clavien classification. RESULTS: In total, 138 patients were included. The mortality rate was 2.2%. The postoperative complication rate was 57.2%. The pancreatic fistula rate was 19.6%; 46 patients (33.3%) presented with a severe complication. A total of 138 CT-scans were analyzed: 44 (31.8%) were abnormal, 94 (68.2%) were normal. Among patients with abnormal CT-scans, 17 (39%) presented with a severe complication requiring an invasive treatment. Among the 94 patients with normal CT-scans, 14 patients (15%) presented a severe postoperative complication. Evaluation of the performance of the CT-scans at the end of the first postoperative week found a sensitivity of 55%, a specificity of 75%, a positive predictive value of 39%, and a negative predictive value of 85%. CONCLUSION: Systematic CT-scans performed at the end of the first postoperative week do not effectively detect severe complications after PD and do not help to prevent them.

The results of seton drainage combined with anti-TNFα therapy for anal fistula in Crohn's disease.

AIM: Combined infliximab and sphincter-sparing surgery can be effective in perianal fistula associated with Crohn's disease (CD). This study aimed to assess the efficacy of local surgery combined with infliximab on sustained fistula closure and to identify predictive factors for response after this combined treatment. METHOD: Between 2000 and 2010, 81 patients with fistulising perianal CD were included in this observational study. Drainage with a loose seton was followed by infliximab therapy. The primary end-points were the rate of complete fistula closure and time required for this to occur. RESULTS: The fistula was complex in 71 (88%) of the 81 patients. Local proctological surgery was carried out in 77 (95%), including seton drainage in 62 (80.5%) of these. This was continued for a median duration of 3.8 months and the patient then received infliximab therapy. The median follow-up after treatment was 64 months (2-263). Initial complete closure of the fistula occurred in 71 (88%) cases at a median interval of 12.4 months (1-147) from the start of treatment. Recurrence was observed in 29 (41%) patients at a median interval of 38.5 months (2-48) from the start of treatment. They were treated again with combined treatment with successful closure in 19 (65.5%) patients. The total rate of closure of the fistula was 75.3%. Female gender, anal stenosis, rectovaginal and complex fistula formation were factors independently associated with failure of combined treatment. CONCLUSION: Seton drainage for several months combined with infliximab therapy is effective in closing the fistula in 75% of patients with complex perianal fistula formation associated with CD.

Gene expression signature of advanced pancreatic ductal adenocarcinoma using low density array on endoscopic ultrasound-guided fine needle aspiration samples.

AIMS: The purpose of this study was to investigate the clinical feasibility and utility of low-density array analysis on samples obtained from endoscopic ultrasound-guided fine needle aspiration biopsy in locally advanced and/or metastatic pancreatic ductal adenocarcinoma and chronic pancreatitis. PATIENTS AND METHODS: In this prospective multicenter study, we quantified candidate gene expression in biopsies sampled from 44 locally advanced and/or metastatic pancreatic carcinoma and from 17 pseudotumoural chronic pancreatitis using dedicated low-density array microfluidic plates. RESULTS: We first demonstrated that 18S gene expression is stable and comparable in normal pancreas and pancreatic cancer tissues. Next, we found that eight genes (S100P, PLAT, PLAU, MSLN, MMP-11, MMP-7, KRT7, KRT17) were significantly over expressed in pancreatic cancer samples when compared to pseudotumoural chronic pancreatitis (p value ranging from 0.0007 to 0.0215): Linear discriminative analysis identified S100P, PLAT, MSLN, MMP-7, KRT7 as highly explicative variables. The area under receiver operating curve establishes the clinical validity of the potential diagnostic markers identified in this study (values ranging from 0.69 to 0.76). In addition, combination of S100P and KRT7 gave better diagnosis performances (Area Under Receiver Operating Curve 0.81, sensitivity 81%, specificity 77%). CONCLUSION: We demonstrate that molecular studies on EUS-guided FNA material are feasible for the identification and quantification of markers in PDAC patients diagnosed with non-resectable tumours. Using low-density array, we isolated a molecular signature of advanced pancreatic carcinoma including mostly cancer invasion-related genes. This work stems for the use of novel biomarkers for the molecular diagnosis of patient with solid pancreatic masses.

Diagnosis and management of prosthetic vascular graft infections.

Prosthetic vascular graft infection is a rare but very severe complication with a high death rate. Its optimal management requires appropriate surgical procedures combined with adequate antimicrobial treatment in reference center. The authors wanted to focus on the management of prosthetic vascular graft infection and define the clinical, microbiological, biological, and radiological criteria of vascular graft infection. Complementary investigations, although these are small series, include CT scan, the gold standard for the diagnosis of acute infection with a sensitivity and specificity reaching 100%, but decreased to 55% in case of chronic infection. More recently, PET-scanning was studied and yielded good results in chronic infections (sensitivity 98%, specificity 75.6%, positive predictive value 88.5%, and negative predictive value 84.4%). Managing prosthetic vascular graft infection, as with the orthopedic and vascular infections, requires replacing the vascular prosthesis. There is no correlation between the microbiological data and the location or type of vascular infection. Thus, the postoperative intravenous antibiotherapy should be bactericidal with a broad-spectrum. After obtaining intra-operative microbiological results, de-escalation therapy must include at least one anti-adherence agent, such as rifampicin in staphylococcal infections.

Characteristics and prognosis in patients with prosthetic vascular graft infection: a prospective observational cohort study.

Prosthetic vascular graft infection (PVGI) is a devastating complication, with a mortality rate of up to 75%, which is especially caused by aortic graft infection. The purpose of this study was to evaluate factors associated with in-hospital mortality of patients with definite graft infection, and with long-term outcome. We reviewed medical records of 85 patients treated for PVGIs defined by positive bacterial culture of intraoperative specimens or blood samples, and/or clinical, biological and radiological signs of infection. In-hospital patient mortality was defined as any death occurring during the initial treatment of the graft infection. Cure was defined as the absence of evidence of relapsing infection during long-term follow-up (≥1 year). Eighty-five patients (54 aortic and 31 limb graft infections) treated by surgical debridement and removal of the infected prosthesis (n=41), surgical debridement without removal of prosthesis (n=34) or antimicrobial treatment without surgery (n=10) were studied. The only microbiological difference observed between patients with early (occurring within 4 months after surgery) vs. late PVGI and between those with aortic vs. limb PVGI was the incidence of PVGI caused by Staphylococcus aureus, which was greater in patients with limb PVGI. Overall cure was observed in 93.2% of 59 patients with a follow-up of a minimum of 1 year. Overall in-hospital mortality was 16.5% (n=14). Two variables were independently associated with mortality: age >70 years (OR 9.1, 95% CI 1.83-45.43, p 0.007) and aortic graft infection (OR 5.6, 95% CI 1.1-28.7, p 0.037).

Duodenal villous atrophy: a cause of chronic diarrhea after solid-organ transplantation.

Persistent diarrhea is commonly observed after solid organ transplantation (SOT). A few cases of mycophenolate mofetil (MMF)-induced duodenal villous atrophy (DVA) have been previously reported in kidney-transplant patients with chronic diarrhea. Herein, we report on the incidence and characteristics of DVA in SOT patients with chronic diarrhea. One hundred thirty-two SOT patients with chronic diarrhea underwent an oesophago-gastroduodenoscopy (OGD) and a duodenal biopsy after classical causes of diarrhea have been ruled out. DVA was diagnosed in 21 patients (15.9%). It was attributed to mycophenolic acid (MPA) therapy in 18 patients (85.7%) (MMF [n = 14] and enteric-coated mycophenolate sodium [n = 4]). MPA withdrawal or dose reduction resulted in diarrhea cessation. The incidence of DVA was significantly higher in patients with chronic diarrhea receiving MPA compared to those who did not (24.6% vs. 5.1%, p = 0.003). DVA was attributed to a Giardia lamblia parasitic infection in two patients (9.5%) and the remaining case was attributed to azathioprine. In these three patients, diarrhea ceased after metronidazole therapy or azathioprine dose reduction. In conclusion, DVA is a frequent cause of chronic diarrhea in SOT recipients. MPA therapy is the most frequent cause of DVA. An OGD should be proposed to all transplant recipients who present with persistent diarrhea.

Endoscopic ultrasound-guided fine-needle aspiration biopsy coupled with KRAS mutation assay to distinguish pancreatic cancer from pseudotumoral chronic pancreatitis.

BACKGROUND AND STUDY AIMS: Differential diagnosis between pancreatic adenocarcinoma (PADC) and pseudotumoral forms of chronic pancreatitis remains difficult. Mutation of KRAS oncogene is present in 75% to 95% of PADC. This study aimed to evaluate whether the combined analysis of KRAS mutation with cytopathological findings from endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) might improve discrimination between PADC and chronic pancreatitis. PATIENTS AND METHODS: This prospective multicenter study included 178 patients with solid pancreatic masses (men 104, women 74; mean age 64.5 years). Cytopathological examination and KRAS mutation analysis (codon-12 and codon-13, restriction fragment length polymorphism [RFLP] and direct sequencing) were performed on EUS-FNAB material. Final diagnoses were obtained on EUS-FNAB analysis and/or a second biopsy and/or clinical follow-up and/or surgery: PADC, n = 129; chronic pancreatitis, n = 27; other pancreatic neoplasms, n = 16; and benign lesions, n = 6. RESULTS: KRAS status analysis was successful in all EUS-FNAB samples. Codon-12 KRAS point mutation was found in 66% of PADC samples. No case of chronic pancreatitis displayed KRAS mutation. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of cytopathology alone for diagnosis of PADC versus chronic pancreatitis were 83%, 100%, 100%, 56% and 86%, respectively. When KRAS mutation analysis was combined with cytopathology, these values reached 88%, 100%, 100%, 63% and 90% respectively. CONCLUSION: Although the value of KRAS analysis in addition to EUS-FNAB is limited for distinguishing pancreatic mass lesions, when chronic pancreatitis presented as a pseudotumor a negative finding (wild-type KRAS), was useful in strongly suggesting a benign lesion.

Early morbidity of endoscopic ultrasound: 13 years' experience at a referral center.

BACKGROUND AND STUDY AIM: Endoscopic ultrasonography (EUS) now has an important place in the diagnosis of gastroenteropancreatic diseases. However, prospective data on the morbidity and mortality related to its use are sparse and often retrospective. We attempted to assess the acute and immediate complications of both diagnostic and interventional EUS. PATIENTS AND METHODS: At our university-affiliated tertiary care referral center, immediate (occurring during the procedure) and acute (occurring within 24 hours) complications of EUS were prospectively investigated. Over a first period, spanning 10 years, complications of diagnostic EUS involving 3207 consecutive patients were assessed. During the second period of 3 years, complications observed after EUS-guided fine-needle aspiration (FNA) biopsy were evaluated from 224 procedures. EUS was mostly done with the patient under sedation with intravenous propofol and spontaneous ventilation, and complications were evaluated by both the operator and the anesthesiologist. RESULTS: There were no deaths, and no surgery was required over the two periods of assessment. Three mild complications occurred among patients who underwent standard diagnostic EUS: two immediate complications were related to anesthesia and one to the procedure. There were five complications associated with interventional EUS; all were related to the procedure (acute pancreatitis, duodenal perforation, upper digestive bleeding, cyst, and mediastinal infection), with a mean delay of occurrence of 30 hours, and mean duration of hospitalization of 7 days. CONCLUSION: In our experience, which is the longest reported in Europe, the morbidity rates of diagnostic EUS and EUS-guided FNA biopsy were 0.093% and 2.2%, respectively, with no mortality.

[Acute necrotizing enterocolitis during a prolonged treatment with neuroleptics]. / Entérocolite aiguë nécrosante au cours d'un traitement prolongé par neuroleptiques.

A 32-year old man treated for several years with phenothiazine for chronic psychosis developed acute necrotizing colitis. The causal relationship with neuroleptics was reinforced by the absence of any other treatment and by histological findings including extensive mucosal necrosis without stenotic lesion and without mesenteric vessels alteration. The patient required emergency total colectomy and was discharged after 7 weeks of hospitalisation in the intensive care unit.