Alexander Katalinic

Impact of skill and experience of the endoscopist on the outcome of endoscopic sphincterotomy techniques

BACKGROUND Our aim was to assess the influence of the skill and experience of the endoscopist on the success and risk of endoscopic sphincterotomy techniques. METHODS The outcome of all endoscopic sphincterotomies (n = 1335) carried out between 1988 and 1995 were retrospectively analyzed with respect to the endoscopist performing the procedure. Endoscopists were differentiated according to whether they had previous experience with endoscopic sphincterotomy techniques (n > 100) and the frequency of endoscopic sphincterotomy during the study period (>40, 26 to 40, 10 to 25, <10 per year). RESULTS Indications for endoscopic sphincterotomy techniques and technical execution had only a minor influence on the results of endoscopic sphincterotomy and were comparable for the individual endoscopists. The overall success rate of endoscopic sphincterotomy was 94.4% and did not significantly differ among the endoscopists. The overall complication rate of endoscopic sphincterotomy was 7.3%. Endoscopists learning endoscopic sphincterotomy techniques with a case frequency of less than 10 procedures per year had a consistently high complication rate (10.5%). Those learning endoscopic sphincterotomy techniques with a case frequency of more than 25 procedures per year had an above-average complication rate for their first 40 endoscopic sphincterotomy procedures and a significant decrease in complication rate as the number of procedures increased. The complication rate for experienced endoscopists was 7.7%. There were distinct and, in one case, significant differences in complication rates between individual endoscopists (11.5% vs. 4.8%, p = 0.01). However, when corrected for multiple testing, there were no significant differences at the p < 0. 05 level. The endoscopic sphincterotomy frequency of the endoscopist was the only significant risk factor for complications. Endoscopists with a frequency of more than 40 procedures per year had a significantly lower complication rate (5.6%) than endoscopists with a lower case frequency (9.3%, p < 0.05). CONCLUSIONS A low endoscopic sphincterotomy frequency is, even for endoscopists with previous experience with the procedure, a risk factor for complications after endoscopic sphincterotomy. The learning of endoscopic sphincterotomy techniques requires a minimum of 40 procedures, but also after 100 procedures a further decrease of the complication rate can be expected.

Influence of circulating c-erbB-2 serum protein on response to adjuvant chemotherapy in node-positive breast cancer patients.

This retrospective case control study investigated the therametricvalue of the circulating c-erbB-2 gene product (Her-2,NEU) as (1) an eligibility criterion for highdoses of chemotherapy and (2) response to standardadjuvant chemotherapy in node-positive breast cancer patients. Preoperativec-erbB-2 levels were measured in 211 locally advanced(> 3 nodes positive), pre- and perimenopausal breastcancer patients to determine if circulating levels ofthe gene product can assist in the determinationof appropriate therapeutic options.152 of 211 breast cancer patients received post-operativelya combination chemotherapy including the anthracycline analog mitoxantrone,while 59 patients were treated with conventional CMFtherapy. Using 120 fmol/ml as a cut-off level,elevated c-erbB-2 values were found in 26 (12.3%)patients with locally advanced breast cancer. In univariateanalysis significant survival differences were detected when c-erbB-2‘positive’ patients were compared with c-erbB-2 ‘negative’ patients.However, no significant survival differences were detected, whenc-erbB-2 ‘positive’ patients were compared according to regimenof adjuvant treatment.In multivariate analysis c-erbB-2 was an independent prognosticfactor for predicting disease-free survival, but not foroverall survival. High levels of c-erbB-2 were associatedwith low estrogen and progesterone receptor concentrations ofthe tumor cytosol. There was no correlation betweenelevated c-erbB-2 values and age, tumor size ordegree of nodal involvement. c-erbB-2 was a betterpredictor of risk of recurrence than extent ofnodal involvement or hormone receptor status.

The Prognostic Significance of c-erbB-2 Serum Protein in Metastatic Breast Cancer

The relationship between c-erbB-2 serum positivity and prognosis was evaluated in 80 patients with metastatic breast cancer. Using 120 fmol/ml as a cutoff level, elevated concentrations were found in 31 patients (38.8%) at the time of detection of metastases. Menopausal status, steroid receptor status, site of recurrence, initial tumor size, initial degree of nodal involvement as well as relapse-free interval were unrelated to c-erbB-2 serum positivity. In addition, no association could be found between adjuvant chemotherapy and positive c-erbB-2 concentrations. Patients with elevated c-erbB-2 levels showed a lower response rate (including complete remission, partial remission, no change) to first-line therapy than those with normal levels (29 vs. 59%, p < 0.01). The median survival time after relapse was 12 months (CI: 3–22 months) for the c-erbB-2-negative patients and only 6 months (CI: 3–8 months) for the c-erbB-2-positive group (p < 0.01). In the multivariate analysis, while c-erbB-2 levels at the time of primary surgery had no significant impact on survival in metastatic breast cancer, serum c-erbB-2 turned out to be the strongest factor for predicting survival after relapse.

Expression of nm23-H1 predicts lymph node involvement in colorectal carcinoma

PURPOSE: Reduced expression of the metastasis suppressor gene nm23-H1 has previously been correlated with high tumor metastatic potential and fatal clinical outcome in some tumors (e.g.,breast). For colorectal carcinomas, the findings are equivocal. METHODS: We have used a monoclonal antibody against nm23-H1 to investigate the expression in colorectal carcinomas at the time of primary curative surgery (RO resection) to assess if there was any relation between nm23-H1 expression and stage or histologic grade at the time of primary tumor removal. RESULTS: Of 100 colorectal carcinomas studied (Stages I, II, and III according UICC, all resected curatively), nm23-H1 immunoreactivity was weak in 41 (41 percent), moderate in 24 (24 percent), and strong in 35 (35 percent) cases. The grade of positivity against nm23-H1 was significantly lower in advanced stages of the disease (Stages II or III) (P <0.001, chi-squared=52.8). In tumors with low or weak immunoreactivity against nm23-H1, frequency of lymph node metastases was significantly higher compared with those with moderate or strong staining (P <0.001; chi-squared=50.58). Therefore, with a sensitivity of 93 percent and a specificity of 58 percent, low nm23-H1 immunoreactivity of the primary tumor, assessed at the time of surgery, is an indicator of the presence of lymph node metastases. CONCLUSIONS: Immunohisto-chemical evaluation of nm23-H1 in the primary tumor or in a biopsy is a useful predictor of stage of disease and presence of lymph node metastases in colorectal carcinomas and may have clinical significance,e.g.,in predicting optimal therapeutic regimes.

Gastric involvement in progressive systemic sclerosis: electrogastrographic and sonographic findings.

OBJECTIVE To determine whether electrogastrography (EGG) can discern sonographically demonstrated motility disorders in patients with progressive systemic sclerosis (SSc) and to evaluate EGG as a possible diagnostic tool. DESIGN Prospective study with control group and testing for reliability. SUBJECTS 15 SSc patients [women aged 33-70 years (mean 53.3 years)] and 15 healthy volunteers. METHODS Bipolar cutaneous EGG was recorded to obtain the following parameters: period dominant frequency (PDF), percentage of gastric dysrhythmia and normogastria (defined as 2-4/min), period dominant power (PDP) and its change after a standardized meal of 500 kcal (2093 kJ), and instability coefficients of dominant frequency and power (DFIC, DPIC). Simultaneously, real-time sonography was performed in the aortomesenteric plane (3.5-MHz curved-array probe). In 10 patients and 13 control subjects, the distance from the anterior wall of the gastric antrum to the abdominal skin was measured. RESULTS Three patients (20%) showed hypomotility of the gastric antrum sonographically. The percentage of bradygastria was significantly lower in these patients, but the PDF, DFIC and DPIC values were not significantly different. The distance between the cutaneous electrodes and the antrum bore a greater relationship to the PDP values than did the sonographically demonstrated number of gastric contractions. CONCLUSIONS Although cutaneous EGG can be performed in SSc patients without apparent derangement in frequency and stability of the signal, it offers no advantage over sonography in diagnosis and follow-up.

Proliferation und Apoptose vor und nach präoperativer simultaner Radiochemotherapie von Rektumkarzinomen

ZusammenfassungZielUm den Einfluß von Radiochemotherapie auf Proliferation und Apoptose und die Rolle von p53 bei Rektumkarzinomen vor und nach simultaner Radiochemotherapie zu untersuchen, wurden diese zellkinetischen Parameter an vor und nach Therapie gewonnenem Tumorgewebe bestimmt.Material und MethodenAn Tumorgewebe, das von 32 Patienten mit lokal fortgeschrittenen Rektumkarzinomen vor und nach simultaner Radiochemotherapie gewonnen wurde, bestimmten wir das Ausmaß apoptotischen Zelluntergangs mittels der In-situ-end-labeling-(ISEL-)Technik. Die proliferative Aktivität wurde immunhistochemisch durch Markierung des Ki67-(MIB-1-)Antigens untersucht. Die Expression von p53 stellten wir ebenfalls immunhistochemisch durch die Verwendung des DO-7-Antikörpers dar. Die jeweiligen Markierungen erfolgten in allen Fällen an korrespondierenden (prätherapeutisch gewonnenen) Biopsien und (posttherapeutischen) Tumorresektaten.ErgebnisseDurch die simultane Radiochemotherapie konnte in 25/32 Fällen (78%) ein klinisch-pathologisches Downstaging erreicht werden. In einem Fall war nach Radiochemotherapie kein Tumor mehr nachweisbar. Die Proliferationsrate (definiert als Anzahl Ki67-[MIB-1-]positiver Zellen pro 100 Tumorzellen) war nach Radiochemotherapie signifikant geringer (47,4±23,4 vs. 36,6±17,9). Die Apoptoserate (Anzahl der apoptotischen Zellen von 100 Tumorzellen) zeigte eine gegenteilige Beeinflussung und war nach Radiochemotherapie signifikant höher (2,5±1,1 vs. 5,0±2,5). In 20/31 (65%) der Tumoren konnte immunhistochemisch p53 nicht nachgewiesen werden. Schlüsselte man diese Daten nach dem p53-Status der Tumoren auf, zeigten p53-negative Tumoren eine höhere Apoptoserate als diejenigen Tumoren, bei denen p53 immunhistochemisch nachgewiesen werden konnte (6,28±1,9 vs. 2,77±1,85).SchlußfolgerungenDie Ergebnisse zeigen, daß die simultane Radiochemotherapie bei lokal fortgeschrittenen Rektumkarzinomen im von uns untersuchten Kollektiv zu einer deutlichen Tumorverkleinerung führte, die mit einer signifikanten Erhöhung apoptotischen Zelluntergangs einherging. Dabei zeigten Rektumkarzinome mit funktionsfähigem, immunhistochemisch nicht nachweisbaren p53-Protein ein deutlich erhöhtes Ausmaß apoptotischen Zelluntergangs.AbstractPurposeTo investigate the relationship between apoptotic cell death, proliferative activity, and the status of the tumor suppressor gene p53 in rectal cancer before and after radiochemotherapy.Materials and MethodsThirty-two patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma prior to radical surgical tumor resection were analysed. In all cases, pretherapy biopsies and the final resected specimens after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) antigen. p53 expression was analysed immunohistochemically as well. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25/32 patients (78%). In one case, no residual tumor was detected after radiochemotherapy.ResultsAfter radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased when comparing biopsies and resected specimens. Tumors that were immunohistochemically negative for p53 generally exhibited a higher apoptotic index than p53 positive tumors. However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis and the degree of clinical-to-pathologic downstaging.ConclusionOur results indicate, that radiochemotherapy induces an increase in apoptotic cell death. The observation of higher rates of apoptosis in p53 negative tumors suggests that p53 might be a regulator of apoptosis in rectal cancer.

Progression of optic neuritis to multiple sclerosis: an 8-year follow-up study

OBJECTIVE The relationship between acute monosymptomatic optic neuritis (AON) and subsequent multiple sclerosis (MS) is still doubtful. We investigated the risk of developing MS in patients from North Bavaria, who were suffering from AON. PATIENTS/METHODS Twenty-nine patients with clinical evidence of AON were included in the study. Initial evaluation included brain resonance imaging (MRI) and a clinical neurological examination. Follow-up examinations were performed after 72-108 months (mean: 96 months) in 26 patients (three patients were lost to follow-up) and consisted of a second complete neurological examination. Diagnosis of MS was established according to the criteria of Poser CM, Paty DW, Scheinberg L. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983:13:227-231. RESULTS At follow-up, 14 of 26 patients (54%) had converted to clinically definite MS. Nine patients (64%) had developed MS within 2 years after the onset of AON. CONCLUSION We observed the development of MS in 54% of the 26 investigated AON patients. The exceptional feature of the present study was the relatively long follow-up period of 8 years.

Wandel und Akzeptanz operativer und nichtinvasiver Therapieverfahren bei Cholezystolithiasis

Zusammenfassung□ HintergrundDie Behandlung der Cholezystolithiasis hat sich durch die Entwicklung nichtoperativer Verfahren (extrakorporale Stoßwellenlithotripsie [ESWL], orale Litholyse) sowie der laparoskopischen Cholezystektomie in den letzten Jahren grundsätzlich geändert.□ Patienten und ErgebnisseDie retrospektive Analyse von 2270 Patienten (1649 Frauen, 621 Männer; Alter: 47,2±14 Jahre), die sich wegen Gallenblassnsteinleiden zwischen 1988 und 1992 mit der Frage nach dem geeignetsten Therapieverfahren in der Spezialsprechstunde einer Universitätsklinik vorstellten, belegt den raschen Wandel im therapeutischen Vorgehen. Die laparoskopische Entfernung der Gallenblase hat die konventionelle Cholezystektomie praktisch vollständig verdrängt, der Anteil der ESWL reduzierte sich innerhalb von fünf Jahren um etwa die Hälfte (von 21 auf 12%). Über die Jahre konstant (um 20%) blieb der Anteil der Patienten, bei denen kein therapeutischer Eingriff indiziert war. Die Therapieempfehlungen der „Experten” wurden in fast 80% der Fälle umgesetzt. Die Mehrzahl der Patienten war mit dem gewählten Therapieverfahren zufrieden (Operation: 93,0%, ESWL: 77,6%), obwohl 44% der ESWL-Patienten und 36% der operierten Patienten auch nach Abschluß der Therapie über anhaltende Beschwerden klagten. Trotz nicht erfolgreicher ESWL (Reststeine bzw. Rezidive) würden 58/95 (61%) der befragten Patienten bei einer erneuten Therapieentscheidung diesem nichtinvasiven Verfahren nochmals den Vorzug geben.□ SchlußfolgerungBereits wenige Jahre nach Einführung hat sich die laparoskopische Cholezystektomie zum dominierenden Behandlungsverfahren entwickelt. Hinsichtlich Akzeptanz und Wertschätzung durch den Patienten genießt aber auch die ESWL als nichtinvasive Behandlungsmethode einen hohen Stellenwert und kann unter Berücksichtigung der heute etablierten, strengeren Auswahlkriterien bei geeigneten Patienten alternativ zur Operation empfohlen werden.Abstract□ BackgroundThe treatment of cholecystolithiasis has changed fundamentally in recent years due to the development of non-surgical techniques (extracorporeal shockwave lithotripsy [ESWL], oral litholysis) and the implementation of laparoscopic cholecystectomy.□ Patients and ResultsRetrospective analysis of 2270 patients (1649 women, 621 men; age: 47,2±14 years) presenting with gallstone disorders in a university medical outpatients department between 1988 and 1992 in order to be instructed as to the most suitable therapy method bear witness to the rapid change in therapeutic procedure. Laparoscopic removal of the gallbladder has virtually supplanted conventional cholecystectomy, and within 5 years the proportionate role of ESWL has declined from 21 to 12%. Over the years, the proportion of patients requiring no therapeutic intervention remained constant (at about 20%). The therapeutic recommendations of the “experts” were implemented in almost 80% of cases. The majority of patients were satisfied with the chosen therapeutic approach (surgery: 93.0%, ESWL: 77.6%), although 44% of ESWL-patients and 36% of surgically managed patients reported complaints which persisted even after completion of therapy. Despite unsuccessful ESWL (residual fragments or recurrent stones) 58/95 (61%) of interviewed patients would again give preference to this noninvasive modality in the event of a renewed therapeutic decision.□ ConclusionOnly a few years after its introduction, laparoscopic cholecystectomy has asserted itself as the predominant treatment option. But as fas as acceptance and preference by the patient are concerned extracorporeal shockwave lithotripsy — as a non-invasive treatment modality — also enjoys high popularity and can be recommended as an alternative to surgery in suitable patients chosen according to the currently established stringent selection criteria.