Microscopic Vascular Invasion is the Most Relevant Prognosticator After Radical Nephrectomy for Clinically Nonmetastatic Renal Cell Carcinoma

Purpose

Although many factors have been considered to predict the outcome after radical nephrectomy, renal cell carcinoma continues to behave unpredictably. In a retrospective study the correlation between microvascular tumor invasion and disease-free survival after surgery for renal cell carcinoma was analyzed.

Materials and Methods

Between 1980 and 1993, 180 patients (mean age 60 years) were followed for a mean of 52 months after radical or partial nephrectomy for clinically localized renal cell carcinoma. The relevance of microscopic vascular invasion was compared to classical tumor staging, grade and tumor diameter.

Results

Microscopic vascular invasion was found in 51 patients (28.3%), including 20 (39.2%) with progression (mean interval to progression 72 months). Of 129 patients with no pathological evidence of microscopic vascular invasion only 8 (6.2%) showed progression at a mean interval of more than 160 months. The difference in disease-free survival as a function of microvascular invasion was statistically highly significant (log rank p <0.00001) and on multivariate analysis this parameter was by far the most relevant predictor of progression.

Conclusions

In patients who underwent radical nephrectomy for clinically nonmetastatic renal cell carcinoma with microvascular invasion but without lymph node involvement or macroscopic vascular invasion the chance of disease progression is estimated at 45% within 1 year. Microvascular invasion is the single most relevant prognosticator after presumed curative radical nephrectomy for renal cell carcinoma.     

Karyotypic evolution and tumor progression in head and neck squamous cell carcinomas

Cytogenetic analysis was performed on primary tumors, and paired recurrent or metastatic lesions, in 14 patients with head and neck squamous cell carcinomas (HNSCC), in order to identify chromosomal aberrations associated with tumor initiation and progression. Abnormal karyotypes were found in 12 of the 14 patients, with distinctive karyotypic similarities shown in all informative pairs. For individual patients, the degree of karyotypic complexity was similar for the primaries and paired recurrent or metastatic lesions. All 22 samples with clonal chromosomal aberrations displayed complex karyotypes with multiple numerical and unbalanced structural rearrangements, resulting in extensive genomic imbalances. The pathway of clonal evolution could be traced in a few patients, supporting the notion that some aberrations or imbalances, particularly partial or entire loss of 3p, i(8q), and homogeneously staining regions commonly mapping to 11q13, were early genetic events in the initiation of HNSCC.     

Chromosomal aberrations in breast cancer: a comparison between cytogenetics and comparative genomic hybridization.

The analysis of chromosomal imbalances in solid tumors using comparative genetic hybridization (CGH) has gained much attention. A survey of the literature suggests that CGH is more sensitive in detecting copy number aberrations than is karyotyping, although careful comparisons between CGH and cytogenetics have not been performed. Here, we compared cytogenetics and CGH in 29 invasive breast cancers after converting the karyotypes into net copy number gains and losses. We found 15 tumors (56%) with a significant agreement between the two methods and 12 tumors (44%) where the methods were in disagreement (two cases failed CGH analysis). Interestingly, in 13 of the 15 tumors where the two methods were concordant, there was also a strong correlation between chromosome index and DNA index by flow cytometry. In the opposite situation, i.e., when chromosome and DNA indices were not matching, there was disagreement between cytogenetics and CGH in 10 of the 12 tumors. Of the discordant cases, all except one had a "simple" abnormal karyotype. Unresolved chromosomal aberrations (marker chromosomes, homogeneously staining regions, double minutes) could not completely explain the differences between CGH and karyotyping. A likely explanation for the discrepancies is that the methods analyzed different cell populations. Gains and losses found by CGH represented the predominant (often aneuploid) clone, whereas the abnormal, near-diploid karyotypes represented minor cell clone(s), which, for unknown reasons, had a growth advantage in vitro.     

Comparative cytogenetic study of spindle cell and pleomorphic leiomyosarcomas of soft tissues: a report from the CHAMP Study Group

Leiomyosarcomas (LMS) of soft tissues frequently show complex karyotypic changes, and no specific aberration has been identified. The aim of this study was to search for recurrent chromosome aberrations in soft tissue LMSs and to correlate these, if present, with morphological and clinical parameters. From a series of soft tissue sarcomas thoroughly reexamined cytogenetically and histopathologically, 45 LMSs were retrieved; 35 were classified microscopically as spindle cell, 3 as epithelioid, and 7 as pleomorphic. Clonal chromosome changes were present in 14, 3, and 3 cases, respectively. This series was combined with 11 previously published, karyotypically abnormal pleomorphic LMSs for cytogenetic-clinico-histopathological correlations. The breakpoints were widely scattered, with no predilection of any of the recurrent breakpoints and losses to any of the morphologic subtypes. Combining numerical and unbalanced structural changes, the most frequently lost segments were 3p21-p23 (11 cases), 8p21-pter, 13q12-q13, 13q32-qter (10 cases each), 1q42-qter, 2p15-pter, 18p11 (9 cases each), 1p36, 11q23-qter (8 cases each), and 10q23-qter (7 cases). The most frequent gain was 1q12-q31 (6 cases). There was a greater frequency of losses in 1p and 8p and a lower frequency of losses in 10q and 13q in tumors that had metastasized than in localized tumors. We conclude that LMSs with clonal abnormalities display highly complex karyotypic changes and extensive heterogeneity. No significant correlation exists between these changes and age and sex of the patients, or with depth of tumor, topography, microscopic subtype, or tumor grade. Losses in 1p36 and 8p21-pter may be associated with increased risk of metastases. Comparison of our findings in soft tissue LMS with those previously reported in LMS in other locations suggest that the karyotypic profile is more dependent on site of origin than on microscopic features.     

Übererregbarkeit der γ-Motoneurone beim „Stiff-man“-Syndrom

Zusammenfassung Es wurde eine 40jährige Frau mit sog. Stiff-man-Syndrom untersucht. In Narkose und Lumbalanaesthesie verschwand die abnorme Muskelverspannung. Ebenso normalisierte sich unter Differentialblockade des N. femoralis durch Procainumspritzung der Tonus im Quadriceps vorübergehend ohne Lähmungserscheinungen. Daraus kann gefolgert werden, daß die-Motoneurone wesentlich am Zustandekommen der Muskelverspannung beteiligt sind. Histologisch ergab sich kein krankhafter Muskelbefund. Elektromyographisch bestand eine langanhaltende Aktivität in den befallenen Muskeln, die sich von Willkürentladungen nicht unterscheiden ließ. Bei passiven Bewegungen wurde eine ungewöhnliche Entdehnungsaktivität registriert. Unter Willkürinnervation bestand ein normal dichtes Muster. Bei Entspannung nach aktiver Innervation trat nach kurzer Entlastungsreaktion Überdauerungsaktivität auf. Einzelpotentiale, Nervenleitgeschwindigkeit, mechanisch und elektrisch (H-Reflex) ausgelöste Muskeleigenreflexe waren normal, die silent period nicht verändert. Der H-Reflex zeigte unter subparalytischer Dosis von Succinylcholin einen Abfall wie beim Gesunden.Unter Behandlung mit Diazepam und einem Amino-Buttersäurederivat verschwand die abnorme Muskelspannung fast vollständig. Es wird die Annahme vertreten, daß es sich bei dieser Form des Stiff-man-Syndroms, die dem Syndrom vonMoersch undWoltman entspricht, um ein Parabiosephänomen der-Motoneurone handelt (Spindelmyotonie). Analog dazu liegt beim Isaacs-Syndrom eine Überaktivität der peripheren -Motoneurone vor (Neuromyotonie). Bei anderen in der Literatur beschriebenen Formen des Stiff-man-Syndroms handelt es sich offensichtlich um primäre Muskel- oder Bindegewebserkrankungen.

---

Summary A 40 years old woman suffering from the so-called stiff-man syndrome is described. The abnormal muscle-tonus disappeared in narcosis and in lumbar anaesthesia. When procaine was infiltrated close to the nervus femoralis, the tonus in the quadriceps muscle was normalised temporarily without the muscle being paralysed. Consequently the-motoneurones may be considered as an essential factor in bringing about the pathological muscle stiffening. Histologycally there was no evidence of muscle disease. The EMG showed a long-lasting activity in the stiffened muscles which did not differ from a normal pattern. During passive shortening of the muscle abnormal activity was registered. An interference pattern was seen with maximum voluntary contraction. Active innervation was followed by anew electrical activity in the relaxing muscle, only interrupted by a short silent interval. Single units, nerve conduction velocity, the potentials of the muscle stretch reflex an the H-reflex were normal. The silent period was not altered. Under subparalytical dosage of succinylcholine the amplitude of the H-reflex showed a decrease in a physiological manner. The muscle stiffness disappeared almost completely when the patient was treated with diazepam (Valium) and a derivate of amino-butyric acid (CIBA 34-647 Ba).There is some reason to believe that this variety of stiff-man syndrome, being identical with the syndrome described byMoersch andWoltman, is caused by the parabiotically diseased-motoneurones (spindlemyotonia). Likewise a hyperactivity of peripheral -motoneurones is known to bring aboutIsaacs syndrome (neuromyotonia). Other varieties of the stiff-man syndrome described by literature are obviously primary diseases of the muscle or connective tissue.

---

---

Herrn ProfessorG. Schaltenbrand zum 70. Geburtstag gewidmet.     

Meningoradiculitis and encephalomyelitis due to Borrelia burgdorferi: a follow-up study of 72 patients over 27 years

Summary In 1987, follow-up studies were conducted on 72 patients who had had meningoradiculitis and encephalomyelitis (8 patients) due to Borrelia burgdorferi 5–27 years previously. These patients had not been treated with antibiotics, either during the acute disease or during the interval prior to follow-up studies. The patients had exhibited the typical symptoms of Bannwarth's syndrome during the acute phase. At the follow-up studies, 33 patients showed no, and 23 only mild, clinical residual symptoms including normal CSF findings and low-positive serum IgG borrelia antibody titres (IFT; ELISA). Three patients without sequelae exhibited persistent intrathecal secretion of oligoclonal B. burgdorferi-specific CSF IgG antibodies (Immunoblot; positive borrelia CSF IgG antibody titres). Thirteen patients exhibited mild-to-medium sequelae with persistent intrathecal formation of oligoclonal B. burgdorferi-specific CSF IgG antibodies, up to 21 years after the acute illness. This persistence can be interpreted as an immunological scar syndrome. Our follow-up studies appear to indicate that neurological manifestations of B. burgdorferi infections are generally (with few exceptions) of a benign nature. Most patients can be classified as having been cured without antibiotic therapy. No late manifestations of chronic progressive CNS borreliosis comparable to that of neurosyphilis have been seen following acute untreated neuroborreliosis.     

Non-traumatic vertebral artery dissection presenting with unilateral cervical pain,hemilateral vision problems and headache

Spontaneous vertebral artery dissection is a rare condition, mainly affecting young adults with non-specific symptoms, which are often considered not severe. We report a case of a non-traumatic vertebral artery dissection in a 30-year-old woman. Our patient presented with unilateral right-sided neck pain and frontal headache during 3 weeks and recently developed right-sided vision problems. History and clinical findings were non-specific. Neurovascular imaging showed a right-sided vertebral artery dissection from C2 to C6 with an intima flap at C5–C6. The patient was observed in the stroke unit for 1 week and antithrombotics were given during 3 months. There was a complete revascularization of the vertebral artery after 3 months. A review of literature is given concerning predisposing factors, clinical symptoms, neurovascular imaging and treatment options.