Long-term quality of life in pouch patients compared with stoma patients following rectal cancer surgery.

AIM: Low and ultralow anterior resection for rectal cancer with colorectal or coloanal anastomosis does not compromise oncological results compared with abdominoperineal excision. Although avoidance of a permanent colostomy is regarded as beneficial for a patient's quality of life (QoL), patients undergoing sphincter-sparing surgery may develop a number of functional problems. A colonic pouch significantly improves functional outcome after rectal resection and low anastomosis and may positively influence QoL. The aim of this study was to compare QoL in long-term survivors who underwent ultralow anterior resection with total mesorectal excision and colonic J-pouch anastomosis (CPA) with patients treated with abdominoperineal excision (APE) and end colostomy for rectal cancer. METHOD: The medical records from our institution's prospectively maintained rectal cancer database of 151 patients who underwent surgery for ultralow rectal cancer from 2001 to 2007 were analysed. QoL in 59 eligible patients was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 core and Colorectal Cancer 29. Results were compared for patients with CPA and APE. RESULTS: The median follow-up in the 59 patients was 74 (37-119) months. QoL was good in all patients, but it was better in CPA than in APE patients. Global health status (P = 0.009), physical functioning (P = 0.0002), role functioning (P = 0.03), cognitive functioning (P = 0.046), social functioning (P = 0.002), body image (P = 0.053), embarrassment (P = 0.002) and urinary frequency (P = 0.003) were significantly improved for patients with CPA. CONCLUSION: QoL after rectal resection and CPA was better than after APE in several respects. However, QoL should not be regarded as an isolated concept but rather as one of several possible clinical outcomes of interest.

Can an endocytoscope system (ECS) predict histology in neoplastic lesions?

BACKGROUND AND STUDY AIMS: An endocytoscope system (ECS) has recently been developed with the possibility of super-high magnification of gastrointestinal mucosa, thus allowing in vivo imaging of living cells. The aim of the present study was to assess the potential of ECS in the prediction of histology in both normal gastrointestinal mucosa and neoplastic lesions. PATIENTS AND METHODS: In total, 76 patients (57 men, 19 women; age range 37-86 years) with neoplastic lesions in the esophagus, stomach, or colon were enrolled into the study and underwent esophagogastroduodenoscopy or colonoscopy. After staining with 1% methylene blue, the mucosa was examined with the ECS probe (x 450 and x 1100 magnification), and video sequences were recorded on video disk. Biopsies from the examined areas were taken for histology and served as the gold standard. The endocytoscope video sequences were evaluated by two blinded pathologists. Finally the results were compared with those resulting from the evaluation of an experienced endoscopist who was aware of the macroscopic endoscopic pictures and the endocytoscope image results. RESULTS: A total of 25 patients with esophageal lesions, 28 patients with colonic lesions, and 23 patients with gastric lesions were examined. The sensitivity and specificity for the evaluation of the blinded pathologists was 81% and 100%, respectively, in the esophagus, 56% and 89% in the stomach, and 79% and 90% in the colon. If an endoscopist evaluated the endocytoscopic pictures in combination with the macroscopic endoscopic images sensitivity and specificity increased significantly. CONCLUSIONS: First experiences with ECS show good sensitivity rates even by blinded assessment for esophageal and colonic lesions. Sensitivity for neoplastic lesions in the stomach is lower because of gastric mucous secretion. Combining the endoscopic and cytoscopic appearance of the lesion may further enhance the diagnostic value of the method.

Ghrelin, anthropometry and nutritional assessment in geriatric hospital patients.

UNLABELLED: Loss of appetite is an important causal factor for malnutrition in the elderly, and age-associated changes of hormone levels seem to be of great relevance in this regard. At present there has been no study exploring the role of the appetite stimulating hormone ghrelin in geriatric hospital patients. STUDY POPULATION: 121 (f 82, m 39) patients from two geriatric wards of our hospital. Mean age was 80.2+/-7.7 years. RESULTS: The basal ghrelin level (mean 158.43+/-144.02 pg/ml) showed no gender difference. No association with the age of the patients could be demonstrated. There was an inverse correlation of basal ghrelin with BMI, upper arm circumference, triceps skin fold, basal leptin and insulin. No correlation between established screening/assessment tools for malnutrition - Mini Nutritional Assessment (MNA), Subjective Global Assessment (SGA), Nutritional Risk Screening (NRS) - could be shown. Even after grouping the ghrelin levels into six different disease categories, no significant difference could be shown between them. CONCLUSION: For our patients aged 67 to 94, no correlation with age could be shown. Nevertheless the basal level of ghrelin is substantially lower when compared to a younger population with similar BMI, while the anorectic hormone leptin shows no substantial difference. This causes a more anorectic hormonal constellation which may contribute to the loss of appetite in geriatric patients.

[Aortoduodenal fistula as a cause of gastrointestinal bleeding--difficulties in endoscopic diagnosis]. / Aortoduodenale Fistel als Ursache der gastrointestinalen Blutung - eine endoskopisch schwierige Differenzialdiagnose.

We report on three patients with severe gastrointestinal bleeding arising from aortoenteric fistula. Two patients presented with a secondary aortoduodenal fistula. In the first case bleeding occurred 8 months after aortobifemoral graft implantation. In the second patient aortobiliacal graft implantation was performed 22 years before. In the third case the aortoenteric fistula was primary and was caused by an abdominal aortic aneurysm without prior vascular intervention. In the first case diagnosis was made by urgent endoscopy visualizing ongoing bleeding from the duodenal fistula. In the two other patients urgent endoscopy and CT as well could not demonstrate the bleeding source. Aortoenteric fistula was diagnosed endoscopically during severe rebleeding some hours later. Two patients underwent surgery with implantation of an axillobifemoral bypass; the third patient declined further intervention and died. The course shows that aortoduodenal fistula can present with severe but intermittent gastrointestinal bleeding making the diagnosis in the non-bleeding interval difficult. In patients with severe gastrointestinal bleeding and a history of aortic disease (aneurysm, prior aortic graft repair or stenting) an aortoduodenal fistula should be suspected and the indication for surgical intervention should be considered early in spite of negative results of endoscopy and CT.

German national case collection of familial pancreatic cancer - clinical-genetic analysis of the first 21 families.

BACKGROUND: The observation of a familial accumulation of ductal pancreatic adenocarcinoma (PC) and the increased risk for PC in certain hereditary tumor syndromes point to a genetic predisposition for PC. In order to evaluate the characteristics of familial PC, a German national case collection for familial pancreas cancer (FaPaCa) was established. PATIENTS AND METHODS: In FaPaCa, families of patients with PC are being collected, who have at least 1 first-degree relative with PC or with malignant melanoma. Histopathologic verification of tumor diagnoses, acquisition of clinical data, and full genetic counselling are prerequisites for the enrollment of PC families in FaPaCa. RESULTS: So far, 21 families fulfilled the criteria for partaking in FaPaCa. In 11 families, PC represented the sole tumor entity. Additional tumors included malignant melanoma in 5, breast cancer in 3, and prostatic, colon or lung cancer in 2 families. Compared to the preceding generation, a younger age at diagnosis of PC was observed in the offspring of PC patients (offspring median 53 years vs. parents median 75.5 years). CONCLUSION: The association of PC and breast cancer, and of PC and malignant melanoma suggests predisposing mutations in the BRCA2 or CDKN2A genes in about one third of the FaPaCa families. Mutational analyses in both candidate genes may help to identify individuals who are at an increased risk for developing PC. A shift towards a younger age at diagnosis in our PC families may indicate genetic anticipation and/or changes of patterns of exogenous risk factors.

Mitochondrial defects by intracellular calcium overload versus endothelial cold ischemia/reperfusion injury.

Questions as to the critical stress factor and primary targets of cold ischemia/reperfusion (CIR) injury were addressed by comparing mitochondrial defects caused by (1) CIR injury and (2) intracellular Ca2+ overload. CIR was simulated in transformed human umbilical vein endothelial cell cultures (tEC) by 8 h cold anoxia in University of Wisconsin solution and reoxygenation at 37 degrees C. Intracellular Ca2+ concentrations were changed by permeabilization of suspended cells with digitonin in culture medium (RPMI, 0.4 mM Ca2+). Binding of free Ca2+ by ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid in RPMI or mitochondrial incubation medium served as controls. Extracellular Ca2+ protected the cell membrane against permeabilization. Mitochondrial functions were determined before and after permeabilization of the cell membrane. After CIR, mitochondrial respiratory capacity declined, but oxygen consumption remained coupled to adenosine triphosphate (ATP) production. In contrast, Ca2+ overload caused uncoupling of mitochondrial respiration. High intracellular Ca2+ overload, therefore, does not reproduce cold ischemia/reperfusion injury in endothelial cells.

Expression of stress proteins, adhesion molecules, and interleukin-8 in endothelial cells after preservation and reoxygenation.

Endothelial activation is a central feature of preservation-induced allograft injury. The present study aims at a quantitative assessment of stress proteins, adhesion molecules, and interleukin-8 in a cell culture-based model of organ preservation. Human umbilical vein endothelial cells were exposed to cold, hypoxic storage in University of Wisconsin (UW), histidine-tryptophane-ketoglutarate (HTK), and EuroCollins solutions for 8 h with subsequent rewarming/reoxygenation (rew/reox) for 1 and 4 h. A cell-based ELISA was designed for detection of heat shock proteins (HSP) 60 and 70, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). Immunohistochemical staining was performed for comparison. Interleukin-8 was quantified by ELISA. HSP 70 was expressed after cold storage in HTK and EuroCollins solution and after rew/reox in all groups. A constitutive expression of HSP 60 was observed with further upregulation after rew/reox following cold storage in all experimental groups. ICAM-1 was clearly upregulated, but VCAM-1 showed only weak expression after cold storage and rew/reox. ELAM-1 was detectable in minimal amounts after cold storage but was considerably upregulated after 4 h of rew/reox. A significant increase of interleukin-8 release could be found after 4 h of rew/reox following storage in EuroCollins solution. Expression of stress proteins can be considered as a new parameter of preservation-associated endothelial activation. Apart from possible protective effects, allograft vasculopathy could be in part a consequence of the antigeneic potential of heat shock proteins connected with effects caused by adhesion molecules and inflammatory cytokines.

Ultrastructural analysis of human endothelial cells after hypothermic storage in organ preservation solutions.

BACKGROUND: Protection of vascular endothelium is a critical factor in organ preservation for transplantation. This study aims at a morphological assessment of endothelial cell injury in a comparison of storage solutions, using a cell culture model of cold preservation and rewarming. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) were cultured in monolayer and exposed to hypothermic storage in University of Wisconsin (UW), histidine-tryptophane-ketoglutarate (HTK), and EuroCollins solutions for 6 h and subsequent rewarming for 30 min or 6 h. Alterations of subcellular structures and cell-cell contacts were analyzed by transmission electron microscopy (TEM) and light microscopic assessment after actin and nuclear staining. RESULTS: Structural alterations of mitochondria, endoplasmic reticulum, nuclei, and cytoskeletal fibers as well as disruption of intercellular contacts were found after cold storage in HTK and EuroCollins solutions. In contrast, storage in UW solution resulted in minimum changes of stress fibers only. A rapid rearrangement of structural alterations was achieved during rewarming in cell culture medium in all experimental groups. CONCLUSIONS: Preservation of endothelial cell structure is best achieved by UW solution. Ultrastructural cell damage is a direct consequence of hypothermic storage and is fully reversible during rewarming after short storage times.

Value of liver biopsy combined with cholecystectomy.

BACKGROUND/AIMS: Many authors value routinely performed liver biopsy concomitant with cholecystectomy as a procedure of great diagnostic importance in regard to diagnosis and treatment of liver disease. Without reason, fewer perioperative liver punctures have been performed since the beginning of minimal invasive surgery, even so, laparoscopic cholecystectomy provides an equal opportunity for taking liver biopsies for diagnostic purposes. This study aims to determine the prevalence and extent of liver disease in patients undergoing cholecystectomy for gall stone disease. METHODOLOGY: Within the pre-laparoscopic era, 565 cholecystectomies with concomitant liver biopsies were performed. The results were evaluated retrospectively. Serious pathohistologic findings were defined by the stage of pathologic changes demanding prognostic and/or therapeutic consequences. RESULTS: One hundred and ten patients (19.5%) had normal liver biopsies. Severe pathologic liver changes were diagnosed in 58 (10.3%). Taking all liver biopsies showing liver changes, prognostic and therapeutic relevance were represented in 52% of our patients. CONCLUSIONS: Having proof of the high rate of pathologic liver changes resulting in liver disease we advocate liver biopsy in connection with cholecystectomy as an important procedure, if open or laparoscopic surgery of the extrahepatic biliary tract is performed.

Respiratory defect as an early event in preservation-reoxygenation injury of endothelial cells.

Characterization of preservation injury in endothelial cells has been primarily accomplished by measurement of cell viability. To analyze early events and cellular mechanisms of preservation-reoxygenation injury, we developed high-resolution respirometry for the study of mitochondrial function in endothelial cells, to provide a quantitative marker for sublethal stress. Cultured human umbilical vein endothelial cells were stored for 4 and 8 hr at 4 degrees C under an atmosphere of 95% N2 and 5% CO2 in University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions. Respiration of suspended cells, measured after reoxygenation in growth medium at 37 degrees C, was significantly reduced in all treatments in comparison to controls not subjected to cold preservation. In contrast, trypan blue staining was unchanged after 4 hr of preservation and was significant only after 8 hr. After 8 hr of cold storage in UW and HTK solutions, respiration was 64+/-5% and 49+/-6%, respectively, of controls (46.5+/-3.3 pmol O2 x s(-1 x 10(-6) cells), indicating significantly better protection by UW solution than HTK solution. A titration regimen with substrate (succinate), uncoupler (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), and inhibitors of complexes I and III (rotenone and antimycin A) resulted in identical respiratory response patterns in all treatments. The plasma membrane remained impermeable to succinate. Inner mitochondrial membrane function was preserved as indicated by a constant relative increase of respiration after uncoupling. These results demonstrate that loss of catalytic capacity for respiration constitutes an early event in preservation-reoxygenation injury, whereas membrane damage is not a primary defect. Respirometric evaluation of sublethal cell injury and localization of cell damage may provide selective guidelines for further optimization of strategies in organ preservation.

[Reflux esophagitis: manometry and Ph measurement]. / Refluxösophagitis: Manometrie und pH-Metrie.

Manometry and pH-metry are essential in the examination of functional disturbances of the esophagus. Proven indications for manometry are dysphagia of unknown origin and noncardiac chest pain; in reflux esophagitis manometry is used for measuring pressure of the lower esophageal sphincter and detecting motility disorders of the esophageal body, pH-metry is used as long-term pH-metry to quantify gastroesophageal reflux during day and night; furthermore long-term pH-metry is important in the classification of atypical esophagitis. Recording gastroesophageal reflux and esophageal motility may influence planning of therapy and predict prognosis. Before antireflux surgery manometry and pH-metry are useful in judging the clearance mechanisms of the esophagus. Used critically, manometry and pH-metry can be very helpful as cost-effective diagnostic tools in the long-term therapy of reflux esophagitis.

Assessment of endothelial preservation in human cell cultures.

BACKGROUND: Impairment of microcirculation due to endothelial cell damage must be considered a limiting factor in organ preservation. The present study aims at a quantitative assessment of preservation-induced injury in cultured human endothelial cells. METHODS: Monolayer cultures of human umbilical vein endothelial cells were exposed to cold (40 degrees C) hypoxic storage in University of Wisconsin solution, histidine-tryptophane-ketoglutarate solution, Euro-Collins solution, and saline solution. Cellular integrity was evaluated by viable cell count, ultrastructural analysis, and prostacyclin release after 24, 48, and 72 hours of storage and subsequent 6 hours of reincubation in culture medium at 37 degrees C. Expression of intercellular adhesion molecule-1 was investigated after 6, 12, and 24 hours of cold preservation and after 6 hours of rewarming. RESULTS: Cellular viability was best maintained with University of Wisconsin and histidine-tryptophane-ketoglutarate solutions with no significant reduction of cell count up to 72 hours; Euro-Collins solution and saline solution caused a significant decline in cell numbers after 24 hours (p < 0.05). Morphology was best preserved by University of Wisconsin solution. Prostacyclin values were elevated after 24 hours in Euro-Collins solution and saline solution, after 48 hours in histidine-tryptophane-ketoglutarate, Euro-Collins, and saline solutions, and after 72 hours in Euro-Collins solution (p < 0.05, compared with University of Wisconsin solution). ICAM expression was weak after cold storage (24 hours) in University of Wisconsin solution, moderate after incubation in histidine-tryptophane-ketoglutarate and Euro-Collins solutions and intensive after storage in saline solution. In contrast, rewarming caused intensive expression of intercellular adhesion molecule-1 in all experimental groups as compared with controls, which showed baseline expression at any time. CONCLUSIONS: From our results we conclude that in this model cellular integrity is best protected by University of Wisconsin solution, increased prostacyclin release is consistent with morphologic alterations and intercellular adhesion molecule-1 expression is clearly up-regulated in endothelial cells under reperfusion conditions after cold hypoxic storage.

T cells from rejected human kidney allografts respond to heat shock protein 72.

The immune response to heat shock proteins (hsps) is gaining more and more interest. Members of the 65 and the 70 kDa hsp families have been shown to be target molecules of the immune system in autoimmune diseases, in cancer immunity and recently in the rejection of rat heart allografts. It was therefore the aim of the present study to investigate whether T cells propagated from two rejected human renal allografts also recognised hsps. In vivo activated interleukin-2 (IL-2) receptor positive T cells were expanded from renal allografts, which had been removed because of irreversible rejection, by 1 week of culture in IL-2 only, followed by stimulation with OKT-3 in combination with IL-2. One T cell line was obtained from each graft. FACS analysis of the lines demonstrated that 51% and 53% of the cells were CD4+ and 45% and 42% CD8+; 4% and 5% were gamma delta + T cells. Both lines had a significant proliferative response when stimulated with recombinant human hsp 72. In contrast, hsp 65 did not induce stimulation. The lines also showed a proliferative response upon stimulation with epithelial kidney cells, purified and cultured from the respective rejected kidneys. These results demonstrate that T cells propagated from rejected human kidney allografts recognize hsp 72. This suggests that hsp-specific T cells may play a role in the rejection process of allograft kidneys.