Detection of Lymphatic Micrometastases in Patients With Stages I and II Colorectal Cancer: Impact on Five-Year Survival

PURPOSE: Despite having removed the whole macroscopic disease (curative intent surgery), one of five patients with Stages I and II colorectal cancer will develop recurrence. Lymphatic micrometastases detected by immunohistochemistry could be one of explanation for recurrence and cancer-related death in patients without lymph node involvement at light microscopy. However, the biologic importance of micrometastases remains unclear. This study was designed to determine the impact of micrometastases in five-year survival in patients with Stages I and II colorectal cancer.METHODS: This retrospective study included patients operated on between May 1989 and January 1999 for colorectal cancer without histopathologic lymph node involvement. Patients who received any adjuvant therapy were excluded. Immunohistochemical staining of the lymph nodes was performed with antipancytokeratin antibodies. Follow-up data were obtained from the clinical database and death certificates. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test.RESULTS: Micrometastases were observed in 26 of 90 patients (28.9 percent). The mean follow-up time was 90.7 (range, 11–160) months. Seventeen cancer-related deaths occurred during follow-up (18.9 percent), 6 of them in patients with micrometastases (23.1 percent) and 11 in patients without micrometastases (17.2 percent; P = 0.559). Cancer-specific five-year survival was 87 percent in the whole group and 81 percent in patients positive for micrometastases vs. 90 percent in negative patients (P = 0.489).CONCLUSIONS: The presence of micrometastases in patients with Stages I and II colorectal cancer seems not to have any impact on cancer-specific survival.Supported by the Apertus Research Program (Andromaco Pharmaceutical Company) and by The National Public Grant (FONDECYT #1000556).     

Antwort auf den Leserbrief von Valhaus et al. Zu unserer Kasuistik „Kardiogener Schock 4 Stunden nach akut-PTCA bei Hinterwandinfarkt“

Ohne Zusammenfassung     

Heart rate variability before the onset of ventricular tachycardia: differences between slow and fast arrhythmias

BACKGROUND: We tested whether or not heart rate variability (HRV) changes can serve as early signs of ventricular tachycardia (VT) and predict slow and fast VT in patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: We studied the ICD stored 1000 beat-to-beat intervals before the onset of VT (131 episodes) and during a control time without VT (74 series) in 63 chronic heart failure ICD patients. Standard HRV parameters as well as two nonlinear parameters, namely 'Polvar10' from symbolic dynamics and the finite time growth rates 'Fitgra9' were calculated. Comparing the control and the VT series, no linear HRV parameter showed a significant difference. The nonlinear parameters detected a significant increase in short phases with low variability before the onset of VT (for time series with less than 10% ectopy, P<0.05). Subdividing VT into fast (cycle length 270 ms) events, we found that the onset of slow VT was characterized by a significant increase in heart rate, whereas fast VT was triggered during decreased heart rates, compared to the control series. CONCLUSIONS: Our data may permit the development of automatic ICD algorithms based on nonlinear dynamic HRV parameters to predict VT before it starts. Furthermore, they may facilitate improved prevention strategies.     

Diagnosing Pouchitis

PURPOSE: Pouchitis represents a serious threat to patients with ulcerative colitis after restorative proctocolectomy with ileal pouch-anal anastomosis. The frequency of pouchitis is high, and it implies the risk of pouch failure and the risk of malignant mucosal transformation in the pouch. Early detection and precise classification of the inflammatory process are required for adequate therapy, which might be facilitated using a scoring system. The aim of the present study was to validate two existing scoring systems in routine outpatient practice. METHOD: The Heidelberg Pouchitis Activity Score and the Pouchitis Disease Activity Index developed at the Mayo Clinic were simultaneously prospectively applied in a consecutive series of 103 outpatient consultations of 41 patients at our hospital and comparatively validated against the diagnosis of pouchitis or no pouchitis concurrently made by a physician and a surgeon. RESULTS: The median score of examinations in which the clinicians diagnosis was consistent with pouchitis were significantly higher than those of examinations inconsistent with pouchitis in both scoring systems (Heidelberg Pouchitis Activity Score, 17 (interquartile range, 14–21) and 8 (interquartile range, 5–10), respectively, P < 0.001; Pouchitis Disease Activity Index, 7 (interquartile range, 5–8) and 2.5 (interquartile range, 1–4), respectively, P < 0.001). The sensitivity and specificity in the two total scores were 84 and 79.5 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 96.2 percent, respectively (Pouchitis Disease Activity Index); in the field clinical manifestations 44 and 73.1 percent, respectively (Heidelberg Pouchitis Activity Score), and 20 and 87.2 percent, respectively (Pouchitis Disease Activity Index); in the field endoscopic manifestations 88 and 83.3 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 89.7 percent, respectively (Pouchitis Disease Activity Index); and in the field histologic manifestations 72 and 76.9 percent, respectively (Heidelberg Pouchitis Activity Score), and 44 and 96.2 percent, respectively (Pouchitis Disease Activity Index). Lowering the cutoff point for diagnosis of pouchitis in the Pouchitis Disease Activity Index by 2 points (pouchitis: score 5) would result in an 88 percent sensitivity and a 67 percent specificity. CONCLUSIONS: Specificity and sensitivity of the Heidelberg Pouchitis Activity Score were satisfactory. The cutoff point for diagnosing pouchitis in the Pouchitis Disease Activity Index would have to be lowered to reach an acceptable sensitivity and specificity. The very poor validity of the field clinical manifestations in diagnosing pouchitis emphasizes the need for endoscopic and histologic examination for detection of pouchitis. The issue of whether the diagnosis of pouchitis should be based on endoscopic and histologic features alone, instead of additionally taking clinical features into account, should be addressed in future studies.     

Huntington's Disease (HD): Neurodegeneration of Brodmann's Primary Visual Area 17 (BA17)

Huntington's disease (HD), an autosomal dominantly inherited polyglutamine or CAG repeat disease along with somatomotor, oculomotor, psychiatric and cognitive symptoms, presents clinically with impairments of elementary and complex visual functions as well as altered visual‐evoked potentials (VEPs). Previous volumetric and pathoanatomical post‐mortem investigations pointed to an involvement of Brodmann's primary visual area 17 (BA17) in HD. Because the involvement of BA17 could be interpreted as an early onset brain neurodegeneration, we further characterized this potential primary cortical site of HD‐related neurodegeneration neuropathologically and performed an unbiased estimation of the absolute nerve cell number in thick gallocyanin‐stained frontoparallel tissue sections through the striate area of seven control individuals and seven HD patients using Cavalieri's principle for volume and the optical disector for nerve and glial cell density estimations. This investigation showed a reduction of the estimated absolute nerve cell number of BA17 in the HD patients (71 044 037 ± 12 740 515 nerve cells) of 32% in comparison with the control individuals (104 075 067 ± 9 424 491 nerve cells) (Mann–Whitney U‐test; P < 0.001). Additional pathoanatomical studies showed that nerve cell loss was most prominent in the outer pyramidal layer III, the inner granular layers IVa and IVc as well as in the multiform layer VI of BA17 of the HD patients. Our neuropathological results in BA17 confirm and extend previous post‐mortem, biochemical and in vivo neuroradiological HD findings and offer suitable explanations for the elementary and complex visual dysfunctions, as well as for the altered VEP observed in HD patients.