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Complex craniofacial injuries (CFI) are induced by high-energy mechanisms of injury, resulting in the simultaneous breaking of many bones, bony displacement and often comminution, soft tissue lacerations or avulsions, and visceral consequences. They can be defined as facial injuries with a CFI score equal to or above 10. In the emergency setting, severe facial injuries can affect the patency of the airway and hemodynamic instability, so essential Damage Control procedures must be well known. These patients often have associated injuries, which can constitute real-life saving priorities. Among these, certainly the most frequent are traumatic brain injuries and cervical spine injuries. This type of patient generally requires long-lasting surgery, with a lack of a solid anatomical reference for reconstruction, a few weeks of hospitalization, and several days in ICU. The definitive treatment of complex craniofacial injuries, therefore, requires high technical skill, but mainly a solid organization of the reconstructive planning and multidisciplinary coordination of priorities and treatment sequences. Technologies and the heavy manipulation of images are nowadays indispensable tools, for a correct diagnosis and personalized surgical planning, and for increasing the level of safety and accuracy of the results. Concurrent skull base fractures and gunshot injuries represent the most complex expressions of severe craniofacial injuries, in which specific definitive treatment protocols are required for proper management.

Simple Summary The treatment of peri-hilar (h-CCA) and intrahepatic (i-CCA) cholangiocarcinoma is an evolving field in hepato-pancreato-biliary surgery. Continuous development of radiological and surgical techniques currently offers different treatment strategies, ranging from traditional hepatectomies to complex approaches involving preoperative portal vein embolization or associating liver partition and portal vein ligation for staged hepatectomy. Recent advances in perioperative chemo-radiotherapy have improved patient survival and have been incorporated into transplant protocols, yielding excellent results. We report a comprehensive review of current surgical and multimodal approaches to h-CCA and i-CCA treatment. Abstract Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, pre-operative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients.

Background: The benefits of pure laparoscopic and robot-assisted liver resections (LLR and RALR) are known in comparison to open surgery. The aim of the present retrospective comparative study is to investigate the role of RALR and LLR according to different levels of difficulty. Methods: The institutional databases of six high-volume hepatobiliary centers were retrospectively reviewed. The study population was divided in two groups: LLR and RALR. The procedures were stratified for difficulty levels accordingly to three classifications. A propensity score matching was implemented to mitigate selection bias. Short-term outcomes were the object of comparison. Results: Nine hundred and thirty-six LLR and 403 RALR were collected. RALR exhibited fewer cases of intraoperative blood loss, lower transfusion and conversion rates (especially for oncological radicality) than LLR in the setting of highly difficult operations, whereas LLR had lower postoperative morbidity and fewer low-grade complications. For intermediate and low-difficulty resections, the intraoperative advantages of RALR gradually decreased to nonsignificant results and LLR remained associated with lower postoperative morbidity. Conclusion: Robot-assisted liver resections do not show operative nor clinically significant benefits over LLR for low- and intermediate-difficulty resections. By reducing conversion rates, RALR can favour the operative feasibility of difficult resections possibly extending the indications of minimally invasive approaches for liver resection.

Mechanical circulatory support (MCS) refers to a range of rescue devices to assist circulation for the treatment of heart failure, including venoarterial extracorporeal membrane oxygenation (VA-ECMO) and ventricular assist devices (VADs). This review aims at evaluating the transplant outcome of the livers procured from brain-dead donors on MCS, who are currently considered as having extended criteria. We identified 22 records (17 on VA-ECMO and 5 on VADs), most of which (68.2%) were case reports. We performed a meta-analysis only when the outcome was reported homogeneously among studies; otherwise, we illustrated the results with narrative synthesis. A total of 156 liver transplants (LTs) have been reported, where VA-ECMO was initiated in the donor with resuscitative intent or as a bridge to donation. Early graft survival approached 100% in most studies. The pooled rate of primary nonfunction was 1% (95% CI: 0-3%). Only three successful LTs from VAD donors have been reported. Particular attention should be paid to cardiological history, biochemical tests, and imaging, as well as MCS parameters, to determine graft eligibility for transplantation. Although further analysis is needed in this field, the results of this review advocate a more systematic consideration of brain-dead patients on MCS as potential liver donors.

Purposes: We sought to investigate the accuracy of abdominal CT scanning for anastomotic leakage and the effect of false-negative scans on the delay in therapeutic intervention and clinical outcome. Method: Data from a prospectively bi-institutionally maintained database of all patients who underwent elective colorectal surgery with primary anastomosis for malignant or benign disease between 2010 and 2017 were reviewed. Patients with confirmed anastomotic dehiscence at reintervention who underwent a postoperative CT scan for suspected leakage were identified and radiological reports were retrieved. Results: Seventy-six patients with anastomotic dehiscence were included in the study. American Society of Anesthesiologists score, sex, type of surgical procedure, malignancy, and type of anastomosis do not correlate with postoperative false-negative CT imaging. Postoperative false-negative CT scan, however, led to delayed reintervention (3 vs. 6h, p = 0.023) and increased mortality (five deaths vs. no deaths, p = 0.043). Free abdominal air (p = 0.001) and extraluminal contrast extravasation (p = 0.001) were found to be predictive of accuracy in anastomotic leakage diagnosis. Conclusion: The suboptimal specificity of a postoperative CT scan in suspected anastomotic leakage after colorectal surgery can delay reintervention and increase mortality.

Introduction No definitive data describing associations between cases of Open Abdomen (OA) and Entero-atmospheric fistulae (EAF) exist. The World Society of Emergency Surgery (WSES) and the Panamerican Trauma Society (PTS) thus analyzed the International Register of Open Abdomen (IROA) to assess this question. Material and methods A prospective analysis of adult patients enrolled in the IROA. Results Among 649 adult patients with OA 58 (8.9%) developed EAF. Indications for OA were peritonitis (51.2%) and traumatic-injury (16.8%). The most frequently utilized temporary abdominal closure techniques were Commercial-NPWT (46.8%) and Bogota-bag (21.9%). Mean OA days were 7.9 ± 18.22. Overall mortality rate was 29.7%, with EAF having no impact on mortality. Multivariate analysis associated cancer (p = 0.018), days of OA (p = 0.003) and time to provision-of-nutrition (p = 0.016) with EAF occurrence. Conclusion Entero-atmospheric fistulas are influenced by the duration of open abdomen treatment and by the nutritional status of the patient. Peritonitis, intestinal anastomosis, negative pressure and oral or enteral nutrition were not risk factors for EAF during OA treatment.

To date, the improvements in survival of patients with liver metastases and advances in technology allowed the surgical indications to be extended. In complex cases, however, the possibility of performing a curative hepatic resection collides with the need to preserve a sufficient liver volume to avoid a postoperative hepatic failure. Currently postoperative liver failure is the major cause of death for these patients. In the attempt to overcome this limit in the last decades, we tried to introduce new measures and develop new surgical techniques. From the introduction by Makuuchi in the 1980s of the preoperative portal embolization, many surgical techniques have been proposed and perfected. The aim of this chapter is to describe the new surgical techniques for the approach of complex hepatic metastases.

Urological cancers (neoplasm of kidney, prostate, bladder, urethra, renal pelvis, ureter and testicles) are an emerging disease representing more than 18% of estimated new cancer cases in United States in 2017. Metastases from urological cancers can occur to all organs. In this chapter we will discuss the management of liver metastases from urological cancer. Liver metastases are a sign of widespread disease and they are associated with a poor prognosis. The treatment of liver metastases is often complex and should be personalized for each patient depending on tumor extension, extrahepatic disease and general status of patients. Therapeutic decision should be undertaken by a multidisciplinary team including oncologists, surgeons, radiologists, anesthesiologists and pathologists in order to perform a tailored treatment for each patient

Posterior Reversible Encephalopathy Syndrome (PRES) is a clinic‐neuroradiologic disease characterized by variable associations of neurological symptoms. The brain imaging abnormalities are often symmetric and predominate in the posterior white matter. PRES can develop in association with a vast array of conditions including hypertensive encephalopathy, eclampsia, and the use of cytotoxic and immunosuppressant drugs. Only few cases in the literature show an association between PRES and acute pancreatitis. We report a case of a 61 yo woman presenting PRES after Endoscopic Retrograde CholangioPancreatography related pancreatitis.

In recent decades, the surgical approach in patients with liver metastasis has seen substantial changes. The encouraging results in terms of survival after surgical resection led to more interventionist attitude, widening indications and bringing more and more patients to curative treatments. Moreover, the technological advancement of surgical devices and the improvement of imaging techniques have made liver surgery safer and more feasible. But, in the most complex cases the attempt to perform surgical curative resections often collided with the inability to preserve an appropriate post-operative volume, necessary to avoid postoperative hepatic failure. In fact the management of liver cirrhosis or small size hepatic remnant still remains a challenge. Currently post-hepatectomy liver failure is the major cause of death after liver resection often associated with sepsis and ischemia-reperfusion injury. In recent years, surgeons have been working to develop new strategies to overcome this limit. Several methods have been proposed for preventing postoperative hepatic failure both in the preoperative, perioperative and postoperative management. Since the introduction of the preoperative portal embolization proposed by Makucchi in the 80’s giant steps have been made. To date in order to limit the damage to parenchyma and to optimize regenerative hepatic capacity many technical considerations have been taken into account. The purpose of this chapter is to describe the new surgical attitudes regarding the treatment of bilobar liver metastases, focusing on surgical techniques that at present seem to be more effective, underlying the benefit and limits of each procedure. In addition to the technical description, a comparison of the various procedures was carried out to demonstrate the feasibility and to check for the critical issue of each one

Metastatic disease is by far the most common malignant liver tumors. The liver is a fertile ground for metastases that spread via blood circulation and although some primary histotypes are more frequent, metastases may develop virtually from any organ. In recent decades, the improvement of chemotherapy drugs and new surgical technologies have significantly improved the prognosis of patients with liver metastases. The chapter aims to give an overview about the development and clinical presentation of liver metastases by focusing on the treatment of the latter. Throughout this chapter, we attempt to clarify the mechanism by which liver is a privileged seat of metastases. We also describe some promising current therapies for liver metastases.

The article by Matthews and colleagues (1) emphasizes the potential impending consequences of underreporting secondary endpoints in studies addressing surgical site infection rates. Generally speaking, this may be a very crucial question about clinical trial methodology and rigor.

Introduction The safety and the protective role of stenting the pancreato-jejunal anastomosis on the occurrence of pancreatic fistula is debated. Aim of this study was to evaluate the outcome of patients who received internal stenting during pancreatoduodenectomy and to review the literature on the related complications. Methods From 2007 to 2014 we performed 207 pancreatoduodenectomies with endto-side duct-to-mucosa pancreato-jejunal anastomosis. We retrospectively analyzed the outcome of 38 high-risk patients with an internal stent through the pancreato-jejunal anastomosis. The occurrence and severity of pancreatic fistula were defined according to International Study Group of Pancreatic Fistula classification. We evaluated the fate and complications of the stents by radiological and clinical follow-up. A literature review was performed through web-search. Results No patients had stent-related symptoms or complications. Seven patients (18.4%) developed clinically relevant pancreatic fistula. We had a mean of 1.9±0.9 (SD) postoperative imaging exams for 33 patients. The median time of follow-up was 3 months (range 1-62). The stent was no longer visible in 17 patients (51.5%); in 8 cases (24.2%) it was in the pancreatic duct, in 7 (21.2%) migrated in the jejunal limb and in 1 patient into the colon. By literature review we retrieved 13 papers reporting on long-term outcomes of internal pancreato-jejunal stenting. Discussion Internal stenting does not seem to be associated with major long-term morbidity, but the short follow-up does not allow definitive judgment on the fate of the stents still in place or dislocated into the jejunal limb. Literature describes a low rate of complications, mainly hepato-biliary infections due to stent migration

Assessment of the severity of acute pancreatitis (AP), together with the patient's nutritional status is crucial in the decision making process that determines the need for artificial nutrition. Both should be done on admission and at frequent intervals thereafter. The indication for nutritional support in AP is actual or anticipated inadequate oral intake for 5-7 days. This period may be shorter in those with pre-existing malnutrition. Substrate metabolism in severe AP is similar to that in severe sepsis or trauma. Parenteral amino acids, glucose and lipid infusion do not affect pancreatic secretion and function. If lipids are administered, serum triglycerides must be monitored regularly. The use of intravenous lipids as part of parenteral nutrition (PN) is safe and feasible when hypertriglyceridemia is avoided. PN is indicated only in those patients who are unable to tolerate targeted requirements by the enteral route. As rates of EN tolerance increase then volumes of PN should be decreased. When PN is administered, particular attention should be given to avoid overfeeding. When PN is indicated, a parenteral glutamine supplementation should be considered. In chronic pancreatitis PN may, on rare occasions, be indicated in patients with gastric outlet obstruction secondary to duodenal stenosis or those with complex fistulation, and in occasional malnourished patients prior to surgery. © 2009 European Society for Clinical Nutrition and Metabolism.

L’adenocarcinoma pancreatico e’ una delle neoplasie con piu’ alta mortalita’ nei paesi occidentali, con una sopravvivenza media di 6 mesi e una percentuale estremamente bassa di sopravvivenza a lungo termine. L’evento principale nello sviluppo dell’adenocarcinoma pancreatico e’ la mutazione del gene KRAS, che tuttavia e’ particolarmente difficile da colpire a livello molecolare. Strategie terapeutiche piu’ efficaci per l’adenocarcinoma pancreatico possono derivare dall’impiego di terapie molecolari. L'obiettivo di questo lavoro e’ quello di identificare nuovi meccanismi e molecolari e strategie terapeutiche per l’adenocarcinoma pancreatico attraverso l’uso modelli cellulari e murini KRAS mutati. Metodi Abbiamo analizzato i risultatiti dello screening di 50 molecole su piu’ di 500 linee cellulari tumorali (incluso 46 di adenocarcinoma pancreatico). Abbiamo disegnato due strategie differenti incluso: 1) un inibitore di JAK2 che inibisce funzionalmente STAT3 e 2) un inibitore di MEK1/2 (AZD-6244), in monoterapia o in combinazione con un inibitore di PI3K (BKM-120 e GDC-0941), in un modello murino KRAS mutato che ricapitola la progressione istopatologica dell’adenocarcinoma pancreatico. Risultati 1) JAK2: lo screening su larga scala di linee cellulari con un inibitore di JAK2 ha mostrato che l’adenocarcinoma pancreatico mostra una sensitivita’ aumentata ( fino a >30 volte) per questa molecola. La sensitivita’ correla con il livello di espressione di pSTAT3 e gp130, un recettore a monte della cascata di STAT3. Abbiamo inoltre osservato che il sottogruppo di adenocarcinoma pancreatico con alti livelli di STAT3 mostra una attivazione costante del pathway IL6/LIF-gp130. Per definire la funzione di STAT3 nell’adenocarcinoma pancreatico, abbiamo quindi sviluppato un modello murino condizionale per STAT3. STAT3 e’ necessario precocemente per lo sviluppo the di lesioni pre-neoplastiche come PanIN (Neoplasia pancretica intraepiteliale) e ADM (Metaplasia acino-duttale). In aggiunta, l’inattivazione di STAT3 blocca lo sviluppo dell’adenocarcinoma pancreatico in un modello ortotopico. I nostri risultati dimostrano che STAT3 ha un ruolo critico nella inizio e progressione dell’adenocarcinoma pancreatico, indicando che la sua inibizione possa essere una strategia terapeutica efficace. Inoltre dimostra che l’espressione di gp130 e pSTAT3 possa essere un biomarker efficace per predire la risposta a un inbitore di JAK2. 2) MEK/PI3K: un altro dato emerso dal nostro screening cellulare e’ che l’adenocarcionoma pancreatico e’ relativamente resistente a monoterapie. Il profilo dell’inibitore di MEK1/2. AZD-6244, ha mostrato una alta efficacia per l’adenocarcinoma pancreatico. Abbiamo tuttavia notato che per indurre apoptosi era necessario associare un inibitore di PI3K (BKM-120 o GDC-0941). Abbiamo testato questa combinazione in modelli murini di adenocarcinoma pacreatico e comparato con trattamento in monoterapia, agenti tradizionali e placebo. La combinazione di MEK e PI3K ha mostrato di ritardare l’insorgenza dei tumori e di aumentare la soopravvivenza in tumori avanzati, sebbene i tumori tendessero a ricorrere nel lungo termine. Conclusioni Questo lavoro dimostra che 1)JAK2 e’ un target molecolare per il trattamento dell’adenocarcinoma pancreatico, in particolare in tumori con alti livelli di GP130; 2) MEK e PI3K sono essenziali nella progressione dell’adenocarcinoma pancreatico e la loro inibizione combinata potrebbe rappresentare una efficace strategia terapeutica. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in western countries, with a median survival of 6 months and an extremely low percentage of long-term surviving patients. KRAS mutations are known to be a driver event of PDAC, but targeting mutant KRAS has proved challenging. As new targeted agents are becoming available for clinical trial we aimed to design improved therapeutic approaches for the treatment of pancreatic ductal adenocarcinoma by means of in vitro and in vivo models of pancreatic adenocarcinoma. Methods We analyzed the results of a high-throughput screening of >500 human cancer cell lines (including 46 PDAC lines), for sensitivity to 50 clinically-relevant compounds. We designed two different strategies including 1) a JAK2 inhibitor that blocks STAT3 function and 2) a MEK1/2 inhibitor, AZD-6244, for efficacy alone or in combination with the PI3K inhibitors, BKM-120 or GDC-0941, in a KRASG12D-driven GEMM that recapitulates the multi-step pathogenesis of human PDAC. Results 1) JAK2 inhibitor: Large-scale screening of cancer cell lines with a JAK2 inhibitor that blocks STAT3 function revealed a >30-fold range in sensitivity in PDAC, and showed a close correlation of sensitivity with levels of tyrosine-phosphorylated STAT3 and of the gp130 receptor, an upstream signaling component. Correspondingly, upregulation of the IL6/LIF-gp130 pathway accounted for the strong STAT3 activation in PDAC subsets. To define functions of STAT3 in vivo, we developed mouse models that test the impact of conditional inactivation of STAT3 in KRAS-driven PDAC. We showed that STAT3 is required for the development of the earliest pre-malignant pancreatic lesions, acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). Moreover, acute STAT3 inactivation blocked PDAC initiation in a second in vivo model. Our results demonstrate that STAT3 has critical roles throughout the course of PDAC pathogenesis, supporting the development of therapeutic approaches targeting this pathway. Moreover, our work suggests that gp130 and phospho-STAT3 expression may be effective biomarkers for predicting response to JAK2 inhibitors. 2) MEK1/2/PI3K inhibitors: In vitro screens revealed that PDAC cell lines are relatively resistant to single-agent therapies. The response profile to the MEK1/2 inhibitor, AZD-6244, was an outlier, showing the highest selective efficacy in PDAC. While MEK inhibition alone was mainly cytostatic, apoptosis was induced when combined with PI3K inhibitors (BKM-120 or GDC-0941). When tested in a PDAC GEMM and compared to the single agents or vehicle controls, the combination delayed tumor formation in the setting of prevention and extended survival when used to treat advanced tumors, although no durable responses were observed. Conclusions: Our studies point to 1)JAK2 as a therapeutic target in GP130 high pancreatic cancers and 2) important contributions of MEK and PI3K signaling to PDAC pathogenesis suggesting that dual targeting of these pathways may provide benefit in some PDAC patients.

Objectives: The prognosis of patients with liver metastases of gastric cancer (LMGC) is dismal, but little is known about prognostic factors in these patients; thus justification for surgical resection is still controversial. The purpose of this study was to review recent outcomes of hepatectomy for LMGC and to determine which patients represent suitable candidates for surgery by assessing surgical results and clinicopathologic features. Methods: Outcomes in 21 patients with LMGC who underwent hepatectomy between 1998 and 2007 were assessed. Isolated metastases and potential to perform a curative resection were requisite indi-cations for surgery. Surgical outcome and clinicopathologic features of the hepatic metastases were analysed. Results: Overall 1-, 3- and 5-year survival rates after hepatic resection were 68%, 31% and 19%, respectively; three patients survived for >5 years without recurrence. Univariate analysis revealed a solitary metastasis, negative margin (R0) resection and the presence of a peritumoral fibrous capsule as significant favourable prognostic factors. These characteristics were present in all of the three patients who survived for >5 years. Conclusions: Solitary metastases from gastric cancer should be treated surgically and confer a better prognosis. Surgical resection should provide microscopically negative margins (R0). A new prognostic factor, the presence of a pseudocapsule, may be associated with improved prognosis.

Background Pneumoperitoneum (PP), established for laparoscopic (LPS) operation, has been associated with potential detrimental effects, such as mesenteric ischemia-reperfusion injury. The objective of the trial was to measure intestinal tissue oxygen pressure (PtiO2) and oxidative damage during laparoscopic (LPS) and open colon surgery and during the postoperative course. Methods Forty patients candidate to left-sided colectomy were randomized to undergo open or LPS resection (20 patients/group). During the operation, PtiO2 was measured at established changes of PP pressure (from 0-15 mmHg) and for 6 days postoperatively. P tiO2 was determined by a polarographic microprobe implanted in the colon wall. Ischemia-reperfusion injury was assessed by plasma malondialdehyde (MDA). ClinicalTrial.gov registration number: NCT01040013. Results LPS was associated with a higher PtiO2 at the beginning of surgery (73.9 ± 9.4 vs. 64.3 ± 6.4 in open; P = 0.04) and at the end of the operation (57.7 ± 7.9 vs. 53.1 ± 4.7 in open; P = 0.03). PtiO2 decreased significantly during mesentery traction vs. beginning in both groups (respectively 58.7 ± 13.2 vs. 73.9 ± 9.4 in LPS and 55.3 ± 6.4 vs. 64.3 ± 6.4 in open group; minimum P = 0.02). During LPS, there was a significant decrease of PtiO2 only when PP was increased to 15 mmHg (63.2 ± 7.5 vs. 76.6 ± 10.7 at 10 mmHg; P = 0.03). PtiO2 also was significantly better in the LPS group during the first 3 days after operation (minimum P = 0.04 vs. open). MDA significantly increased in both groups after mesentery traction and at the end of operation vs. baseline levels with no difference between techniques. Conclusions LPS seems to be associated with a better intra- and postoperative PtiO2. High-pressure PP may impair PtiO2.

The outcome of HCC after transplantation (OLT) in children is not well known. Unfavorable features based on adult reports may lead to contraindicate OLT even in children. We reviewed a cohort of children with cirrhosis and HCC to evaluate their outcome after primary transplantation. We considered children with cirrhosis and HCC who had a primary OLT. We retrospectively recorded demographic, medical and surgical features, and MC as predictors of outcome. Among 456 children transplanted in the last 15 yr, 10 (2%), median age at diagnosis 1.8 yr (range 0.5-7.2), had HCC in biliary atresia (3), BSEP deficiency (3), tyrosinemia type 1 (2), complications of choledocal cyst and glycogen storage disease type IV (1 each). At HCC discovery, median AFP was 2322 ng/mL (3-35,000), high or rising in 9/10 patients. Six patients were outside the MC. Median time on the waiting list was 38 days (1-152). Two patients died from early complications of OLT. In the other eight patients, there was no tumor recurrence after a median follow-up of four yr. Children with cirrhosis may develop HCC at a very young age. The outcome appears excellent even outside MC. Primary liver transplantation is advisable for children with cirrhosis, HCC, and no extrahepatic disease.

Objective: The aim of this study was to evaluate whether perioperative intravenous glutamine supplementation can affect metabolic parameters and outcome. Design: This was a prospective, randomized, phase III, multicenter clinical trial. Patients and methods: Well-nourished patients (n = 428) who were candidates for elective major gastrointestinal surgery for cancer were allocated to received either intravenous infusion of l-alanine-l-glutamine dipeptide (0.40 g/kg per day; equal to 0.25 g of free glutamine) (glutamine group, n = 212) or no supplementation (control group, n = 216). Glutamine infusion began the day before the operation and continued postoperatively for at least 5 days. No postoperative artificial nutrition was allowed unless patients could not adequately eat by day 7. At different time points, plasma or urine was obtained in 166 patients per group to measure standard biochemistry parameters and urinary nitrogen loss. Results: Both postoperative hyperglycemia and urine nitrogen loss were significantly reduced in the glutamine group compared with controls (minimum p = 0.03), while no significant differences between groups were observed for protein synthesis, liver function, and inflammation markers. Overall postoperative complication rate was 34.9% (74/212) in the glutamine group and 32.9% (71/216) in control group (p = 0.65). Infectious morbidity was 19.3% (41/212) in the glutamine group and 17.1% (37/216) in controls (p = 0.55). The rate of patients requiring postoperative artificial nutrition was 13.2% (28/212) in the glutamine group and 12.0% (26/216) in controls (p = 0.71). Conclusions: Despite selective metabolic advantages, perioperative glutamine does not seem to affect surgical outcome in well-nourished gastrointestinal cancer patients

AIM: To investigate whether probiotic bacteria, given perioperatively, might adhere to the colonic mucosa, reduce concentration of pathogens in stools, and modulate the local immune function. METHODS: A randomized, double-blind clinical trial was carried out in 31 subjects undergoing elective colorectal resection for cancer. Patients were allocated to receive either a placebo (group A, n = 10), or a dose of 107 of a mixture of Bifidobacterium longum (BB536 ) and Lactobacillus johnsonii (La1 ) (group B, n = 11), or the same mixture at a concentration of 109 (group C, n = 10). Probiotics, or a placebo, were given orally 2 doses/d for 3 d before operation. The same treatment continued postoperatively from day two to day four. Stools were collected before treatment, during surgery (day 0) and 5 d after operation. During the operation, colonic mucosa samples were harvested to evaluate bacterial adherence and to assess the phenotype of dendritic cells (DCs) and lymphocyte subsets by surface antigen expression (flow cytometry). The presence of BB536 and La1 was evaluated by the random amplified polymorphism DNA method with specific polymerase chain reaction probes. RESULTS: The three groups were balanced for baseline and surgical parameters. BB536 was never found at any time-points studied. At day 0, La1 was present in 6/10 (60%) patients in either stools or by biopsy in group C, in 3/11 (27.2%) in group B, and none in the placebo group (P = 0.02, C vs A). There was a linear correlation between dose given and number of adherent La1 (P = 0.01). The rate of mucosal colonization by enterobacteriacae was 30% (3/10) in C, 81.8% (9/11) in B and 70% (7/10) in A (P = 0.03, C vs B). The Enterobacteriacae count in stools was 2.4 (log10 scale) in C, 4.6 in B, and 4.5 in A (P = 0.07, C vs A and B). The same trend was observed for colonizing enterococci. La1 was not found at day +5. We observed greater expression of CD3, CD4, CD8, and naive and memory lymphocyte subsets in group C than in group A with a dose response trend (C > B > A). Treatment didnot affect DC phenotype or activation, but after ex vivo stimulation with lipopolysaccharides, groups C and B had a lower proliferation rate compared to group A (P = 0.04). Moreover, dendritic phenotypes CD83-123, CD83-HLADR, and CD83-11c (markers of activation) were significantly less expressed in patients colonized with La1 (P = 0.03 vs not colonized). CONCLUSION: La1 , but not BB536 , adheres to the colonic mucosa, and affects intestinal microbiota by reducing the concentration of pathogens and modulates local immunity. © 2010 Baishideng. All rights reserved.

Sclerosing mesenteritis is a rare, idiopatic, usually benign, inflammatory process of the mesenteric adipose tissue. The most common site of involvement is the small bowel mesentery. We present a case of sclerosing mesenteritis of the rectosigmoid colon as a cause of severe abdominal pain, abdominal obstruction, and ischemic colic mucosal lesions. Contrast enema, colonoscopy, angiography, and CT were the imaging modalities used. A 20 cm diameter, fibrotic mass causing extensive compression of rectosigmoid colon was found at laparotomy. Histological examination showed extended fibrosis, inflammatory cells infiltration, lipophages, and granulomas within the mesenteric adipose tissue associated with erosive colitis. Clinical presentation and treatment are discussed.

OBJECTIVE:: To investigate whether perioperative intravenous glutamine supplementation may affect surgical morbidity. SUMMARY BACKGROUND DATA:: Small-sized randomized trials showed a trend toward a reduction of postoperative infections in surgical patients receiving glutamine. METHODS:: A randomized, multicentre trial was carried out in 428 subjects who were candidates for elective major gastrointestinal surgery. Inclusion criteria were: documented gastrointestinal cancer, weight loss 18 years. Patients received either intravenous infusion of L-alanine-L-glutamine dipeptide (0.40 g/kg/d; equal to 0.25 g of free glutamine) (Ala-Glu group, n = 212), or no supplementation (control group, n = 216). Glutamine infusion began the day before operation and continued postoperatively for at least 5 days. No postoperative artificial nutrition was allowed unless patients could not adequately eat by day 7. Postoperative morbidity was assessed by independent observers according to a priori definition. RESULTS:: Patients were homogenous for baseline and surgical characteristics. Mean percent of weight loss was 1.4 (2.7) in controls and 1.4 (2.4) in Ala-Glu group. Overall postoperative complication rate was 34.9% (74/212) in Ala-Glu and 32.9% (71/216) in control group (P = 0.65). Infectious morbidity was 19.3% (41/212) in Ala-Glu group and 17.1% (37/216) in controls (P = 0.55). The rate of major complications was 7.5% (16/212) in Ala-Glu group and 7.9% (17/216) in controls (P = 0.90). Mean length of hospitalization was 10.2 days (4.8) in Ala-Glu group versus 9.9 days (3.9) in controls (P = 0.90). The rate of patients requiring postoperative artificial nutrition was 13.2% (28/212) in Ala-Glu group and 12.0% (26/216) in controls (P = 0.71). CONCLUSIONS:: Perioperative glutamine does not affect outcome in well-nourished GI cancer patients. Copyright © 2009 by Lippincott Williams & Wilkins

Background and aims: Innate immunity cells play a crucial role in host anticancer defense: cancer patients with high levels of natural killer (NK) cells and eosinophils have a better prognosis. Recombinant interleukin-2 (rIL-2) immunotherapy stimulates innate immunity cells. This study aims to evaluate the toxicity of pre- and postoperative rIL-2 treatment and the effects on innate immunity both in peripheral blood and in cancer tissue of patients with resectable pancreatic adenocarcinoma. Materials and methods: Seventeen patients received high dose rIL-2 preoperative subcutaneous administration and two low dose postoperative cycles. We evaluated NK cell and eosinophil count in blood and in pancreatic surgical specimens. Results: Toxicity was moderate. In the early postoperative period, blood NK cells and eosinophils significantly increased compared to basal values (p < 0.02). Histopathological analysis did not find significant intratumoral infiltration of NK cells nor of eosinophils. Conclusions: Preoperative high dose rIL-2 administration is able to counteract surgery-induced deficiency of NK cells and eosinophils in peripheral blood in the early postoperative period, although it cannot overcome local mechanisms of immune tumor escape in cancer tissue. The amplification of innate immunity, induced by immunotherapy, may improve the control of metastatic cells spreading in the perioperative period. © 2008 Springer-Verlag.

Several studies have shown that there is a paucity of immune cells within the stroma of pancreatic adenocarcinoma, a very aggressive cancer with a median survival of about 18 months. A 65-year-old man presented with jaundice. Abdominal ultrasound revealed intra- and extrahepatic bile duct dilatation and a 45-mm diameter hypoechoic solid mass within the pancreatic head; a computed tomography scan excluded vascular infiltration and metastatic lesions. The patient received immunotherapy consisting of 6,000,000 IU human recombinant interleukin-2 administered subcutaneously twice a day for 3 consecutive days. Thirty-six hours after the last dose, he underwent a pylorus-preserving pancreatoduodenectomy. Because of the presence of high-grade dysplasia detected by intraoperative histological examination of a distal section, a spleen preserving total pancreatectomy was performed. The postoperative course was uneventful. The patient died 32 months after surgery because of local recurrence. Histopathology showed G3 pancreatic ductal adenocarcinoma infiltrating the anterior and posterior peripancreatic tissue, duodenal wall and intrapancreatic common bile duct, with sarcoma-like foci and a component of intraductal tumor involving the common bile duct. In the distal pancreas, widespread foci of pancreatic intraepithelial neoplasia (PanIN2-3) were found. The Ki-67 proliferation index was 16%. TNM staging was pT3 pN1 R1. Sections were immunostained for the T-lymphocyte marker CD3 and for the dendritic cell marker CD 1a. Intratumoral infiltration was high for CD1a+ cells and mild for CD3+ cells. Preoperative immunotherapy with interleukin-2 may contribute to massive stromal infiltration of immune cells in pancreatic adenocarcinoma. This may prolong the survival even in the presence of negative prognostic factors (age >65 years, tumor diameter >20 mm, Rl, tumor grade G3).

Background: Laparoscopic splenectomy (LS) is considered the gold standard for the treatment of hematologic disease of the spleen. Intraoperative bleeding is the main complication and main cause of conversion during LS. In this paper, we present our experience with 112 LS procedures, comparing two different techniques and instruments for spleen dissection and hilar vascular control. Methods: We have performed a total of 112 LS procedures in 9 years in two affiliated university hospitals. There were 48 males and 64 females (median age, 32.8 years). Indications were as follows: idiopathic thrombocytopenic purpura (ITP) in 42 patients, hereditary spherocitosis in 28, 6 with β-talassemia, 1 with hemolitic anemia, 27 with lymphoma, 2 with leukemia, 3 with splenic cysts, and 3 PPT cases. Associated procedures were present in 25 cases (17 cholecystectomy and 4 liver/lymphnodal biopsies + lysis of adhesions). Patients were divided in two groups according to the method of dissection and hilar section (group 1, endostapler + monopolar coagulation with 38 patients; group 2, the Ligasure™ Vessel Sealing System (Valleylab, Boulder, CO) with 74 patients). Results: Groups were well matched according to age, indications, spleen sizes, and procedures associated. Conversion rates (10 cases, 9%; 5 in each group), postoperative hospital stay (median 4 days in each group), and intra- and postoperative complications were similar in the 2 groups without any mortality in each group, while intraoperative blood loss (loss of 100 mL in 55 patients in group 2, 78%; and in 21 patients in group 1, 52%), transfusion rates (8 patients in group 1 versus 4 patients in group 2), and operative mean time (150 minutes in group 1 versus 125 minutes in group 2) were minor in the Ligasure Vessel Sealing System group, with a statistical significance. Conclusions: The approach to spleen dissection and hilum section was safe and efficacy in each case, otherwise the use of Ligasure results in a gain of time. Furthermore the average intraoperative bleeding and average transfusion rates of this series were lower in group 2. © 2007 Mary Ann Liebert, Inc.

Hemangioma is a common benign tumor of the liver that is usually asymptomatic. If >4 cm (giant hemangioma), it could present symptoms related to bleeding, thrombosis, comsumptive coagulopathy, or adjacent abdominal organ compression. If symptomatic surgical treatment should be considered, liver resection as well as enucleation are considered. Recurrences after surgical resection are rare. We herein present a case of woman admitted to the emergency room for acute severe respiratory distress. She had undergone 2 surgical resections of liver hemangiomas. The respiratory syndrome, as showed by chest x-ray, computed tomography scan, and nuclear magnetic resonance imaging, was related to a recurrent giant multiple hemangioma, creating a prominent compression of right lung with left mediastinal shift and left heart dislocation. It resulted in pulmonary parenchymal compression associated with reduced chest wall compliance and increased pulmonary pressure. The patient was not eligible for surgical treatment because of the disease extension and her clinical conditions. She died 6 months later from respiratory insufficiency and hypercapnic coma. © 2006 Springer Science+Business Media, Inc.

Introduction. Blood loss and bile leakage are well-known risk factors for morbidity and mortality during liver resection. Bleeding usually occurs during parenchymal transection, and surgical technique should be considered an important factor in preventing intraoperative and postoperative complications. Objective. Many approaches and devices have been developed to limit bleeding and bile leakage. The aim of the present study was to determine whether a bipolar vessel sealing device allows a safe and careful liver transection without routine inflow occlusion, achieving a satisfactory hemostasis and bile stasis, thus reducing blood loss and bile leak and related complications. Patients and methods. A total of 50 consecutive patients (24 males, 26 females, with a mean age of 57 years) underwent major and minor hepatic resections using a bipolar vessel sealing device. A clamp crushing technique followed by energy application was used to perform the parenchymal transection. Inflow occlusion was used when necessary to control blood loss but not as a routine. No other devices were applied to achieve hemostasis. Results. The instrument was effective in 45 patients and failed to achieve hemostasis in 5 cases, all of whom had a cirrhotic liver. Median blood loss was 490 ml (range 100-2500 ml) and intraoperative blood transfusions were required in eight cases (16%). Mean operative time was 178 min (range 50-315 min). Inflow occlusion was necessary in 16 (32%) patients. The postoperative complication rate was 24%, with a postoperative hemorrhage in a cirrhotic patient. There was no clinical evidence of bile leak or procedure-related abdominal abscess. Conclusion. We conclude that the device is a useful tool in standard liver resection, achieving good hemostasis and bile stasis in patients with normal liver parenchyma, but its use should be avoided in cirrhotic patients.

Carcinoma showing thymic-like elements (CASTLE) is a rare tumor affecting thyroid and neck soft tissues, which has to be distinguished from squamous cell and anaplastic thyroid carcinoma, because it has a better prognosis. We report a new case of CASTLE which occurred in a patient submitted to total thyroidectomy with central neck dissection. The tumor stained positively for CD5, which seems to be the most useful marker in the differential diagnosis. By the analysis of the 18 cases reported in literature, total thyroidectomy with selective modified neck dissection should be the treatment of choice and radiotherapy should be considered for patients with positive nodal status.

Background and aims: Thrombosis of the portal system is a potentially life-threatening complication after splenectomy. The reported incidence is low (≅1%), however may be underestimated due to difficult in making the diagnosis. The factors associated with its development and the clinical outcome are poorly characterized. The aim of this study was to assess the incidence, risk factors, treatment, and outcome in series of consecutive cases. Materials and methods: All patients who had undergone a splenectomy (both open and laparoscopic) between January 1997 and December 2004 at the Department of Surgery of University of Milan Bicocca were retrospectively reviewed. Twelve cases of thrombosis (7.6%) among 158 splenectomies were identified. No significant differences were noted in age, gender, and surgical approach between patients who developed thrombosis and those who did not. Indication for splenectomy in patients with thrombosis were myeloproliferative disorders (n=5), hemolytic disease (n=4), and lymphoproliferative disorder (n=3). All patients had splenomegaly (mean 1.380 kg, range 0.400-3.120 kg). Results: Among patients with myeloproliferative disorders, five (33%) developed the complication, compared with 4 of 35 (11.5%) with hemolytic disease. Patients with both splenic weight >2.500 kg and myeloproliferative disorders had 80% incidence of portal thrombosis. Preoperative prophylactic anticoagulant therapy with low molecular weight heparin was administered in each case. All these patients had fever, abdominal pain, or leukocytosis. All diagnoses were made by contrast-enhanced computed tomography (CT) scan and ecocolordoppler ultrasonography, and anticoagulation therapy was initiated immediately. Treatment within 15 days after splenectomy was successful in all patients, while delayed treatment was ineffective. Conclusions: Portal thrombosis should be suspected in patients with fever or abdominal pain after splenectomy. Patients with myeloproliferative disorders and hemolitic diseases are at higher risk, as well as patients with marked splenomegaly. A high index of suspicion, early diagnosis, and prompt anticoagulation therapy are the keys to a successful outcome. © Springer-Verlag 2006.

We report a case of the contemporaneous presence of two histologically different pancreatic neoplasms, one renal cancer and one embryogenic duodenal anomaly in a single patient. A 66-year-old man underwent ultrasound examination because of urinary disorders; a solid neoformation within the inferior pole of the left kidney was observed. Computed tomography confirmed the renal lesion, but also a heterogeneous mass within the pancreatic head appeared without bile ducts dilatation. Abdominal magnetic resonance revealed a multiloculated cystic component of the pancreatic mass. A second CT scan confirmed the renal and biliary findings, but it revealed a modest enlargement of the pancreatic asymptomatic mass. A resection of the left kidney inferior pole and a pylorus-preserving pancreaticoduodenectomy were performed. Histopathologic analysis of the surgical specimen revealed mild differentiated papillary renal carcinoma, intraductal papillary mucinous adenoma of the pancreatic head, foci of intraepithelial pancreatic neoplasm and pancreatic heterotopy of duodenal muscular and submucosal layers. The coexistence of several primaries and anomalies in one patient led us to suppose a genetic predisposition to different lesions, even in the absence of known familial genetic syndromes. The study of such cases may help to improve the investigation of molecular correlations and etiological factors of different solid tumors. Nowadays, surgery is the only effective cure.

Thrombosis of the portal system is a potentially life-threatening but otherwise underappreciated complication after splenectomy. Nonspecific and mild onset symptoms are the cause of delay in diagnosis, and the short hospital stay after laparoscopic approach could even contribute to the difficulty of early detection of this condition. The aim of this study was to verify if planned imaging controls are able to discover this complication leading to a prompt treatment. Thirty-eight patients (19 males and 19 females with a mean age of 24 years) who underwent laparoscopic splenectomy at our institution were studied to identify clinical signs of thrombosis of the portal venous system and eventually associated factors. All the patients were enrolled in a protocol of imaging surveillance using a doppler ultrasound method. Postoperative thrombosis of the spleno-portal axis occurred in 7 patients (18.9%) of the series. In 3 cases (8.1%) the thrombus extended from the splenic vein to occlude the portal axis. The complication was symptomatic in 4 cases (10.8%), whereas in 3 cases, the thrombosis was an ultrasonographic surprise in totally asymptomatic patients. Thrombosis occurred even as late as 2 months after splenectomy. Splenomegaly was the only significant factor predictive of thrombosis. Only those patients who had an early detection of portal or splenic vein thrombosis had a recanalization of the veins with anticoagulant therapy. Patients with splenomegaly who underwent laparoscopic splenectomy are at risk of thrombosis of the portal system and should undergo strict imaging surveillance and aggressive anticoagulation therapy. Copyright © 2006 by Lippincott Williams & Wilkins.

Background: Bleeding is the main complication and cause of conversion during laparoscopic splenectomy (LS). We present the advantages of the LigaSure vessel sealing system added to the lateral approach for achieving safe vascular control. Methods: We performed 63 consecutive LS in a 3-year period using LigaSure in two affiliated university hospitals. We employed a right semilateral position technique with dissection of the spleen and vessel sealing using LigaSure. Forty-two patients had benign hematological disease, 19 had malignant disease, and two had splenic cysts. Results: A total of 58 LS were completed with five conversions due to hilar bleeding (three cases), difficult dissection (one), and massive splenomegaly (one). In all but five patients, blood loss was less than 100 ml. No transfusions were needed. There were five postoperative complications: portal thrombosis (one case), hemoperitoneum (two), surgical wound infection (one), and pleural effusion (one). Conclusions: The use of LigaSure, and the semilateral position, results in a gain of time and safety. Furthermore, average intraoperative bleeding is very low. © Springer Science+Business Media, Inc. 2006.

Morgagni-Larrey hernia is a congenital type of diaphragmatic hernia. It is quite uncommon, particularly when it occurs on the left side of the diaphragm. This is a report of a case of a large left-side diaphragmatic hernia through the foramen of Morgagni treated by laparoscopy. The hernia was repaired by incorporating and fixing a polypropylene double-filament mesh into the defect, leaving the sac in mediastinum. The patient recovered promptly after the hernia repair, and there was no recurrence or complaints 30 months after surgery. Our conclusion is that laparoscopically repairs of Morgagni hernias with a prosthetic material are a safe and effective treatment. A literature review also shows that laparoscopic techniques are the gold standard in diaphragmatic hernias repairs.

Cystic hepatic metastases arising from lung cancer are rare. We herein describe a case of a 71-year-old women admitted to our hospital for abdominal pain 6 months after the resection of a lung adenocarcinoma. Two cystic lesions of the liver were discovered at abdominal ultrasonography and computerized tomography scan. An ERCP excluded a biliary adenoma or adenocarcinoma, and an ultrasound-guided liver biopsy was negative for malignant cells. For persistence of symptoms and lack of a diagnosis, the patient underwent an exploratory laparotomy, a surgical biopsy with a diagnosis of adenocarcinoma, and a consequent right hepatectomy. After 2 years of follow-up, the patient is well and disease free. Although cystic liver metastasis are rare and a differential diagnosis difficult, the malignant nature should always be considered in the differential diagnosis of hepatic cysts to offer the patient the best treatment.

OBJECTIVE: The effect of recombinant murine granulocyte macrophage colony-stimulating factor (rmGM-CSF) on survival and host defense was studied using two clinically relevant models of infection that included transfusion-induced immunosuppression. SUMMARY BACKGROUND DATA: Granulocyte macrophage colony-stimulating factor improves resistance in several models of infection, but its role in transfusion-induced immunosuppression and bacterial translocation (gut-derived sepsis) has not been defined. METHODS: Balb/c mice were treated with 100 ng of rmGM-CSF or placebo for 6 days in a model of transfusion, burn, and gavage, or cecal ligation and puncture (CLP). Translocation was studied in the first model. RESULTS: Survival after transfusion, burn, and gavage was 90% in rmGM-CSF-treated animals versus 35% in the control group (p < 0.001). After CLP, survival was 75% in the rmGM-CSF group versus 30% in the control group (p = 0.01). Less translocation and better killing of bacteria was observed in the tissues in animals treated with rmGM-CSF. CONCLUSION: The ability of rmGM-CSF to improve gut barrier function and enhance killing of translocated organisms after burn injury-induced gut origin sepsis was associated with improved outcome. Granulocyte macrophage colony-stimulating factor also improved survival after CLP.

The relationship between hypermetabolism and bacterial translocation was investigated in guinea pigs receiving a 40% burn. Animals were infused intragastrically with a complete enteral diet or Ringer's solution for 48 h, given 10(10) 14C-labeled Escherichia coli intragastrically, and killed 4 h later. Resting metabolic expenditure (RME), translocation (dpm of the 14C-labeled E. coli) to the portal blood and ileal mucosa, plasma cortisol, and urinary vanillylmandelic acid (VMA) were determined. Enterally fed animals had significantly lower RME, cortisol, VMA, and dpm, but higher mucosal and body weight than the Ringer's group. Disintegrations per minute (dpm) in the blood were positively correlated with RME (r = 0.856), cortisol (r = 0.872), VMA (r = 0.759), and dpm mucosa (r = 0.836) and inversely correlated with mucosal weight (r = -0.883). We conclude that bacterial translocation is reduced by early feeding and is an important cause of hypermetabolism and stress hormone production after burn injury.

The effectiveness of perioperative administration of thymopentin in preventing postoperative infection was evaluated in 206 patients with cancer (54 gastric, 152 colorectal) who underwent elective major surgery. Comparable subsets of patients were obtained with respect to age (proportion over 65 years) and nutritional status (patients with serum albumin level less than 30 g/l or weight loss of 10 per cent or more of usual body-weight were considered to be malnourished). Patients were then randomly assigned to a control group or to a group receiving thymopentin. All patients received perioperative short-term antibiotic prophylaxis and postoperative parenteral nutrition. Levels of CD3-, CD4- and CD8-positive T cell subsets were evaluated before and after surgery in 20 (ten elderly) patients from each group. The severity of postoperative infection was evaluated using a sepsis score. In elderly patients thymopentin prevented the postoperative drop in CD3- and CD4-positive T cell subpopulations that was observed in controls (P < 0·05). The postoperative infection rate was 17·5 per cent in the group given thymopentin and 24·3 per cent in controls (P not significant). The mean(s.d.) sepsis score was 6·7(3·1) in the group receiving thymopentin and 9·4(5·8) in controls (P not significant). Considering only elderly patients, the mean(s.d.) sepsis score was significantly lower in those treated with thymopentin than in control patients (6·9(2·1) versus 11·3(4·7)). In conclusion, administration of thymopentin did not significantly reduce the postoperative infection rate. However, it prevented the drop in number of CD3- and CD4-positive T cells after operation and reduced the severity of postoperative infection in elderly patients.

To investigate the effect of: a) starvation during the preburn period and b) immediate postburn enteral nutrition on the permeability of the gut to microorganisms and the ability of the host to kill translocated bacteria.Prospective, randomized, experimental trials.Laboratory.Balb/c mice and Hartley guinea pigs.In the first experiment, mice were starved for 0, 6, 12, 18, or 24 hrs before receiving gavage with 10(10) 14C-labeled Escherichia coli and a 20% burn injury. In the second experiment, guinea pigs received a 40% burn injury and were randomized to receive a complete enteral diet (175 kcal/kg/day) or infusion of an equal volume of lactated Ringer's solution via a previously placed gastrostomy for 6, 24, or 48 hrs. After each feeding period, 10(10) 14C Escherichia coli were infused intragastrically. In both experiments, the animals were killed 4 hrs after gavage, and mesenteric lymph nodes, spleen, liver, lungs, peritoneal fluid, and blood were harvested aseptically.For each tissue or fluid, the number of viable E. coli and radionuclide counts of the 14C E. coli were measured and the percentage of translocated bacteria that remained alive was calculated.In mice, 18 and 24 hrs of preburn starvation increased translocation only to the mesenteric lymph nodes, but it also enhanced bacterial killing in all tested tissues. Guinea pigs that were fed enterally for 6, 24, and 48 hrs postburn had significantly lower bacterial translocation in all tissues compared with animals infused with lactated Ringer's solution. Additionally, enhanced killing of translocating organisms was observed after 24 and 48 hrs of feeding.Starvation preburn has different consequences than starvation postburn on translocation and bacterial killing. Postburn enteral nutrition decreases the load of viable bacteria in the tissues via a double mechanism: an initial decreased translocation and a subsequent improved ability to kill bacteria that do translocate.

Objective: To establish the primary anatomic site of bacterial translocation in the intestinal tract. Design: Prospective randomized experimental trials. Setting: Laboratory. Materials: Hartley guinea pigs. Interventions: In guinea pigs, 10-cm closed loops of upper jejunum, distal ileum, or proximal colon were created. The animals then received intraluminal injections ofEscherichia colilabeled with radioactive carbon (14C) before a 50% full-thickness burn was inflicted. Four hours after the burn injury, the animals were killed, and the intestinal loops, mesenteric lymph nodes, spleen, liver, and lung were harvested. Intestinal loops were irrigated and then treated with ethylenedinitroilotetraacetic acid to separate the enterocytes and colonocytes from the lamina propria. Radionuclide counts were determined in the effluents, the enterocytes (or colonocytes), lamina propria, and other organs. Colony-forming units of Ecoliwere also determined in mesenteric lymph nodes, spleen, liver, and lung. Measurements and Main Results: No significant differences were noted in the radionuclide counts in the lamina propria and epithelial cell fraction related to the type of loop. In addition, no significant differences were noted in the radionuclide counts in the mesenteric lymph nodes, liver, spleen, and lung related to the type of loop, but more viable bacteria were recovered when bacteria were injected into the jejunal loop. Conclusions: Translocation of bacteria occurred with similar intensity throughout the gut, but more bacteria were killed in the process of translocation across the lower part of the intestinal tract. (Arch Surg. 1994;129:53-58)

Translocation of enteric bacteria from the gut to the mesenteric lymph nodes and beyond can cause life-threatening infection and multiple-organ failure in immunocompromised and traumatized patients. One of the conditions that promotes bacterial translocation is disruption of the normal gut flora, which results in bacterial overgrowth. In vitro methods were used to determine whether the fibers pectin, cellulose, chitosan, kaolin, lignin, or soy had bactericidal properties. Our results indicated that only chitosan and lignin significantly reduce microbial growth in vitro. A burned mouse model (20% total-body surface area) was used to study the effects of dietary lignin, cellulose, pectin, and chitosan on burn-induced bacterial translocation. Animals were fed a standard mouse diet containing no fiber, pectin, cellulose, lignin, or chitosan (10% of diet) for 14 days ad libitum. On day 14, all animals were burned. Four hours later the animals were killed and the mesenteric lymph nodes, spleen, liver, and cecum were aseptically harvested for determination of quantitative aerobic microbial growth. The animals which received chitosan, and lignin to a lesser extent, added to their diet had significantly lower levels of bacteria in the cecum, mesenteric lymph nodes, and liver. We suggest that addition of chitosan and possibly lignin to the diet may reduce the amount of bacterial translocation after burn injury, presumably by reducing the bacterial population of the cecum.

The aim of this study was to evaluate the ability of basic fibroblast growth factor (bFGF) and sucralfate to prevent bacterial translocation after burn injury. Four groups of Balb/c mice (n = 10/group) were treated by gavage with bFGF (10 micrograms/kg/d), sucralfate (15 mg/kg/d), bFGF plus sucralfate, or saline for 4 days prior to receiving a gavage with 1 x 10(10) 14C-radiolabeled Escherichia coli and a 20% full-thickness burn. Four hours after burn, the mesenteric lymph nodes, liver, spleen, and blood were harvested aseptically. For each tissue, the number of viable bacteria and radionuclide counts of the translocated 14C-labeled E. coli were measured, and the percentage of translocated organisms that remained alive was calculated. The results indicated that treatment with either bFGF or sucralfate alone had a partial effect on translocation, whereas the combined treatment with bFGF plus sucralfate significantly decreased the magnitude of translocation in all tested tissues (p < 0.05, ANOVA), which was associated with complete preservation of gut mucosal integrity. None of the treatments affected the ability of the host to kill translocated bacteria when the results were compared with those of the controls. The additive effect of the combined therapy may be due to the high affinity of sucralfate for bFGF, decreasing the degradation of bFGF by gastric acid.

The aim of this study was to investigate the ability of two prostaglandin E1 (PGE1) analogues, misoprostol and enisoprost, to alter bacterial translocation following burn injury. Balb/c mice were treated with misoprostol (n = 36) or enisoprost (n = 36) for 3 days with different doses (20 or 200 micrograms/kg/day) prior to receiving a 20% full-thickness burn and simultaneous gavage with 1 x 10(10) 14C-Escherichia coli. Animals were sacrificed 4 and 24 hr postburn, and blood, peritoneal fluid, mesenteric lymph nodes, spleen, liver, and lungs were harvested aseptically. Radionuclide counts, number of viable bacteria, and percentage of translocating bacteria remaining alive in each tissue suggested that the high doses of misoprostol or enisoprost decreased the magnitude of 14C-E. coli translocation, while the low dose of both drugs enhanced bacterial clearance. Therefore, both misoprostol and enisoprost reduce bacterial translocation, and modulate bacterial clearance in a dose-dependent manner.

Splanchnic ischemia is associated with increased bacterial translocation, but previous observations showed that translocation of Candida albicans did not occur uniformly among individual intestinal villi. This study was performed to investigate the relationship between the degree of Candida translocation and the microcirculation of individual villi. Thiry-Vella intestinal loops were created in eight guinea pigs. One week later, the distal aorta and right carotid artery were cannulated, and systemic blood pressure was recorded throughout the entire experiment. C. albicans (1 x 10(10)) was introduced into the Thiry-Vella loop, and the animals underwent a 40% full-thickness burn. Systolic hypotension was observed in the first 75 minutes postburn; then the systemic blood pressure returned to a normal range. Four hours after burn, 8 x 10(7) microspheres (10 microns) were injected into the aorta. The animals were sacrificed, and the Thiry-Vella loops were harvested and processed for light microscopy. At the microscopic level, within each villus, both the number of beads trapped in the arterioles and the number of Candida translocated into the enterocytes were counted. An inverse linear correlation between number of beads and number of translocated yeast per individual villus was found (r = -0.78; P < 0.005). These data provide further evidence that blood flow is an important determinant of the magnitude of microbial translocation, even within individual villi.

The authors present 4 cases of Krukenberg tumour of the ovary, secondary to carcinoma of the stomach (3 cases) and carcinoma of the breast (1 case). Pathologically it is characterized by the presence of typical signet ring cells and a diffuse infiltration of the stroma that gives the appearance of a sarcoma. Clinical data, computed tomography (CT) and sonographic findings in these four cases are analyzed. A review of the literature concerning this condition is provided and the treatment of the disease is discussed emphasizing the role of prophylactic oophorectomy.

The process of microbial translocation was studied using Candida albicans, Escherichia coli, or endotoxin instilled into Thiry-Vella loops of thermally injured guinea pigs and rats. Translocation of C. albicans occurred by direct penetration of enterocytes by a unique process different from classical phagocytosis. Translocation between enterocytes was not observed. Internalization was associated with a disturbance of the plasma membrane and brush border, but most internalized organisms were not surrounded by a plasma membrane. Passage of the candida into the lamina propria appeared to be associated with disruption of the basal membrane with extrusion of cytoplasm of the cell and candida. Organisms in the lamina propria were commonly phagocytized by macrophages but also were found free in lymphatics and blood vessels. Translocation of E. coli and endotoxin also occurred directly through enterocytes rather than between them, but translocated endotoxin diffused through the lamina propria and muscular wall of the bowel wall by passing between rather than through the myocytes. These descriptive phenomena provide new insight into the role of the enterocyte and intestinal immune cells in the translocation process.

The ability of perioperative short-term antibiotic prophylaxis to reduce the predictive significance of nutritional indicators for postoperative infections was evaluated in 162 patients undergoing major surgery for gastric or colorectal cancer. All patients were randomly assigned to a group receiving such prophylaxis or a group with postoperative antibiotic treatment. Preoperative serum albumin, total iron-binding capacity and weight loss were the nutritional indicators, and the evaluation included delayed hypersensitivity response. Postoperative infections occurred in 29% of the total series, with highest incidence in the group with postoperative antibiotics (p less than 0.001) and in anergic patients (p less than 0.05). Increased risk of postoperative infection was related also to the number of altered nutritional indicators (p less than 0.005). Multiple logistic analyses showed that the short-term prophylaxis independently contributed to fall in the infection rate and reduced the prognostic importance of nutritional and immunologic factors. Indeed, heightened incidence of postoperative infection was found only when all three nutritional factors were altered.

A case of giant adenoma of the kidney is described with special regard to the histological and ultrastructural features of the neoplastic cells. The tumoral proliferation consisted mainly of clear and dark epithelial cells among which cells of a third type are occasionally interspersed. A possible origin of this last population from the coelomatic lining is suggested and the hypothesis of a dysontogenetic nature of the neoplasia is proposed.