Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: A randomized, controlled trial.

UNLABELLED: Bleeding is a feared complication of invasive procedures in patients with cirrhosis and significant coagulopathy (as defined by routine coagulation tests) and is used to justify preprocedure use of fresh frozen plasma (FFP) and/or platelets (PLT). Thromboelastography (TEG) provides a more comprehensive global coagulation assessment than routine tests (international normalized ratio [INR] and platelet count), and its use may avoid unnecessary blood product transfusion in patients with cirrhosis and significant coagulopathy (defined in this study as INR >1.8 and/or platelet count <50 × 10(9) /L) who will be undergoing an invasive procedure. Sixty patients were randomly allocated to TEG-guided transfusion strategy or standard of care (SOC; 1:1 TEG:SOC). The TEG group would receive FFP if the reaction time (r) was >40 min and/or PLT if maximum amplitude (MA) was <30 mm. All SOC patients received FFP and/or PLT per hospital guidelines. Endpoints were blood product use and bleeding complications. Baseline characteristics of the two groups were similar. Per protocol, all subjects in the SOC group received blood product transfusions versus 5 in the TEG group (100% vs. 16.7%; P < 0.0001). Sixteen SOC (53.3%) received FFP, 10 (33.3%) PLT, and 4 (13.3%) both FFP and PLT. In the TEG group, none received FFP alone (P < 0.0001 vs. SOC), 2 received PLT (6.7%; P = 0.009 vs. SOC), and 3 both FFP and PLT (not significant). Postprocedure bleeding occurred in only 1 patient (SOC group) after large-volume paracentesis. CONCLUSIONS: In patients with cirrhosis and significant coagulopathy before invasive procedures, TEG-guided transfusion strategy leads to a significantly lower use of blood products compared to SOC (transfusion guided by INR and platelet count), without an increase in bleeding complications. Remarkably, even in patients with significant coagulopathy, postprocedure bleeding was rare, indicating that TEG thresholds should be reevaluated.

Immunological advantages of everolimus versus cyclosporin A in liver-transplanted recipients, as revealed by polychromatic flow cytometry.

Several immunosuppressive drugs with different mechanisms of action are available to inhibit organ rejection after transplant. We analyzed different phenotypic and functional immunological parameters in liver-transplanted patients who received cyclosporin A (CsA) or Everolimus (Evr). In peripheral blood mononuclear cells (PBMC) from 29 subjects receiving a liver transplant and treated with two different immunosuppressive regimens, we analyzed T cell activation and differentiation, regulatory T cells (Tregs) and Tregs expressing homing receptors such as the chemokine receptor CXCR3. T cell polyfunctionality was studied by stimulating cells with the superantigen staphylococcal enterotoxin B (SEB), and measuring the simultaneous production of interleukin (IL)-2 and interferon (IFN)-γ, along with the expression of a marker of cytotoxicity such as CD107a. The analyses were performed by polychromatic flow cytometry before transplantation, and at different time points, up to 220 days after transplant. Patients taking Evr had a higher percentage of total CD4⁺ and naïve CD4⁺ T cells than those treated with CsA; the percentage of CD8⁺ T cells was lower, but the frequency of naïve CD8⁺ T cells higher. Patients taking Evr showed a significantly higher percentage of Tregs, and Tregs expressing CXCR3. After stimulation with SEB, CD8⁺ T cells from Evr-treated patients displayed a lower total response, and less IFN-γ producing cells. The effects on the immune system, such as the preservation of the naïve T cell pool and the expansion of Tregs (that are extremely useful in inhibiting organ rejection), along with the higher tolerability of Evr, suggest that this drug can be safely used after liver transplantation, and likely offers immunological advantages.

HHV-6A in syncytial giant-cell hepatitis.

Syncytial giant-cell hepatitis is a rare but severe form of hepatitis that is associated with autoimmune diseases, drug reactions, and viral infections. We used serologic, molecular, and immunohistochemical methods to search for an infectious cause in a case of syncytial giant-cell hepatitis that developed in a liver-transplant recipient who had latent infection with variant B of human herpesvirus 6 (HHV-6B) and who had received the organ from a donor with variant A latent infection (HHV-6A). At the onset of the disease, the detection of HHV-6A (but not HHV-6B) DNA in plasma, in affected liver tissue, and in single micromanipulated syncytial giant cells with the use of two different polymerase-chain-reaction (PCR) assays indicated the presence of active HHV-6A infection in the patient. Expression of the HHV-6A-specific early protein, p41/38, but not of the HHV-6B-specific late protein, p101, was demonstrated only in liver syncytial giant cells in the absence of other infectious pathogens. The same markers of HHV-6A active infection were documented in serial follow-up samples from the patient and disappeared only at the resolution of syncytial giant-cell hepatitis. Neither HHV-6B DNA nor late protein was identified in the same follow-up samples from the patient. Thus, HHV-6A may be a cause of syncytial giant-cell hepatitis.

Role of chemoembolization as a rescue treatment for recurrence of resected hepatoblastoma in adult patients.

INTRODUCTION: Hepatoblastoma is the most common malignant liver tumor in children, but it is extremely rare in adults. MATERIALS AND METHODS: A 33-year-old man was admitted with nausea, vomiting, weight loss, and right upper quadrant pain. A preoperative magnetic resonance imaging showed a nodular hepatic lesion infiltrating the lesser curvature of the stomach. A left hepatectomy and a subtotal gastrectomy were performed. The histological diagnosis was hepatoblastoma. A recurrence in the right lobe was seen. RESULTS: Three cycles of transcatheter arterial chemoembolization (TACE) were performed 40, 70, and 130 days after surgery. No sign of recurrence was present at the time of the second chemoembolization. CONCLUSION: The TACE was well tolerated by the patient and controlled the recurrence. The patient survived 11 months after recurrence of disease and died 1 year after the liver resection. The use of TACE to treat the hepatic recurrence was never described.

Comparison of the prognostic accuracy of the sixth and seventh editions of the TNM classification for intrahepatic cholangiocarcinoma.

BACKGROUND: The seventh TNM edition introduced a new, specific staging structure for intrahepatic cholangiocarcinoma (IHC). OBJECTIVE: To compare the accuracy of the sixth and the new seventh edition to predict survival after hepatectomy for IHC. METHODS: In all, 434 consecutive patients who underwent hepatectomy at 16 tertiary-care centres (1990-2008) were identified. End points were overall (OS) and recurrence-free survival (RFS) for both T cohorts and stage strata. RESULTS: After a median follow-up of 32.4 months, 3- and 5-year OS and RFS estimates were 47.1% and 32.9%, and 26.5% and 19.1%, respectively. Overall, both the editions were statistically significant discriminators of OS and RFS (P < 0.05). However, the survival curves of the new T2a and T2b cohorts appear superimposed. Conversely, the old T2 and T3 cohorts accurately stratify patients into distinct prognostic groups (P < 0.01). The seventh edition does not show monotonicity of gradients (the T4 category demonstrates significantly better OS and RFS compared with T2 patients). The seventh edition stage I and II are significantly different whereas the old stage I and II were not. CONCLUSIONS: The new seventh edition of the AJCC/UICC Staging System proved to be adequate although further studies are need to confirm its superiority compared with the previous edition.

Intermittent gastric outlet obstruction due to a gallstone migrated through a cholecysto-gastric fistula: a new variant of "Bouveret's syndrome".

Bouveret's syndrome, defined as gastric outlet obstruction due to a large gallstone, is still one of the most dramatic biliary gallstone complications. Although new radiological and endoscopic techniques have made pre-surgical diagnosis possible in most cases and the death rate has dropped dramatically, "one-stage surgery" (biliary surgery carried out at the same time as the removal of the gut obstruction) should be still considered as the gold standard for the treatment of gallstone ileus.In this case, partial gastric outlet obstruction resulted in an atypical and insidious clinical presentation that allowed us to perform the conventional one-stage laparatomic procedure that completely solved the problem, thus avoiding any further complications.

Laboratory test variability and model for end-stage liver disease score calculation: effect on liver allocation and proposal for adjustment.

BACKGROUND: The use of the Model for End-Stage Liver Disease (MELD) score to prioritize patients on liver waiting lists must take the bias of different laboratories into account. METHODS: We evaluated the outcome of 418 patients listed during 1 year whose MELD score was computed by two laboratories (lab 1 and lab 2). The two labs had different normality ranges for bilirubin (maximal normal value [Vmax]: 1.1 for lab 1 and 1.2 for lab 2) and creatinine (Vmax: 1.2 for lab 1 and 1.4 for lab 2). The outcome during the waiting time was evaluated by considering the liver transplantations and the dropouts, which included deaths on the list, tumor progression, and patients who were too sick. RESULTS: Although the clinical features of patients were similar between the two laboratories, 36 (13.1%) out of 275 were dropped from the list in lab 1, compared to 5 (3.5%) out of 143 in lab 2 (P<0.01). The differences were mainly due to the deaths on the list (8% lab 1 vs. 2.1% lab 2, P<0.05). The competing risk analysis confirmed the different risk of dropout between the two labs independently of the MELD score, blood group, and preoperative diagnosis. The bias on MELD calculation was considered and bilirubin and creatinine values were "normalized" to Vmax of lab 1 (corrected value=measured value x Vmax lab 1/Vmax lab 2). By comparing receiver operating characteristic curves, the ability of MELD to predict the 6-month dropouts significantly increased from an area under the curve of 0.703 to 0.716 after "normalization" (P<0.05). CONCLUSIONS: Normalization of MELD is a correct and good compromise to avoid systematic bias due to different laboratory methods.

Preoperative selective portal vein embolization (PSPVE) before major hepatic resection. Effectiveness of Doppler estimation of hepatic blood flow to predict the hypertrophy rate of non-embolized liver segments.

Hepatocellular carcinoma may be unresectable for volumetric reasons. The future remaining liver after hepatectomy might be too small to ensure survival. Preoperative selective portal vein embolization of the tumorous lobe can induce hypertrophy of the future remaining liver and enable safer surgery. A 76-year-old patient with hepatocellular carcinoma needed right lobectomy however, the future remaining liver was judged insufficient to ensure an uneventful postoperative course. The left lobe to whole liver volumetric ratio was to small (29.7%) and a preoperative selective portal vein embolization of the right portal branch via a percutaneous, transhepatic, contralateral approach was performed without side effects. A Doppler estimation of left branch portal blood flow and velocity was carried out before and after preoperative selective portal vein embolization. After 21 days the left lobe volume increased by about 44.2% with a safe left lobe/whole liver ratio of 40.8%. The portal blood flow and portal blood flow velocity showed an increase of 253% and 122%, respectively. A right lobectomy was performed without complications. Three months later, computed tomography scan showed no hepatocellular carcinoma recurrence. Preoperative selective portal vein embolization is a safe technique which can enable major hepatectomy to be performed in situations otherwise judged unresectable for a life-threatening volumetric insufficiency. The portal blood flow and portal blood flow velocity evaluations can easily predict the hypertrophy rate of non-embolized liver segments.

Treatment of wounds colonized by multidrug resistant organisms in immune-compromised patients: a retrospective case series.

BACKGROUND: Immune-compromised patients incur a high risk of surgical wound dehiscence and colonization by multidrug resistant organisms. Common treatment has been debridement and spontaneous secondary healing.We report on the results obtained in nine such patients whose wounds were treated by debridement, negative pressure dressing and direct closure. METHODS: All immune-compromised patients referred to our Institution between March 1, 2010 and November 30, 2011 for dehiscent abdominal wounds growing multidrug resistant organisms were treated by serial wound debridements and negative pressure dressing. They were primarily closed, despite positive microbiological cultures, when clinical appearance was satisfactory.As a comparison, records from patients treated between March 1, 2008 and February 28, 2010 who, according to our Institution's policy at that time, had been left to heal by secondary intention, were retrieved and examined. RESULTS: Nine patients were treated by direct wound closure, five had been treated previously by secondary intention healing.Overall, ten patients had received liver transplant, 1 kidney transplant, 1 was HIV infected, 1 suffered from multi-organ failure, 1 was undergoing hemodialysis.Wound dehiscence involved skin and subcutaneous layers in all patients, in two the muscular layer was also involved.Mean healing time was significantly shorter in patients treated more recently by primary intention in comparison with historical patients (28 vs 81 days). The only complication observed was a small superficial abscess that developed around a non-absorbable stitch 10 months after closure in a patient treated by primary closure. CONCLUSIONS: According to our results, fast healing can be safely obtained by closure of a clinically healthy wound, despite growth of multidrug resistant organisms, even in immune-compromised patients.

A Randomized Multicenter Study Comparing a Tacrolimus-Based Protocol with and without Steroids in HCV-Positive Liver Allograft Recipients.

Allograft reinfection with hepatitis C virus (HCV) occurs universally in liver transplant recipients. Corticosteroids can contribute to HCV recurrence. This randomized study evaluated HCV recurrence in HCV-positive liver allograft recipients using steroid-free immunosuppression. All patients received tacrolimus (TAC) at an initial dose of 0.10-0.15 mg/kg. The steroid-free arm (TAC/daclizumab (TAC/DAC, n = 67)) received daclizumab induction, and the steroid arm (TAC/steroid (TAC/STR, n = 68)) received a steroid bolus (≤ 500mg) followed by 15-20 mg/day with discontinuation after month 3. Median HCV viral load at month 12, the primary endpoint, was similar at 5.46 (0.95-6.54) IU/mL with TAC/DAC and 5.91 (0.95-6.89) IU/mL with TAC/STR. Small numerical differences in the estimated rate of freedom from HCV recurrence (19.1 versus 13.8%) and freedom from biopsy proven rejection (78.4 versus 66.1%) were observed between TAC/DAC and TAC/STR. Patient survival estimates were significantly lower with TAC/DAC than with TAC/STR (83.1 versus 95.5%; 95% CI, -0.227 to -0.019%), and graft survival was numerically lower (80.1 versus 91.1%, P = NS). Completion rates (45 versus 82%) indicated poorer tolerability with TAC/DAC than with TAC/STR. Steroid-free immunosuppression had no real impact on HCV viral load. HCV recurrence was higher with TAC/STR. Results are inconclusive due to the unexpected lower completion rates in the TAC/DAC arm.

Surgical Approach for Long-term Survival of Patients With Intrahepatic Cholangiocarcinoma: A Multi-institutional Analysis of 434 Patients.

OBJECTIVES To examine the outcomes of a hepatectomy for intrahepatic cholangiocarcinoma (IHC) and to clarify the prognostic impact of a lymphadenectomy and the surgical margin. Large series of patients who were surgically treated for IHC are scarce. Thus, prognostic factors and long-term survival after resection of IHC remain uncertain. DESIGN Prospective study of patients who were surgically treated for IHC. Clinicopathologic, operative, and long-term survival data were analyzed. SETTING Prospectively collected data of all consecutive patients with pathologically confirmed IHC who had undergone liver resection with a curative intent at 1 of 16 tertiary referral centers were entered into a multi-institutional registry. PATIENTS All consecutive patients who underwent a hepatectomy with a curative intent for IHC (1990-2008) were identified from a multi-institutional registry. RESULTS A total of 434 patients were included in the analysis. Most patients underwent a major or extended hepatectomy (70.0%) and a systematic lymphadenectomy (62.2%). The incidence of lymph node metastases (overall, 36.9%) increased with increased tumor size, with 24.4% of patients with a small IHC (diameter ≤3 cm) having N1 disease. Almost one-third of patients required an additional major procedure to obtain a R0 resection in 84.6% of the cases. In these patients, the median time of survival was 39 months, and the 5-year survival rate was 39.8%. Lymph node metastases (hazard ratio, 2.21; P < .001), multiple tumors (hazard ratio, 1.50; P = .009), and an elevated preoperative cancer antigen 19.9 level (hazard ratio, 1.62; P = .006) independently predicted an adverse prognosis. Conversely, survival was not influenced by the width of a negative resection margin (P = .61). The potential survival benefit of a lymphadenectomy was assessed with the therapeutic value index, which was calculated to be 5.9 points. CONCLUSIONS Survival rates after a hepatectomy with a curative intent for IHC at tertiary referral centers exceed the survival rates reported in most study series in single institutions, which strengthens the value of an aggressive approach to radical resection. Lymph node metastases and multiple tumors are associated with decreased survival rates, but they should not be considered selection criteria that prevent other patients from undergoing a potentially curative resection. Lymphadenectomy should be considered for all patients.

Fusarium verticillioides fungemia in a liver transplantation patient: successful treatment with voriconazole.

Fusarium is an opportunistic fungal pathogen which is emerging as a significant cause of morbidity and mortality in immunocompromised hosts. We present a rare case of F. verticillioides fungemia that occurred in a patient who underwent a second orthotopic liver transplantation for chronic rejection and completely responded to treatment with voriconazole.

Long-term follow-up and outcome of liver transplantation from anti-hepatitis C virus-positive donors: a European multicentric case-control study.

BACKGROUND: The growing prevalence of hepatitis C virus (HCV) infection in the general population has resulted in an increased frequency of potential organ donors that carry the virus. Given the significant disparity between organ supply and demand for transplantation, it becomes essential to consider whether livers from anti-HCV-positive donors may be considered suitable for transplantation. METHODS: Based on a multicenter European database, 694 patients with HCV-related cirrhosis underwent liver transplantation and 11% of them received the graft from anti-HCV-positive donors. Of this group, we selected 63 patients (study group) and, after a 1:1 case-control approach, compared them with 63 patients that received an anti-HCV-negative donor graft (control group). Only grafts with preperfusion liver biopsy results with a fibrosis score of not more than 1 were used for transplantation. RESULTS: Patients who received anti-HCV-positive grafts had a cumulative survival rate of 83.6% and 61.7% at 1 and 5 years, respectively, vs. 95.1% and 68.2% for the control group. In comparing overall patient and graft survival, there was no statistically significant difference between the two groups (P=0.22 and 0.11). Recurrence of hepatitis C tended to be more rapid in the group of patients who received anti-HCV-positive grafts, although it did not reach statistical significance (P=0.07). CONCLUSIONS: We do not recommend the indiscriminate use of anti-HCV-positive donors, especially if HCV-RNA positive, as the use of this kind of graft could be linked to an advanced stage of fibrosis, the main risk factor we observed for earlier hepatitis C recurrence.

Pancreatic metastases from renal cell carcinoma: the state of the art.

Pancreatic metastases are rare, with a reported incidence varying from 1.6% to 11% in autopsy studies of patients with advanced malignancy. In clinical series, the frequency of pancreatic metastases ranges from 2% to 5% of all pancreatic malignant tumors. However, the pancreas is an elective site for metastases from carcinoma of the kidney and this peculiarity has been reported by several studies. The epidemiology, clinical presentation, and treatment of pancreatic metastases from renal cell carcinoma are known from single-institution case reports and literature reviews. There is currently very limited experience with the surgical resection of isolated pancreatic metastasis, and the role of surgery in the management of these patients has not been clearly defined. In fact, for many years pancreatic resections were associated with high rates of morbidity and mortality, and metastatic disease to the pancreas was considered to be a terminal-stage condition. More recently, a significant reduction in the operative risk following major pancreatic surgery has been demonstrated, thus extending the indication for these operations to patients with metastatic disease.

Liver resection for colorectal metastases in older adults: a paired matched analysis.

OBJECTIVES: To assess the safety and long-term results of hepatic resection of colorectal liver metastases (CLM) in older adults. DESIGN: Case-control. SETTING: Single liver and multivisceral transplant center. PARTICIPANTS: Individuals with CLM: 32 aged 70 and older (older group) and 32 younger than 70 (younger group) matched in a 1:1 ratio according to sex, primary tumor site, liver metastases at diagnosis, number of metastases, maximum tumor size, infiltration of cut margin, type of hepatic resection, and hepatic resection timing. MEASUREMENTS: Postoperative complications and survival rates. RESULTS: There was no significant difference in preoperative clinical findings between the two study groups. The incidence of cumulative postoperative complications was similar in the older (28.1%) and younger (34.4%) groups (P = .10). One-, 3-, and 5-year disease-free survival rates were 57.6%, 32.9%, and 16.4%, respectively, in the younger group and 67.9%, 29.2%, and 19.5%, respectively, in the older group (P = .72). One-, 3-, and 5-year participant survival rates were 84.1%, 51.9%, and 33.3%, respectively, in the older group and 93.6%, 63%, and 28%, respectively, in the younger group (P = .50). CONCLUSIONS: Resection of colorectal liver metastases in older adults can be performed with low mortality and morbidity and offers a long-time survival advantage to many of these individuals. Based on the results of this case-control study, older adults should be considered for surgical treatment whenever possible.

Do not deny pancreatic resection to elderly patients.

INTRODUCTION: Radical resection is the only potential cure for pancreatic malignancies and a useful treatment for other benign diseases, such as pancreatitis. Over the last two decades, medical and surgical improvements have drastically changed the postoperative outcome of elderly patients undergoing pancreatic resection, and appropriate treatment for elderly potential candidates for pancreatic resection has become an important issue. MATERIALS AND METHODS: Ninety-eight consecutive patients undergoing radical pancreatic resection between 2003 and 2006 at the Surgery Unit of the University of Modena, Italy, were considered and divided into two age groups, i.e., over 75-year-olds (group 1, 23 patients) and under 75-year-olds (group 2, 75 patients). The two groups were compared as regards demographic features, American Society of Anesthesiologists scores, comorbidities, previous major surgery, surgical procedure, postoperative mortality, and morbidity. RESULTS: There were no significant differences between the two groups concerning postoperative mortality, and the duration of hospital stay and days in the postoperative intensive care unit were also similar. Complications such as pancreatic fistulas, wound infections, and pneumonia were more frequent in the older group, but the differences were not statistically significant. The overall median survival was 29.4 months and did not differ significantly between the two groups when calculated using the log-rank test (p = 0.961). DISCUSSION: In the light of these findings and as reported for other series, old age is probably not directly related with any increase in the rate of postoperative complications, but comorbidities (which are naturally related to the patients' previous life) may have a key role in the postoperative course.

Cystic pancreatic neuroendocrine neoplasms with uncertain malignant potential: report of two cases.

Neuroendocrine tumors of the pancreas (NETP) represent only 1%-2% of all pancreatic neoplasms. They can be classified as functioning or non-functioning, respectively, according to the presence or absence of paraneoplastic syndrome. Case 1 concerned a 70-year-old woman with a cystic lesion of the pancreatic head and body. All tumor markers were negative. The patient underwent a distal pancreatectomy. The histology revealed a well-differentiated endocrine tumor with uncertain malignant potential. Case 2 was a 61-year-old man with chronic polyserositis. The serum tumor markers were negative, while he was strongly positive for intracystic tumor markers carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, and CA 125. The patient underwent a cephalo-pancreatic duodenectomy. The preoperative differential diagnosis of cystic NETP is still a challenge due to the high rate of the nonfunctional variant. Although cystic NETPs are well differentiated, they are still tumors with a malignant potential, and therefore an early diagnosis and radical surgical resection could be associated with a better long-term survival.