Ischemic complications after pancreaticoduodenectomy: incidence, prevention, and management.

OBJECTIVE: To assess prevalence, prevention, and management strategy of visceral ischemic complications after pancreaticoduodenectomy (PD). BACKGROUND: Ischemic complications after PD resulting from preexisting celiac axis (CA), superior mesenteric artery (SMA), stenosis, or intraoperative arterial trauma appear as an underestimated cause of death. Their prevention and adequate management are challenging. METHODS: From 1995 to 2006, 545 PD were performed in our institution. All patients were evaluated by thin section multidetector computed tomography (CT) with arterial reconstruction to detect and class SMA or CA stenosis. Hemodynamical significance of stenosis was assessed preoperatively by arteriography for atherosclerotic stenosis and intraoperatively by gastroduodenal artery clamping test for CA compression by median arcuate ligament. Significant atherosclerotic stenosis was stented or bypassed, whereas CA compression was treated by median arcuate ligament division during PD. Multidetector-CT accuracy to detect arterial stenosis, results of revascularization procedures, and both prevalence and prognosis of ischemic complications after PD were analyzed. RESULTS: Among 62 (11%) stenoses detected by multidetector-CT, 27 (5%) were hemodynamically significant, including 23 CA compressions by median arcuate ligament, 2 CA, and 2 SMA atherosclerotic stenoses, respectively. All atherosclerotic stenoses were successfully treated by preoperative stenting (n = 3) or bypass (n = 1). Among the 23 cases who underwent median arcuate ligament division, 3 (13%) failed due to 1 CA injury and 2 misdiagnosed intrinsic CA stenoses. Overall, 6 patients developed ischemic complications, due to intraoperative hepatic artery injury (n = 4), unrecognized SMA atherosclerotic stenosis (n = 1), or CA fibromuscular dysplasia (n = 1). Five (83%) of them died, representing 36% of the 14 deaths of the whole series (overall mortality = 2.6%). Overall, CT detected significant arterial stenosis with a 96% sensitivity and determined etiology of CA stenosis with a 92% accuracy. CONCLUSIONS: Ischemic complications are an underestimated cause of death after PD and are due to preexisting stenoses of CA and SMA, or intraoperative hepatic artery injury. Preexisting arterial stenoses are detected by routine multidetector CT. Preoperative endovascular stenting for intrinsic stenosis, division of median arcuate ligament for extrinsic compression, and meticulous dissection of the hepatic artery can contribute to minimize ischemic complications.

Gastrosplenic Fistula with Gastrointestinal Bleeding: a Rare and Potentially Fatal Complication After Sleeve Gastrectomy.

BACKGROUND: Although the surgical technique is safe and standardized, laparoscopic sleeve gastrectomy (LSG) is associated with serious and potentially life-threatening complications, such as gastric leak and bleeding. METHODS: In this retrospective study, three French university hospitals reviewed their experience with LSG. Between September 2014 and May 2016, three cases of gastrosplenic fistula complicated by massive upper gastrointestinal hemorrhage (UGIH) were recorded. RESULTS: Patient number 1 experienced a massive UGIH 2 months after LSG. After blood transfusion, a transcatheter embolization of the splenic artery branch was successfully performed. Patient number 2 was admitted to the emergency department for massive UGIH 5 years after LSG. After several unsuccessful endoscopic attempts, she underwent a midline laparotomy, and an "en bloc" staple line resection and splenectomy was performed. Patient number 3 arrived at the hospital with an unstable hemodynamic status 16 days after the LSG and was given emergency surgery. She died as a consequence of hemorrhagic shock. CONCLUSIONS: Post-LSG gastrosplenic fistula (GSF) is a rare and dreaded complication necessitating emergency management. Angiography with arterial embolization seems to be the treatment of choice for GSF following SG, allowing diagnosis and treatment when hemodynamic stability is warranted. In a life-threatening situation, hemostatic splenectomy remains the treatment of choice.

Laparoscopic Sleeve Gastrectomy in Kidney Transplant Candidates: a Case Series.

BACKGROUND: Patients with a body mass index (BMI) >35 kg/m2 who need kidney transplant present with increased postoperative mortality and reduced kidney graft survival compared to patients with a lower BMI. For this reason, obese patients are often excluded from the transplantation waiting list. The aim of this study was to evaluate the feasibility and the results of laparoscopic sleeve gastrectomy (LSG) for obese patients awaiting a kidney transplant. METHODS: This was a retrospective study on patients with dialysis-dependent renal failure (DDRF) operated on at two first-level bariatric centers in Paris (France). All the patients were contraindicated for kidney transplantation due to the presence of morbid obesity. RESULTS: Nine DDFR patients with a mean BMI of 45.9 kg/m2 underwent LSG for the treatment of obesity. Furthermore, all patients presented with hypertension and sleep apnea and six out nine were diabetics. In the immediate postoperative period, all patients were transferred to the intensive care unit (mean stay of 2.1 days). The only major adverse event was a delayed weaning from mechanical ventilation in one patient. The mean hospital stay was 5.5 days (3-12). The total weight loss (TWL) was 27.1, 33.6, and 39.5 kg at 6, 12, and 18 months, respectively. One patient underwent renal transplantation 18 months after LSG, and the other five patients were actively listed for kidney transplantation. CONCLUSIONS: According to the results of this small sample series, LSG seems to be an effective and safe procedure in DDRF patients with concomitant obesity and can increase access to transplantation.

Effect of bile contamination on immediate outcomes after pancreaticoduodenectomy for tumor.

BACKGROUND: The influence of preoperative biliary drainage on the postoperative course of patients undergoing pancreaticoduodenectomy (PD) remains controversial. Among drawbacks of biliary drainage, bile contamination and its consequences are incompletely evaluated. This study aimed to compare outcomes after PD in patients with sterile and those with infected bile. STUDY DESIGN: Seventy-nine consecutive patients underwent PD for periampullary tumor with routine bile culture and antibiotic prophylaxis with cefazolin. The postoperative course of 35 patients with infected bile (group B+) was compared with that of 44 patients with sterile bile (group B-). RESULTS: The distribution of tumors was comparable except for ampullary carcinoma, which was more frequent in group B+ patients (p = 0.001). Interventional biliary endoscopy was performed preoperatively in 80% of patients in group B+ versus 14% in group B- (p < 0.001), including 9 isolated sphincterotomies (20% versus 5%, p < 0.03) and 20 endoprosthesis insertions (57% versus 0%, p < 0.0001). More patients in group B+ were classified as American Society of Anesthesiologists (ASA) 2 (p = 0.04). Operative time and blood loss were similar in both groups. One patient died postoperatively (group B+). Overall morbidity was increased in group B+ (77% versus 59%, p = 0.05). Postoperative infectious complications, all demonstrated bacteriologically, were more frequent in group B+: (65% versus 37%, p = 0.003). In group B+, bile was polybacterial in 54% of patients and isolated microorganisms were resistant to cefazolin in 97%. In patients with infectious complications, the same germ was isolated in bile and another sample in 49%. CONCLUSIONS: In patients undergoing PD, bile infection is related to previous interventional biliary endoscopy in 80% of patients and is associated with an increased rate of postoperative infections. During PD for ampullary carcinoma or after interventional biliary endoscopy, a specific antibioprophylaxis should be evaluated.

Fatty pancreas and increased body mass index are risk factors of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Pancreatic fistula (PF) after pancreatoduodenectomy (PD) remains a challenging problem. The only commonly accepted risk factor is the soft consistency of the pancreatic remnant. METHODS: In all, 100 consecutive patients underwent PD. All data, including commonly accepted risk factors for PF and PF defined according to the International Study Group of Pancreatic Fistula, were collected prospectively. On the pancreatic margin, a score of fibrosis and a score of fatty infiltration were assessed by a pathologist blinded to the postoperative course. RESULTS: PF occurred in 31% of patients. In univariate analysis, male sex, age greater than 58 years, body mass index (BMI) > or =25 kg/m(2), pre-operative high blood pressure, operation for nonintraductal papillary and mucinous neoplasm (IPMN) disease and for ampullary carcinoma, operative time, blood loss, soft consistency of the pancreatic remnant, absence of pancreatic fibrosis, and presence of fatty infiltration of the pancreas were associated with a greater risk of PF. In a multivariate analysis, only BMI > or =25 kg/m(2), absence of pancreatic fibrosis, and presence of fatty pancreas were significant predictors of PF. A score based on the number of risk factors present divided the patient population into 4 subgroups carrying a risk of PF that ranged from 7% (no risk factor) to 78% (3 risk factors) and from 0% to 81%, taking into account only symptomatic PF (grade B and C). CONCLUSION: The presence of an increased BMI, the presence of fatty pancreas, and the absence of pancreatic fibrosis as risk factors of PF allows a more precise and objective prediction of PF than the consistency of pancreatic remnant alone. A predictive score based on these 3 factors could help to tailor preventive measures.

Hemorrhage after pancreaticoduodenectomy: when is surgery still indicated?

BACKGROUND: This study analyzed presentation and management of hemorrhage after pancreaticoduodenectomy (PD) to determine the respective role of surgery and embolization. METHODS: From January 1992 to March 2005, 411 patients underwent PD and were analyzed with regard to postoperative hemorrhage. RESULTS: Hemorrhage occurred in 27 patients (7%), either within the first 3 postoperative days ("early" hemorrhage, n = 11) or after day 8 ("delayed" hemorrhage, n = 16, including 4 with "sentinel" bleeding). At the time of bleeding, 12 patients (44%) (all with delayed hemorrhage) had associated abdominal complications. Two patients had successful conservative treatment. Two stable patients with pseudoaneurysm, diagnosed by computed tomography scan, underwent successful embolization. Four patients with active bleeding underwent unsuccessful angiography. Overall, 23 patients were reoperated on without any completion pancreatectomy, 3 rebled, and 3 (11%) died (including 2 with delayed hemorrhage). CONCLUSIONS: Both embolization and surgery have a role in the management of hemorrhage after PD. For early hemorrhage, reoperation is appropriate. In case of sentinel bleeding, pseudoaneurysms can be detected by computed tomography scan and treated by embolization. For delayed active hemorrhage, reoperation is still indicated.

Reg2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post-hepatectomy in mice.

Reg2/RegIIIbeta is the murine homologue of the human secreted HIP/PAP C-type lectin. HIP/PAP transgenic mice were protected against acetaminophen-induced acute liver failure and were stimulated to regenerate post-hepatectomy. To assess the role of Reg2, we used Reg2-/- mice in a model of fulminant hepatitis induced by Fas and in the post-hepatectomy regeneration. Within 4 hours of J0-2 treatment (0.5 microg/g), only 50% of the Reg2-/- mice were alive but with an increased sensitivity to Fas-induced oxidative stress and a decreased level of Bcl-xL. In contrast, HIP/PAP transgenic mice were resistant to Fas, with HIP/PAP serving as a sulfhydryl buffer to slow down decreases in glutathione and Bcl-xL. In Reg2-/- mice, liver regeneration was markedly impaired, with 29% mortality and delay of the S-phase and the activation of ERK1/2 and AKT. Activation of STAT3 began on time at 3 hours but persisted strongly up to 72 hours despite significant accumulation of SOCS3. Thus, Reg2 deficiency induced exaggerated IL-6/STAT-3 activation and mito-inhibition. Because the Reg2 gene was activated between 6 and 24 hours after hepatectomy in wild-type mice, Reg2 could mediate the TNF-alpha/IL-6 priming signaling by exerting a negative feed-back on STAT3/IL-6 activation to allow the hepatocytes to progress through the cell cycle. In conclusion, Reg2 deficiency enhanced liver sensitivity to Fas-induced oxidative stress and delayed liver regeneration with persistent TNF-alpha/IL6/STAT3 signaling. In contrast, overexpression of human HIP/PAP promoted liver resistance to Fas and accelerated liver regeneration with early activation/deactivation of STAT3. Reg2/HIP/PAP is therefore a critical mitogenic and antiapoptotic factor for the liver.

HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice.

Human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein HIP/PAP is a secreted C-type lectin belonging to group VII, according to Drickamer's classification. HIP/PAP is overexpressed in liver carcinoma; however, its functional role remains unclear. In this study, we demonstrate that HIP/PAP is a paracrine hepatic growth factor promoting both proliferation and viability of liver cells in vivo. First, a low number of implanted hepatocytes deriving from HIP/PAP-transgenic mice (<1:1,000) was sufficient to stimulate overall recipient severe combined immunodeficiency liver regeneration after partial hepatectomy. After a single injection of HIP/PAP protein, the percentages of bromodeoxyuridine-positive nuclei and mitosis were statistically higher than after saline injection, indicating that HIP/PAP acts as a paracrine mitogenic growth factor for the liver. Comparison of the early events posthepatectomy in control and transgenic mice indicated that HIP/PAP accelerates the accumulation/degradation of nuclear phospho-signal transducer activator transcription factor 3 and tumor necrosis factor alpha level, thus reflecting that HIP/PAP accelerates liver regeneration. Second, we showed that 80% of the HIP/PAP-transgenic mice versus 25% of the control mice were protected against lethal acetaminophen-induced fulminate hepatitis. A single injection of recombinant HIP/PAP induced a similar cytoprotective effect, demonstrating the antiapoptotic effect of HIP/PAP. Comparison of Cu/Zn superoxide dismutase activity and glutathione reductase-like effects in control and transgenic liver mice indicated that HIP/PAP exerts an antioxidant activity and prevents reactive oxygen species-induced mitochondrial damage by acetaminophen overdose. In conclusion, the present data offer new insights into the biological functions of C-type lectins. In addition, HIP/PAP is a promising candidate for the prevention and treatment of liver failure.

Underestimation of the influence of satellite nodules as a risk factor for post-transplantation recurrence in patients with small hepatocellular carcinoma.

Liver transplantation offers good results in patients with small hepatocellular carcinoma. However, 3 to 15% of patients still have recurrence, suggesting that factors other than the size and number of nodules are implicated. The aim of our study was to identify predictive factors of recurrence in patients with small hepatocellular carcinoma. Seventy consecutive patients fulfilling Milano criteria and who were transplanted for hepatocellular carcinoma were studied. Forty-six patients had pretransplantation adjuvant local therapy. The size and number of tumors, the clinical and biological characteristics of the patients were recorded before liver transplantation, and histological analysis was performed on the explanted liver. Overall survival rates at 1 and 3 years were 81% and 66%, respectively. Recurrence-free survival rates at 1 and 3 years were 80% and 65%, respectively. Seven patients had tumor recurrence with 1- and 3-year recurrence rates of 5% and 10%, respectively. Satellite nodules on the explanted liver were the only statistically significant predictor of recurrence (P=.0003). None of the patients who did not have satellite nodules had recurrence. There was a significant correlation between satellite nodules and microvascular invasion. Patients with pretransplantation adjuvant therapy had significantly more tumor necrosis, but did not have less satellite nodules. In conclusion, microscopic satellite nodules are a significant predictive factor of tumor recurrence in patients transplanted for small hepatocellular carcinoma.

Resection prior to liver transplantation for hepatocellular carcinoma.

OBJECTIVE: To evaluate the feasibility and postoperative course of liver transplantation (LT) in cirrhotic patients who underwent liver resection prior to LT for HCC. SUMMARY BACKGROUND DATA: Although LT provides longer survival than liver resection for treatment of small HCCs, donor shortage and long LT wait time may argue against LT. The feasibility and survival following LT after hepatic resection have not been previously examined. METHODS: Between 1991 and 2001, among 107 patients who underwent LT for HCC, 88 met Mazzafero's criteria upon pathologic analysis of the explant. Of these, 70 underwent primary liver transplantation (PLT) and 18 liver resection prior to secondary liver transplantation (SLT) for recurrence (n = 11), deterioration of liver function (n = 4), or high risk for recurrence (n = 3). Perioperative and postoperative factors and long-term survival were compared. RESULTS: Comparison of PLT and SLT groups at the time of LT revealed similar median age (53 vs. 55 years), sex, and etiology of liver disease (alcohol/viral B/C/other). In the SLT group, the mean time between liver resection and listing for LT was 20 months (range 1-84 months). Overall time on LT waiting list of the two groups was similar (3 vs. 5 months). Pathologic analysis after LT revealed similar tumor size (2.2 vs. 2.3 cm) and number (1.6 vs. 1.7). Perioperative and postoperative courses were not different in terms of operative time (551 vs. 530 minutes), blood loss (1191 vs. 1282 mL), transfusion (3 vs. 2 units), ICU (9 vs. 10 days) or hospital stay (32 vs. 31 days), morbidity (51% vs. 56%) or 30-day mortality (5.7% vs. 5.6%). During a median follow-up of 32 months (3 to 158 months), 3 patients recurred after PLT and one after SLT. After transplantation, 3- and 5-year overall survivals were not different between groups (82 vs. 82% and 59 vs. 61%). CONCLUSIONS: In selected patients, liver resection prior to transplantation does not increase the morbidity or impair long-term survival following LT. Therefore, liver resection prior to transplantation can be integrated in the treatment strategy for HCC.