Harald R. Rosen

Influence of early diagnosis on prognosis of recurrent breast cancer

Between 1980 and 1986 676 patients with primary breast cancer were operated on with curative intention at the Department of Surgery, Hanusch Medical Center, Vienna, Austria. Of these, 133 had recurrences. The patients were closely followed at the Outpatient Clinic. The authors have retrospectively analyzed this patient collective to evaluate the impact of routine technical and laboratory‐chemical follow‐up programs on the detection rate of subclinical distant metastases and improvement of prognosis. There was no difference in outcome in terms of survival after recurrence and overall survival between patients with detection or recurrence in the asymptomatic stage who received general antitumoral therapy immediately, and a second group whose therapy was initiated upon clinical manifestation. The authors discuss the results in view of the screening costs. They emphasize the potential of follow‐up programs due to timely detection of local recurrence, and observation of the contralateral breast, as well as the psychological aspect of a stable doctor‐patient relationship.

Local gentamicin application for perineal wound healing following abdominoperineal rectum excision

A major complication of abdominoperineal rectum excision for rectal or anal carcinoma is local wound infection. The main reason for this infection is that systemically administered antibiotic prophylaxis does not reach sufficiently high concentrations of antibiotic in the tissue of the sacroperineal wound. Since gentamicin-polymethylmethacrylate (PMMA) in the form of chains of beads has been confirmed as a useful tool in the treatment of local infection in bone and soft tissue surgery, we have evaluated its effect on the abdominoperineal rectum excision in a prospective, randomized trial. Forty-four patients with rectal or anal carcinoma entered the study. Only patients with stage Dukes D were excluded from the trial. Following randomized selection, the patients were treated either with local gentamicin and drainage (Group A) or drainage alone (Group B), using the Lloyd-Davies procedure. The two groups were comparable regarding age, sex, tumor stage and level, and risk factors predisposing for an infectious complication (anemia, nutritional status, blood transfusion). The postoperative mortality rate was 0% in both series. Analysis of local perineal wound healing revealed a statistically significant higher percentage of primary wound healing in Group A than in Group B (87% versus 46%; p less than 0.01). This led to a significantly shorter hospitalization period for patients in Group A (p less than 0.01). Gentamicin-PMMA chains have been demonstrated to exert a favorable effect on local wound healing and the postoperative outcome of patients with abdominoperineal rectum excision.

Fluorouracil plus racemic leucovorin versus fluorouracil combined with the pure l-isomer of leucovorin for the treatment of advanced colorectal cancer: a randomized phase III study.

PURPOSE To compare the efficacy and toxicity of fluorouracil (FU) and racemic leucovorin (d,l-LV) versus FU combined with the l-isomer of leucovorin (l-LV) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS A total of 248 patients with advanced measurable colorectal cancer previously unexposed to chemotherapy were randomly assigned to treatment with either FU (400 mg/m2/d by intravenous [I.V.] infusion for 2 hours) and racemic LV (100 mg/m2/d by I.V. bolus injection) given for 5 consecutive days, or the combination of FU and the pure l-isomer of LV using the same dose schedule. In both treatment arms, courses were administered every 28 days if toxicity allowed for a total of 6 months, unless evidence of tumor progression was documented earlier. RESULTS There were no significant differences between the FU/racemic LV and the FU/l-LV arm in the overall response rate (25% v 32%), duration of response (7.2 v 8.0 months), median time to progression or death (6.25 v 8.0 months), or median overall survival time (14.5 v 15.0 months). Except for minor myeloid toxic effects associated with FU/l-LV, there was also no significant difference in terms of adverse reactions. Gastrointestinal symptoms, specifically mucasitis and diarrhea, were less frequent and less severe in both treatment arms compared with other trials with FU/racemic LV reported in the literature, which might be because of the prolonged administration of FU used in both arms. CONCLUSION The combination of FU/l-LV produced response rates, response durations, and survival times similar to those with FU/d,l-LV. Biochemical modulation of FU by either pure l-LV or racemic LV thus appears to result in equivalent clinical efficacy.

Nuclear pleomorphism, a strong prognostic factor in axillary node-negative small invasive breast cancer

SummaryWe have evaluated established risk factors (tumor size, menopausal status, receptor status, tumor histology, and grading according to Bloom & Richardson including subfactor analysis) as well as local therapeutic procedures in a series of 121 patients with axillary node-negative (ANN) breast cancer stage T1a and T1b. The patients were operated on at a single institution (Department of Surgery, Hanuschkrankenhaus, Vienna) from 1969 to 1989. After a median observation time of 185 months, a total of 16 patients (13%) had a recurrence; of these, 6 had died of the primary disease by the control date (Dec 1, 1990). Grading (distant recurrence-free survival (DRFS) p=0.01, overall survival (OS) p=0.006, mitosis rate (DRFS p=0.006, OS p=0.02), and particularly nuclear pleomorphism (DRFS p=0.0002, OS p=0.00001) proved to have prognostic impact on distant recurrence-free survival and/or overall survival (Mantel-Cox log rank test; level of significance: p=0.006 after adjustment for multiple testing by Bonferroni correction). Therapeutic procedures had a borderline-significant impact on local recurrence (p=0.09). No other parameters had statistically significant impact. Thus, our long-term analysis confirms the superior prognostic relevance of histologic grading and nuclear pleomorphism in patients with ANN breast cancer stage T1a and T1b.

Treatment of patients with advanced colorectal cancer with cisplatin, 5-fluorouracil, and leucovorin.

Based on in vitro studies that have demonstrated synergy between 5‐fluorouracil (5‐FU), leucovorin (LV), and cisplatin (CDDP) against human colon cancer cell lines, a clinical trial was initiated to determine the effects of this combination in patients with advanced unresectable colorectal carcinoma. Fifty‐nine patients were enrolled in the study and 12 of them had received prior conventional 5‐FU chemotherapy. Treatment consisted of 4 weekly courses of high‐dose LV (200 mg/m2) administered by intravenous (IV) bolus, followed by 5‐FU (550 mg/m2) and CDDP (20 mg/m2) each administered as a 2‐hour infusion on 4 consecutive days. After a median of 5.5 treatment cycles, objective tumor response was seen in 20 of 59 patients (34%) (this included 3 complete remissions). The response rate in the 47 previously untreated patients was 38% (95% confidence limits, 26% to 53%). Stable disease occurred in 16 (27%) patients, whereas the tumor progressed in 23 (39%) patients. The median survival time was 11.5 months, with 15% of the patients alive at 2 years. The regimen was well tolerated and the primary side effects were mild and reversible gastrointestinal symptoms and myelosuppression. There was no episode of life‐threatening toxicity. Eastern Cooperative Oncology Group (ECOG) Grade III adverse reactions that required 25% dose reductions occurred in only 14% of the patients. The results of this trial suggest that 5‐FU, LV, and CDDP is an active, safe, and well‐tolerated combination regimen in patients with advanced colorectal cancer.

Impaired primary antibody responses after vaccination against hepatitis B in patients with breast cancer

SummaryThe response to hepatitis B (HBV) vaccination was studied in 32 breast cancer patients who were HBV antigen- and antibody-negative at the time of diagnosis. Ten of the patients included into the study received radical mastectomy without adjuvant therapy, 15 patients underwent breast-conserving surgery with subsequent irradiation with or without tamoxifen treatment, and 7 patients were treated by modified radical mastectomy plus adjuvant chemotherapy. Eight patients received the first dose of vaccine 3 months after irradiation therapy. Seven patients were first vaccinated 6 months following irradiation therapy. Seven healthy age-matched persons were vaccinated as controls. Antibody response in the patients was significantly delayed. Four weeks after the second vaccination 6 out of 7 controls showed a significant (>10IU/ml) HBs antibody titer, while only 6 out of 32 patients responded. In addition, HBs antibody titers were also significantly lower after the second vaccination even in those patients treated with surgery alone, although they were first vaccinated 3 months after surgery and had no residual tumors. This difference disappeared after the second booster immunization, at which time the frequency of significant antibody titers and the levels of HBs antibody titers were comparable between patients and controls. As the population of patients undergoing treatment for breast cancer is increasing, additional studies are needed to determine optimal immunization regimens in this group of patients.

Nuclear polymorphism — a prognostic parameter to evaluate local recurrence of female breast cancer

SummaryBetween 1980 and 1986 676 patients underwent surgery for primary breast cancer. Of these, 35 patients developed locoregional recurrence. Retrospective analysis of the spontaneous postoperative development revealed 2 groups: group A had subsequent distant metastases, group B was tumor-free after surgical treatment of local recurrence. Analysis of the commonly employed characterization criteria of primary tumors (tumor size, lymph node involvement, estrogen receptors, histologic grading of primary tumors, and excised locoregional recurrence) showed no statistically significant difference between the two groups. However, a more detailed differentiation of the subcriteria for the histologic grading according to Bloom and Richardson revealed a prevalence of anaplastic nuclei in the primary tumors of group A (9/11). Even in this small patient population the parameter of nuclear polymorphism revealed a highly significant statistical difference between the two groups.

Chemically-induced chronic nerve compression in rabbits--a new experimental model for the carpal tunnel syndrome.

ZusammenfassungDie vorliegende Studie versuchte eine chemisch induzierte, chronische Kompression des N. medianus in einem experimentellen Kaninchenmodell, ohne Verwendung der bis dato implantierten Fremdkörper (Silikon-oder Gummischläuche, Tourniquets, etc.) zu verursachen. Nach Darstellung des N. medianus wurde bei neun weiblichen Kaninchen 1 ml Äthoxysklerol® perineural im Karpalkanal instilliert. Die andere vordere Extremität diente als Kontrolle und wurde mit der gleichen Menge Kochsalzlösung behandelt. Elektroneurophysiologische Parameter wurden präoperativ, 1 und 6 Monate nach dem Eingriff bestimmt, histomorphologische Untersuchungen mittels Licht- und Elektronenmikroskopie wurden nach 6 Monaten durchgeführt. 6 Monate nach Behandlung mit Äthoxysklerol® fand sich eine signifikante Verlängerung der distalen Latenzzeit sowie eine signifikante Erniedrigung der Summenpotentialamplitude. In Übereinstimmung mit diesen Befunden zeigte sich morphologisch überschieβendes Granulationsgewebe um den N. medianus mit Zeichen der Demyelinisierung. Unsere Ergebnisse zeigen, daβ wir die Entstehung von Granulationsgewebe im Karpalkanal von Kaninchen provozieren konnte, welche mit einer nachfolgenden Nervenkompression einherging. Diese Veränderung manifestierte sich sowohl histomorphologisch als im Rahmen der Nervenleitgeschwindigkeit.SummaryIn order to create an experimental model for the carpal tunnel syndrome without the use of the commonly applied foreign bodys (silicone or rubber tubes, tourniquets etc.), the present study tried to induce a chemically provoked compression of the median nerve in rabbits. In 9 female rabbits 1 ml of Aethoxskerol® 3% (Hydrox-polyethoxy dodecan) was instilled into the carpal tunnel around the median nerve after visualisation of the nerve. The other foreleg served as the control and was treated with the same amount of saline solution. Electroneurophysiologic parameters were registered preoperatively, 1 month and 6 months post surgery and histomorphologic investigations by light and electron microscopy were performed after 6 months. 6 months after treatment with Aethoxysklerol®, a statistically significant lenghtening of the distal latency period as well as a significant reduction of the compound potential amplitude could be observed. In accordance with these findings, morphological investigation revealed the presence of extensive granulation tissue around the median nerve together with signs of demyelination. Our results indicate that we were able to produce the development of extensive granulation tissue in the carpal tunnel of rabbits with subsequent compression of the median nerve which was confirmed by histomorphologic investigation as well as by measurement of nerve conductive velocity.

Splenektomie bei idiopathisch-thrombocytopenischer Purpura (ITP)

SummaryIn the period between 1978 to 1987 16 female and 11 male patients with a median age of 35 years (range: 14 years to 85 years) underwent splenectomy for ITP. There was no lethality in the postoperative period. 77.8% of all patients are in a complete remission, only 22.2% showed a recurrence and need further conservative therapy.ZusammenfassungIm Zeitraum von 1978 bis 1987 unterzogen sich 11 Männer und 16 Frauen mit einem Altersmedian von 35 Jahren (14 Jahre bis 85 Jahre) einer therapeutischen Splenektomie wegen chronisch-idiopathischer, thrombocytopenischer Purpura. Kein Patient verstarb postoperativ im Rahmen des stationären Aufenthaltes. 77,8 (21 Patienten) verblieben in einer dauerhaften Remission. Nur 6 Patienten - davon 4 Cortison-NonResponder - rezidivierten und benötigten weiterhin konservative Therapie.

Konsekutive Serie von 100 Colonresektionen mit einer modifizierten fortlaufenden Nahttechnik

SummaryBased on a consecutive series it is reported about a modified type of “continuous” suture on the colon, used especially in elderly patients for being a secure and prompt method of anastomosing. The rate of insufficiency and mortality, as far as the clinical relevance is concerned, turns out to be 2% each and there was no relation between mortality and insufficient anastomosis. The complication rate was 11%, whereby the urological complications predominated with 6% of the total.ZusammenfassungEs wird anhand einer konsekutiven Serie über eine modifizierte fortlaufende Nahttechnik am Colon berichtet, die gerade bei älteren Patienten eine sichere und rasche Methode der Anastomosierung darstellt. Die klinisch relevante Insuffizienzrate sowie auch die Letalitätsrate betrugen in dieser Serie je 2%, wobei die Ursachen für die Letalität aber keine Folge der Insuffizienz waren. Die Komplikationsrate betrug 11%, die urologischen Komplikationen mit 6% standen hierbei im Vordergrund.