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1.
Semin Cancer Biol ; 60: 334-343, 2020 02.
Article in English | MEDLINE | ID: mdl-31445220

ABSTRACT

More than 70% of gastrointestinal (GI) cancers are diagnosed with metastases, leading to poor prognosis. For some cancer patients with limited sites of metastatic tumors, the term oligometastatic disease (OMD) has been coined as opposed to systemic polymetastasis (PMD) disease. Stephan Paget first described an organ-specific pattern of metastasis in 1889, now known as the "seed and soil" theory where distinct cancer types are found to metastasize to different tumor-specific sites. Our understanding of the biology of tumor metastasis and specifically the molecular mechanisms driving their formation are still limited, in particular, as it relates to the genesis of oligometastasis. In the following review, we discuss recent advances in general understanding of this metastatic behavior including the role of specific signaling pathways, various molecular features and biomarkers, as well as the interaction of carcinoma cells with their tissue microenvironments (both primary and metastatic niches). The unique features that underlie OMD provide potential targets for localized therapy. As it relates to clinical practice, OMD is emerging as treatable with surgical resection and/or other local therapy options. Strategies currently being applied in the clinical management of OMD will be discussed including surgical, radiation-based therapy, ablation procedures, and the results of emerging clinical trials involving immunotherapy.


Subject(s)
Gastrointestinal Neoplasms/etiology , Gastrointestinal Neoplasms/metabolism , Biomarkers , Combined Modality Therapy , Disease Management , Disease Progression , Disease Susceptibility , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Humans , Karyotype , Neoplasm Metastasis , Phenotype , Treatment Outcome
2.
Nervenarzt ; 92(7): 701-707, 2021 Jul.
Article in German | MEDLINE | ID: mdl-33025071

ABSTRACT

BACKGROUND: Since the beginning of the outbreak, the COVID-19 pandemic has caused an increased demand for psychosocial support for patients, their family members, and healthcare workers. Concurrently, possibilities to provide this support have been hindered. Quarantine, social isolation, and SARS-CoV­2 infections represent new and severe stressors that have to be addressed with innovative psychosocial care. OBJECTIVE AND METHOD: This article describes the COVID-19 psychosocial first aid concept at the University Hospital Munich (LMU Klinikum) developed by an interdisciplinary team of psychiatric, psychological, spiritual care, psycho-oncological, and palliative care specialists. RESULTS: A new psychosocial first aid model has been implemented for COVID-19 inpatients, family members, and hospital staff consisting of five elements. CONCLUSION: The concept integrates innovative and sustainable ideas, e.g. telemedicine-based approaches and highlights the importance of multidisciplinary collaboration to cope with challenges in the healthcare system.


Subject(s)
COVID-19 , Psychiatric Rehabilitation , Hospitals , Humans , Pandemics , Psychosocial Support Systems , SARS-CoV-2
3.
Gesundheitswesen ; 82(5): 431-440, 2020 May.
Article in German | MEDLINE | ID: mdl-31394580

ABSTRACT

Medical care provided at the hospital emergency rooms in Germany has hardly been explored. On the occasion of restructuring the Municipal Hospital, the Munich City Council initiated the "Round Table Emergency Care" in order to determine reference figures for capacity planning. The present study was designed to analyze treatment data from 14 emergency departments which mainly carry the city's hospital emergency service. For inpatient cases, data were used in accordance with §21 Hospital Charges Act, for outpatient cases - as far as available - similar data were used, anonymized and combined with data from prehospital emergency medical services (EMS). In order to describe the domains treatment urgency, diagnostic/therapeutic effort and bed requirements, data were categorized in a 4-stage system. Over 12 months, 524,716 treatment cases were recorded: 34% were admitted to hospital, 80% came without EMS. One in 7 patients who independently went to an emergency room needed a bed in the intensive care or intermediate care unit (ICU/IMC). There were 64 cases per day and per 100,000 inhabitants requiring 7 ICU/IMC and 15 regular ward beds. Most cases (66%) were treated as outpatients and presented to the hospital's emergency department at times when facilities of the ambulatory care system would have been available. Urgency of these cases was usually low (50.9%), but effort was often high, due to diagnostics and surgical procedures. This study offers fundamental knowledge for planning emergency care. A large proportion of the presentations, especially those with injuries and those with diagnosis that require a more differentiated work-up, seem to be medically justified, which is why appropriate capacities have to be planned in. The study also shows that capacity planning on the basis of EMS cases alone is an inappropriate, one-sided approach.


Subject(s)
Emergency Medical Services , Emergency Service, Hospital , Ambulatory Care , Critical Care , Germany , Humans
4.
Semin Cancer Biol ; 53: 139-155, 2018 12.
Article in English | MEDLINE | ID: mdl-30081228

ABSTRACT

A small subpopulation of cells within the bulk of tumors share features with somatic stem cells, in that, they are capable of self-renewal, they differentiate, and are highly resistant to conventional therapy. These cells have been referred to as cancer stem cells (CSCs). Recent reports support the central importance of a cancer stem cell-like niche that appears to help foster the generation and maintenance of CSCs. In response to signals provided by this microenvironment, CSCs express the tumorigenic characteristics that can drive tumor metastasis by the induction of epithelial-mesenchymal-transition (EMT) that in turn fosters the migration and recolonization of the cells as secondary tumors within metastatic niches. We summarize here recent advances in cancer stem cell research including the characterization of their genetic and epigenetic features, metabolic specialities, and crosstalk with aging-associated processes. Potential strategies for targeting CSCs, and their niche, by regulating CSCs plasticity, or therapeutic sensitivity is discussed. Finally, it is hoped that new strategies and related therapeutic approaches as outlined here may help prevent the formation of the metastatic niche, as well as counter tumor progression and metastatic growth.


Subject(s)
Neoplasms/genetics , Neoplastic Stem Cells/metabolism , Stem Cell Niche/genetics , Tumor Microenvironment/genetics , Anilides/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , Hedgehog Proteins/antagonists & inhibitors , Hedgehog Proteins/genetics , Hedgehog Proteins/metabolism , Humans , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplastic Stem Cells/drug effects , Pyridines/therapeutic use , Signal Transduction/drug effects , Signal Transduction/genetics , Stem Cell Niche/drug effects , Tumor Microenvironment/drug effects
5.
Gastric Cancer ; 19(3): 713-22, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26260874

ABSTRACT

BACKGROUND: Gastric cancer accounts for 5 % of cancer deaths. Proportions of older stomach cancer patients are increasing. Despite the still poor prognosis, standardised treatment has achieved improvements; nonetheless it is questionable whether all age groups have benefitted. Age and outcome need to be examined in a population-based setting. METHODS: Analyses included Munich Cancer Registry (MCR) data from 8601 invasive gastric cancer patients, diagnosed between 1998 and 2012. Tumour and therapy characteristics and outcome were analysed by two age groups (<70 vs. ≥70 years). Survival was analysed using the Kaplan-Meier method and relative survival was computed as an estimation for cancer-specific survival. Additional landmark analyses were conducted by calculating conditional survival of patients who survived more than 6 months. RESULTS: Fifty-nine per cent of the cohort were ≥70 years old. These patients had tumours with a slightly better prognosis and were treated with less radical surgery and adjuvant therapy than younger patients. The 5-year relative survival was 40 % for the youngest (<50 years) and 23 % for the oldest patients (≥80 years). Survival differences were diminished or eliminated after landmark analyses: The 5-year relative survival in age groups 50-59, 60-69 and 70-79 years was comparable (between 48 and 49.6 %) and slightly worse in the youngest and oldest (45 %), which may be explained by more aggressive tumours and effects of cellular senescence, respectively. CONCLUSION: The treatment and care of elderly gastric cancer patients in the MCR catchment area seems appropriate: if a patient's general condition allows oncologic resection and chemotherapy, it is conducted and the result is comparable between age groups.


Subject(s)
Adenocarcinoma/mortality , Carcinoma, Signet Ring Cell/mortality , Stomach Neoplasms/mortality , Adenocarcinoma/epidemiology , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Signet Ring Cell/epidemiology , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/therapy , Combined Modality Therapy , Female , Follow-Up Studies , Gastrectomy , Germany/epidemiology , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Registries , Stomach Neoplasms/epidemiology , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Survival Rate , Young Adult
7.
Dis Colon Rectum ; 58(1): 74-82, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25489697

ABSTRACT

BACKGROUND: Perioperative allogeneic red blood cell transfusion has been conclusively shown to be associated with adverse oncologic outcomes after resection of nonmetastatic colorectal adenocarcinoma. OBJECTIVE: The aim of the study was to identify risk factors for a perioperative transfusion and to assess the effects of transfusion on survival after curative-intended resection of hepatic metastases in patients featuring stage IV colorectal cancer. DESIGN: This was an observational study with a retrospective analysis of a prospective data collection. SETTING: The study was conducted at a tertiary care center. PATIENTS: A total of 292 patients undergoing curative-intended liver resection for colorectal liver metastases were included in the study. MAIN OUTCOME MEASURES: Univariate and multivariate analyses were performed identifying factors influencing transfusion, recurrence-free survival, and overall survival. RESULTS: A total of 106 patients (36%) received allogeneic red blood cells. Female sex (p = 0.00004), preoperative anemia (p = 0.001), major intraoperative blood loss (p < 0.00001), and major postoperative complications (p = 0.02) were independently associated with the necessity of transfusion. Median recurrence-free and overall survival were 58 months. Allogeneic red blood cell transfusion was significantly associated with reduced recurrence-free survival (32 vs 72 months; p = 0.008). It was reduced further by administration of >2 units (27 months; p = 0.02). Overall survival was not significantly influenced by transfusion (48 vs 63 months; p = 0.08). When multivariately adjusted for major intraoperative blood loss and factors univariately associated, namely comorbidities, tumor load, and positive resection margins, transfusion was an independent predictor for reduced recurrence-free survival (p = 0.03). LIMITATIONS: These include the retrospective and observational design, as well as the impossibility to prove causality of the association between transfusion and poor outcome. CONCLUSIONS: In patients undergoing liver resection for colorectal liver metastases, perioperative transfusion is independently associated with earlier disease recurrence. This emphasizes appropriate blood management measures, including the conservative correction of preoperative anemia, the use of low transfusion triggers, and the minimization of intraoperative blood loss.


Subject(s)
Colorectal Neoplasms/pathology , Erythrocyte Transfusion/adverse effects , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Comorbidity , Female , Hepatectomy , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Retrospective Studies , Risk Factors , Survival Rate , Treatment Outcome
8.
Ann Surg ; 260(5): 749-54; discussion 754-6, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25379845

ABSTRACT

OBJECTIVE: To determine whether regional hyperthermia (RHT) in addition to chemotherapy improves local tumor control after macroscopically complete resection of abdominal or retroperitoneal high-risk sarcomas. BACKGROUND: Within the prospectively randomized EORTC 62961 phase-III trial, RHT and systemic chemotherapy significantly improved local progression-free survival (LPFS) and disease-free survival (DFS) in patients with abdominal and extremity sarcomas. That trial included macroscopically complete and R2 resections. METHODS: A subgroup analysis of the EORTC trial was performed and long-term survival determined. From 341 patients, 149 (median age 52 years, 18-69) were identified with macroscopic complete resection (R0, R1) of abdominal and retroperitoneal soft-tissue sarcomas (median diameter 10 cm, G2 48.3%, G3 51.7%). Seventy-six patients were treated with EIA (etoposide, ifosfamide, doxorubicin)+RHT (≥5 cycles: 69.7%) versus 73 patients receiving EIA alone (≥5 cycles: 52.1%, P=0.027). LPFS and DFS as well as overall survival were determined. RESULTS: RHT and systemic chemotherapy significantly improved LPFS (56% vs 45% after 5 years, P=0.044) and DFS (34% vs 27% after 5 years, P=0.040). Overall survival was not significantly improved in the RHT group (57% vs 55% after 5 years, P=0.82). Perioperative morbidity and mortality were not significantly different between groups. CONCLUSIONS: In patients with macroscopically complete tumor resection, RHT in addition to chemotherapy resulted in significantly improved local tumor control and DFS without increasing surgical complications. Within a multimodal therapeutic concept for abdominal and retroperitoneal high-risk sarcomas, RHT is a treatment option beside radical surgery and should be further evaluated in future trials.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hyperthermia, Induced/methods , Retroperitoneal Neoplasms/therapy , Sarcoma/therapy , Abdomen , Adolescent , Adult , Aged , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Treatment Outcome
9.
Anticancer Drugs ; 25(9): 1095-101, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25029236

ABSTRACT

Pancreatic adenocarcinomas are associated with a poor survival prognosis. Besides curative surgical resection, only limited therapies with modest impact are available. New evidence suggests that the mammalian target of rapamycin pathway may be involved in the pathogenesis of neuroendocrine tumors, and breast and renal cell cancer. The phase I study described here was therefore designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of escalating doses of the mammalian target of rapamycin inhibitor everolimus in combination with gemcitabine in patients with advanced pancreatic cancer. Eligible patients had histologically confirmed locally advanced and/or metastatic pancreatic carcinoma and were administered 5 mg everolimus every second day (cohort 1, 2, 3) or 5 mg daily (cohort 4, 5) in combination with escalating low-dose gemcitabine. It was found that if two patients showed DLTs, MTD was reached and gemcitabine dose escalation was stopped at this level. Twenty-seven patients were enrolled in the study (cohort 1: n=3; cohort 2: n=4; cohort 3: n=6; cohort 4: n=7; cohort 5: n=7) and received a maximum 600 mg gemcitabine/week. In cohort 5, two of the six patients experienced DLTs (grade 3 liver toxicity lasting for>7 days). MTD was measured as 400 mg/m/week gemcitabine plus 5 mg/day everolimus. The MTD of a low-dose gemcitabine treatment in combination with everolimus was determined and no new safety concerns were identified in patients with advanced pancreatic cancer.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neovascularization, Pathologic/drug therapy , Pancreatic Neoplasms/drug therapy , TOR Serine-Threonine Kinases/antagonists & inhibitors , Adenocarcinoma/blood supply , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Angiogenesis Inhibitors/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cohort Studies , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Everolimus , Female , Humans , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Metastasis , Pancreas/blood supply , Pancreatic Neoplasms/blood supply , Pancreatic Neoplasms/pathology , Sirolimus/administration & dosage , Sirolimus/analogs & derivatives , TOR Serine-Threonine Kinases/metabolism , Gemcitabine
10.
J Surg Res ; 192(1): 187-94, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24948544

ABSTRACT

BACKGROUND: Augmenter of Liver Regeneration (ALR), a protein synthesized in the liver is suggested to be protective against oxidative stress-induced cell death. Hepatic ischemia-reperfusion (I/R) injury is triggered by reactive oxygen species. Here, we tested the hypothesis that ALR attenuates hepatic I/R injury in vivo. METHODS: C57BL6 mice were subjected to warm hepatic ischemia for 90 min. Either recombinant ALR (100 µg/kg) or vehicle were administered to mice prior ischemia. During reperfusion, neutrophil and CD4+ T cell migration and sinusoidal perfusion were analyzed using intravital microscopy. Alanine aminotransferase-aspartate aminotransferase (plasma) and caspase-3 (tissue) activities were determined as markers of hepatocellular necrotic and apoptotic injury. RESULTS: Hepatic I/R led to dramatic enhancement of neutrophil and CD4+ T cell recruitment in hepatic microvessels, sinusoidal perfusion failure, and strong elevation of aspartate aminotransferase-alanine aminotransferase and caspase-3 activities. During early reperfusion (60 min), the pretreatment with ALR improved postischemic perfusion failure (P < 0.05) and attenuated liver enzyme activities. Recruitment of CD4+ T cells, but not of neutrophils was attenuated. After 240 min of reperfusion, the protective effect of ALR was stronger, since the liver enzyme activity, perfusion failure, and leukocyte influx were significantly attenuated. As shown by the measurement of caspase-3 activity, postischemic apoptosis was reduced in the ALR-treated group. CONCLUSIONS: Our in vivo data show that ALR has a therapeutic potential against postischemic liver injury. As a mechanism, we suggest a direct protective effect of ALR on apoptotic and necrotic death of hepatocytes and an attenuation of inflammatory cell influx into the postischemic tissue.


Subject(s)
Liver Regeneration/immunology , Oxidative Stress/immunology , Oxidoreductases Acting on Sulfur Group Donors/immunology , Reperfusion Injury/immunology , Animals , Apoptosis/immunology , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/immunology , Cell Communication/immunology , Cell Movement/immunology , Endothelial Cells/cytology , Endothelial Cells/immunology , Female , Liver Circulation/immunology , Liver Regeneration/drug effects , Mice, Inbred C57BL , Microcirculation/immunology , Neutrophils/cytology , Neutrophils/immunology , Oxidoreductases Acting on Sulfur Group Donors/pharmacology , Recombinant Proteins/immunology , Recombinant Proteins/pharmacology , Reperfusion Injury/drug therapy
11.
Transpl Int ; 27(11): 1120-4, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24975042

ABSTRACT

In Germany, long-term commitment of surgeons to transplantation is rare. Most surgeons leave transplant surgery after a short stint and follow careers in other surgical fields. This rapid turnover of liver transplant surgeons may result in poor resource utilization and potentially compromise patient safety. In this report, we have analyzed the caseload and the careers of 25 surgeons in liver transplantation over a period of 22 years. The median time in liver transplantation was short. Of all surgeons who engaged in liver transplantation, the median time was 3.5 years. Surgeons who completed their training remained in the field for 7 years. Surgeons who prematurely stopped their training remained for 2 years. Individual total caseloads of transplant surgeons were relatively low. The median number of procedures was 40 for all surgeons, 153 for currently active surgeons, 51 for surgeons who completed training, 27 for surgeons currently in training, and a median of four liver transplantations for surgeons who prematurely stopped liver transplantation. The vast majority (75%) of surgeons prematurely quit liver transplantation to follow alternate surgical careers. Structural changes in academic transplant surgery have to be made to facilitate long-term commitments of interested surgeons and to avoid "futile" transplant careers.


Subject(s)
General Surgery/education , Liver Transplantation/education , Academic Medical Centers , Career Choice , Germany , Humans , Internship and Residency , Time Factors , Workload
12.
Surg Endosc ; 28(4): 1119-25, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24202710

ABSTRACT

BACKGROUND: Recent studies demonstrated favorable short- and mid-term results after laparoscopic surgery for rectal cancer. However, long-term results from large series are lacking. The present study analyses long-term results of laparoscopic rectal cancer surgery from a large-volume center. METHODS: From January 1998 until March 2005, 225 patients underwent laparoscopic rectal resection due to carcinoma at the Medical Centre of the University of Regensburg. From 224 patients, a follow-up over 10 years was performed using the data of the Tumour Centre of the University of Regensburg. The data were analysed using oncological data (tumour recurrence) as well as overall survival. In addition, the effect of conversion to open resection on overall survival was analysed. RESULTS: With a median of 10 years at follow-up, the overall and disease-free survival was 50.5 and 50.1 %, respectively. Local recurrence of all patients was 5.8 % and none of the converted patients was within this group. The median time interval for the development of local recurrence was 30 months. Six of the 13 patients with local recurrence (46.1 %) had received neoadjuvant radiochemotherapy before surgery. Patients with a conversion to open surgery had primarily a significantly worse outcome than patients resected completely laparoscopically (p = 0.003). However, this difference was no longer apparent using a multivariant analysis (hazard ratio 1.221; p = 0.478). CONCLUSIONS: Overall survival and local recurrence rate of patients undergoing laparoscopic resection of rectal cancer are comparable to open surgery. However, in our analysis, patients undergoing laparoscopic anterior resection had a higher survival rate compared with patients with abdominoperineal resection.


Subject(s)
Colectomy/methods , Forecasting , Laparoscopy/methods , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Conversion to Open Surgery , Disease-Free Survival , Female , Germany/epidemiology , Humans , Incidence , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Proportional Hazards Models , Rectal Neoplasms/mortality , Retrospective Studies , Survival Rate/trends
13.
Langenbecks Arch Surg ; 399(3): 349-57, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24590429

ABSTRACT

BACKGROUND: Intra-abdominal adhesions following surgery are a major source of morbidity and mortality including abdominal pain and small bowel obstruction. This study evaluated the safety of PVA gel (polyvinyl alcohol and carboxymethylated cellulose gel) on intestinal anastomoses and its potential effectiveness in preventing adhesions in a clinically relevant large animal model. METHODS: Experiments were performed in a pig model with median laparotomy and intestinal anastomosis following small bowel resection. The primary endpoint was the safety of PVA on small intestinal anastomoses. We also measured the incidence of postoperative adhesions in PVA vs. control groups: group A (eight pigs): stapled anastomosis with PVA gel compared to group B (eight pigs), which had no PVA gel; group C (eight pigs): hand-sewn anastomosis with PVA gel compared to group B (eight pigs), which had no anti-adhesive barrier. Animals were sacrificed 14 days after surgery and analyzed. RESULTS: All anastomoses had a patent lumen without any stenosis. No anastomoses leaked at an intraluminal pressure of 40 cmH2O. Thus, anastomoses healed very well in both groups, regardless of whether PVA was administered. PVA-treated animals, however, had significantly fewer adhesions in the area of stapled anastomoses. The hand-sewn PVA group also had weaker adhesions and trended towards fewer adhesions to adjacent organs. CONCLUSION: These results suggest that PVA gel does not jeopardize the integrity of intestinal anastomoses. However, larger trials are needed to investigate the potential of PVA gel to prevent adhesions in gastrointestinal surgery.


Subject(s)
Anastomosis, Surgical/adverse effects , Carboxymethylcellulose Sodium/therapeutic use , Intestine, Small/surgery , Polyvinyl Alcohol/therapeutic use , Suture Techniques/adverse effects , Tissue Adhesions/prevention & control , Animals , Disease Models, Animal , Female , Gels , Laparotomy , Swine , Tissue Adhesions/etiology , Tissue Adhesions/pathology , Wound Healing
14.
PLoS Pathog ; 7(11): e1002366, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22114552

ABSTRACT

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+) heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+) transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination.


Subject(s)
Cytomegalovirus Infections/virology , Endothelial Cells/virology , Muromegalovirus/pathogenicity , Animals , Endothelium, Vascular/virology , Heart/virology , Heart Transplantation/adverse effects , Kidney/virology , Kidney Transplantation/adverse effects , Mice , Mice, Transgenic , Viremia/virology
15.
J Surg Oncol ; 107(8): 859-64, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23637007

ABSTRACT

BACKGROUND: Pancreatic metastases are rare and only sparse data exists on treatment options. After recent advances in pancreatic surgery, metastasectomies have become promising treatment alternatives. METHODS: Twenty-six patients underwent pancreatic metastasectomy between 1991 and 2010 at our institution. Data was evaluated retrospectively. RESULTS: Renal cell carcinoma was the most common origin of pancreatic metastases (n = 16; 62%). Other primaries include gall bladder carcinoma, leiomyosarcoma, colon cancer (all n = 2), and others. The median time interval between primary tumor and pancreatic resection was 5.3 years [0-24]. Eleven pancreatic head resections (42%), fourteen distal pancreatectomies (54%), and one total pancreatectomy were performed (4%). The estimated 3- and 5-year survival rates were 73.2% and 52.3%, respectively. The estimated median overall survival was 63 months (CI: 37.8-88.1 months). There' was no perioperative death. The complication rate and relaparotomy rate was 31% and 19%, respectively. Patients suffering from synchronous metastases at the time of pancreatic surgery had a statistically significant shorter median overall survival time (11 months vs. 64 months). CONCLUSIONS: Despite the operative risk involved, we believe that pancreatic resection should be considered in selected patients with good performance status, stable disease and isolated pancreatic metastases.


Subject(s)
Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/pathology , Pancreatectomy , Pancreatic Neoplasms/secondary , Pancreatic Neoplasms/surgery , Adult , Aged , Female , Humans , Kaplan-Meier Estimate , Length of Stay , Male , Middle Aged , Morbidity , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/prevention & control , Neoplasm, Residual/diagnosis , Pancreatectomy/adverse effects , Pancreatectomy/methods , Retrospective Studies , Treatment Outcome
16.
Transpl Int ; 26(10): 999-1006, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23952102

ABSTRACT

De novo malignancies are a major cause of late death after liver transplantation. Aim of the present study was to determine whether use of cyclosporine versus tacrolimus affects long-term tumor incidence considering potential confounders. De novo malignancies in 609 liver transplant recipients at Munich Transplant Centre between 1985 and 2007 were registered. In 1996, the standard immunosuppressive regimen was changed from cyclosporine to tacrolimus. Different effects of those drugs on long-term tumor incidence were analyzed in multivariate analysis. During 3765 patient years of follow-up (median 4.78 years), 87 de novo malignancies occurred in 71 patients (mean age 47.5 ± 13.3 years, mean time after liver transplantation 5.7 ± 3.7 years). The cumulative incidence of de novo malignancies was 34.7% for all tumor entities after 15 years as compared to 8.9% for a nontransplanted population. The most frequent tumors observed were nonmelanoma skin cancers (44.83%). Moreover, post-transplant lymphoid disease, oropharyngeal cancer (n = 6, 6.9%), upper gastrointestinal tract cancer (n = 4, 4.6%), lung cancer (n = 4, 4.6%), gynecological malignancies (n = 4, 4.6%), and kidney cancer (n = 3, 3.45%) were detected. Multivariate analysis revealed recipient age [hazards ratio (HR) 1.06], male gender (HR 1.73), and tacrolimus-based immunosuppression (HR 2.06) as significant risk factors. Based on those results, a tacrolimus-based immunosuppression should be discussed especially in older male patients. Whether reducing tacrolimus target levels may reduce the risk for de novo malignancies has yet to be determined in prospective trials.


Subject(s)
Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Liver Failure/therapy , Liver Transplantation/methods , Neoplasms/epidemiology , Tacrolimus/therapeutic use , Adult , Female , Follow-Up Studies , Humans , Immunosuppression Therapy , Incidence , Liver Failure/complications , Male , Middle Aged , Multivariate Analysis , Neoplasms/complications , Neoplasms/immunology , Proportional Hazards Models , Risk Factors , Sex Factors , Treatment Outcome
17.
Transpl Int ; 26(1): 90-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23237579

ABSTRACT

The role of intraoperative porto-caval shunts in orthotopic liver transplantation (OLT) is controversial. Aim of this study was to analyze the effects of an intraoperative, porto-caval catheter-shunt on graft function and survival following cava sparing OLT. Four hundred and forty-eight piggy back liver transplantations with or without a temporary spontaneous porto-caval shunt between 1997 and 2010 were analyzed (shunt n = 274 vs. no shunt n = 174). Lab MELD scores and donor risk indices (DRI) were calculated. Hepatic injury (ALT, AST), -function (bilirubin, prothrombin ratio), postreperfusion liver blood flow and graft survival were registered [mean follow-up: 50.5 (0-163.0) months]. The impact of a shunt on graft survival was determined using multivariate analysis. Usage of a porto-caval shunt was associated with reduced hepatic injury (ALT, AST), whereas graft function was not affected. The shunt group showed a significantly increased portal venous blood flow after reperfusion. Retransplantation rate was decreased (7.7% vs. 20.1%, P = 0.001) and long-term graft survival was significantly increased with a porto-caval shunt (hazard ratio 2.1, P < 0.001). This effect was even more pronounced for marginal organs. Usage of intraoperative porto-caval catheter-shunts is beneficial in cava sparing OLT and is associated with reduced ischemia-reperfusion injury and improved organ survival in particular for recipients of marginal organs.


Subject(s)
Liver Transplantation/methods , Portacaval Shunt, Surgical , Adult , Aged , Female , Graft Survival , Humans , Liver Circulation , Male , Middle Aged , Multivariate Analysis , Reoperation
18.
Surg Endosc ; 27(4): 1186-95, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23232989

ABSTRACT

PURPOSE: Percutaneous endoscopic gastrostomy (PEG) or percutaneous endoscopic jejunostomy (PEJ) are substantial for patients with swallowing disorders to maintain enteral nutrition or to decompress palliatively intractable small bowel obstruction. Endoscopic placement can be impossible due to previous (gastric) operation, obesity, hepato-splenomegaly, peritoneal carcinosis, inadequate transillumination, or obstructed passage. Computed tomography (CT)-fluoroscopic guidance with or without endoscopy can enable placement of CT-PG/CT-PJ or CT-PEG/CT-PEJ if endoscopically guided placement fails. In this retrospective study, we will evaluate the feasibility and safety of this method. METHODS: A total of 101 consecutive patients were referred to our department for feeding support (n = 87) or decompression (n = 14). Reasons were: ENT tumor (n = 51), esophageal cancer (n = 19), mediastinal mass (n = 2), neurological disorder (n = 15). Decompression tubes were placed because of cancer (n = 13) or Crohn's disease (n = 1). The following approaches were chosen: CT fluoroscopy and simultaneous gastroscopy (n = 61), inflation of the stomach via nasogastric tube (n = 29), and direct puncture under CT-fluoroscopic guidance (n = 11). RESULTS: CT fluoroscopy-guided gastrostomy was feasible in 89 of 101 patients. No procedure-related mortality was observed. One tube was misplaced into the colon in a patient with a history of gastrectomy. No complication was seen after removal. Minor complications: dislodgement (n = 17), peristomal leakage (n = 7), wound infection (n = 1), superficial skin infection (n = 6), tube obstruction (n = 2). CONCLUSIONS: CT fluoroscopy-guided PG/PJ or PEG/PEJ is feasible and safe and provides adequate feeding support or decompression. It offers the benefits of minimally invasive therapy even in patients with contraindications to established endoscopic methods, combining the advantages of both techniques. Long-term complications-mainly tube-related problems-are easily treated.


Subject(s)
Endoscopy, Gastrointestinal , Enteral Nutrition/methods , Gastrostomy/methods , Intubation, Gastrointestinal , Jejunostomy/methods , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Female , Fluoroscopy , Gastroscopy , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
19.
Ann Vasc Surg ; 27(4): 498.e9-13, 2013 May.
Article in English | MEDLINE | ID: mdl-23541777

ABSTRACT

BACKGROUND: Primary leiomyosarcoma (LMS) of the hepatic vena cava is a rare malignancy that has only been published in case reports. Only a few cases with successful R0 resection have been reported in the literature. METHODS: We report 2 similar cases of extended primary LMS of the intrahepatic inferior vena cava (IVC). Both patients previously underwent operations in nonspecialized centers that resulted in inadequate tumor resection. After admission to a high-volume center focusing on the treatment of patients with sarcoma, R0 resection was feasible with a multimodal therapeutic treatment approach. RESULTS: Radical complete tumor resection was achieved by means of extended right-sided hemihepatectomy (segments V-VIII and I), en bloc resection, and prosthetic replacement of the IVC and nephrectomy in 1 patient. Both patients are currently tumor-free and healthy 6 months postoperatively. CONCLUSIONS: Patients with such complex tumors should be referred to centers with specialized surgeons who can preoperatively estimate whether complete resection may be possible and who are capable of performing such delicate interventions.


Subject(s)
Hepatectomy/methods , Leiomyosarcoma/surgery , Vascular Neoplasms/surgery , Vascular Surgical Procedures/methods , Vena Cava, Inferior , Adult , Female , Humans , Leiomyosarcoma/diagnosis , Middle Aged , Tomography, X-Ray Computed , Vascular Neoplasms/diagnosis
20.
Langenbecks Arch Surg ; 398(4): 487-99, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23430290

ABSTRACT

BACKGROUND: High-quality biospecimens of human origin with annotated clinical and procedural data are an important tool for biomedical research, not only to map physiology, pathophysiology and aetiology but also to go beyond in translational research. This has opened a new special field of research known as 'biobanking', which focuses on how to collect, store and provide these specimens and data, and which is substantially supported by national and European funding. PURPOSE: An overview on biobanking is given, with a closer look on a clinical setting, concerning a necessary distinction from clinical trials and studies as well as a comparison of prospective sample collection with secondary use of archived samples from diagnostics. Based on a summary of possible use and scientific impact of human tissue in research, it is shown how surgical expertise boosts the scientific value of specimens and data. Finally, an assessment of legal and ethical issues especially from a surgical perspective is given, followed by a model of interdisciplinary biobanking within a joint 'centre' that as synergistic structure merges essential input from surgery as well as laboratory medicine, pathology and biometry. CONCLUSION: Within the domain of biobanking, surgeons have to develop a better awareness of their role within translational research, not only on the level of medical faculties but also as nationally and internationally funded initiatives. Therefore, the authors suggest a platform for biobanking within the German association of surgeons in analogy to the existing special interest group for clinical trials.


Subject(s)
Biological Specimen Banks/organization & administration , Cooperative Behavior , Data Collection , General Surgery/organization & administration , Interdisciplinary Communication , Physician's Role , Translational Research, Biomedical/organization & administration , Biological Specimen Banks/legislation & jurisprudence , Data Collection/legislation & jurisprudence , Europe , General Surgery/legislation & jurisprudence , Humans , Informed Consent/legislation & jurisprudence , Research Support as Topic/legislation & jurisprudence , Research Support as Topic/organization & administration , Tissue and Organ Harvesting/legislation & jurisprudence , Translational Research, Biomedical/legislation & jurisprudence
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