[Critical assessment of a new endoscopic anatomic concept for the so-called cardia in the sense of the notions of Parmenides and Martin Heidegger]. / Kritische Betrachtung neuer Konzepte zur endoskopischen Anatomie des ösphagogastralen Übergangs im Sinne des Denkens von Parmenides und Martin Heidegger.

Current endoscopic anatomy interposes the gastric cardia between the tubular oesophagus and the proximal stomach. In contrast to that, recent evidence unfolds a different view. Using "PubMed" and "Scopus" searches, we examined if the novel understanding regarding the cardia goes in line with the concept of unfolding, as described by Heidegger based on the ancient didactic poetry of Parmenides. What has been taken as gastric cardia in fact represents reflux-damaged, dilated, columnar lined oesophagus (CLO): dilated distal oesophagus (DDO). Due to its macroscopic gastric appearance it cannot be discriminated from the stomach by endoscopy. Differentiation between DDE and proximal stomach requires the histopathology of measured multi-level biopsies obtained from the DDO and the proximal stomach. Cardaic, onxytocardiac mucosa and intestinal metaplasia (IM; Barrett's oesophagus) define CLO and thus the oesophageal location, while oxyntic mucosa (OM) of the proximal stomach verifies a gastric biopsy location. Endoscopically visible CLO and DDO define the morphological manifestation of reflux: the squamo-oxyntic gap (SOG). Biopsies obtained from the level of the diaphragmatic impressions allow differentiation between an enlarged hiatus with normal anatomic content (CLO; oesophagus) vs. hernia with abnormal content (OM; stomach). Non-dysplastic Barrett's oesophagus exists in 10 %-17 % of asymptomatic and in 20 %-100 % (with increasing CLO length) of reflux symptom-positive individuals (annual cancer risk: 0.2 %-0.7 %). These data justify biopsy of an endoscopically normal appearing squamocolumnar junction for the exclusion of Barrett's oesophagus and cancer risk. In the absence of contraindications, cancer risk-based therapy of dysplastic Barrett's oesophagus includes radiofrequency ablation (RFA) ± endoscopic resection. The perception of the cardia as reflux damaged DDO mirrors the concept of unfolding, as described by the interpretation of the didactic poem of Parmenides by Heidegger. Our data recommend to omit the term "cardia" and allocate morphology either to the oesophagus (CLO, DDO) or to the proximal stomach or indicate that allocation is impossible (i. e.. tumour-induced). Future studies will have to test the value of this novel concept for diagnosis, treatment of gastro-oesophageal reflux disease and cancer prevention.

Is there a role for dynamic swallowing MRI in the assessment of gastroesophageal reflux disease and oesophageal motility disorders?

OBJECTIVES: To evaluate the diagnostic value of dynamic MRI swallowing in patients with symptoms of Gastroesophageal Reflux Disease (GERD). METHODS: Thirty-seven patients (17 m/20f) with typical signs of GERD underwent MR swallowing in the supine position at 1.5 T with a phased-array body coil. Using dynamic, gradient echo sequences (B-FFE) in the coronal, sagittal and axial planes, the bolus passages of buttermilk spiked with gadolinium chelate were tracked. MRI, pH-metry and manometry were performed within 31 days and results were compared. RESULTS: MRI results were concordant with pH-metry in 82% (23/28) of patients diagnosed with abnormal oesophageal acid exposure by pH-metry. Five patients demonstrated typical symptoms of GERD and had positive findings with pH monitoring, but false negative results with MRI. In four of six patients (67%), there was a correct diagnosis of oesophageal motility disorder, according to manometric criteria, on dynamic MRI. The overall accuracy of MRI diagnoses was 79% (27/34). A statistically significant difference was found between the size of hiatal hernia, grade of reflux in MRI, and abnormal acid exposure on pH-monitoring. CONCLUSIONS: MR fluoroscopy may be a promising radiation-free tool in assessing the functionality and morphology of the GE junction. KEY POINTS: • Swallowing MRI can assess anatomy and function of the gastroesophageal-junction • Swallowing MRI can help identifying reflux and motility disorders • Definition of the size of hiatal hernias is possible in all three planes in MR. • Short duration of swallowing MRI enables its application in routine clinical practice.

Dynamic MR imaging of the gastroesophageal junction in healthy volunteers during bolus passage.

PURPOSE: To evaluate the feasibility of noninvasive dynamic fast magnetic resonance imaging (MRI) during swallowing in healthy volunteers, and to determine esophageal function at the gastroesophageal junction during swallowing. MATERIALS AND METHODS: A total of 20 healthy volunteers underwent MRI while swallowing in the supine position. Dynamic gradient-echo (GRE) sequences (balanced fast field echo [B-FFE]) were employed in three planes on a 1.5T unit using a phased-array body coil. Buttermilk spiked with gadolinium (Gd) chelate (40:1) for bolus passage was used as an oral contrast agent. We evaluated visualization of esophageal bolus transit, bolus transit time (BTT), peristalsis, identification of the gastroesophageal junction, and reflux during the Valsalva maneuver. RESULTS: The mean visible length of the esophagus was 16.2+/-5.3 cm in the sagittal view, and 13.8+/-4.9 cm in the coronal view. In the sagittal view the BTT was defined in 15 of 20 volunteers and was 7.6+/-1.4 seconds. The BTT in the coronal view was measured in seven of 20 volunteers and was 8+/-1.3 seconds on average. The axial view yielded higher scores (2.25) than the coronal (1.98) and sagittal (1.78) views for identification of the cardia and during the Valsalva maneuver. Bolus contrast was better displayed in the sagittal (2.2) view than in the coronal (2.08) or axial (1.73) planes. In six volunteers, gastroesophageal abnormalities, such as axial hernia, reflux, and nonperistaltic contractions, were identified. For statistical analysis we used the Friedman test and a one-way analysis of variance (ANOVA). CONCLUSION: The results indicate that dynamic MR swallowing is a feasible and reproducible technique that warrants further studies in patients.

[Inguinal hernia as a diagnostic error in ruptured groin aneurysm]. / Inguinalhernie als Fehldiagnose bei rupturiertem Leistenaneurysma.

Anastomotic aneurysms observed with an incidence of 0.5% to 5.0% are considered a known complication following arterial surgery, especially when fabric grafts in the inguinal region are implanted. An anecdotal report is presented describing a 64-year old male patient, who developed, 10 years following an autologous femoro-tibial vein graft, a huge mass in the left groin. The lesion was considered an incarcerated inguinal hernia and the patient was admitted to the Department of Surgery for emergency repair. Clinical examination, duplexsonography and CT scan clarified the diagnosis of an aneurysm with a diameter of 13 cm. The aneurysm was resected, and a femoro-profundal vein graft was implanted orthotopically, the graft was covered with a sartorius muscle flap. The postoperative course was uneventful. The diagnosis is suspected by clinical examination and usually confirmed by duplexsonography. The exact etiology of suture line aneurysms is unknown; in the present case progression of the underlying arteriosclerotic arterial disease after a follow up of 10 years is likely. For the treatment the usual methods of complicated aneurysm repair and preservation of the arterial circulation--using autologous in situ methods or extraanatomic bypass grafts--with additional biologic coverage are at hand.

Outcomes of surgical, percutaneous endoscopic, and percutaneous radiologic gastrostomies.

OBJECTIVES: To evaluate and compare outcomes and complications in patients having undergone gastrostomy by surgical (SG), percutaneous endoscopic (PEG), or percutaneous radiological (PRG) procedure. DESIGN: Retrospective analysis. SETTING: University-based tertiary care center. PATIENTS: Of 82 patients who met inclusion criteria, 14 patients (median age, 40 years) received a surgical tube placement (SG), in 24 patients (median age, 55 years) a PEG procedure was performed, and in 44 patients (median age, 57 years) the tube was placed under fluoroscopic guidance (PRG). Indications for gastrostomy were similar in all groups, representing mainly cancer of the oropharyngeal, head and neck region (51 [61%]) as well as the upper gastrointestinal tract (6 [8%]), neurological disorders (15 [18%]), and others (10 [13%]). MAIN OUTCOME MEASURES: Catheter function rates, major and minor procedure-related complications, and survival. RESULTS: Median follow-up was 17.2 months. Ten patients (71%) died in the SG group 7 to 855 days (median, 67 days) after the procedure, 7 patients (29%) died 5 to 263 days (median, 103 days) after PEG placement, and 30 patients (68%) died within 3 to 621 days (median, 112 days) after PRG, of their underlying disease or disease-related complications; 1 procedure-related death occurred 6 days after radiological tube placement. We observed a rate of minor complications of 43% (6 patients), 33% (8), and 36% (16) and a major complication rate of 14% (2 patients), 17% (4), and 11% (5) in the SG, PEG, and PRG groups, respectively. Tube function rates at 1 year were 67% (9 patients) and 68% (20) in the SG and PEG groups, respectively, and 10% lower (39) in the PRG group, although the difference was not statistically significant. CONCLUSIONS: There is no major difference between SG, PEG, and PRG concerning procedure-related complications. Tube function tends to be inferior after radiological tube placement.

Inhibition of P-glycoprotein-mediated vinblastine transport across HCT-8 intestinal carcinoma monolayers by verapamil, cyclosporine A and SDZ PSC 833 in dependence on extracellular pH.

The ability of the multidrug resistance modifiers R- and R,S-verapamil (VPL), cyclosporine A (CsA) and its non-immunosuppressive derivative SDZ PSC 833 (PSC 833) to inhibit P-glycoprotein (P-gp)-mediated transepithelial flux of tritiated vinblastine was investigated using tight and highly resistant (R > 1,400 omega cm2) monolayer cultures of intestinal adenocarcinoma-derived HCT-8 cells grown on permeable tissue-culture inserts. Apical addition of these chemosensitizers inhibited drug flux (137 pmol h-1 cm-2; range, 133-142 pmol h-1 cm-2) in the basal to apical secretory direction at clinically relevant concentrations, with PSC 833 showing the highest activity, exhibiting inhibition at concentrations as low as 10 ng/ml (9 nM). Acidification of the modulator-containing apical compartment to an extracellular pH (pHo) of 6.8 had no influence on MDR reversal by CsA at 1 microgram/ml (0.9 microM; flux inhibition, 52%) or by PSC 833 at 100 ng/ml (0.09 microM; flux inhibition, 60%), in contrast to R,S- and R-VPL, which showed decreased inhibition and caused less accumulation of vinblastine in HCT-8 cells under this condition (flux inhibition of 35% and 23%, respectively, at pHo 6.8 vs 50% and 43%, respectively, at pHo 7.5). P-gp-mediated rhodamine 123 efflux from dye-loaded single-cell suspensions of HCT-8 cells as measured by flow cytometry was not impeded at pHo 6.8 in comparison with pHo 7.5 in standard medium, but at low pHo the inhibitory activity of R-VPL (29% vs 60% rhodamine 123 efflux inhibition) was diminished significantly, again without a reduction in the effect of PSC 833 (rhodamine 123 flux inhibition, 75%). In conclusion, drug extrusion across polarised monolayers, which offer a relevant model for normal epithelia and tumour border areas, is inhibited by the apical presence of R,S- and R-VPL, CsA and PSC 833 at similar concentrations described for single-cell suspensions, resulting in increased (2.2- to 3.7-fold) intracellular drug accumulation. Functional apical P-gp expression, the absence of paracellular leakage and modulator-sensitive rhodamine 123 efflux in single HCT-8 cells indicate a P-gp-mediated transcellular efflux in HCT-8 monolayers. In addition to its high MDR-reversing capacity, the inhibitory activity of PSC 833 is not affected by acidic extracellular conditions, which reduce the VPL-induced drug retention significantly. As far as MDR contributes to the overall cellular drug resistance of solid tumours with hypoxic and acidic microenvironments, PSC 833 holds the greatest promise for clinical reversal of unresponsiveness to the respective group of chemotherapeutics.

The multidrug-resistance modifiers verapamil, cyclosporine A and tamoxifen induce an intracellular acidification in colon carcinoma cell lines in vitro.

In this study we have investigated the effects of the multidrug-resistance (MDR) modifiers verapamil (VPM), cyclosporin A (CsA) and tamoxifen (TMX) on the intracellular pH(pHi) of four colon carcinoma-derived cell lines with low P-glycoprotein expression (CaCo-2, HT-29, SW 620 and SW 480). Addition of VPM (1 mu M), CsA (1 microgram/ml) or TMX (2 microM) in HEPES- or bicarbonate/CO2-buffered Ringer's solution was followed by dose-dependent and reversible decreases of the pHi (0.1-0.3 units) of all cell lines, as measured ratiometrically by the changes in the pH-dependent fluorescence of bis(carboxyethyl)carboxyfluorescein (BCECF). Testing the effects of the resistance modifiers on the Na+/H+ antiporter and bicarbonate trans-porters under appropriate buffer conditions and addition of inhibitors (amiloride, DIDS) revealed that the chemomodulator-induced acidification does not interfere with the function of these major pHi-regulating acid-base transporters. The induction of changes in pHi shows no correlation with MDR-reversing activity of the drugs and our data do not support the P-gp-inhibition-mediated accumulation of acidic substrates as underlying mechanism. In addition to the P-gp-directed MDR-reversal, chemomodulator-induced intracellular acidification may enhance the chemosensitivity of the cells especially under alkaline extracellular conditions, and contribute to the decreased efficacy of MDR-modifiers in acidic extracellular environments and to the chemosensitising effect of VPM in P-gp-negative cell lines.