Aristotelis Perrakis

Management of the focal nodular hyperplasia of the liver: evaluation of the surgical treatment comparing with observation only

BACKGROUND Long-term results of both surgery and observation for patients with focal nodular hyperplasia (FNH) in a large single-center experience do not exist. Accordingly, the aim of this study was to compare long-term outcomes in patients with FNH who underwent either elective hepatectomy or observation alone. METHODS A retrospective single-institution analysis of 185 patients with FNH, treated from 1990 to 2009, was performed. RESULTS Seventy-eight patients underwent elective hepatectomy and 107 patients observation alone, with a median follow-up period of 113 months. There was no perioperative mortality. Postoperative complications were recorded in 12 patients, and 92% of patients reported symptomatic reductions. Among observation patients, 9 (13%) developed additional symptoms; tumor enlargement was seen in 3 patients (4%). CONCLUSIONS Elective liver resection for FNH is a safe procedure at high-volume centers. This single-center experience showed that 13% of observed patients had protracted symptoms. This justifies the therapeutic algorithm that elective surgery should be considered in symptomatic patients or in those with marked enlargement.

Procalcitonin in the Setting of Complicated Postoperative Course after Liver Transplantation

BACKGROUND Orthotopic liver transplantation (OLT) is a treatment for end-stage liver disease. The shortage of available organs leads to the acceptance of marginal grafts, thereby increasing the risk of perioperative complications such as acute rejection, infection, and graft dysfunction Procalcitonin (PCT) has been shown to be a reliable marker for a complicated course after traumatic injury as well as in the courses of systemic inflammatory response syndrome and sepsis. The aim of our study was to evaluate PCT as an early prognostic marker for the occurrence of complication during the postoperative course after OLT. METHOD We analyzed PCT levels and clinical and paraclinical data of 32 patients who underwent 33 OLTs. The highest PCT was termed as peak-PCT. Patients were stratified into noncomplication and complication groups. Renal replacement therapy, respiratory insufficiency, postoperative bleeding, refractory ascites, pleural effusion, rejection, sepsis, and fatal outcome were defined as complications. A secondary stratification, using a peak-PCT of 5 ng/mL, was used to analyzed the risk of a complication. We also analyzed the course of PCT after OLT in each group. RESULTS The peak-PCT, which occurred between the first and third postoperative day in 30 patients, was followed by halving of the value every second day. Three subjects died because of sepsis. A constantly rising PCT or a secondary rise observed in 2 patients was associated with a fatal outcome. The noncomplication group included 18 patients, 8 of them showing a peakPCT <5 ng/mL and 10 above. The complication group included 14 patients who underwent 15 transplantations; Only 1 displayed a peakPCT <5 ng/mL. When the peak-PCT was >5 ng/mL, the odds ratio of a complication was 11.2 (95% Confidence interval, 10.81-11.59; P < .025). However, not before the 7th postoperative day was the course of mean PCT levels significantly different between the complication and noncomplication groups. In transplant patients, an elevation of PCT was observed only in the presence of bacterial infection and not rejection or wound infection. PCT rose during respiratory failure and sepsis, but not renal replacement therapy, ascites, pleural effusion, rejection, or bleeding. CONCLUSION PCT was a reliable marker. A decline was observed in 31 cases with subject, who both had fatal outcomes showing a constantly rising level. An initial high PCT indicated a poor prognosis; some members of the noncomplication group also had levels >15 ng/mL. The patients in the complication group showed a higher mean PCT, which was significant at 7 days, most probably because of the high variation among levels. Still, a peak-PCT >5 ng/mL showed an odds ratio of 11.2 for patients to experience a complication.

Biliary Tract Complications after Orthotopic Liver Transplantation: Still the “Achilles Heel”?

Postoperative biliary tract complications after liver transplantation (LT) still lead to early and late morbidity and mortality. Modern interventional endoscopic techniques can replace surgical repair as the first line of treatment. Nevertheless surgical intervention plays an important role in specific situations. We performed a retrospective analysis of patients with biliary complications after LT over a 12-year period. We compared treatment programs based on duration and success rate. The rate of biliary complications was 24.5% (60/245). The side-to-side choledocholedochostomy (CDC) technique showed the significantly lowest rate. The rate of complications after hepaticojejunostomy (HJS) was considerably lower, albeit not significantly. Eighty-one percent of complications after CDC were treated with interventional endoscopy. The duration of treatment of strictures, was 10 times greater than that of leakages. Surgical repair was necessary for 19% of complications occurring after CDC. The treatment options after HJS largely comprised surgical repairs. From a surgical standpoint, choosing the correct method for biliary reconstruction and ensuring normal arterial flow are the best preventive techniques to avoid biliary complications. Over the past 10 years, the primary treatment regimen has moved from surgical repair to interventional endoscopy. Only when endoscopy fails, should one consider surgical repair. The treatment after HJS is still primarily surgical. Percutaneous transhepatic approaches should be avoided. Creation of an inspection stoma to allow endoscopic access is an option.

Pioneering Robotic Liver Surgery in Germany: First Experiences with Liver Malignancies.

Background Minimally invasive liver surgery is growing worldwide with obvious benefits for the treated patients. These procedures maybe improved by robotic techniques, which add several innovative features. In Germany, we were the first surgical department implementing robotic assisted minimally invasive liver resections. Material and methods Between June 2013 and March 2015, we performed robotic based minimally invasive liver resections in nine patients with malignant liver disease. Five off these patients suffered from primary and four from secondary liver malignancies. We retrospectively analyzed the perioperative variables of these patients and the oncological follow up. Results Mean age of the patients was 63 years (range 45–71). One patient suffered from intrahepatic cholangiocellular, four from hepatocellular carcinoma, and four patients from colorectal liver metastases. In six patients, left lateral liver resection, in two cases single segment resection, and in one case minimally invasive guided liver ablation were performed. Five patients underwent previous abdominal surgery. Mean operation time was 312 min (range 115–458 min). Mean weight of the liver specimens was 182 g (range 62–260 g) and mean estimated blood loss was 251 ml (range 10–650 ml). The mean tumor size was 4.4 cm (range 3.5–5.5 cm). In all cases, R0 status was confirmed with a mean margin of 0.6 cm (range 0.1–1.5 cm). One patient developed small bowel fistula on postoperative day 5, which could be treated conservatively. No patient died. Mean hospital stay of the patients was 6 days (range 3–10 days). During a mean follow up of 12 months (range 1–21 months), two patients developed tumor recurrence. Conclusion Robotic-based liver surgery is feasible in patients with primary and secondary liver malignancies. To achieve perioperative parameters comparable to open settings, the learning curve must be passed. Minor liver resections are good candidates to start this technique. But the huge benefits of robotic-based liver resections should be expected in extended procedures beyond minor liver resections with the currently available technology.

The Effect and Safety of the Treatment of Recurrent Hepatitis C Infection After Orthotopic Liver Transplantation With Pegylated Interferon α2b and Ribavirin

INTRODUCTION Recurrent hepatitis C infection in the posttransplant setting is a serious problem. The aim of this study was to evaluate the efficacy, safety, indications, optimal time of administration and adequate duration of antiviral therapy with pegylated interferon alpha 2 b (PEG-IFN) and ribavirin (RIB). PATIENTS AND METHODS Between 2003 and 2009, 16 patients received antiviral therapy (PEG-IFN: 0.8-1.6 μg/kg/wk, RIB 800-1200 mg/d) for at least 6 months. Patients with a biochemical without a virologicalresponse after 12 months of therapy received antiviral treatment for a further 6 months. Hepatitis C virus load was determined at 1, 3, 6, and 12 months after start of therapy. Liver biopsy was performed in all patients before the beginning and after the end of treatment. RESULTS The mean period of antiviral therapy was 14 months. The four patients who received the full-length treatment (12 months, 33%) showed sustained virological responses (SVR) and 8 showed virological and biochemical responses (VR, BR). Patients with SVR showed significant improvement in the grading and staging of HAI (histological activity index; P=.03). Nine patients had several side effects under antiviral treatment. Acute rejection episodes were not observed. CONCLUSION The antiviral treatment combination using PEG-IFN and RIB for recurrent hepatitis C is effective procedure. The SVR of 33% after 12 months of treatment with significant improvement in HAI grading and staging and stable HAI in all treated patients favor early initiation and 12-month administration of antiviral treatment. Furthermore, all patients with BR without VR, who underwent antiviral treatment for a further 6 months, achieved a VR. However, the optimal duration of treatment needs to be investigated in large prospective studies.

Impact of the Conversion of the Immunosuppressive Regimen from Prograf to Advagraf or to Sirolimus in Long-term Stable Liver Transplant Recipients: Indications, Safety, and Outcome

BACKGROUND Compliance problems have arisen due to the twice a day administration of calcineurin inhibitors (CNI). We examined the safety, indications, and efficacy in terms of graft and patient survivals after conversion from tacrolimus to sirolimus or advagraf. PATIENTS AND METHODS Between January 2006 and December 2009, 36 orthotopic liver transplantation patients underwent conversion of the immunosuppressive regimen from prograf to either sirolimus (group 1; n=10) or advagraf (group 2; n=26). A group of patients taking prograf was used as a control group (group 3; n=15). We identified 51 patients of mean age 57 years and male:female percentages of 57%:43% from a prospective database. Renal and liver graft functions, patient survival, as well as laboratory and clinical data over at least 12 months (mean, 38) were the investigated parameters. RESULTS Patients converted to sirolimus did not show significantly improved renal function at 12 months as evidenced by creatinine levels (1.31 mg/dL+/-0.47 vs 1.34 mg/dL+/-0.78) and glomerular filtration rate (GFR, 57+/-16 vs 56+/-16 mL/min). However, there were significant antiproliferative effects. Patients with a hepatocellular carcinoma in the pretransplantation phase remained without a recurrence. The side effects including ankle edema, aphthae, and tachyarrhythmia absoluta, required reconversion to the CNI. Patients prescribed advagraf reported a better life quality because of the single administration and a slight, insignificant improvement in renal function. An acute rejection episode was evidenced under either immunosuppresant. CONCLUSION Sirolimus is a safe immunosuppressive option in liver transplant recipients suffering from hepatocellular carcinoma. Advagraf showed a lower incidence of side effects than prograf and probably is not as harmful for renal function, offering better compliance and better life quality.

The Value of Pre-emptive Therapy for Cytomegalovirus after Liver Transplantation

BACKGROUND Cytomegalovirus (CMV) infections are among the most common infections following liver transplantation. The main preventive methods for CMV infections are universal prophylaxis and pre-emptive therapy. In our study, we adopted a pre-emptive strategy in a higth-risk group of donor CMV-positive (D+)/recipient CMV-negative (R-) casses. We investigated whether this strategy was safe and effective to prevent CMV disease. METHODS One hundred fifty-nine liver transplantation recipients who underwent over a 15-year period were retrospectively analyzed after follow-up for at least 6 months (mean, 63 months). Weekly quantitative polymerase chain reaction (PCR) measurements were performed to detect viral DNA. No CMV drug prophylaxis was given: antiviral CMV therapy was initiated when the PCR for CMV-DNA was >400 copies/mL. RESULTS Fifty-one of 159 liver transplant recipients enrolled in the study received antiviral therapy. High-risk patients (D+/R-) developed CMV infections significantly more often than D-/R- serostatus (P = .005). CMV disease was diagnosed in 12% of CMV-positive patients. Independent of serostatus in 14 cases (27.5%) virological recurrence of CMV infection occurred after primary treatment. Survival analysis showed no significant difference between patients with versus without CMV infection (P = .950). No relationship could be found between transplant rejection and CMV infection (P = .349). CONCLUSION Our results showed that a pre-emptive strategy to prevent CMV disease was possible, even among the serological high-risk group. Only 12% of cases with CMV infection went on to manifest CMV disease with organ involvement. Survival curves were similar among patients with versus without CMV infections.

Long-term outcome of liver transplantation as treatment modality in patients with hepatocellular carcinoma in cirrhosis: a single-center experience.

BACKGROUND Hepatocellular carcinoma (HCC) is among the most frequent malignant diseases worldwide. In the vast majority of cases, it is associated with liver cirrhosis. Liver transplantation (OLT) is potentially the gold standard treatment for patients suffering HCC in cirrhosis, because of synchronous eradication of HCC and of the underlying hepatic disease. The aim of this study was to evaluate long-term outcomes of OLT in HCC patients. MATERIAL AND METHODS Between January 2000 and December 2011, 43 patients who were diagnosed with HCC in liver cirrhosis and underwent OLT in our department, were identified from a prospective database. All patients received their grafts from deceased donors. We analyzed demographic data, laboratory values, number and size of lesions, primary liver disease, diagnostic methods, bridging therapy modalities, and postoperative outcomes, including complications, recurrences, and their treatment. RESULTS Patient follow-up as of January 2012 or to death ranged from 0 to 138 months (median, 59; mean, 63). None of the patients were lost to follow-up. The gender bias was 85%:15% (male:female) and the median age, 57.8 years (range, 44-69). The most common underlying diseases for cirrhosis and HCC were alcoholic (n = 12) and hepatitis C (n = 16). Thirty-one subjects underwent bridging therapy through transarterial chemoembolization (TACE), and/or radiofrequency ablation. All patients underwent OLT within the Milan criteria according to the preoperative evaluation and histopathologic examination of the explanted liver. Twenty-one of them suffered postoperative complications (48.8%). HCC recurrence, which occurred in 5 (10.4%), was treated by surgery (n = 3), systemic chemotherapy with sorafenib (n = 1), or TACE (n = 1). CONCLUSIONS OLT for HCC in cirrhosis, displays a relatively high complication rate. It shows good survivals with and low recurrence.

What is Changing in Indications and Treatment of Focal Nodular Hyperplasia of the Liver. Is There Any Place for Surgery

Focal nodular hyperplasia (FNH) is a common benign liver tumor, which occurs in the vast majority of the cases in young women. FNH represents a polyclonal lesion characterized by local vascular abnormalities and is a truly benign lesion without any potential for malignant transformation. A retrospective single institution analysis of 227 FNH patients, treated from 1990 to 2016 and a review of studies reporting surgical therapy of overall 293 patients with FNH was performed. Indications for resection with a focus on diagnostic workup, patient selection, surgical mode and operative mortality and morbidity have been analysed. Ninety three patients underwent elective hepatectomy and 134 patients observation alone, where median follow-up was 107 months. Postoperative complications were recorded in 14 patients, 92% of patients reported an improvement with respect to their symptoms. Overall among 293 patients underwent surgery in the series, included to this review, there was a morbidity of 13%, where median follow-up was 53 months. Systematic follow-up remains the gold standard in asymptomatic patients with FNH. However elective surgery should be considered in symptomatic patients, in those with marked enlargement and in case of uncertainty of diagnosis. Surgery for FNH is a safe procedure with low morbidity and very good long term results as far as quality of life after surgery is concerned and surely an integral part of the modern management of FNH.Focal nodular hyperplasia (FNH) is a common benign liver tumor, which occurs in the vast majority of the cases in young women. FNH represents a polyclonal lesion characterized by local vascular abnormalities and is a truly benign lesion without any potential for malignant transformation. A retrospective single institution analysis of 227 FNH patients, treated from 1990 to 2016 and a review of studies reporting surgical therapy of overall 293 patients with FNH was performed. Indications for resection with a focus on diagnostic workup, patient selection, surgical mode and operative mortality and morbidity have been analysed. Ninety three patients underwent elective hepatectomy and 134 patients observation alone, where median follow-up was 107 months. Postoperative complications were recorded in 14 patients, 92% of patients reported an improvement with respect to their symptoms. Overall among 293 patients underwent surgery in the series, included to this review, there was a morbidity of 13%, where median follow-up was 53 months. Systematic follow-up remains the gold standard in asymptomatic patients with FNH. However elective surgery should be considered in symptomatic patients, in those with marked enlargement and in case of uncertainty of diagnosis. Surgery for FNH is a safe procedure with low morbidity and very good long term results as far as quality of life after surgery is concerned and surely an integral part of the modern management of FNH.

Prognostic and diagnostic value of procalcitonin in the post-transplant setting after liver transplantation

Introduction The aim of the study was to assess the diagnostic accuracy of procalcitonin (PCT) as a marker for complications and as a prognostic factor for mortality after liver transplantation. Material and methods Liver transplant patients between January 2007 and April 2011 were prospectively included in the study. Procalcitonin serum concentration was recorded before, 6 h after reperfusion and then daily. Postoperative clinical course was prospectively analyzed from admission to discharge. Main surgical data such as operating procedure, type of reperfusion, operating and ischemic times, high urgency (HU) status and MELD score at the time of transplantation were also recorded. Results Sixteen patients with initial PCT > 5 ng/ml suffered ≥ 1 complication (p = 0.03). However, there was no association between the level of the 1st peak PCT and the further postoperative course or the occurrence of complications. Patients in whom a 2nd PCT peak occurred had a significantly higher risk for a complicated course, for a complicated sepsis course and for mortality (p < 0.0001). Warm ischemic time over 58 min, operating time over 389 min and HU status were significant independent factors for a complicated postoperative course (p < 0.001, p < 0.001 and p = 0.03 respectively). Conclusions Based on our results, we believe that PCT course and the occurrence of a 2nd peak seem to possess important diagnostic and prognostic power in the post-transplant setting after liver transplantation.