[Ventral Hernia Repair in Endoscopically Total Extrapertoneal Technique (eTEP) - Evaluation of Postoperative Outcome and One Year Follow-up]. / Ventralhernienversorgung in endoskopischer total extraperitonealer Technik (eTEP) ­ Evaluation der postoperativen Ergebnisse und des 1-Jahres-Follow-ups.

BACKGROUND: Several recent meta-analyses have identified the retromuscular plane as the preferred mesh position in ventral hernia repair. Open surgery used to be the standard technique for these procedures. However, new minimally invasive techniques with totally extraperitoneal access and mesh positioning in the retromuscular plane have evolved. METHODS: Between September 2018 and March 2019, 18 consecutive patients with ventral hernia were treated endoscopically in the totally extraperitoneal technique. Depending on the localisation and size of the hernia, the appropriate access was chosen and an uncoated mesh was placed in the retromuscular space in all patients. Data of patients' characteristics as well as peri- and postoperative parameters were collected. One year after surgery, patients were asked about recurrence, pain and complications, using the questionnaire of the herniamed data base. RESULTS: No intraoperative complications were noted. Postoperatively, there was one retromuscular seroma that did not need treatment, one temporary paralysis of the radial nerve and one pulmonary embolism. None of these complications led to persistent problems. 17 of 18 patients were available for follow-up. One year follow-up showed no hernia recurrence. One patient had pain at rest requiring treatment. CONCLUSIONS: Totally extraperitoneal endoscopic hernia surgery is a safe and promising new technique that is also feasible in complex hernias and with satisfactory 1 year results. This technique can combine the advantages of minimally invasive surgery with those of extraperitoneal mesh placement.

When You Operate on Friends and Relatives: Results of a Survey among Surgeons.

OBJECTIVE: We designed a questionnaire to collect data on surgeons' views and experiences of operating on friends or relatives. SUBJECTS AND METHODS: A link to a 38-item online survey was sent to all 16,849 members of the Professional Board of German Surgeons (Bund Deutscher Chirurgen, BDC) several times. Standard interview software was used. The questionnaire collected a wide variety of information concerning how surgeons have experienced, think about, and deal with the situation when they operate on friends or relatives. RESULTS: Of the 16,849 BDC members notified of the survey, 1,643 completed the questionnaires (9.8%). Of these, 1,275 (77.6%) had previously performed surgery on friends or relatives. Overall, the surgeons willingly accepted doing so without experiencing any difficulties. However, the surgeons frequently used different techniques when operating on friends and relatives (123 [10%] when self-assessed compared to 527 [35%] when observed by others). Out of the whole sample, 506 (30.8%) would appreciate having a guideline or ethical code and 370 (41.2%) of those who have not yet operated on friends and relatives would like to have such an ethical code. CONCLUSION: Most of the surgeons who responded accepted the task of operating on friends or relatives. Performing surgery on friends or relatives was a complex matter because objectivity was not guaranteed. Negative implications on personal relationships were rare. We recommend that this matter should be well considered and discussed with the patient and an ethical guideline or code should be created.

Adjuvant gemcitabine after resection of pancreatic cancer without significant difference in overall survival: a retrospective cohort study.

International guidelines recommend adjuvant chemotherapy after resection of pancreatic adenocarcinoma. The administration of gemcitabine has become part of the interdisciplinary treatment concept. The authors aim to prove whether the benefit in overall survival (OS) reported in randomized controlled trials (RCTs) could be reached also for patients treated in their department. Materials and methods: The authors retrospectively analyzed the OS of all patients who underwent pancreatic resection at their clinic because of ductal adenocarcinoma between January 2013 and December 2020 in dependence on adjuvant treatment with gemcitabine. Results: Overall 133 pancreatic resections were performed between 2013 and 2020 due to malignant pancreatic pathology. Seventy-four patients had ductal adenocarcinoma. Forty patients received adjuvant gemcitabine chemotherapy postoperatively, 18 patients underwent only surgical resection, and 16 patients received other chemotherapy regimens. The authors compared the group receiving adjuvant gemcitabine (n=40) with the group undergoing surgery alone (n=18). The median age was 74 years (range: 45-85), and the median OS was 16.5 months [95% confidence interval (CI) 13-27]. Follow-up time was at least 23 months (range 23-99). No statistically significant difference in median OS was observed in the group who received adjuvant chemotherapy compared to the operation-only group [17.5 months (range: 5-99, 95% CI 14-27) versus 12.5 months (range: 1-94, 95% CI 5-66), P=0.75]. Conclusion: OS with and without adjuvant chemotherapy with gemcitabine was comparable to the results of those RCTs which serve as the basis of guideline recommendations. However, the analyzed patient cohort did not profit significantly from the adjuvant treatment.

Prolyl hydroxylase-2 (PHD2) exerts tumor-suppressive activity in pancreatic cancer.

BACKGROUND: Pancreatic cancer is 1 of the most common and poorly treated tumors. In search of new therapeutic approaches, the oxygen sensors prolyl hydroxylases (PHD) are potential targets. PHD2 is considered the key oxygen sensor-regulating hypoxia-inducible factor (HIF). Currently, there is conflicting evidence regarding the exact role of PHD2 in tumorigenesis. The objective of this study was to investigate the role of PHD2 in pancreatic cancer growth and progression. METHODS: PHD2 expression was analyzed by quantitative real-time polymerase chain reaction analysis and immunohistochemistry in human tissue specimens and cell lines. Knockdown of PHD2 was done by using short-interfering RNAs (siRNAs) specific against PHD2, and PHD2 overexpression was achieved by stable combinational DNA transfection. In vivo, an orthotopic murine model was used. Angiogenic cytokines were assessed with enzyme-linked immunosorbent assays, and invasion was studied with Matrigel assays. RESULTS: PHD2 expression was not altered substantially in cancer tissues and their metastases. Lymph node-negative tissues had higher levels of PHD2 than lymph node-positive tissues. PHD2 was hypoxia-inducible in pancreatic cancer cell lines and regulated cell growth through cyclin D1 down-regulation samples with PHD2 suppression and through p21 up-regulation in samples with of PHD2 overexpression. In vivo, PHD2 caused tumor growth retardation and reduced tumor invasion by inhibiting angiogenesis. This observation was caused by the suppression of angiogenic cytokines and tumor invasion. CONCLUSIONS: The current results indicated that PHD2 plays an important role in pancreatic tumorigenesis. In summary, the authors concluded that PHD2 may function as a tumor suppressor gene in pancreatic cancer and, thus, may define a potential target for the treatment of pancreatic cancer.

Patients with non-[18 F]fludeoxyglucose-avid advanced hepatocellular carcinoma on clinical staging may achieve long-term recurrence-free survival after liver transplantation.

There is increasing evidence that a relevant number of patients with hepatocellular carcinoma (HCC) exceeding the Milan criteria may benefit from liver transplantation (LT). We retrospectively analyzed the prognostic significance of [(18) F]fludeoxyglucose ([(18) F]FDG) positron emission tomography (PET) for identifying appropriate LT candidates with advanced HCC on clinical staging. Between 1995 and 2008, 111 patients with HCC were listed for LT. All underwent a pretransplant PET evaluation. LT was performed for 91 of these patients. The tumor recurrence rate after LT was 3.6% for patients with non-[(18) F]FDG-avid (PET(-) ) tumors, but it was 54.3% for patients with [(18) F]FDG-avid (PET(+) ) tumors (P < 0.001). The 5-year recurrence-free survival rates were comparable for patients with tumors meeting the Milan criteria (86.2%) and patients with PET(-) HCC exceeding the Milan criteria (81%) at LT, but these rates were significantly higher than the rate for liver recipients with [(18) F]FDG-avid advanced HCC (21%, P = 0.002). In a multivariate analysis, negative PET findings (odds ratio = 21.6, P < 0.001), an alpha-fetoprotein level <400 IU/mL (odds ratio = 3.3, P = 0.013), and a total tumor diameter <10 cm (odds ratio = 3.0, P = 0.022) were identified as pretransplant prognostic variables for recurrence-free survival. A PET(+) status was assessed as the only independent clinical predictor of tumor-related patient dropout from the waiting list (hazard ratio = 5.7, P = 0.01). Patients with non-[(18) F]FDG-avid HCC beyond the Milan criteria according to clinical staging may achieve excellent long-term recurrence-free survival after LT.

Heparin-induced thrombocytopenia (HIT II) in liver transplant recipients: a retrospective multivariate analysis of prognostic factors.

We investigated the prevalence of HIT II in liver transplant recipients and analysed associated factors. In recipients with clinically suspected HIT II in the 4Ts pretest clinical scoring system HIPA-assay was performed. Next, 37 clinical variables were analysed retrospectively for their association with HIT II. Factors significantly correlated to our findings in univariate analysis were included in a multivariate model and binary logistic regression analysis. Among 46 recipients 21 patients were suspicious in the 4Ts pretest and 14 of them (30.4%) were diagnosed HIT-antibody positive. Patient's age (P = 0.001), postoperative dialysis (P = 0.028), and postoperative hospital stay (P = 0.035) were significantly associated with development of HIT-antibodies in univariate analysis. Postoperative dialysis and postoperative hospital stay turned out as epiphenomena of patient's age, the only independent predictor (P = 0.021). Using multiple χ(2) -testing, a cut-off could be calculated, assigning patients younger than 59 years to a low risk group and patients of 59 years and older to a high risk group. High incidence of peri-operative HIT II seroconversion in liver transplant recipients is not associated with factors known to induce thrombocyte activation, like blood products or cell-saver. Only patients' age was identified as independent predictor.

Establishment of minimally invasive ventral hernia repair with extraperitoneal mesh placement in a primary care hospital using the robotic platform.

Background: The progressive availability of robotic surgical systems opens new perspectives in abdominal wall surgery due to excellent visibility and dexterity of instruments. While complex hernias until today were treated primarily through an open access, we evaluated if this promising technology is suitable for treating the entire spectrum of a hernia center, including complex hernias. Material/methods: In 2017, minimally invasive hernia surgery with extraperitoneal mesh placement was started in Kempten hospital. Since 2019, a Da Vinci X system has been available for this purpose. In order to observe the process of transition we retrospectively analyzed all patients who underwent ventral hernia repair in the department of general and visceral surgery at our hospital between January 2016 and December 2020 and were indicated for mesh implantation. Results: In 2016, the percentage of minimally invasive procedures was 37.3%. In all of these cases an intraperitoneal mesh was implanted into the abdominal cavity. Open surgery was performed in 62.7%, of which an a retromuscular mesh was implanted in 75.7%, an intraperitoneal mesh in 21.6%, and an onlay mesh in 2.7%. In 2020, minimally invasive surgery accounted for 87.5%, of which 85.7% were performed robotically and 14.3 laparoscopically. In 94.3% of these minimally invasively treated patients the mesh was implanted in extraperitoneal position (75.8% in retromuscular and 24.2% in preperitoneal position). The percentage of complex hernias increased from 20.3% to 35.0% during the same period. Conclusion: The majority of ventral hernia procedures can be performed safely using the robot in a minimally invasive technique with extraperitoneal mesh placement without leading to an increase in complications. Robotically-assisted hernia repair is a promising new technique that is also practical for complex hernias.

Robotically assisted enhanced-view totally extraperitoneal repair (eTEP) of a recurrent umbilical hernia in a patient with peritoneal dialysis.

Background: Abdominal wall hernias are frequent in patients with peritoneal dialysis. Guidelines recommend an open hernia repair with extraperitoneal mesh placement to avoid access to the abdominal cavity. Method: We performed a lateral docking robotically assisted enhanced-view totally extraperitoneal repair (eTEP) of a recurrent umbilical hernia with diastasis recti in a patient with peritoneal dialysis due to polycystic kidney disease. After suturing of the midline a 20 x 28 cm mesh was placed in the retrorectus space, covering the whole area of preparation while also overlapping all trocar sites. A drainage was left in the retrorectus space until the first session of PD did not sample any form of leakage. Result: Robotically assisted totally extraperitoneal hernia repair was feasible. The patient was able to continue peritoneal dialysis without intermittent hemodialysis. There was no leakage of the dialysate to the retrorectus space. Postoperative recovery was uneventful. 6 months after surgery the patient was free from pain and showed no signs of recurrence. Conclusion: Robotically assisted totally extraperitoneal hernia repair in patients with umbilical hernia and peritoneal dialysis could be a promising surgical technique to combine the advantages of minimally-invasive surgery with totally extraperitoneal mesh placement without access to the abdominal cavity.

A prospective, non-randomized phase II trial of Trastuzumab and Capecitabine in patients with HER2 expressing metastasized pancreatic cancer.

BACKGROUND: Pancreatic cancer is the fourth most common cause of cancer related death in Western countries. Advantages in surgical techniques, radiation and chemotherapy had almost no impact on the long term survival of affected patients. Therefore, the need for better treatment strategies is urgent. HER2, a receptor tyrosine kinase of the EGFR family, involved in signal transduction pathways leading to cell growth and differentiation is overexpressed in a number of cancers, including breast and pancreatic cancer. While in breast cancer HER2 has already been successfully used as a treatment target, there are only limited data evaluating the effects of inhibiting HER2 tyrosine kinases in patients with pancreatic cancer. METHODS: Here we report the design of a prospective, non-randomized multi-centered Phase II clinical study evaluating the effects of the Fluoropyrimidine-carbamate Capecitabine (Xeloda) and the monoclonal anti-HER2 antibody Trastuzumab (Herceptin) in patients with non-resectable, HER2 overexpressing pancreatic cancer. Patients eligible for the study will receive Trastuzumab infusions on day 1, 8 and 15 concomitant to the oral intake of Capecitabine from day 1 to day 14 of each three week cycle. Cycles will be repeated until tumor progression. A total of 37 patients will be enrolled with an interim analysis after 23 patients. DISCUSSION: Primary end point of the study is to determine the progression free survival after 12 weeks of bimodal treatment with the chemotherapeutic agent Capecitabine and the anti-HER2 antibody Trastuzumab. Secondary end points include patient's survival, toxicity analysis, quality of life, the correlation of HER2 overexpression and clinical response to Trastuzumab treatment and, finally, the correlation of CA19-9 plasma levels and progression free intervals.

Association of axon guidance factor semaphorin 3A with poor outcome in pancreatic cancer.

Neural alterations and aberrantly expressed nerve-specific factors promoting tumor progression are known to contribute to pancreatic cancer's extremely poor prognosis. Despite hints that axon guidance factor semaphorin 3A (SEMA3A) may function as a tumor inhibitor, its clinical importance and therapeutic potential have not yet been explored. The present study investigated the role of SEMA3A and its receptors-plexins A1-A4 (PLXNA1-A4) and neuropilin-1 (NRP1)-in pancreatic cancer. QRT-PCR and immunohistochemical analyses revealed overexpression of SEMA3A, NRP1 and PLXNA1 in metaplastic ducts, malignant cells and nerves of cancerous specimens, and showed that elevated levels of corresponding mRNA (6.8-fold, 2.0-fold and 1.5-fold, respectively) clearly correlated with negative clinicopathological manifestations such as shorter survival (SEMA3A and PLXNA1) and a lesser degree of tumor differentiation (NRP1) in Stages I-III patients. High SEMA3A expression in pancreata of Stage IV M1 patients and in peritoneal metastases, and consequent functional studies indicated that poor clinical outcome might be related to the ability of SEMA3A to promote dissemination and invasiveness of pancreatic cancer cells through activation of multiple pathways involving Rac1, GSK3b or p42/p44 MAPK, but not E- to N-cadherin switch, MMP-9 or VEGF induction. Thus, this study is the first to quantify expression of the SEMA3A system in human malignancy and to show that overexpression of SEMA3A by nerves and transformed cells leads to a SEMA3A-rich environment which may favor malignant activities of tumor cells. Furthermore, negative clinicopathological correlations suggest that SEMA3A might represent a novel intervention target but not a treatment option for pancreatic cancer patients.

Clinical and mechanistic aspects of glucocorticoid-induced chemotherapy resistance in the majority of solid tumors.

BACKGROUND: Glucocorticoids have been used widely in conjunction with cancer therapy due to their ability to induce apoptosis in hematological cells and to prevent nausea and emesis. However, recent data including ours, suggest induction of therapy-resistance by glucocorticoids in solid tumors, although it is unclear whether this happens only in few carcinomas or is a more common cell type specific phenomenon. MATERIAL AND METHODS: We performed an overall statistical analysis of our new and recent data with 157 tumor probes evaluated in vitro, ex vivo and in vivo. The effect of glucocorticoids on apoptosis, viability and cell cycle progression under diverse clinically important questions was examined. RESULTS: New in vivo results demonstrate glucocorticoid-induced chemotherapy resistance in xenografted prostate cancer. In an overall statistical analysis we found glucocorticoid-induced resistance in 89% of 157 analysed tumor samples. Resistance is common for several cytotoxic treatments and for several glucocorticoid-derivatives and due to an inhibition of apoptosis, promotion of viability and cell cycle progression. Resistance occurred at clinically achievable peak plasma levels of patients under anti-emetic glucocorticoid therapy and below, lasted for a long time, after one single dose, but was reversible upon removal of glucocorticoids. Two nonsteroidal alternative anti-emetic agents did not counteract anticancer treatment and may be sufficient to replace glucocorticoids in cotreatment of carcinoma patients. CONCLUSION: These data demonstrate the need for prospective clinical studies as well as for detailed mechanistic studies of GC-induced cell-type specific pro- and anti-apoptotic signalling.

Preclinical differentiation between apparently safe and potentially hepatotoxic applications of TRAIL either alone or in combination with chemotherapeutic drugs.

PURPOSE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) exhibits potent antitumor activity on systemic administration in nonhuman primates without deleterious side effects for normal tissue. However, there is a controversy about the potential toxicity of TRAIL on human hepatocytes. The use of different recombinant TRAIL forms only partially explains the contradicting reports on TRAIL sensitivity in primary human hepatocytes (PHH). EXPERIMENTAL DESIGN: To clarify this issue, we comprehensively tested four different recombinant forms of TRAIL for their apoptosis-inducing capacity on PHH obtained from a total of 55 human livers between day 1 and day 8 of in vitro culture. RESULTS: One day after single-cell isolation, all but one recombinant form of TRAIL [i.e., an untagged form of TRAIL (TRAIL.0)] induced apoptosis in PHH. Apoptosis induction by TRAIL in these cells could only be fully inhibited by concomitant blockade of TRAIL receptor 1 and TRAIL receptor 2. At day 4 of in vitro culture, when surrogate markers indicated optimal hepatocyte in vitro function, only high doses of cross-linked FLAG-TRAIL killed PHH whereas the other three recombinant TRAIL forms did not. Strikingly, cotreatment of day 4 PHH with cisplatin sensitized for TRAIL-induced apoptosis whereas 5-fluorouracil, etoposide, gemcitabine, irinotecan, or oxaliplatin, which are commonly used in the treatment of gastrointestinal cancers, did not. CONCLUSION: Our data show that whereas TRAIL alone or together with selected chemotherapeutic drugs seems to be safe, the combination of TRAIL with cisplatin is toxic to PHH.

Role of lymphangiogenesis and lymphangiogenic factors during pancreatic cancer progression and lymphatic spread.

Treatment options for ductal adenocarcinoma of the pancreas are limited by early lymphatic spread, but the lymphatic vessels in pancreatic carcinoma have not been studied to date. Here, we present a histomorphological analysis of lymphatic vessels in pancreatic cancer resection specimens. Both intratumoral and peritumoral tissue were devoid of active lymphangiogenesis. Intratumoral lymphatics were frequently collapsed and non-functional, whereas peritumoral lymphatic vessels were enlarged, and numerous lymphatic vessels were seen in metastases. In addition, we screened pancreatic cancer tissue and pancreatic carcinoma cell lines for mRNA expression of the lymphangiogenic growth factor, VEGF-C; its receptor, VEGFR-3/flt4; and Prox1, a transcription factor essential for embryonic development of both lymphatic vessels and the pancreatic bud. VEGF-C was abundantly expressed in pancreatic cancer tissue and -cell lines and VEGFR-3/flt4 was expressed in cancer stromal cells. Prox1 was strongly expressed in the normal exocrine pancreas but significantly reduced in pancreatic cancer specimens from patients with short survival rates. Well-differentiated cell lines displayed higher levels of Prox1 mRNA than poorly differentiated ones. These results suggest that active lymphangiogenesis is not required for lymphovascular spread of pancreatic cancer. VEGF-C may promote local tumor growth via paracrine signaling to stromal cells expressing VEGFR-3 and support the entry of cancer cells into peritumoral lymphatics. Furthermore, loss of Prox1 function may be a driving force behind pancreatic carcinoma progression.

Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma.

Glucocorticoids (GCs) such as dexamethasone (DEX) have been widely used as co-medication in cancer therapy because they have potent proapoptotic properties in lymphoid cells, can reduce nausea, and alleviate acute toxic effects in healthy tissue. However, GCs are used in a supportive-care role, even though no prospective clinical studies have assessed the effect of these steroids on the growth of solid tumours. Data from preclinical and, to some extent, clinical studies, suggest that GCs induce treatment resistance in some solid tumours. Since it is unknown whether GC-induced resistance occurs only occasionally or is a more common phenomenon, we performed a screening study using several established cell lines from bone, brain, breast and cervix carcinoma as well as melanoma and neuroblastoma together with fresh surgical resections from patients with breast cancer. We found that DEX inhibits cisplatin and 5-fluorouracil-induced apoptosis and promotes the growth of the majority of examined malignant cells. In contrast, and as expected, DEX acted pro-apoptotically and promoted the cytotoxic effect of chemotherapy in established and primary lymphoid cells. Thus, these data demonstrate the need for detailed molecular studies to clarify the mechanism of differential glucocorticoid signaling as well as controlled, prospective clinical studies.

Corticosteroid co-treatment induces resistance to chemotherapy in surgical resections, xenografts and established cell lines of pancreatic cancer.

BACKGROUND: Chemotherapy for pancreatic carcinoma often has severe side effects that limit its efficacy. The glucocorticoid (GC) dexamethasone (DEX) is frequently used as co-treatment to prevent side effects of chemotherapy such as nausea, for palliative purposes and to treat allergic reactions. While the potent pro-apoptotic properties and the supportive effects of GCs to tumour therapy in lymphoid cells are well studied, the impact of GCs to cytotoxic treatment of pancreatic carcinoma is unknown. METHODS: A prospective study of DEX-mediated resistance was performed using a pancreatic carcinoma xenografted to nude mice, 20 surgical resections and 10 established pancreatic carcinoma cell lines. Anti-apoptotic signaling in response to DEX was examined by Western blot analysis. RESULTS: In vitro, DEX inhibited drug-induced apoptosis and promoted the growth in all of 10 examined malignant cells. Ex vivo, DEX used in physiological concentrations significantly prevented the cytotoxic effect of gemcitabine and cisplatin in 18 of 20 freshly isolated cell lines from resected pancreatic tumours. No correlation with age, gender, histology, TNM and induction of therapy resistance by DEX co-treatment could be detected. In vivo, DEX totally prevented cytotoxicity of chemotherapy to pancreatic carcinoma cells xenografted to nude mice. Mechanistically, DEX upregulated pro-survival factors and anti-apoptotic genes in established pancreatic carcinoma cells. CONCLUSION: These data show that DEX induces therapy resistance in pancreatic carcinoma cells and raise the question whether GC-mediated protection of tumour cells from cancer therapy may be dangerous for patients.

Pancreatic regeneration in chronic pancreatitis requires activation of the notch signaling pathway.

Chronic pancreatitis as an inflammatory process characterized by morphological changes, pancreatic dysfunction, and pain. During pancreatic injury and repair the Notch signaling pathway is reinstated. The current study analyzed this pathway in chronic pancreatitis and characterized its influence on fibrogenesis. Real-time quantitative PCR and immunohistochemistry were used for expression studies. Notch activation was determined by a specific luciferase-HES-1-reporter gene constructs. Cells were stimulated with alcohol, glucose, bile acids, and steroids. Notch-2, -3, and -4 mRNA, were overexpressed in chronic pancreatitis specimens. The ligands Jagged-1, -2, and Delta-1 were highly overexpressed. Jagged-1 and Notch receptors were observed in nerves, regenerating exocrine cells, and endocrine cells. Delta staining was present in ductal but not in acinus cells and not in nerves. Activation of Notch signaling was detectable upon cell stimulation with glucose, steroids, and bile acids. High glucose levels were further associated with increased collagen-I production. The Notch pathway is reactivated during chronic pancreatitis. Among the stimuli activating the Notch pathway are steroids, high glucose levels, and bile acids. These findings suggest a possible role of the Notch pathway during pancreatic regeneration since Jagged-1 inhibits inducible collagen-1 production, suggesting a new mechanism of tissue repair in this disease.

A new tool for experimental tumour research.

Surgical resected tumours are often stored for hours in the clinic upon transfer to the bench leading to apoptosis of tumour cells making them no longer suitable for molecular analysis and diagnostic procedures. The way out of this problem may be a new oxygen-enriched solution (OES). We tested this agent using surgical resections of carcinomas of lung, rectum and pancreas. Immediately after resection, one part of each individual tumour was stored in PBS and the other part in OES, and the content of viable or dead cells was determined by trypan blue exclusion and MTT-assay. We found that OES keeps tumour cells up to 3 days and longer more viable than PBS and reduces the percentage of dead cells without inducing therapy resistance and affecting the outcome of experimental procedures. Thus, storing freshly resected tumours in OES may save time for tumour transfer and initiation of experiments.

Splenic and portal vein thrombosis in pancreatic metastasis from renal cell carcinoma.

BACKGROUND: Pancreatic metastases from previously treated renal cell carcinoma are uncommon. Surgical resection of pancreatic metastasis remains the only worthwhile modality of treatment. CASE PRESENTATION: A case where pancreatic metastasis from previously resected right sided renal cell carcinoma was resected with a subtotal left pancreatectomy is described. An unusual feature was the presence of a large splenic vein tumor thrombus extending into the portal vein with associated portal hypertension. The patient underwent an uneventful portal vein resection with primary anastomosis. CONCLUSION: This is possibly the first documented case of portal vein renal tumor thrombosis in a case of isolated pancreatic metastasis from previously operated renal cell carcinoma in published world surgical literature.

Combination therapy for advanced pancreatic cancer using Herceptin plus chemotherapy.

The HER2/neu oncogene is overexpressed in up to 70% of human pancreatic cancer specimens when compared to normal pancreatic tissue. This cell surface receptor can be targeted specifically by the neutralizing antibody Herceptin. Herceptin has been successfully used in combination with other chemotherapeutic agents in breast cancer, a cancer in which only 30% of patients harbor elevated HER2/neu levels. In the present study, we investigated the therapeutic efficacy of Herceptin in combination with gemcitabine and docetaxel. Gemcitabine is currently the standard chemotherapeutic agent used to treat pancreatic cancer. In contrast, docetaxel, a taxane, is only just being investigated in pancreatic cancer. Tumor cell resistance to taxanes is at least in part mediated by the HER2/NEU oncogene. We have previously characterized HER2/NEU expression in human pancreatic cancer cell lines and studied the anti-tumor activity of Herceptin monotherapy in vitro and in vivo. In the present study, combination therapy resulted in a dramatic improvement of animals bearing human pancreatic cancer xenografts. Furthermore, metastasis and production of ascites was lower when a combination of these three agents was used. We conclude that, as with breast cancer, the anti-tumor activity of Herceptin may be improved by combination with taxanes or gemcitabine.