Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients.

BACKGROUND: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis. METHODS: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used. RESULTS: From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact. CONCLUSION: The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.

Longterm Risk of Solid Organ De Novo Malignancies After Liver Transplantation: A French National Study on 11,226 Patients.

De novo malignancies are one of the major late complications and causes of death after liver transplantation (LT). Using extensive data from the French national Agence de la Biomédecine database, the present study aimed to quantify the risk of solid organ de novo malignancies (excluding nonmelanoma skin cancers) after LT. The incidence of de novo malignancies among all LT patients between 1993 and 2012 was compared with that of the French population, standardized on age, sex, and calendar period (standardized incidence ratio; SIR). Among the 11,226 LT patients included in the study, 1200 de novo malignancies were diagnosed (10.7%). The risk of death was approximately 2 times higher in patients with de novo malignancy (48.8% versus 24.3%). The SIR for all de novo solid organ malignancies was 2.20 (95% confidence interval [CI], 2.08-2.33). The risk was higher in men (SIR = 2.23; 95% CI, 2.09-2.38) and in patients transplanted for alcoholic liver disease (ALD; SIR = 2.89; 95% CI, 2.68-3.11). The cancers with the highest excess risk were laryngeal (SIR = 7.57; 95% CI, 5.97-9.48), esophageal (SIR = 4.76; 95% CI, 3.56-6.24), lung (SIR = 2.56; 95% CI, 2.21-2.95), and lip-mouth-pharynx (SIR = 2.20; 95% CI, 1.72-2.77). In conclusion, LT recipients have an increased risk of de novo solid organ malignancies, and this is strongly related to ALD as a primary indication for LT.

Life-threatening postoperative pancreatic fistula (grade C) after pancreaticoduodenectomy: incidence, prognosis, and risk factors.

BACKGROUND: Pancreatic fistula (PF) is one of the most common postoperative complications of pancreatoduodenectomy (PD). A recent International Study Group on Pancreatic Fistula (ISGPF) definition grades the severity of PF according to the clinical impact on the patient's hospital course. Although PF is generally treated conservatively (grade A), some cases may require interventional procedures (grade B) or may be life-threatening and necessitate emergency reoperation (grade C). The aim of the present study was to evaluate the incidence of postoperative grade C PF after PD and to assess the prognosis and risk factors for this life-threatening condition. STUDY DESIGN: Between January 2000 and December 2006, 680 consecutive patients underwent PD in 5 digestive surgery departments in the northwest region of France (Lille, Amiens, Rouen, and Caen). PF was defined as drain output of any measurable volume of fluid on or after postoperative day 3 with amylase content greater than 3 times the serum amylase activity (ISGPF guidelines). To identify possible risk factors for grade C PF, we reviewed the records of 111 (16.3%) patients with postoperative PF and compared grade C cases with grade A+B cases. RESULTS: The median age was 59 years (range 22-87). The male-to-female ratio was 1.6:1. Fifty-six (50.4%) PDs were performed via pancreaticogastrostomy and 55 via pancreaticojejunostomy. Overall mortality was 2% (n = 14). Grade C PF was observed in 36 (32%) patients, of whom 17 (47%) had sepsis due to an abdominal collection, 16 (44%) had postoperative bleeding, 10 (27.7%) had bleeding associated with abdominal collection, and 3 (9%) had multi-organ failure due to other causes. Of these 36 patients, 35 (97%) underwent reoperation. The mortality rate in grade C PF patients was 38.8%. The major causes of death were sepsis (n = 6) and recurrent bleeding after reoperation (n = 5). Grade C PF increased the duration of postoperative hospitalization (46 vs 29 days, P < .001). Univariate analysis showed that peroperative soft pancreatic parenchyma, peroperative blood transfusion, and postoperative bleeding were significant risk factors for grade C PF, with P values of .011, .003, and .001, respectively. No risk factors for grade C PF were identified in a multivariate analysis. The sensibility, specificity, positive predictive value, and negative predictive value of the presence of the 3 risk factors for grade C PF were 13.89%, 100%, 100%, and 70.75%, respectively. CONCLUSION: Sixteen percent of patients had PF after PD. Among them, 30% had grade C PF, with a mortality rate of about 40%. Achievement of a 100% predictive positive value for grade C PF after PD in individuals with 3 discriminant risk factors (peroperative soft pancreatic parenchyma, peroperative transfusion, and postoperative bleeding) is a first step towards the identification of high-risk patients who should be managed differently from other patients with PF during or after PD.

Usefulness of follow-up after pancreatoduodenectomy for carcinoma of the ampulla of Vater.

BACKGROUND: The prognosis for carcinoma of the ampulla of Vater (CAV) is better than for pancreatic cancer. The 5-year survival median rate after resection of CAV is 45%, but late recurrences remain possible. Several survival factors have been identified (lymph nodes, perineural invasion), but few data are available on the type of recurrences, their impact and their management. PATIENTS AND METHODS: A total of 41 patients treated by pancreatoduodenectomy (PD) for CAV from 1980 to 2003 were studied retrospectively. Patient selection, long-term survival recurrence rate and recurrence treatment were reviewed. Univariate and multivariate proportional hazards analysis were conducted on this series. RESULTS: The mean follow-up was 48 months. Five-year survival was 62.8%. Eleven patients had recurrences (6-67 months). Recurrence was associated with time to all-causes death (hazard ratio [HR] 4.3, p=0.003). Factors predictive of recurrence were perineural invasion (HR 5.3, p=0.02), lymph node invasion (HR 5.3, p=0.02) and differentiation (HR 0.2, p=0.05). Three patients underwent surgical R0 treatment of their recurrences. Two who presented with solitary liver metastasis are alive and disease-free. CONCLUSIONS: Recurrence represents a serious threat in the prognosis of CAV after surgery. Some of these recurrences, in particular liver metastases, are accessible for a curative treatment. This finding supports the usefulness of a close and long-term follow-up after surgery to improve survival of patients with CAV, especially in the group of patients with a good prognosis.

Mortality and morbidity after resection for adenocarcinoma of the gastroesophageal junction: predictive factors.

BACKGROUND: Resection for adenocarcinoma of the gastroesophageal junction (AGEJ) is associated with severe mortality and morbidity. This retrospective study aimed to evaluate mortality and morbidity after resection for AGEJ and to determine their predictive factors. STUDY DESIGN: Data from 1,192 patients (mean age 65 +/- 11 years) who underwent resection for AGEJ by members of French Association of Surgery from 1985 to 2000 were collected. A stepwise logistic regression model was built to identify by multivariate analysis the variables independently associated with mortality, morbidity, anastomotic leakage, and major pulmonary complications. RESULTS: Distribution of Siewert's type was: I = 480 (40%), II = 500 (42%), and III = 212 (18%). Most type I and II tumors were treated by esophagectomy and proximal gastrectomy (93% and 58%, respectively), using an approach including a thoracotomy (82% and 64%, respectively); type III tumors were treated mainly by total gastrectomy and distal esophagectomy (83%), through an exclusive transabdominal approach (69%). Seventy-six (6%) patients died postoperatively. Only American Society of Anesthesiologists (ASA) scores III and IV (p < 0.001) and period of study (p = 0.025) were predictive of mortality. Predictive factors of overall morbidity (overall rate = 35%) were high ASA score (p < 0.001), age more than 60 years (p = 0.020), male gender (p = 0.039), and cervical anastomosis (p = 0.001). Factors predictive of anastomotic leakage (overall rate = 9%) were high ASA score (p = 0.006) and manual anastomosis (p = 0.010). Factors predictive of major pulmonary complications (overall rate = 23%) were high ASA score (p = 0.015), age more than 60 years (p < 0.001), anastomotic leakage (p < 0.001), and abdominal complications (p = 0.003). CONCLUSIONS: ASA score is a reliable predictive factor of operative mortality and morbidity after resection of AGEJ.