Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12.

BACKGROUND: Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48- and 62-month follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months. PATIENTS AND METHODS: Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/days) or anastrozole (1 mg/days), both with or without ZOL (4 mg every 6 months) for 3 years. The primary end point was DFS; recurrence-free survival and overall survival (OS) were secondary end points. RESULTS: After 94.4-month median follow-up (range, 0-114 months), relative risks of disease progression [hazard ratio (HR) = 0.77; 95% confidence interval (CI) 0.60-0.99; P = 0.042] and of death (HR = 0.66; 95% CI 0.43-1.02; P = 0.064) are still reduced by ZOL although no longer significant at the predefined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR = 1.63; 95% CI 1.05-1.45; P = 0.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. CONCLUSION: These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term. CLINICALTRIALSGOV: NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).

Prognostic relevance of tumour-associated macrophages and von Willebrand factor-positive microvessels in colorectal cancer.

Tumour-associated macrophages (TAM) are involved in tumour angiogenesis and anti-tumour immune response. In colorectal cancer (CRC), an association of high microvascular density (MVD) and unfavourable prognosis has been reported by some investigators. However, heterogeneous patient groups were studied. We, therefore, analysed the correlation between TAM and MVD and the prognostic relevance of MVD, TAM and T lymphocyte infiltration for long-term survival in a homogeneous group of 70 patients with moderately differentiated cancers of the International Union Against Cancer (UICC) stages II and III, who did not receive chemotherapy. MVD was evaluated using immunohistochemistry with antibodies against CD34 and von Willebrand factor (vWF). TAM and T lymphocytes were visualised with antibodies against CD68 and CD3, respectively. Statistical analysis did not reveal a significant correlation between TAM and T lymphocyte numbers and MVD. Multivariate analysis of immunohistochemical data from all CRC patients and the subgroup of patients with UICC stage-II CRC identified TAM- and vWF-positive microvessel numbers as prognostically relevant markers. Low numbers of TAM- and high numbers of vWF-positive microvessels were associated with an unfavourable prognosis. In conclusion, TAM- and vWF-positive microvessel numbers may serve as independent prognostic markers for patients with UICC stage-II and -III CRC and may help to identify patients with an unfavourable prognosis.

Recurrent nerve palsy after thyroid operations--principal nerve identification and a literature review.

BACKGROUND: Recurrent laryngeal nerve paralysis is one of the most frequent and serious complications after thyroid operation. The routine dissection and demonstration of the recurrent nerve remain controversial. In a retrospective study in an endemic region, patients operated on with principal nerve identification were investigated for vocal paralysis. METHODS: Eight hundred and three consecutive goiter operations were analyzed. Because six patients had undergone isthmusectomies only, the recurrent laryngeal nerves were at risk in 797 operations. For 736 patients the surgical procedure was primary for benign disease, for 40 patients the operation was secondary for recurrent goiters, and 21 patients underwent operation for thyroid cancer. All patients underwent preoperative and postoperative laryngoscopic examination of the vocal cords by an ear, nose, and throat specialist. RESULTS: Rate of primary postoperative vocal cord paralysis was 3.6%, and the permanent palsy rate was 0.5% with a recurrent laryngeal nerve recovery rate of 86%. In a literature survey, reports with identification of the recurrent nerve had significantly lower primary and permanent palsy rates when compared with reports without obligatory identification of the nerve (p < 0.01). CONCLUSIONS: Our results and those of reports in the literature indicate that recurrent nerve paralysis is a less frequent complication when the nerve is identified.

[Value of surgery in treatment of complicated gastroduodenal ulcer]. / Stellenwert der Chirurgie in der Behandlung des komplizierten gastroduodenalen Ulkus.

The surgical procedure in acute complications of gastroduodenal ulcers is examined with regard to risk factors and mortality. Emergency admissions to an Austrian district hospital between 1. 1. 1984 and 31. 8. 1992 for peptic ulcer are retrospectively analyzed. 293 patients were admitted with a history of bleeding ulcers. Endoscopic haemostasis was achieved in 91 of 130 (70%) patients with active haemorrhage (Forrest Ia, Ib). For the other 39 patients with active haemorrhage as well as for 16 of 65 patients with signs of previous bleeding (Forrest II) emergency surgery was necessary. 33 patients were admitted for perforated ulcers and all underwent emergency surgery. Distral gastric resections were performed in 98% of cases (54/55) with bleeding ulcers and in 91% of cases (30/33) with perforated ulcers. The surgically treated patients had a high percentage of accompanying illness and females were significantly older (mean 68 years) than males (55 years) (p < 0.01). Postoperative mortality was 9.1% (5/55) for bleeding peptic ulcers and 6.1% (2/33) for perforated ulcers. Furthermore, mortality was zero in patients younger than 60 years (0/44), but 15.9% (7/44) in patients older than 60 years. Distal gastric resection was chosen as standard procedure for emergency operations.

[Double stapling suture anastomosis in deep anterior rectum resection. Experiences and results]. / Die Doppel-Klammernaht-Anastomose bei tiefer anteriorer Rectumresektion. Erfahrungen und Ergebnisse.

Between 1.1. 1984-31.12. 1989, 263 rectal carcinomas were operated at the Department of Surgery, St. Veit/Glan. The resection rate was 68.4%, the excision rate was 27.8%, other procedures were carried out in 3.8%. Staple devices were used for all anastomoses following rectum resection. Whenever technically possible, the single-stapled procedure was used (EEA, ILS). For difficult or very low anastomoses, the double-stapled technique (DST) was utilized. The DST was employed in 47 cases. This approach contributed essentially to a relatively high resection rate at our department.

Improving survival rates for patients with colorectal cancer.

Between 1 January 1984 and 31 December 1990, 575 patients were operated on for colorectal cancer. The surgical procedure was performed consistently and no patients were lost to follow-up. Almost half of the patients (284 of 575) had tumours of stage I or II, with 5-year survival rates over 90 per cent. After extending the resection margins in 28 cases of colonic carcinoma there has been no case of tumour recurrence. The overall 5-year survival rate for patients with colonic carcinoma was 81 per cent. Complete resection of the mesorectum was mandatory for rectal resection. One-third of the carcinomas in the lower third of the rectum could be resected with maintenance of bowel continuity and an abdominoperineal resection avoided. Not only was the tumour recurrence rate in the former patients lower (10.5 per cent) compared with that in those undergoing abdominoperineal resection (14.3 per cent) but the 5-year survival rate at 90 versus 52 per cent was significantly higher. The overall 5-year survival rate for patients with rectal carcinoma was 71 per cent.

Extraperitonealization of the anastomosis and sacral drain in restorative surgery for rectal carcinoma: a safety mechanism in the absence of a covering stoma.

A retrospective 10-year study was conducted on 473 patients who underwent rectal cancer surgery, to evaluate a surgical procedure which has been generally abandoned, but which we believe has a significant potential to reduce the incidence of the severe and often fatal complications caused by anastomotic breakdown following low anterior resection, especially when a covering stoma is absent. This procedure involves separating the anastomosis and sacral drain from the abdominal cavity by suturing the parietal peritoneum to the colon and mesocolon, and placing the sacral drain outside the peritoneal cavity, whereby contamination of the abdominal cavity is avoided should anastomostic leakage occur. Sphincter preservation was possible in 343 patients (72.5%) while 116 (24.5%) underwent abdominoperineal resection (APR). Of 331 patients who underwent sphincter-saving resection (SSR), 31 (9.4%) had primary protective colostomies. Radical RO-resection according to the International Union Against Cancer (UICC) was performed in 405 patients, and 65 (19.6%) underwent extended resections. Anastomotic leakage became clinically manifest in 33 patients (10%; or 11% when those with primary colostomies were excluded). Only 1 patient required relaparotomy while 32 were successfully treated with temporary loop colostomy in the right epigastrium. No deaths occurred following anastomotic leakage breakdown. Overall operative hospital mortality was 3.0%; 2.7% and 2.6% in the SSR and APR groups, respectively. The adjusted 5-year survival rates were 60% for APR and 72% for SSR.

Simultaneous resection of colorectal carcinoma and synchronous liver metastases in a district hospital.

Of 491 patients operated for carcinomas of the colon or rectum between 1984 and 1989, 106 were tumour stage IV, U.I.C.C.(Dukes' 'D') at time of operation. In 22 of these cases a radical resection of the carcinoma of the colon or rectum and of synchronous liver metastases was performed simultaneously. In 20 patients the metastases were confined to one, in two they were found in both hepatic lobes. In one case a solitary metastasis of the lower lobe of the right lung was resected additionally. Three right-sided hemihepatectomies, one extended right hemihepatectomy, five left-sided hemihepatectomies, three left-sided lateral segmentectomies, seven atypical segmental resections and three wedge resections were performed. The mean operation time for the radical resection of the carcinomas of the colon or rectum as well as of the liver metastases was 3.5 (3-5.2)hours. An average of 3 (0-9) blood units were needed intraoperatively. The major liver resections were performed in complete normothermic vascular ischaemia using the finger fracture method. The time of ischaemia ranged between 8 and 25 min. Only 1 of 22 patients died postoperatively (30 days postoperative hospital mortality rate 4.5%). Five of 17 patients were free of tumour 2 years after operation. Eight of 22 were alive 2 years after operation (non-age corrected 2-year survival rate 36.4%), 2 of them are alive more than 5 years after treatment. Our results demonstrate that simultaneous resection of colon or rectum carcinoma and of synchronous (resectable) liver metastases can be performed successfully, even in a district hospital.

[Surgical therapy and results in stomach cancer at an Austrian regional hospital]. / Chirurgische Therapie und Ergebnisse beim Magenkarzinom an einem Osterreichischen Regionalkrankenhaus.

The resection rate of 216 gastric carcinomas, which were treated between January 1984 and October 1988, was 81.5%. Total gastrectomies were performed in 65.3%, distal resections in 33% and proximal resections in 1.7%. 68.1% of the operations were performed with curative intention, 13.4% were palliative, 18.5% were bypass operations and explorative laparotomies. In 52% the operations were extended to other organs. The total lethality of gastrectomies was 6.3% (for operations with curative intention 3.1%, for palliative ones 21%). None of the patients died of insufficiency of the anastomosis. The total lethality of distal and proximal resections was 3.7% (for operations with curative intention 0%, for palliative ones 20%). Explorative laparotomies and bypass operations had a lethality of 10%. According to the histo-pathological classification of the WHO 6% were well, 31% moderately and 46.8% poorly differentiated adenocarcinomas. Signet ring cell carcinomas were diagnosed in 9.3% of the cases. A histological classification of metastasis only was done in 3.2%. 3.7% of the cases were not examined histologically. 55.7% corresponded to the intestinal, 29.6% to the diffuse and 7% to the mixed type of Lauren. A Lauren classification was not possible in 7.8%. According to the UICC-criteria 13% were stage IA, 14.35% IB, 10.2% II, 14.35% IIIA, 10.2% IIIB and 6% IV(RO). In 31.9% a residual tumor (R1/R2) had to be left behind. The percentage of early cancer was 16%. 14 of the 34 early cancers corresponded to the mucosa and 20 to the submucosa type.(ABSTRACT TRUNCATED AT 250 WORDS)

[Surgical emergency interventions in acute diseases of the large intestine]. / Der chirurgische Notfalleingriff bei akuten Dickdarmerkrankungen.

Emergency operations due to acute colonic disease between 1. 1. 1984 and 31. 12. 1991 were retrospectively analyzed with regard to causality, surgical procedure, complications and mortality. 55 of 1105 colonic operations were emergency cases requiring immediate surgical intervention. Primary continuity preserving resections were carried out whenever possible, attending not only to the acute situation but also to the primary disease. The mean age of the 26 females and 29 males was 69 [1, 9] years. 29 patients had a colonic ileus, 21 a diffuse peritonitis and 5 patients had an uncontrolled haemorrhage. Colorectal carcinomas were initially diagnosed in 20 of the 50 patients; 14 of these patients (70%) could be operated for potential cure and primary continuity preserving resections were also possible for 14 patients (70%). Continuity preserving resections were possible for 18 of 21 patients with peritonitis and 3 colonic perforations were oversutured. In the 5 patients with acute haemorrhage, 4 resections and one transanal intervention were performed. Postoperative complications were observed in 19 patients (35%). Postoperative mortality was 16% (9/55), 5% for operations due to peritonitis, 24% for operations due to colonic ileus and 20% for operations due to haemorrhage. Primary continuity preserving resections were possible for 39 of 55 patients (71%).

Long-term prognosis for colon cancer related to consistent radical surgery: multivariate analysis of clinical, surgical, and pathologic variables.

Despite the improvement in its prognosis in most Western countries, death from colon cancer is still a major problem. In a prospectively planned observation study, a large patient collective from a single institution in Austria was analyzed in terms of the surgical approach and factors influencing survival. A total of 696 patients with colonic carcinomas were admitted to our surgical department between January 1, 1984 and December 31, 1997. Radical surgery for localized tumors was consistently performed, including wide resection margins and complete removal of the regional lymph drainage zones. Clinical, histopathologic, and therapy-related factors were examined for their influence on long-term survival by means of univariate and multivariate analysis. The overall tumor resection rate was 99.3% (691/696); complete tumor removal (R0) was possible for 84.8% (590/696) of all patients. The overall postoperative hospital mortality rate was 3.2% (22/696), and it was 13% (7/556) for potentially curative resections. Five- and ten-year tumor-specific survival rates for stage I to III R0 resections were 83.8% and 78.8%, respectively. Adjuvant chemotherapy reduced tumor recurrence for stage III patients by 52.4%. The depth of tumor infiltration, lymph node status, and adjuvant chemotherapy were found to have an independent influence on survival as identified by the Cox models. In conclusion, a consistent radical surgical approach for potentially curative resected colonic cancer patients had survival rates that surpassed those of most published series without sacrificing low complication rates. In addition, adjuvant chemotherapy for stage III substantially improved survival.