Wellington Andraus

Pancreatic fistula after pancreaticoduodenectomy: the conservative treatment of choice

BACKGROUND A pancreatic fistula (PF) is the most common complication after pancreaticoduodenectomy (PD), and its reported incidence varies from 2% to 28%. The aim of the present study was to analyse the treatment of a complicated PF comparing the surgical approach with conservative techniques. METHODS From January 2000 through to August 2006, 121 patients were submitted for PD. The study consisted of 70 men and 47 women, with a median age of 60 years (SD +/- 12). The main indications for PD were pancreatic duct carcinoma in 52 patients (44.5%), ampullary carcinoma or adenoma in 18 (15.4%) and islet cell tumour in 11 (9.4%). Reconstruction by pancreatogastrostomy was performed in 65 patients (55.6%), and pancreatojejunostomy in 52 patients (44%). RESULTS Thirty-five patients (30%) developed a PF. Amongst these, 20 were managed conservatively and 14 were reoperated. These two groups of patients were compared with patients without a PF for analysis. There was no significant difference in the mean age, the gender ratio, American Society of Anesthesiologists (ASA) classification, surgical time and blood replacement, number of associated procedures, vascular resection and type of reconstruction between the three groups. There were five post-operative deaths (4.2%), three patients (21.4%) in the surgical treatment group (P < 0.01). Mean total number of complications (P= 0.02) and mean length of hospital stay (P < 0.001) were greater in the surgical group. The medium delay between the pancreatic resection and reoperation was 10 days (range, 3-32 days). Completion splenopancreatectomy was required in five patients whereas conservative treatment including debridement and drainage was applied in nine patients. CONCLUSION The surgical approach for a PF is associated with a higher mortality and morbidity. There is no advantage in performing completion pancreatectomy (CP) instead of extensive drainage as a result of the same mortality and morbidity rates and the risk of endocrine insufficiency. In cases of complicated PF, radiological or surgical conservative treatment is recommended.

Experimental models of liver fibrosis

Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

Lessons Learned from the First 100 Laparoscopic Liver Resections: Not Delaying Conversion May Allow Reduced Blood Loss and Operative Time

BACKGROUND The laparoscopic approach to liver resective surgery is slowly spreading to specialized centers. Little is known about factors influencing the immediate postoperative outcome. STUDY DESIGN The purpose of the study was to evaluate the immediate outcome of laparoscopic liver resection (LLR), with particular emphasis on intraoperative bleeding and conversion. A retrospective analysis of demographic, clinical, and surgical data, including conversion, morbidity/mortality, and hospital stay, of the first 100 patients at our institution undergoing LLR from February 1997 through March 2007 was performed. RESULTS Indication for LLR was benign lesion in 28 patients, malignancy in 33, and living donation in 39. Seventy-five resections involved two or more segments. Mean blood loss was 120 ± 127.6 mL. One patient (1%) required transfusion. Mean operative time was 253 ± 91.6 minutes. No patient died. Postoperative complications occurred in 21 patients. The conversion rate was 17%. Variables related to conversion were American Society of Anesthesiologists Class II, body mass index, cirrhosis, necessity for the Pringle maneuver, and intraoperative blood loss. Conversion did not influence the operative time. Patients with conversion had more complications and a longer hospital stay. CONCLUSIONS Liver resection by laparoscopy is feasible and safe, implying low intraoperative blood loss. Not perfect physical conditions, cirrhosis, high body mass index, and, intraoperatively, blood loss and the necessity of a Pringle maneuver should be considered risk factors for conversion. A meticulous dissection by bipolar coagulation, Harmonic(®) (Ethicon) scalpel, and ultrasound dissector, other than the attitude not to delay conversion in difficult cases, may allow for low blood loss without prolongation of operative time, with a possible, slight increase of the conversion rate.

Tumor growth pattern as predictor of colorectal liver metastasis recurrence

BACKGROUND Surgical resection is the gold standard therapy for the treatment of colorectal liver metastases (CRM). The aim of this study was to investigate the impact of tumor growth patterns on disease recurrence. METHODS We enrolled 91 patients who underwent CRM resection. Pathological specimens were prospectively evaluated, with particular attention given to tumor growth patterns (infiltrative vs pushing). RESULTS Tumor recurrence was observed in 65 patients (71.4%). According to multivariate analysis, 3 or more lesions (P = .05) and the infiltrative tumor margin type (P = .05) were unique independent risk factors for recurrence. Patients with infiltrative margins had a 5-year disease-free survival rate significantly inferior to patients with pushing margins (20.2% vs 40.5%, P = .05). CONCLUSIONS CRM patients with pushing margins presented superior disease-free survival rates compared with patients with infiltrative margins. Thus, the adoption of the margin pattern can represent a tool for improved selection of patients for adjuvant treatment.

Intestinal transplantation including anorectal segment in the rat

Transplantation of small bowel and colon has been recently advocated, aiming to prevent dehydration, reduce stoma output, and promote earlier post-transplant weaning from parental nutrition. Some patients needing intestinal transplantation may also have anorectal dysfunction or a permanent colostomy, which impairs quality of life. The inclusion of the anorectal segment in the intestinal graft may be an attractive improvement for such patients. In this letter, we describe a model of en bloc intestinal transplantation in the rat, including jejunum, ileum, cecum, entire colon, rectum, and the anus. In donor operation, we performed a combined perianal and midline abdominal incision (Fig. 1A). The completely dissected anorectal segment was mobilized to inside the abdomen through the perineum, sectioning rectal vessels and pudendal nerves and preserving the inferior mesenteric artery and vein. The superior mesenteric and portal veins were separated from the pancreas by division of duodenal, splenic, and left gastric veins. The abdominal aorta was dissected from the iliac bifurcation up to the diaphragm by dividing lumbar and renal arteries and the celiac trunk (Fig. 1B). After heparinization, we tied the aorta distally to the inferior mesenteric artery and cut it near the diaphragm and after the tie to perform a long aortomesenteric conduit including the superior and inferior mesenteric arteries. The portal vein was dissected and cut near the hepatic hilum, the proximal jejunum was sectioned, and the graft was removed and placed in cold preservation solution. During back table procedures, we placed a cuff in portal vein, as previously described (Fig. 1C). In the recipient, we performed the same combined incision and anorectal mobilization. The infrarenal abdominal aorta was cross-clamped, and a continuous end-to-side hand-sewn microanastomosis was performed between recipient’s aorta and donor’s aortomesenteric conduit. Below the second jejunal branch, we dissected approximately 1 cm of the recipient superior mesenteric vein, which was clamped and sectioned. The donor portal cuff was introduced in the recipient’s superior mesenteric vein, and an encircling ligature was performed to fix the cuff and complete the anastomosis. Subsequently, we tied and divided the superior and inferior mesenteric arteries and removed en bloc the native mesentery, jejunum, ileum, cecum, entire colon, rectum, and anus. After clamps removal, immediate pulsation of the aortomesenteric conduit and flow throughout the portal vein were observed (Fig. 1D). To restore the intestinal tract, recipient’s and donor’s jejunum were anastomosed, and the anorectal segment was replaced in its ortothopic position and fixed by stitches between donor’s skin surrounding the anus and recipient’s perineal skin. Total operating time was about 3 hours and total ischemia time was about 60 minutes. This intestinal transplantation modification of our previously described models preserves bowel intrinsic innervation, ileocecal valve, and anal sphincter, which may improve graft physiology. It also allows studies evaluating the regeneration of intestinal and anorectal innervation by anorectal electromyography and manometry. Furthermore, it maintains physiological portal drainage and may be useful for metabolic and Presented at the 10th Congress of the International Society for Experimental Microsurgery (ISEM), São Paulo, Brazil, October 29th–November 1st, 2010. *Correspondence to: Flávio Henrique Ferreira Galvão, Av. Dr. Arnaldo, 455Cerqueira Cesar, Room 3206, São Paulo, SP, Brazil. E-mail: fgalvao@usp.br Received 30 April 2011; Accepted 9 August 2011 Published online 17 October 2011 in Wiley Online Library (wileyonlinelibrary. com). DOI 10.1002/micr.20958

Phase angle obtained by bioelectrical impedance analysis independently predicts mortality in patients with cirrhosis

AIM To evaluate the prognostic value of the phase angle (PA) obtained from bioelectrical impedance analysis (BIA) for mortality prediction in patients with cirrhosis. METHODS In total, 134 male cirrhotic patients prospectively completed clinical evaluations and nutritional assessment by BIA to obtain PAs during a 36-mo follow-up period. Mortality risk was analyzed by applying the PA cutoff point recently proposed as a malnutrition marker (PA ≤ 4.9°) in Kaplan-Meier curves and multivariate Cox regression models. RESULTS The patients were divided into two groups according to the PA cutoff value (PA > 4.9°, n = 73; PA ≤ 4.9°, n = 61). Weight, height, and body mass index were similar in both groups, but patients with PAs > 4.9° were younger and had higher mid-arm muscle circumference, albumin, and handgrip-strength values and lower severe ascites and encephalopathy incidences, interleukin (IL)-6/IL-10 ratios and C-reactive protein levels than did patients with PAs ≤ 4.9° (P ≤ 0.05). Forty-eight (35.80%) patients died due to cirrhosis, with a median of 18 mo (interquartile range, 3.3-25.6 mo) follow-up until death. Thirty-one (64.60%) of these patients were from the PA ≤ 4.9° group. PA ≤ 4.9° significantly and independently affected the mortality model adjusted for Model for End-Stage Liver Disease score and age (hazard ratio = 2.05, 95%CI: 1.11-3.77, P = 0.021). In addition, Kaplan-Meier curves showed that patients with PAs ≤ 4.9° were significantly more likely to die. CONCLUSION In male patients with cirrhosis, the PA ≤ 4.9° cutoff was associated independently with mortality and identified patients with worse metabolic, nutritional, and disease progression profiles. The PA may be a useful and reliable bedside tool to evaluate prognosis in cirrhosis.

Factors Associated with Mortality and Graft Failure in Liver Transplants: A Hierarchical Approach

Background Liver transplantation has received increased attention in the medical field since the 1980s following the introduction of new immunosuppressants and improved surgical techniques. Currently, transplantation is the treatment of choice for patients with end-stage liver disease, and it has been expanded for other indications. Liver transplantation outcomes depend on donor factors, operating conditions, and the disease stage of the recipient. A retrospective cohort was studied to identify mortality and graft failure rates and their associated factors. All adult liver transplants performed in the state of São Paulo, Brazil, between 2006 and 2012 were studied. Methods and Findings A hierarchical Poisson multiple regression model was used to analyze factors related to mortality and graft failure in liver transplants. A total of 2,666 patients, 18 years or older, (1,482 males; 1,184 females) were investigated. Outcome variables included mortality and graft failure rates, which were grouped into a single binary variable called negative outcome rate. Additionally, donor clinical, laboratory, intensive care, and organ characteristics and recipient clinical data were analyzed. The mortality rate was 16.2 per 100 person-years (py) (95% CI: 15.1–17.3), and the graft failure rate was 1.8 per 100 py (95% CI: 1.5–2.2). Thus, the negative outcome rate was 18.0 per 100 py (95% CI: 16.9–19.2). The best risk model demonstrated that recipient creatinine ≥ 2.11 mg/dl [RR = 1.80 (95% CI: 1.56–2.08)], total bilirubin ≥ 2.11 mg/dl [RR = 1.48 (95% CI: 1.27–1.72)], Na+ ≥ 141.01 mg/dl [RR = 1.70 (95% CI: 1.47–1.97)], RNI ≥ 2.71 [RR = 1.64 (95% CI: 1.41–1.90)], body surface ≥ 1.98 [RR = 0.81 (95% CI: 0.68–0.97)] and donor age ≥ 54 years [RR = 1.28 (95% CI: 1.11–1.48)], male gender [RR = 1.19(95% CI: 1.03–1.37)], dobutamine use [RR = 0.54 (95% CI: 0.36–0.82)] and intubation ≥ 6 days [RR = 1.16 (95% CI: 1.10–1.34)] affected the negative outcome rate. Conclusions The current study confirms that both donor and recipient characteristics must be considered in post-transplant outcomes and prognostic scores. Our data demonstrated that recipient characteristics have a greater impact on post-transplant outcomes than donor characteristics. This new concept makes liver transplant teams to rethink about the limits in a MELD allocation system, with many teams competing with each other. The results suggest that although we have some concerns about the donors features, the recipient factors were heaviest predictors for bad outcomes.

Adoption of MELD score increases the number of liver transplant

Background Liver transplantation is performed at large transplant centers worldwide as a therapeutic intervention for patients with end-stage liver diseases. Aim To analyze the outcomes and incidence of liver transplantation performed at the University of São Paulo and to compare those with the State of São Paulo before and after adoption of the Model for End-Stage Liver Disease (MELD) score. Method Evaluation of the number of liver transplantations before and after adoption of the MELD score. Mean values and standard deviations were used to analyze normally distributed variables. The incidence results were compared with those of the State of São Paulo. Results There was a high prevalence of male patients, with a predominance of middle-aged. The main indication for liver transplantation was hepatitis C cirrhosis. The mean and median survival rates and overall survival over ten and five years were similar between the groups (p>0.05). The MELD score increased over the course of the study period for patients who underwent liver transplantation (p>0.05). There were an increased number of liver transplants after adoption of the MELD score at this institution and in the State of São Paulo (p<0.001). Conclusion The adoption of the MELD score led to increase the number of liver transplants performed in São Paulo.

Graft-versus-host disease after liver transplantation

Graft-versus-host disease (GVHD) following liver trans-plantation (LT) is an uncommon complication but has highmortality and represents a major diagnostic challenge.GVHD occurs when immunocompetent donor lymphocytesoriginating from the transplanted liver undergo activationand clonal expansion, allowing them to mount a destructivecellular immune response against recipient tissues.Humoral GVHD is usually seen after an ABO-mismatchedliver transplant, but cellular GVHD is directed against themajor histocompatibility complex and often results in severemultisystem disease with high mortality.

Left‐to‐right approach facilitates total hepatectomy with caval flow preservation

Liver transplantation (LT) techniques have changed continually over the last 4 decades. Caval preservation, first reported by Calne and Williams in 1968 and popularized by Tzakis et al. in 1989 as the piggyback (PB) technique, has been adopted by many transplant teams. In 1992, we described a procedure preserving the caval flow during the whole procedure. Hemodynamic stability was sought by the adjunction of a temporary portocaval shunt. Preservation of the vena cava has gained many indications because it allows the implantation of a partial graft (split and living donor). Although preservation of both caval and portal flow avoids the need of venous bypass, its hemodynamic superiority is contrabalanced by the risk of outflow obstruction. It was shown in 2001 that a very large side caval anastomosis, if necessary with temporary caval clamping during the anastomosis procedure, is necessary for good graft liver function. All these technical modifications focus on graft implantation and vascular reconstruction. Technical procedures used during total hepatectomy with caval preservation and its effects on hemodynamic variations have not been exhaustively described. One particular point linked to this technique is that hemodynamic changes related to torsion of the vena cava can occur during explantation of the native liver. The aim of this article is to describe a “left-to-right approach total hepatectomy,” which allows removal of the recipient liver with minimal mobilization of the vena cava, limiting hemodynamic disturbances related to variation of the caval flow. LEFT-TO-RIGHT TOTAL HEPATECTOMY: TECHNIQUE