Fritz Klein

Prognostic Factors for Long-Term Survival in Patients with Ampullary Carcinoma: The Results of a 15-Year Observation Period after Pancreaticoduodenectomy

Introduction. Although ampullary carcinoma has the best prognosis among all periampullary carcinomas, its long-term survival remains low. Prognostic factors are only available for a period of 10 years after pancreaticoduodenectomy. The aim of this retrospective study was to identify factors that influence the long-term patient survival over a 15-year observation period. Methods. From 1992 to 2007, 143 patients with ampullary carcinoma underwent pancreatic resection. 86 patients underwent pylorus-preserving pancreaticoduodenectomy (60%) and 57 patients underwent standard Kausch-Whipple pancreaticoduodenectomy (40%). Results. The overall 1-, 5-, 10-, and 15-year survival rates were 79%, 40%, 24%, and 10%, respectively. Within a mean observation period of 30 (0–205) months, 100 (69%) patients died. Survival analysis showed that positive lymph node involvement (P = 0.001), lymphatic vessel invasion (P = 0.0001), intraoperative administration of packed red blood cells (P = 0.03), an elevated CA 19-9 (P = 0.03), jaundice (P = 0.04), and an impaired patient condition (P = 0.01) are strong negative predictors for a reduced patient survival. Conclusions. Patients with ampullary carcinoma have distinctly better long-term survival than patients with pancreatic adenocarcinoma. Long-term survival depends strongly on lymphatic nodal and vessel involvement. Moreover, a preoperative elevated CA 19-9 proved to be a significant prognostic factor. Adjuvant therapy may be essential in patients with this risk constellation.

Blood group determinates incidence for pancreatic cancer in Germany

Background: Genetic risk factors for sporadic pancreatic cancer are largely unknown but actually under high exposure. Findings of correlations between the AB0 blood group system (Chromosome 9q34,1—q34,2) and the risk of pancreatic cancer (PC) in patients from Asia, America and south Europe have already been published. So far it is unclear, whether this correlation between blood group an PC incidence can be found in German patients as well. Methods: One hundred and sixty-six patients who underwent a resection of PC were evaluated in a period between 2000 and 2010. Blood group reference distribution for the German population is given as: 0: 41%; A: 43%; B: 11%; AB: 5%; Rhesus positive: 85%; Rhesus negative: 15%. Analyses were done using the non-parametric Chi2-test (p-value two sided; SPSS 19.0). Results: Median age was 62 (34–82) years. Gender: female 73/44%; male: 93/56%. Observed blood group proportions: 0: 43 (25.9%)/A: 94 (56.6%)/B: 16 (9.6%)/AB: 13 (7.8%)/Rhesus positive: 131 (78.9%)/negative: 35 (21.1%). We detected a significant difference to the German reference distribution of the AB0 system (Chi2 19.34, df 3, p < 0.001). Rhesus factor has no impact on AB0-distribution (Chi2 4.13, df 3, p = 0.25), but differs significantly from reference distribution—probably due to initial AB0-variation (Chi2 4.82, df 1, p = 0.028). The odds ratio for blood group A is 2.01 and for blood group 0 is 0.5. Conclusions: The incidence of PC in the German cohort is highly associated with the AB0-system as well. More patients with blood group A suffer from PC (p < 0.001) whereas blood group 0 was less frequent in patients with PC (p < 0.001). Thus, our findings support the results from other non-German surveys. The causal trigger points of this carcinogenesis correlation are still not known.

The Impact of Simultaneous Liver Resection for Occult Liver Metastases of Pancreatic Adenocarcinoma

Backround. Pancreas resection is the only curative treatment for pancreatic adenocarcinoma. In the event of unexpected incidental liver metastases during operative exploration patients were traditionally referred to palliative treatment arms. With continuous progress in the surgical expertise simultaneous pancreas and liver resections seem technically feasible nowadays. The aim of this study therefore was to analyze the impact of synchronous liver-directed therapy on operative outcome and overall survival in patients with hepatic metastasized pancreatic adenocarcinoma (HMPA). Methods. 22 patients who underwent simultaneous pancreas resection and liver-directed therapy for HMPA between January 1, 2004 and January 1, 2009 were compared to 22 patients who underwent classic pancreas resection for nonmetastasized pancreatic adenocarcinoma (NMPA) in a matched pair study design. Postoperative morbidity, preoperative, and operative data and overall survival were analyzed. Results. Overall survival was significantly decreased in the HMPA group. Postoperative morbidity and mortality and median operation time did not significantly differ between the groups. Conclusion. The results of our study showed that simultaneous pancreas resection and liver-directed therapy may safely be performed and may therefore be applied in individual patients with HMPA. However, a potential benefit of this radical surgical approach with regard to overall survival and/or quality of life remains to be proven.

Pathology of flupirtine-induced liver injury: a histological and clinical study of six cases

Drug-induced liver injury may cause impairment of liver function and is a leading cause of acute liver failure. Identification of the causative substance in patients receiving several drugs is often difficult in clinical practice. Evaluation of liver biopsies in suspected drug-induced injury is a challenging task that requires close clinico-pathological correlation. Recognizing a characteristic morphological pattern of liver injury may contribute to identification of the causative drug. Flupirtine, a non-opioid analgesic, has been reported to cause liver injury of idiosyncratic type in rare instances. We wished to characterize the histopathological features of flupirtine-induced liver injury, which have not been reported so far. Liver biopsies of five patients with severe liver injury and one explanted liver of a patient with flupirtine-induced acute liver failure that required transplantation were assessed. In addition clinical presentation and course were reviewed and clinical follow up was performed. Extensive perivenular necrosis with associated ceroid pigment-laden macrophages and a mild to moderate lymphocytic infiltrate was a common feature in all cases. Histological extent of liver necrosis corresponded well to serum amino-transferase levels. Accidental reexposure of one patient resulted in a plasma cell rich hepatitis with perivenular necrosis. This study provides evidence that flupirtine can cause substantial liver injury of hepatocellular type. Liver damage is associated with a characteristic morphological picture, the recognition of which will aid in causality assessment of drug-induced liver injury. Clinical and histological features raise the possibility of an immune-mediated toxicity.

Significant impact of patient age on outcome after liver resection for HCC in cirrhosis.

OBJECTIVE Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The majority of patients with HCC have cirrhosis. Beside liver transplantation the resection is an established curative treatment option for patients with HCC in cirrhosis. However, the long term success is limited by a high tumor recurrence rate. Furthermore, by many patients surgical resection is restricted by poor liver function. The purpose of this study was to investigate the influence of patient age on long term outcome after liver resection in patients with HCC in cirrhotic liver. Further purpose was to define the potential prognostic factors. PATIENTS AND METHODS The outcome of 141 patients with liver cirrhosis after curative resection was analyzed using a prospective database. Only patients with postoperative histological assurance of HCC were included in the database. Patients with fibrolamellar HCC were excluded. RESULTS By patients below 70 years of age the 1-, 3- and 5-year survival rates were 78.5%, 56.5% and 47.1%. By patients over 70 years the 1-, 3- and 5-year survival rates were 59.9%, 40.3% and 6.7%. Cumulative survival of the total collective was significant influenced by patient age, Clavien grade, positive lymph vessels, mechanical ventilation and BMI. The overall postoperative morbidity was 44.7%. No intraoperative deaths were observed, but 11 patients (8 older than 70 and 3 younger than 70 years) died during the hospital stay. Clavien grade correlated with preoperative increased GGT, need for intraoperative blood and fresh frozen plasma transfusion. CONCLUSIONS Patient age and postoperative complications are more relevant for the outcome than many tumor factors, especially by patients over 70 years of age. In contrast, the prognosis of patients below 70 years of age is significantly better and a 5 year survival rate above 50% could be shown in our patients. However, by carefully selected elderly patients with HCC in cirrhosis an acceptable long term survival is reachable.

Safety of Pancreatic Surgery in Patients with Simultaneous Liver Cirrhosis: A Single Center Experience

Background/Aims: Pancreatic surgery is associated with an increased risk of postoperative complications. We therefore investigated the impact of an additional liver function disorder on the postoperative outcome using a case-control study of patients with or without liver cirrhosis who underwent pancreatic surgery at our department. Methods: Between 1998 and 2008, 1,649 pancreatic resections were performed. Of these, 32 operations were performed in patients who also suffered from liver cirrhosis (30× Child A, 2× Child B). For our case-control study, we selected another 32 operated patients without cirrhosis who were matched according to age, sex, diagnosis and tumor classification. The following parameters were compared between both groups: operating time, number of transfusions, duration of ICU and hospital stay, incidence of complications, rate of reoperation, mortality. Results: Patients with cirrhosis experienced complications significantly more often (69 vs. 44%; p = 0.044), especially major complications (47 vs. 22%; p = 0.035) requiring reoperation (34 vs. 12%; p = 0.039). These patients also had a prolonged hospital stay (27.9 vs. 24.3 days) and a significantly longer ICU stay (8.6 vs. 3.7 days; p = 0.033), and required twice as many transfusions. Overall, 3 patients died following surgery, 1 with Child A (3% of all Child A patients) and 2 with Child B cirrhosis. Conclusion: Pancreatic surgery is associated with an increased risk of postoperative complications in patients with liver cirrhosis, and is therefore not recommended in patients with Child B cirrhosis. In Child A cirrhotic patients the mortality is, however, comparable to noncirrhotic patients. Due to the demanding medical efforts that these patients require, they should be treated exclusively in high-volume centers.

Pancreatoenteral anastomosis or direct closure of the pancreatic remnant after a distal pancreatectomy: a single-centre experience

BACKGROUND A major complication of a distal pancreatectomy (DP) is the formation of a post-operative pancreatic fistula (POPF). In spite of the utilization of numerous surgical techniques no consensus on an appropriate technique for closure of the pancreatic remnant after DP has been established yet. The aim of this study was to analyse the impact of pancreatoenteral anastomosis (PE) vs. direct closure (DC) of the pancreatic remnant on POPF. METHODS A total of 198 consecutive patients who underwent a distal pancreatectomy between 2002 and 2010 at our institution were retrospectively analysed for post-operative morbidity and mortality. RESULTS One hundred and fifty-one patients (76.3%) received DC whereas PE was performed in 47 patients (23.7%). The incidence of POPF was higher in the DC group (22% vs. 11%), whereas the rate of post-operative haemorrhage was higher in the PE group (11% vs. 7%). However, these differences were not significant. Additionally, there were no significant differences in overall post-operative morbidity and mortality between the groups. CONCLUSIONS The performance of PE instead of DC may be considered as a safe alternative in individual patients, but it does not significantly lead to a general improvement in post-operative outcome after DP. An interdisciplinary collaboration in the prevention and treatment of POPF therefore remains essential.

Predictive Factors for Extrahepatic Recurrence of Hepatocellular Carcinoma Following Liver Transplantation.

Recurrence of hepatocellular carcinoma (HCC) in patients treated with liver transplantation (LT) is associated with diminished survival. Particularly, extrahepatic localization of HCC recurrence contributes to poor prognosis.

Patient and tumour biology predict survival beyond the Milan criteria in liver transplantation for hepatocellular carcinoma.

BACKGROUND Patients with hepatocellular carcinoma (HCC) beyond the Milan criteria are not considered for liver transplantation (LT) in many centres; however, LT may be the only treatment able to achieve long-term survival in patients with unresectable HCC. The aim of this study was to assess the role of recipient age and tumour biology expressed by the DNA index in the selection of HCC patients for LT. PATIENTS Clinicopathological data of 364 patients with HCC who underwent LT between 1989 and 2010 were evaluated. Overall survival (OS) was analysed by patient age, tumour burden based on Milan criteria and the DNA index. RESULTS After a median follow-up time of 78 months, the median survival was 100 months. Factors associated with OS on univariate analysis included Milan criteria, patient age, hepatitis C infection, alpha-fetoprotein (AFP) level, the DNA index, number of HCC, diameter of HCC, bilobar HCC, microvascular tumour invasion and tumour grading. On multivariate analysis, HCC beyond Milan criteria and the DNA index >1.5 independently predicted a worse OS. When stratifying patients by both age and Milan criteria, patients ≤ 60 years with HCC beyond Milan criteria had an OS comparable to that of patients >60 years within Milan criteria (10-year OS: 33% versus 37%, P = 0.08). Patients ≤ 60 years with HCC beyond Milan criteria but a favourable DNA index ≤ 1.5 achieved excellent long-term outcomes, comparable with those of patients within Milan criteria. CONCLUSIONS Patients ≤ 60 years may undergo LT for HCC with favourable outcomes independently of their tumour burden. Additional assessment of tumour biology, e.g. using the DNA index, especially in this subgroup of patients can support the selection of LT candidates who may derive the most long-term survival benefit, even if Milan criteria are not fulfilled.

Formation of a chronic pain syndrome due to mesh shrinkage after laparoscopic intraperitoneal onlay mesh (IPOM).

The case of a 58-year-old male patient who developed a chronic pain syndrome after laparoscopic intraperitoneal onlay mesh for treatment of a large symptomatic umbilical hernia combined with rectus diastasis is reported. Twelve months after an uncomplicated initial surgery, the patient presented with progressive signs of a foreign body sensation and pain in the anterior abdominal wall. Computed tomography examination revealed no pathologic findings but a marked shrinkage of the mesh implant. Because of further progressive symptoms, explorative laparotomy was performed. Mesh shrinkage and adhesions with a surrounding chronic tissue reaction were found as the cause of the pain syndrome. This case demonstrates a case of a chronic pain syndrome due to mesh shrinkage 12 months after initial ventral hernia repair. Mesh shrinkage should therefore be taken into consideration in patients with progressive pain chronic syndromes after laparoscopic ventral hernia repair.