Efficacy of tamoxifen ± aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial.

BACKGROUND: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial. METHODS: ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5-24.9 kg m(-)(2)), overweight (BMI=25-29.9 kg m(-)(2)), and obese (30 kg m(-)(2)) according to WHO criteria. RESULTS: Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients. CONCLUSION: BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen.

Axillary Dissection in the Case of Positive Sentinel Lymph Nodes: Results of the Innsbruck Consensus Conference.

The prognosis of breast cancer is most heavily influenced by the status of the axillary nodes. Until a few years ago, this knowledge was gained through radical axillary lymph node clearance. In the meantime, sentinel lymph node clearance has become an established part of the surgical treatment of breast cancer. With the development of this procedure, the morbidity caused by axillary dissection has been reduced significantly. Although comprehensive prospective, randomised data regarding the safe use of the sentinel concept are only now available, the focus currently, however, is on the question of whether in the case of positive sentinel lymph nodes, an axillary dissection can be done away with altogether without having any negative impact on the risk of loco-regional recurrence or on progression-free survival and overall survival. The results of the American ACOSOG-Z001 study have changed the fundamental perspective of this. In this study on the advantages of axillary dissection following the confirmation of tumour tissue in the sentinel lymph nodes, there were no statistically significant advantages from axillary dissection for women with a favourable overall risk profile who had received radiotherapy and systemic therapy. If this concept takes hold, the surgical treatment of node-positive breast cancer, at least in the axilla, would be reduced to a minimum, and the focus of treatment would in future lie more on the systemic treatment of this condition. As part of an interdisciplinary consensus meeting, a standardised approach for Austria with regard to this question was decided upon.

Adjuvant intraperitoneal chemotherapy with carbon-adsorbed mitomycin in patients with gastric cancer: results of a randomized multicenter trial of the Austrian Working Group for Surgical Oncology.

PURPOSE: Previous studies have demonstrated a beneficial effect of intraperitoneally applied mitomycin bound to activated carbon particles (M-CH) in preventing intraabdominal recurrence following curative surgery for gastric cancer. The Austrian Working Group for Stomach Cancer, a subgroup of the Austrian Working Group for Surgical Oncology, initiated a multicentric phase III trial to evaluate the safety and efficacy of this treatment regimen. PATIENTS AND METHODS: A total of 91 patients with a radically resected gastric cancer infiltrating the serosal surface were randomly assigned to receive either 50 mg mitomycin bound to a solution of 375 mg carbo adsorbens intraperitoneally before closure of the abdominal wound (n = 46) or served as a surgical control group (n = 45). Postoperative complications and recurrence-free and overall survival were evaluated to analyze the risks and benefits of this treatment. RESULTS: After a median observation period of 597 days (range, 72 to 1,096), a significantly higher postoperative complication rate was observed in the M-CH group (35%) compared with the control group (16%) (P < .02). In accordance with this finding, the postoperative (60 days) mortality rate was also significantly elevated in the M-CH group (11% v 2% in the control group). Since analysis of overall and recurrence-free survival failed to show any beneficial effect of M-CH therapy, the protocol committee decided to stop further recruitment of patients onto this study. CONCLUSION: Adjuvant intraperitoneal therapy of gastric cancer by mitomycin bound to activated carbon particles is associated with an increased rate of postoperative complications. However, no benefit for prognosis following radical resection of locally advanced tumors was observed in this multicenter phase III trial.

Laparoscopic repair of recurrent inguinal hernias.

BACKGROUND: Repair of recurrent inguinal hernias is associated with recurrence rates as high as 30% and complication rates higher than for primary hernias. PATIENTS AND METHODS: In a prospective study, results were evaluated after laparoscopic transabdominal preperitoneal hernia repair in 192 patients with 200 recurrent inguinal hernias. A total of 132 hernia repairs followed one previous repair, 41 followed two repairs, 17 followed three repairs, 6 followed four, 3 followed five, and 1 followed six previous repairs. The surgical technique is described. RESULTS: Follow-up ranged from 9 to 31 months (mean 18.4). Twelve patients (6%) had groin seromas or hematomas; 3 (1.5%) had transient thigh numbness. One patient (0.5%) underwent laparoscopy a second time because of a large hematoma. In 1 patient (0.5%), a staple on the n. cutaneus femoris lateralis was removed laparoscopically. Patients described postoperative pain as being much less severe compared with their previous operation. Of the total group, 76% of patients were able to return to work within 2 weeks of surgery. One recurrence (0.5%) occurred after 6 months because of too small a prosthetic mesh. CONCLUSIONS: This laparoscopic technique can be applied to recurrent hernias, even in difficult cases, with low morbidity rates. Recurrence rates as low as for laparoscopic repair of primary hernias can be expected.

Simultaneous transplantation of isolated hepatocytes reduces rejection of small bowel allografts and improves survival in the rat.

Hepatocytes transplanted some days prior to vascularized allografts were shown to have the potential to prolong allograft survival in the rat. In the present study, hepatocytes and small bowel allografts were transplanted simultaneously in a Lewis (donor)-Brown Norway (recipient) rat model. 8-15 x 10(6) liver cells were injected into the spleen of small bowel recipients. The administration of at least 10 mg cyclosporine A (CyA)/kg over 3 days was necessary to prevent early rejection of hepatocytes. In groups simultaneously receiving hepatocytes, small bowel grafts and 10 mg CyA/kg over 3 days, a significant mitigation of rejection and a prolongation of survival was achieved, compared to groups receiving solely small bowel grafts and 10 mg CyA/kg over 3 days. We conclude that simultaneously transplanted hepatocytes exert a protective effect on a grafted organ from the same donor, provided that early rejection of hepatocytes is prevented by sufficient immunosuppression.

Sonography in the postoperative evaluation of laparoscopic inguinal hernia repair.

We evaluated the use of sonography as a means of assessing hernial occlusion and possible postoperative changes such as hematomas or seromas in the inguinal and scrotal regions after 1139 laparoscopic repairs of hernias between August 1992 and November 1994. Changes after laparoscopic hernia repair were found in 307 patients (27%). Hematomas or seromas were seen in 132 patients, protrusion of the prosthetic mesh in 17, mesh infection in two, and small bowel entrapment in an insufficient peritoneal suture in two. Recurrences were diagnosed correctly in six patients, mobile preperitoneal lipomas in five. Sonography is useful in the evaluation of complications after laparoscopic hernia repair, including recurrent hernia. In the absence of symptoms, sonography is not indicated.

Hepatocellular transplantation into the lung in chronic liver failure following bile duct obstruction in the rat.

Injection of hepatocytes or cell-free supernatant into the lung was able to prevent death from surgically induced fulminant hepatic failure in the rat in over 90% and 53% of subjects, respectively. The aim of this study was to investigate whether this technique can be applied in chronic liver failure. Chronic liver failure was induced in Lewis rats by ligation and transection of the common bile duct, which led to cirrhosis after 3-5 wk in all animals. Four groups of animals were formed: group 1 (n = 5), normal rats, serving as control; group 2 (n = 15), cirrhotic rats, no further treatment; group 3 (n = 14), hepatocyte transplantation by injection of cell suspension transcutaneously into the right lung of cirrhotic animals four wk after bile duct ligation; group 4 (n = 17), injection of 1 mL cell-free supernatant intravenously at two-day intervals, starting 4 wk after ligation. Liver function tests, prothrombin time and serum protein levels were measured weekly before and every two days after transplantation. In group 2 all animals had died 56 (49-69) days after ligation. Survival in groups 3 and 4 was similar: all rats had died from liver failure 61 (51-72) and 60 (49-76) days following bile duct ligation. Survival rates and laboratory investigations showed no significant differences between treated and untreated cirrhotic animals. These data suggest that hepatocyte transplantation into the lung as well as supernatant injection do not have any significant effect on chronic hepatic failure, at least in the rat model.

[Laparoscopic surgery of inguinal hernia by transperitoneal implantation of an artificial mesh. Technique and early results]. / Laparoskopische Leistenhernienoperation durch transperitoneale Implantation eines Kunststoffnetzes. Technik und Frühergebnisse.

We report on 250 patients with 342 inguinal hernias operated laparoscopically by pre-peritoneal implantation of a prosthetic mesh. 167 hernias were indirect, 175 direct, including 92 bilateral, 71 recurrent and 4 femoral hernias. There were four major complications: two lesions of the urinary bladder, treated in one case by laparotomy and two foreign body reactions against the mesh, which had to be removed. Two recurrences (0.6%) occurred during a 2-12 months follow-up. The mean hospital stay was 4 (3-10) days. Return to full activity was possible after one week.

[Is selective use of intraoperative cholangiography in elective cholecystectomy justified?]. / Ist der selektive Einsatz der intraoperativen Cholangiographie (IC) bei der elektiven Cholecystektomie (CHE) gerechtfertigt?

Operative cholangiography (IC) represents the most reliable investigation for common bile duct stones even during laparoscopic cholecystectomy (CHE). To reduce operating time, safety of selective IC was analysed in the last 308 consecutive patients undergoing conventional elective CHE. Obvious indication for common bile duct investigation excluded, IC was performed only in case of elevated liver function tests (n = 83, 26.9%), in 12 cases (14.5%) with positive in 2 cases (2.4%) with false positive result. In 255 (73.9%) patients IC was omitted. All patients were controlled after 4 months: no retained duct stone became evident in any case. Selective IC is safe and cuts time.

Hepatocellular transplantation into the lung for temporary support of acute liver failure in the rat.

Because hepatocyte transplantation into the spleen or the peritoneal cavity, although successful in rats, is more difficult and less successful in larger animals, the lung was chosen for its accessibility and its high oxygen content as a new site for hepatocyte implantation for treatment of acute hepatic failure. Acute hepatic failure was induced by a combination by a portocaval side-to-side shunt and an 80% liver resection, which was associated with a greater than 90% mortality. Hepatocyte transplantation was performed either by injection of 1 x 10(7) cells via the jugular vein (100% mortality) or 5-7 x 10(7) cells transcutaneously into the right lung (92% survival). After injection of the cell-free supernatant into the lung, 53.3% of the animals survived. If more than 90% of the liver was resected, none of the animals survived despite hepatocyte or supernatant injection. From these findings, it is concluded that the lung is a suitable home for hepatocytes. However, the hepatocytes survived only in cases of acute hepatic failure with some remaining vital liver parenchyma.

Hepatocyte transplantation into the lung for treatment of acute hepatic failure in the rat.

The lung was investigated as a matrix for transplanted hepatocytes in the rat model. Surgically induced fulminant hepatic failure was successfully treated by injection of 5 to 7 x 10(7) isolated hepatocytes into the pulmonary parenchyma in 86% of the animals. No animal, however, survived injection of hepatocytes into the jugular vein. It was found that liver failure is a prerequisite for the intrapulmonary survival of hepatocytes. After regeneration of the native liver, the majority of hepatocytes are cleared away within 6 months.

Chromogranin A and B in parathyroid tissue of cases of primary hyperparathyroidism: an immunohistochemical study.

Routinely processed parathyroid tissues from 26 cases with primary hyperparathyroidism (19 adenomas, 7 multiglandular hyperplasia) and 8 normal human parathyroid glands were investigated with antibodies against chromogranin A and B and parathyroid hormone (PTH). Normal parathyroids were immunohistochemically positive for PTH and chromogranin A but negative for chromogranin B. Hyperplastic glands showed a focal staining for PTH and chromogranin A without correlation of the staining pattern on serial sections. Adenomas were either uniformly positive for both PTH and chromogranin A or showed a staining pattern similar to that seen in hyperplastic glands. Focal chromogranin B positivity (less than 10% of cells) was found in 3 cases (1 hyperplastic gland and 2 cases of parathyroid adenoma with an immunohistochemical staining pattern similar to hyperplastic glands). Our immunohistochemical results may support previously published findings that most parathyroid adenomas are monoclonal neoplasms whereas hyperplastic glands are of polyclonal origin.

Silver stained nucleolar organizer region proteins (Ag-NORs) as a predictor of prognosis in colonic cancer.

Using a one-step silver nitrate staining technique, routinely processed tumour tissues of 49 carcinomas of the colon were investigated to demonstrate silver-stained nucleoli (Ag-nus) and argyrophilic proteins associated with the so-called nucleolar organizer regions (Ag-NORs). Patients with attempted curative resections and tumour stages Dukes' A, B, C1 and C2, with an uneventful follow-up period of at least 48 months (N = 17), showed a statistically significant (P = 0.0001) lower mean number of scattered Ag-NORs (3.04; SD: 1.08) compared to patients who developed metastases during their follow-up period (N = 15; 5.40; SD: 1.28), as well as to patients who underwent palliative surgical treatment (N = 17; 4.48; SD: 1.67). Mean numbers of scattered Ag-NORs per nucleus and staging of the tumour were strongly related (P = 0.0001) to cancer-specific survival. The results indicate that the evaluation of silver-stained particles according to their different distribution patterns is of great value with regard to the clinical outcome of colonic carcinoma and may even allow a more accurate prognostic assessment of these patients than the WHO grading system, UICC staging system, the so-called Jass-scoring system, and Dukes' classification.

[Malignant hemangioendothelioma of the thyroid gland. Pathology, clinical aspects and prognosis]. / Das maligne Hämangioendotheliom der Schilddrüse. Pathologie, Klinik und Prognose.

Malignant hemangioendothelioma (MHE) of the thyroid still constitutes a relatively important part of our surgical material, with 23 MHE (2.0%) among 1153 primary thyroid tumors diagnosed between 1952 and 1987 (biopsy material of the Innsbruck Pathology Institute). 18 of these cases were investigated immunohistochemically; in 14 cases the data on clinical findings and follow-up were complete. Immunohistochemical results confirm the endothelial origin of this tumor and allow MHE to be definitively distinguished from anaplastic carcinomas. Follow-up and prognosis are determined by the aggressive nature of local tumor spread. 13 patients died after a median survival period of 2.4 months (R: 1.2-9.4). Only one patient has remained alive since over 4 1/2 years now. An improvement of the hitherto dismal prognosis is thought to depend on early tumor diagnosis and an ameliorated combined modality treatment.

[Intestinal angiodysplasia as a cause of severe intestinal hemorrhage--report of 4 cases]. / Intestinale Angiodysplasie als Ursache schwerer Dünndarmblutungen--Bericht über vier Fälle.

Angiodysplasia of the small intestine alone cannot be differentiated histologically from hereditary hemorrhagic telangiectasia (Morbus Rendu-Osler-Weber). Isolated localisation in the small intestine is rare and requires surgery in the event of massive bleeding. Four cases of bleeding from angiodysplasias of the small intestine in patients having undergone surgery at our institution over a ten-year period are presented. In three patients the particular intestine was resected. Two of these patients had an uneventful follow-up of even and ten years, one patient relapsed and was rehospitalized for surgical treatment. The fourth patient, who showed angiodysplasias scattered over the entire small intestine, had no further bleeding over a three-year period after transmural ligations of the lesions found by intraoperative endoscopical diaphany.

Malignant hemangioendothelioma of the thyroid. Its immunohistochemical discrimination from undifferentiated thyroid carcinoma.

Eighteen cases of malignant hemangioendothelioma (MHE) of the thyroid and 16 cases of undifferentiated thyroid carcinoma were investigated immunohistochemically with antibodies against endothelial cell specific markers (factor VIII-related antigen, BMA 120, blood group isoantigens, Ulex europaeus agglutinin I), thyroglobulin, and the intermediate filament proteins vimentin and cytokeratin. All MHE were positive for factor VIII-related antigen and vimentin, in 14 of 18 cases for BMA 120, and in 9 of 18 cases for U. europaeus. All other markers were negative in MHE. Endothelial cell specific markers were commonly negative in undifferentiated carcinomas with one exception (one case was moderately positive for U. europaeus). Twelve of 16 undifferentiated carcinomas showed vimentin positivity, and 8 of 16 showed cytokeratin positivity. Four cases showed a vimentin/cytokeratin coexpression. It is concluded that the endothelial origin of MHE can be shown by certain endothelial cell markers in almost all cases.