Roman Havlik

Pseudoaneurysm of the gastroduodenal artery following pancreatoduodenectomy. Stenting for hemorrhage

Postpancreatectomy hemorrhage (PPH) and pancreatic fistula are main and serious complications following pancreaticoduodenectomy. Postpancreatectomy hemorrhage is considered life-threatening for its high rate of mortality. Postpancreatectomy hemorrhage is defined as early, occurring within 24 h after surgery, and late. The authors present a case of late PPH which developed in the third week following pylorus-preserving pancreaticoduodenectomy. A 58-year-old man was operated on for cancer of the pancreatic head. Hemorrhage occurred when the patient was in full health, convalescing at home. The cause was bleeding from a pseudoaneurysm of the stump of the gastroduodenal artery directly into the gastrointestinal tract. Diagnosis was established based on computed tomography angiography. Treatment was performed using minimally invasive technique during angiography. The implantation of a stent graft into the common hepatic artery for bridging the stump of the gastroduodenal artery was performed. This method thus enabled at once both diagnosis and successful minimally invasive treatment.

Different clinical presentations of metachronous pulmonary metastases after resection of pancreatic ductal adenocarcinoma: Retrospective study and review of the literature

AIM To analyze pancreatic cancer patients who developed metachronous pulmonary metastases (MPM) as a first site of recurrence after the curative-intent surgery. METHODS One-hundred-fifty-nine consecutive pancreatic ductal adenocarcinoma (PDAC) patients who underwent radical pancreatic surgery between 2006 and 2013 were included in this retrospective analysis. The clinical data including age, sex, grade, primary tumor location, pTNM stage, lymph node infiltration, microangioinvasion, perineural invasion, lymphovascular invasion, the therapy administered, and follow-up were all obtained from medical records. Further analysis covered only patients with metachronous metastases. Clinical and histopathological data (age, sex, grade, primary tumor location, pTNM stage, lymph node infiltration, microangioinvasion, perineural invasion, lymphovascular invasion, the therapy administered and follow-up) of patients with metachronous non-pulmonary metastases and patients with metachronous pulmonary metastases were statistically assessed. Disease-free survival (DFS) from pancreas resection until metastases onset and overall survival (OS) were calculated. Wilcoxon test, χ2 test and survival functions computed by the Kaplan-Meier method were used. Statistical significance was evaluated by the log-rank test using SPSS. A P-value of less than 0.05 was considered statistically significant. RESULTS Metachronous pulmonary metastases were observed in 20 (16.9%) and were operable in 3 (2.5%) of PDAC patients after a prior curative-intent surgery. Patients with isolated pulmonary metastases (oligometastases and multiple metastases) had estimated prior DFS and OS of 35.4 and 81.4 mo, respectively, and those with metachronous pulmonary metastases accompanied by other metastases had prior DFS and OS of 17.3 and 23.4 mo, respectively. Patients with non-pulmonary metastases had prior DFS and OS of 9.4 and 15.8 mo, respectively. Different clinical scenarios according to the presentation of MPM were observed and patients could be divided to three subgroups with different prognosis which could be used for the selection of treatment strategy: isolated pulmonary oligometastases, isolated multiple pulmonary metastases and pulmonary metastases accompanied by other metastases. CONCLUSION Surgery should be considered for all patients with isolated pulmonary oligometastases, but the risk of intervention has to be individually weighted for each patient.

Occult tumour cells in peritoneal lavage are a negative prognostic factor in pancreatic cancer

AIMS The aim of this study was to test the hypothesis that occult tumour cells in peritoneal lavage are a negative prognostic factor in pancreatic adenocarcinoma. METHODS Real-time RT-PCR analysis of CEA, EGFR and hTERT transcript levels was used to identify occult tumour cells in peritoneal lavage samples from 96 pancreatic cancer patients. RESULTS We found significant association between CEA expression levels in peritoneal lavage and clinical stage. We also found that EGFR transcript levels were higher in peritoneal lavage samples from patients with high grade tumours than in samples from patients with low grade tumours. Detection of CEA and/or EGFR occult tumour cell markers in the peritoneal lavage was associated with significantly shorter overall survival and increased hazard ratio for disease recurrence. CONCLUSIONS The results show that the presence of occult tumour cells in peritoneal lavage is a negative prognostic factor for survival in pancreatic cancer patients, and that detection of occult tumour cells using PCR-based methods can identify patients with advanced disease for whom radical surgery is likely to have little benefit.

Long-term survival after resections for pancreatic ductal adenocarcinoma. Single centre study

AIM To analyse the 5-year survival rate of patients undergoing radical surgery for pancreatic ductal adenocarcinoma (PDAC) and to identify prognostic factors. METHODS A prospectively maintained database of 90 consecutive patients who underwent radical resection for PDAC was analysed. Survival was evaluated using the Kaplan-Meier method. Log-rank test and Cox regression analysis were used for the evaluation of prognostic factors. P values less than 0.05 were considered significant. RESULTS Mean age (± standard deviation) was 63.2±8.6 years (female 28.9% and male 71.1%). Tumour localisation was in the head in 76 (84.5%), multifocal in 3 (3.3%) and in the body/tail in 11 (12.2%). Pancreatic head resection was performed in 75 (83.3%), total pancreatectomy in 4 (4.4%) and distal pancreatectomy with splenectomy in 11 (12.2%), with standard lymphadenectomy. Venous resection was in 4 (4.4%). Thirty-day and in-hospital mortality occurred in 1 (1.1%), 90-day mortality was 3.3%. On univariate analysis absence of perineural and vascular invasion, stage, absence of lymph node infiltration and no need for transfusion were associated with improved overall survival. On multivariate analysis vascular invasion HR=3.137 (95%CI: 1.692-5.816; P = 0.0003) and postoperative complications HR=2.004 (95%CI: 1.198-3.354; P = 0.008) were identified as significant independent predictors of survival. The five-year survival rate was 18.9%, with five-year recurrence-free survival of 16.7%. CONCLUSION Vascular invasion and postoperative complications were independent prognostic factors after curative resections of pancreatic cancer in studied cohort.

Dysregulation of KRAS signaling in pancreatic cancer is not associated with KRAS mutations and outcome

Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a poor prognosis, and no targeted therapy is currently available. The aim of the present study was to investigate the prognostic significance of the expression of V-Ki-ras2 Κirsten rat sarcoma viral oncogene homolog (KRAS), downstream signaling pathway genes and the association with clinical characteristics in PDAC patients undergoing radical surgery. Tumors and adjacent non-neoplastic pancreatic tissues were examined in 45 patients with histologically verified PDAC. KRAS and B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene mutation analysis was performed using the KRAS/BRAF/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α array. The transcript profile of 52 KRAS downstream signaling pathway genes was assessed using quantitative-polymerase chain reaction. KRAS mutation was detected in 80% of cases. The genes of four signaling pathways downstream of KRAS, including the phosphoinositide 3-kinase/3-phosphoinositide-dependent protein kinase 1/V-akt murine thymoma viral oncogene homolog 1, RAL guanine nucleotide exchange factor, Ras and Rab interactor 1/ABL proto-oncogene-1, non-receptor tyrosine kinase, and RAF proto-oncogene serine/threonine-protein kinase/mitogen-activated protein kinase pathways, exhibited differential expression in PDAC compared with that in the adjacent normal tissues. However, no significant differences in expression were evident between patients with KRAS-mutated and wild-type tumors. The expression of KRAS downstream signaling pathways genes did not correlate with angioinvasion, perineural invasion, grade or presence of lymph node metastasis. Additionally, the presence of KRAS mutations was not associated with overall survival. Among the KRAS downstream effective signaling pathways molecules investigated, only v-raf-1 murine leukemia viral oncogene homolog 1 expression was predictive of prognosis. Overall, KRAS mutation is present in the majority of cases of PDAC, but is not associated with changes in the expression of KRAS downstream signaling pathways and the clinical outcome. This may partly explain the failure of KRAS-targeted therapies in PDAC.

Association of urinary neopterin, neutrophil-to-lymphocyte, lymphocyte-to-monocyte and platelet-to-lymphocyte ratios with long-term survival of patients with breast cancer

Abstract The immune response crucially determines the survival of patients with malignant tumors including breast carcinoma. The aim of the present study was to evaluate retrospectively an association of peripheral blood cell count (PBC)-derived ratios and urinary neopterin concentration with prognosis in breast cancer patients. Urinary neopterin, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) were retrospectively analyzed in a cohort of 474 breast cancer patients. NLR and PLR correlated positively with each other and negatively with LMR, but no correlation between neopterin concentrations and PBC-derived ratios was observed. Increased urinary neopterin concentration was a significant predictor of poor survival in patients with active disease, but PLR, NLR or LMR were not significantly associated with survival in multivariate analysis. In conclusion, increased urinary neopterin was a significant predictor of poor survival in patients with breast cancer and active disease.

Peripheral blood leukocyte populations and urinary neopterin during chemotherapy in patients with breast cancer

Abstract The aim of the present study was to investigate serial changes in urinary neopterin and the populations of peripheral blood lymphocytes in breast cancer patients treated with primary chemotherapy. Thirty patients with breast cancer, including 20 patients undergoing primary chemotherapy treated with the combination of doxorubicin and cyclophosphamide with sequential administration of paclitaxel-based therapy (cohort A), and 10 patients presenting for first-line therapy of metastatic disease and treated with the combination of bevacizumab, taxane and carboplatin (cohort M) were studied. Healthy female blood donors served as control group. Significant differences were observed in baseline relative and absolute counts of peripheral blood lymphocyte subpopulations between both patient cohorts and controls. Significant changes of peripheral blood lymphocyte subpopulations were also observed during the course of chemotherapy. However, no significant changes of urinary neopterin concentrations and no correlation between urinary neopterin and peripheral blood lymphocyte counts were observed. In conclusion, present data demonstrate the presence of significant differences in peripheral blood leukocyte phenotype in breast cancer patients even before the start of primary chemotherapy. Significant changes were observed during the course of chemotherapy.

Prolonged response to pemetrexed-based chemotherapy in a patient with peritoneal mesothelioma: a case report and review of the literature

Abstract Peritoneal mesothelioma is a rare tumor typically presenting with ascites and associated with occupational asbestos exposure with a latency period of 20–40 years. Intensive multi-modality approach combining cytoreductive surgery, intraperitoneal chemotherapy and possibly radiotherapy can be considered, but otherwise the prognosis is rather poor. Palliative chemotherapy may be an option in these rare cases. However, no approved systemic treatment exists for peritoneal mesothelioma. We present here a patient with peritoneal mesothelioma who was treated with the combination of pemetrexed with cisplatin shortly after the failure of hyperthermic intraperitoneal chemotherapy. The patient experienced durable partial response to the treatment, resolution of ascites, and returned to his normal daily life activities. With the exception of palliative chemotherapy in case of patients in good condition, therapeutic options in patients with peritoneal mesothelioma are currently very limited. The combination of pemetrexed and cisplatin can lead to long-term control in selected patients.

Emergency surgical treatment of complicated acute pancreatitis after kidney transplantation with acute rejection: Case report and literature review

Introduction Acute pancreatitis is a rare but frequently fatal complication in patients following kidney transplantation. The first case of acute pancreatitis in patients following a kidney transplant was described by Starzl in 1964. The incidence of acute pancreatitis is stated at between 1 and 5%. The mortality rate amongst these patients reaches as high as 50–100%. Presentation of case Here we present a case of acute pancreatic abscess in a caucasian female – shortly following a kidney transplant complicated by the development of acute rejection, in which immunosuppressant therapy is a potential etiological agent. Emergency surgical treatment was indicated, which included drainage of the abscesses irrigation of the abdominal cavity. Immunosuppressive medication was considered a possible etiological factor, and as a result administration of tacrolimus and mycophenolate mofetil was discontinued. This was successful and three months later, diagnostic rebiopsy of the graft was performed without signs of rejection. Discussion The etiology of this illness is multifactorial. The clinical manifestation of acute pancreatitis in patients following kidney transplantation is the same as in the remainder of the population. However, in patients following transplantation with long-term immunosuppression, it usually manifests a more rapid development and a more severe, frequently fatal course. Conclusions With regard to the patients comorbidities, early surgical therapy was indicated – drainage and closed lavage and immunosuppressive medication as a suspected tobe ethiological factor was discontinued. This course of treatment led to a complete recovery with preservation of good function of the cadaverous kidney.

Mitochondrial changes in adenocarcinoma of the pancreas.

Abstract The aim of our study was to analyse the mitochondrial ultrastructure in primary ductal adenocarcinomas of the pancreas and to compare it with normal pancreatic cells. 52 samples of adenocarcinoma of the pancreas obtained by surgical resection or by endosonographic biopsy were examined. Compared to normal mitochondrial ultrastructure in non-tumorous cells, the mitochondria in cancer cells had a dense matrix and condensed configuration or with lucent-swelling matrix associated with disarrangement and distortion of cristae and partial or total cristolysis. Functionally, these structural alterations presume the presence of hypoxia-tolerant and hypoxia-sensitive cancer cells.