Etienne Wenzl

Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels.

Background: Different changes of plasma ghrelin levels have been reported following gastric banding, Roux-en-Y gastric bypass, and biliopancreatic diversion. Methods: This prospective study compares plasma ghrelin levels and weight loss following laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) in 20 patients. Results: Patients who underwent LSG (n=10) showed a significant decrease of plasma ghrelin at day 1 compared to preoperative values (35.8 ± 12.3 fmol/ml vs 109.6 ± 32.6 fmol/ml, P=0.005). Plasma ghrelin remained low and stable at 1 and 6 months postoperatively. In contrast, no change of plasma ghrelin at day 1 (71.8 ± 35.3 fmol/ml vs 73.7 ± 24.8 fmol/ml, P=0.441) was found in patients after LAGB (n=10). Increased plasma ghrelin levels compared with the preoperative levels at 1 (101.9 ± 30.3 fmol/ml vs 73.7 ± 24.8 fmol/ml, P=0.028) and 6 months (104.9 ± 51.1 fmol/ml vs 73.7 ± 24.8 fmol/ml, P=0.012) after surgery were observed. Mean excess weight loss was higher in the LSG group at 1 (30 ± 13% vs 17 ± 7%, P=0.005) and 6 months (61 ± 16% vs 29 ± 11%, P=0.001) compared with the LAGB group. Conclusions: As a consequence of resection of the gastric fundus, the predominant area of human ghrelin production, ghrelin is significantly reduced after LSG but not after LAGB. This reduction remains stable at follow-up 6 months postoperatively, which may contribute to the superior weight loss when compared with LAGB.

25-Hydroxyvitamin D3-1α-hydroxylase Expression in Normal and Malignant Human Colon

1,25-dihydroxyvitamin D3 has anti-mitotic, pro-differentiating, and pro-apoptotic activity in tumor cells. We demonstrated that the secosteroid can be synthesized and degraded not only in the kidney but also extrarenally in intestinal cells. Evaluation of 1,25-dihydroxyvitamin D3-synthesizing CYP27B1 hydroxylase mRNA (real-time PCR) and protein (immunoblotting, immunofluorescence) showed enhanced expression in high- to medium-differentiated human colon tumors compared with tumor-adjacent normal mucosa or with colon mucosa from non-cancer patients. In high-grade undifferentiated tumor areas expression was lost. Many cells co-expressed CYP27B1 and the vitamin D receptor. We suggest that autocrine/paracrine antimitotic activity of 1,25-dihydroxyvitamin D3 could prevent intestinal tumor formation and progression. (J Histochem Cytochem 52:985–989, 2004)

Multicentric Breast Cancer: A New Indication for Sentinel Node Biopsy—A Multi-Institutional Validation Study

PURPOSE Multicentric breast cancer has been considered to be a contraindication for sentinel node (SN) biopsy (SNB). In this prospective multi-institutional trial, SNB-feasibility and accuracy was evaluated in 142 patients with multicentric cancer from the Austrian Sentinel Node Study Group (ASNSG) and compared with data from 3,216 patients with unicentric cancer. PATIENTS AND METHODS Between 1996 and 2004, 3,730 patients underwent SNB at 15 ASNSG-affiliated hospitals. Patient data were entered in a multicenter database. One hundred forty-two patients presented with multicentric invasive breast cancer and underwent SNB. RESULTS Intraoperatively, a mean number of 1.67 SNs were excised (identification-rate, 91.5%). The incidence of SN metastases was 60.8% (79 of 130). This was confirmed by axillary lymph node dissection (ALND) in 125 patients. Of patients with positive SNs, 60.8% (48 of 79) showed involvement of nonsentinel nodes (NSNs), as did three patients with negative SNs (false-negative rate, 4.0). Sensitivity, negative predictive value, and overall accuracy were 96.0%, 93.3%, and 97.3%, respectively. Ninety-one percent of the patients underwent mastectomy, and 9% were treated with breast conserving surgery. None of the patients have shown axillary recurrence so far (mean follow-up, 28.8 months). Compared with 3,216 patients with unicentric cancer, there was a significantly higher rate of SN metastases as well as in NSNs, whereas there was no difference in detection and false-negative rates. CONCLUSION Multicentric breast cancer is a new indication for SNB without routine ALND in controlled trials. Given adequate quality control and an interdisciplinary teamwork of surgical, nuclear medicine, and pathology units, SNB is both feasible and accurate in this disease entity.

Establishment of primary cultures from human colonic tissue during tumor progression: Vitamin‐D responses and vitamin‐D‐receptor expression

Primary cultures derived from pre‐cancerous and cancerous human colon tissue are essential for understanding normal and abnormal growth function in the large intestine. Here presented are (i) the methodology for routine establishment of primary cultures of normal, adenoma‐ and carcinoma‐derived cells, and (ii) data for the apparently protective role of vitamin‐D compounds in colon carcinogenesis. The steroid hormone 1,25‐dihydroxyvitamin D3 and some non‐hypercalcemic analogs reduce the high mitotic rate of adenoma cells to that of normal colonocytes. After vitamin‐D treatment, tumor cells are less proliferative and differentiation is enhanced. Primary‐colon‐cancer cultures display a mosaic pattern of vitamin‐D‐receptor expression, at the mRNA level and at the protein level, with varying intensity of expression in positive cells. This suggests that, in human colorectal tumors in vivo, a large fraction of cells will respond to genomic action of vitamin‐D compounds. Int. J. Cancer 75:467–472, 1998.

Bacteroides fragilis toxin 2 damages human colonic mucosa in vitro

BACKGROUND Strains ofBacteroides fragilis producing a 20 kDa protein toxin (B fragilis toxin (BFT) or fragilysin) are associated with diarrhoea in animals and humans. Although in vitro results indicate that BFT damages intestinal epithelial cells in culture, the effects of BFT on native human colon are not known. AIMS To examine the electrophysiological and morphological effects of purified BFT-2 on human colonic mucosa in vitro. METHODS For resistance (R) measurements, colonic mucosa mounted in Ussing chambers was exposed to luminal or serosal BFT-2 (1.25–10 nM) and after four hours morphological damage was measured on haematoxylin and eosin stained sections using morphometry. F actin distribution was assessed using confocal microscopy. RESULTS Serosal BFT-2 for four hours was four-, two-, seven-, and threefold more potent than luminal BFT-2 in decreasing resistance, increasing epithelial3H-mannitol permeability, and damaging crypt and surface colonocytes, respectively (p<0.05). Confocal microscopy showed reduced colonocyte F actin staining intensity after exposure to BFT-2. CONCLUSIONS BFT-2 increases human colonic permeability and damages human colonic epithelial cells in vitro. These effects may be important in the development of diarrhoea and intestinal inflammation caused by B fragilis in vivo.

Acid stimulated alkaline secretion in the rabbit duodenum is passive and correlates with mucosal damage.

Low luminal acid concentrations stimulate alkaline secretion (AS) by the duodenal mucosa. We investigated acid stimulated alkaline secretion by proximal rabbit duodenal mucosa in an Ussing-chamber under different luminal acid concentrations and its relation to mucosal damage. Luminal alkalinisation and potential difference (PD) were measured and mucosal damage was investigated histologically. Luminal acid caused an increase of alkaline secretion over baseline (0.95 +/- 0.19 mu Eq/cm2/10 min; n = 55): 0.1 mmol: 7%, 1 mmol/l: 17%, 5 mmol/l: 22%, 10 mmol/l: 33%, 20 mmol/l: 34%, 50 mmol: 39%, 100 mmol/l: 27%. At acid concentrations of 10 mmol/l and above the PD fell from 2.0 +/- 1.0 mV to zero. Histology showed [H+]-dependent mucosal damage ranging from villus tip lesions to deep mucosal injury. Stimulation of alkaline secretion was not specific for acid. Ethanol (14%) stimulated alkaline secretion by 26%, and 28% ethanol by 40% over baseline. Ouabain and/or anoxia sensitive (active) alkaline secretion constituted 80% and 100% respectively of basal alkaline secretion. After exposure to various luminal acid concentrations passive diffusion (sensitive only to removal of nutrient HCO3-) was solely responsible for the rise in alkaline secretion. Only after 14% ethanol a small rise in ouabain and/or anoxia sensitive HCO3- transport was observed. Under the conditions of this study stimulation of duodenal alkaline secretion is not specific for luminal acid, but occurs also with luminal ethanol; both agents stimulate alkaline secretion depending on their concentration. In this model passive diffusion of HCO3- associated with increasing mucosal damage is the major component of the rise in alkaline secretion.

Effects of extracellular pH on intracellular pH-regulation and growth in a human colon carcinoma cell-line

Mechanisms of intracellular pH (pHi) regulation seem to be involved in cellular growth and cell division. Little is known about how extracellular acidosis, known to occur in central regions of solid tumors, or alkaline conditions affect pHi regulation in colonic tumors. pHi changes in the colonic adenocarcinoma cell-line SW-620 were recorded by spectrofluorimetric monitoring of the pH-sensitive, fluorescent dye BCECF, and proliferative activity was assessed by [3H]thymidine uptake. Resting pHi in Hepes-buffered solution was 7.53 +/- 0.01 (n = 36). Both 1 mM amiloride and Na(+)-free solution inhibited pHi recovery from acidification and decreased pHi in resting cells. In HCO3-/CO2-buffered media resting pH1 was 7.42 +/- 0.01 (n = 36). Recovery from acidification was Na(+)-dependent, CI(-)-independent, and only partially blocked by 1 mM amiloride. In the presence of amiloride and 200 microM H2DIDS pHi recovery was completely inhibited. In Na(+)-free solution pHi decreased from 7.44 +/- 0.04 to 7.29 +/- 0.03 (n = 6) and no alkalinization was observed in CI(-)-free medium. Addition of 5 microM tributyltin bromide (an anion/OH-exchange ionophore) caused pHi to decrease from 7.43 +/- 0.05 to 7.17 +/- 0.08 (n = 5). The effects of pH0 on steady-state pHi, pHi recovery from acidification and proliferative activity after 48 h were investigated by changing buffer [CO2] and [HCO3-]. In general, increases in pH0 between 6.7 and 7.4 increased pHi recovery, steady-state pHi and growth rates. In summary, SW-620 cells have a resting pHi > 7.4 at 25 degrees C, which is higher than other intestinal cells. Acid extrusion in physiological bicarbonate media is accomplished by a pHi-sensitive Na+/H+ exchanger and a pHi-insensitive Na(+)-HCO3-cotransporter, both of which are operational in control cells at the resting pHi. No evidence for activity of a CI-/HCO3- exchanger was found in these cells, which could account for the high pHi observed and may explain why the cells continue to grow in acidic tumor environments.

Rekonstruktion ausgedehnter Schleimhautdefekte im Mundhöhlen- und Oropharynxbereich mit dem revaskularisierten Jejunumtransplantat

ZusammenfassungGrundlagen: Seit 1990 werden in einer interdisziplinärer Zusammenarbeit ausgedehnte Weichteilverluste nach radikaler Resektion von Mundhöhlen- und Oropharynxkarzinomen mit revaskularisierten Dünndarmtransplantaten gedeckt. Methodik: In den vergangenen 3 Jahren wurden bei 46 Patienten mikrovaskuläre Jejunumtransplantationen durchgeführt. 35 Patienten mit einer Nachbeobachtungszeit von mindestens 6 Monaten wurden nachuntersucht. Mit nur 2 Transplantatteilverlusten hat sich die Dünndarmtransplantation bei uns von Beginn an als sichere Methode erwiesen. Demgegenüber steht jedoch eine mit 5 Patienten hohe perioperative Mortalität, mitverursacht durch, in dieser Patientengruppe nicht seltene, organische Vorschäden. Ergebnisse: In der aus onkologischer Sicht sehr kurzen Beobachtungszeit sind bisher 8 Patienten an einem Tumorrezidiv verstorben. Neben 2 Todesfällen aus anderer Ursache sind derzeit 20 Patienten rezidivfrei. Schlußfolgerungen: Die Vorteile der Rekonstruktion mit Darmschleimhaut liegen in dem praktisch unbegrenzten Transplantatangebot, weiters in der, nach eingetretener Oberflächenatrophie, guten Anpassung an die Konturen und Strukturen der Mundhöhle. Die geringe Schrumpfung und die fehlende narbige Induration führt zur guten funktionellen Wiederherstellung. Die verbleibende Schleimproduktion des Transplantats bewirkt einen Ausgleich der nach präoperativer Radiochemotherapie zumeist entstehenden Mundtrockenheit.SummaryBackground: Since 1990 at the Department of Oral and Maxillofacial Surgery, University of Vienna, large soft tissue defects following radical resection of squamous cell carcinomas of the oral cavity and the oropharynx have been covered with revascularized jejunal grafts, in cooperation with the Department of Plastic and Reconstructive Surgery. Methods: In the past 3 years in 46 patients jejunal grafts were performed. In this study, 35 patients with a observation time of more than 6 months were investigated. The transplantation of the small bowel confirmed to be a safe method and a low risk transplant, showing only 2 cases of partial loss of the transplant. In contrary, a high perioperative mortality (5 patients) had to be observed. Results: During the short observation time, from the oncologic point of view, 8 patients died due to tumor recurrence. Besides 2 cases of death because of other reasons, 20 patients presented no evidence of disease. Conclusions: The advantage of reconstruction with jejunal mucosa is the vast amount of available mucosa. The flexibility of the graft provides perfect lining of the oral cavity. The limited shrinking and the missing cicatricial induration support the functional restoration. Mucus production prevents xerostomia following preoperative radiochemotherapy.

Peptic esophageal stricture: is surgery still necessary?

B a l b a n demonstriert 1. neuerdings den yon 0 p p e n h e l m in der vorigen Sitzung vorgeste]lten Fall yon U l z e r a t i o n e n d e s h a r t e n u n d w e i e h e n G a u m e n s . Es wurde damals die Vermutung ausgesprochen, dab es sich um eine Kombination yon Lues mit Tuberkulose handeln kSnnte. Der therapeutische Effekt hat jedoch gezeigt, d a d es sieh um relne Gummen handelte, denn nach der dritten halben t tgSalizyl-Injektion war die Affektion fast vS1]ig geheilt. 0 p p e n h e i m : Vor 14 Tagen wurde der Fall yon mir als u l z e r 5 s e S y p h i 1 is des harten und weichen Gaumens vorgestellt, wobei ich mit Riicksicht auf kleine miMare Gesehwiirchen i n der Umgebung der Ulzerationen und auf kleine graue KnStchen den Verdacht ausslorach, es kSnnte sieh um eine n a c h t r ~ g l i c h e M i s e h i n f e k t i o n m i t T u b e r k u l o s e h a n d e l n . Naeh dem E r f o l g der Quecksilberbehandlung mug die Diagnose Tuberkulose fallen und darauf hingewiesen werden, wie ~ihnJ lich sieh Syphilis und Tuberkulose der Mundschleimhaut dokumentieren kSnnen.

Behandlung der Achalasie

SummaryAchalasia is a condition of unknown etiology. It represents a motor disorder of the esophagus characterized by absent or incomplete relaxation of the lower esophageal sphincter upon swallowing and by nonpropulsive swallow-induced contraction waves or amotility of the esophageal body. Dysphagia and regurgitation of ingesta are the most frequent symptoms. Medical treatment, i.e. by calcium-channel blockers and nitric oxide donors, may be tried in patients with mild dysphagia or in elderly patients but rarely yields adequate symptom relief. Mechanical dilatation of the achalasic sphincter may be performed as an initial treatment option. Intrasphincteric injections of botulinum toxin seemed to be a promising alternative, but it has become obvious that, in most cases, repeated applications of the toxin are required to maintain patients symptom-free. Myotomy of the achalasic sphincter with or without fundoplication to prevent gastroesophageal reflux, is employed mainly in patients in whom dilatations have failed, but since the introduction of minimally invasive surgery, myotomy has become the primary treatment at many centers. This article aims to provide an overview of the development of the conservative and surgical treatment of achalasia.ZusammenfassungDie Achalasie ist eine Motilitätsstörung der Speiseröhre unklarer Ätiologie. Sie ist durch eine fehlende oder nur geringe Relaxation des gastroösophagealen Sphinkters während des Schluckaktes und durch zumindest zum Teil nichtpropulsive Kontraktionswellen oder eine komplette Amotilität des Ösophaguskörpers gekennzeichnet. Klinisch äußert sie sich vor allem in Dysphagie und Regurgitationen. Eine medikamentöse Therapie ist bei geringgradiger Dysphagie möglich, bei ausgeprägter Dysphagie stellt die mechanische Dilatation eine initiale Therapieoption dar. Botulinumtoxin-Injektionen in den ösophagogastrischen Übergangsbereich schienen zunächst vielversprechend, es erwies sich aber, dass die Wirkung nur kurz anhält und wiederholte Applikationen erforderlich sind. Die chirurgische Behandlung, nämlich die Myotomie mit oder ohne Antirefluxplastik, wird vor allem nach erfolglosen Dilatationen durchgeführt, seit der Einführung minimal-invasiver chirurgischer Techniken aber zunehmend als primäre Therapie angewandt. Die vorliegende Arbeit gibt einen Überblick über die Entwicklung der konservativen und chirurgischen Behandlungsmethoden.Achalasia is a condition of unknown etiology. It represents a motor disorder of the esophagus characterized by absent or incomplete relaxation of the lower esophageal sphincter upon swallowing and by non-propulsive swallow-induced contraction waves or amotility of the esophageal body. Dysphagia and regurgitation of ingesta are the most frequent symptoms. Medical treatment, i.e. by calcium-channel blockers and nitric oxide donors, may be tried in patients with mild dysphagia or in elderly patients but rarely yields adequate symptom relief. Mechanical dilatation of the achalasic sphincter may be performed as an initial treatment option. Intrasphincteric injections of botulinum toxin seemed to be a promising alternative, but it has become obvious that, in most cases, repeated applications of the toxin are required to maintain patients symptom-free. Myotomy of the achalasic sphincter with or without fundoplication to prevent gastroesophageal reflux, is employed mainly in patients in whom dilatations have failed, but since the introduction of minimally invasive surgery, myotomy has become the primary treatment at many centers. This article aims to provide an overview of the development of the conservative and surgical treatment of achalasia.