Randomized clinical trial of prevention of seroma formation after mastectomy by local methylprednisolone injection.

BACKGROUND: Seroma formation, the most prevalent postoperative complication after mastectomy, is an inflammatory process that is potentially preventable via local steroid administration. This study investigated the effect of local steroid administration on seroma formation. METHODS: This was a double-blind randomized placebo-controlled intervention study of a single dose of 80 mg methylprednisolone versus saline on seroma formation after mastectomy. Patients were further classified according to the surgical axillary procedure: mastectomy with sentinel lymph node biopsy (M + SLNB) or mastectomy with level I-II axillary lymph node dissection (M + ALND). Treatments were administered into the wound cavity via the drain orifice following removal of the drain on the first day after surgery. The primary endpoint was seroma formation; secondary endpoints included the frequency of side-effects and complications. RESULTS: A total of 212 women scheduled for mastectomy for primary breast cancer were included. After M + SLNB, 32 (46 per cent) of 69 women developed a seroma in the methylprednisolone group, compared with 52 (78 per cent) of 67 in the saline group (P < 0.001). The mean cumulative seroma volume in the intention-to-treat population for the first 10 and 30 days was significantly lower in the methylprednisolone group (24 ml versus 127 ml in the saline group, and 177 versus 328 ml respectively) (P < 0.001). After M + ALND, similar proportions of patients developed a seroma in the methylprednisolone (35 of 37, 95 per cent) and saline (34 of 36, 94 per cent) groups, and methylprednisolone administration had no significant effect on seroma formation. No differences in infection rate were observed. CONCLUSION: Methylprednisolone administered into the wound cavity on the first day after M + SLNB exerted a highly significant preventive effect against seroma formation during the next 30 days. This effect was not seen in the M + ALND group. Future studies may clarify whether higher or repeated methylprednisolone doses increase the efficacy.

Impact on regional recurrence and survival of axillary surgery in women with node-negative primary breast cancer.

BACKGROUND: This study examined whether axillary lymph node dissection (ALND) with removal of many normal lymph nodes resulted in a reduced rate of axillary recurrence and better survival, as reported in recent studies. METHODS: The follow-up analyses were based on 8657 patients with node-negative primary breast cancer treated solely by surgery. Median follow-up was 9 years. RESULTS: The number of lymph nodes removed correlated with a reduction in the rate of subsequent axillary recurrence (from 2.1 to 0.4 per cent; P = 0.037), local recurrence (from 7.4 to 3.8 per cent; P < 0.001) distant metastases (from 15.0 to 10.3 per cent; P < 0.001) and death as first event (from 7.5 to 5.5 per cent; P = 0.012). CONCLUSION: When ALND is indicated, at least ten axillary lymph nodes should be retrieved. The role of ALND as primary treatment has decreased significantly during the past decade. The findings leave the concept of the sentinel node biopsy intact, as a highly specific procedure compared to ALND.

Sentinel lymph node biopsy in operations for recurrent breast cancer.

BACKGROUND: In a pilot prospective consecutive series on 50 patients with recurrent breast cancer, results of sentinel lymph node biopsy (SLNB) are reported. The interval between primary operation and recurrence was 8years (range 1-18years). Only three patients had not undergone dissection of the axilla (ALND). RESULTS: In 51% of patients scintigraphy disclosed sentinel nodes (SN). At operation SN was identified in 45% of patients corresponding to 83% of the SN's visualized by the scintigraphy. SN contained metastases in seven cases (16%), and the treatment plan was changed as a consequence of the SN examination. CONCLUSION: SLNB can identify SN at a high rate, and the findings may influence further planning of treatment. SLNB should be a future standard procedure in operations for recurrent breast cancer. Next step should be a randomized study.

Axillary staging during surgery for breast cancer.

BACKGROUND: Axillary lymph node status remains the single most important prognostic parameter in patients with breast cancer. In approximately half of operations sentinel lymph node biopsy cannot be employed and axillary dissection is indicated. Retrieval of ten nodes has hitherto been considered sufficient, but it remains questionable whether the removal of more lymph nodes might improve staging. METHODS: Data from 31 679 breast cancer operations in Denmark were analysed. RESULTS: The number of axillary lymph nodes retrieved was an independent and strong predictor of node positivity. The more lymph nodes retrieved, the better the staging of the disease; this was evident for all sizes of tumour. Dissection of 20 or more nodes rather than ten to 14 increased the probability of node positivity from 14.2 to 25.9 per cent for 1-5-mm tumours, from 38.6 to 47.9 per cent for 11-20-mm tumours, and from 80.6 to 90.0 per cent for tumours with diameter greater than 50 mm. CONCLUSION: The number of metastatic lymph nodes increased as more nodes were retrieved. These findings underline the need for high-quality specialist surgical and pathological services in breast cancer treatment.

No association of breast cancer risk with integrin beta3 (ITGB3) Leu33Pro genotype.

To pursue a borderline increased risk of breast cancer for carriers of two integrin beta(3) (ITGB3) 33Pro alleles found in a recent prospective study, we conducted a case-control study of 1088 women with breast cancer and 4815 female controls. Leu33Pro heterozygotes, homozygotes and heterozygotes+homozygotes vs noncarriers had odds ratios for breast cancer of 1.0 (95% confidence interval: 0.8-1.1), 0.8 (0.5-1.2) and 1.0 (0.8-1.1), respectively. After stratification for conventional risk factors, odds ratio for breast cancer in heterozygotes, homozygotes and heterozygotes+homozygotes vs noncarriers were not increased above 1.0 in any of the 14 strata examined. This was also true after stratification for tumour histological subtype and cancer stage at the time of diagnosis.

Surgical treatment of gynecomastia: liposuction combined with subcutaneous mastectomy.

The purpose of the present work has been to evaluate surgical treatment of gynecomastia performed by liposuction combined with subcutaneous mastectomy. It was designed as a prospective consecutive registration of 21 patients (28 breasts) operated in a four month period. Treatment was done in local anaesthesia in the out-patient clinic. Treatment was in one patient complicated with a haematoma. In 86% of cases the patients were satisfied with the postoperative result. Liposuction combined with surgical excision of the gland performed as an out-patient treatment in local anaesthesia is followed by few complications and good cosmetic results.

Radioisotope-guided surgical biopsy of costal metastases in breast cancer patients.

Radioisotope bone scanning is a sensitive indicator of metastatic disease. Localization of the hot spot for biopsy is difficult. Today, a hand-held gamma probe enables the surgeon intraoperatively to accomplish the localization procedure easily. As this technique is described in American literature exclusively, more recent European findings is presented here. During one month two patients were diagnosed with breast cancer. Bone scanning disclosed minor hot spots in the ribs. On the day of surgical biopsy the localization of the hot spots was guided by a gamma probe. For the biopsy a dermal punch biopsy needle was employed, and fine needle aspiration biopsies were also taken. The procedures were easy and completed within a few minutes. The post-operative courses were uneventful. In one patient, final histology showed malignancy in both biopsies. In the other patient, only the fine needle aspiration biopsy was malignant. The punch biopsy was abnormal, but did not contain malignant tissue. The gamma probe is an important tool in the performance of rib biopsies of nonpalpable lesions. The punch biopsy technique is simple and combined with fine needle aspiration biopsy the method has proven to be sensitive and accurate. The punch biopsy technique furthermore reduces the risk of postoperative pneumothorax.

Impact of axillary dissection on staging and regional control in breast tumors < or = 10 mm--the DBCG experience. The Danish Breast Cancer Cooperative Group (DBCG), Rigshisoutalet, Copenhagen, Denmark.

Data from 4771 patients with tumor diameters < or = 10 mm were analyzed. Results of surgery and pathoanatomical examinations indicated that nodal status was related to diameter, but not to number of nodes removed. More axillary metastases were found in group T1b tumors than in T1a. In 8% of tumors, at least 4 positive nodes were identified. Mean number of positive nodes was related to number of nodes removed, and when 10 or more nodes were removed a significantly lower axillary recurrence rate and better recurrence-free survival were demonstrated, confirming that axillary surgery has two goals: staging and regional disease control. Age, receptor status, grade and histological type, but not tumor location, were related to prognosis. In accordance with the classical prognostic factors, it was not possible to define a patient group where axillary surgery was superfluous. We conclude that proper staging and regional control renders a full axillary level I-II dissection necessary.

Sentinel node localization in breast cancer patients using intradermal dye injection.

In a series of 161 consecutive breast cancer operations, intradermal injection of Patent Blue was used to localize the sentinel node (SN). The surgical localization rate was 60%. Including the blue lymph nodes found by the pathologist, localization rate was 70%. After the first 103 operations, the surgical procedure was changed, resulting in a localization rate of 83%. Ten surgeons participated, but only one had previous experience with SN dissection. The others experienced a steep learning curve. Metastasis was found in 42 of 97 SNs (43%). In 15 cases (36%) metastasis was recognized only after step-sectioning and immunohistochemical staining for cytokeratin. In one case a benign epithelial inclusion was found. The sentinel node was false negative in 9.1% of cases. The consensus from the literature is that the best results are achieved using a combination of dye and isotopic techniques.

[Sentinel node--malignant melanoma and primary breast cancer. The significance of sentinel node in the treatment of malignant melanoma and primary breast cancer]. / "Sentinel node"--malignt melanom og cancer mammae. "Skildvagtslymfeknudens" betydning ved behandling af malignt melanom og primoer cancer mammae.

Dissection of regional lymph nodes plays an important role in surgical treatment of melanoma and breast cancer. However, the dissection of regional nodes is connected with a high morbidity and dissection in the 50-75% of the patients, who have no regional metastases, represents an overtreatment. No diagnostic procedures are available which could select patients who should have a regional lymph node dissection. The sentinel node (SN) is the first node in the lymphatic basin that drains the primary tumour. SN can be localized by means of dye or isotope or a combination. SN can be localized in melanoma or breast cancer patients in 98% of the operations. In 0-1% (melanoma) or 0-5% (breast cancer) SN was false negative. In some melanoma centers SN technique is an established routine. If the SN is normal, no regional lymph node dissection is needed. In breast cancer technical improvements must be achieved before SN examination can be used routinely. Future studies must clarify if examination of SN could have clinical significance in other malignant tumour diseases.

Lansoprazole and omeprazole in the prevention of relapse of reflux oesophagitis: a long-term comparative study.

BACKGROUND: Proton pump inhibitors are superior to H2-receptor antagonists in the prevention of relapse of oesophagitis, but few data directly compare the relative efficacies of lansoprazole and omeprazole in preventing oesophagitis relapse over a prolonged period. METHODS: Patients with healed Grade II, III or IV oesophagitis were treated with lansoprazole 30 mg o.d. or omeprazole 20 mg o.d. for 48 weeks. Endoscopy and symptom assessment were performed after 12. 24 and 48 weeks of treatment and an additional symptom assessment 36 weeks after starting treatment. RESULTS: Intention-to-treat analysis included 248 patients (lansoprazole n = 126, omeprazole n = 122). Comparison of time to endoscopic and/or symptomatic relapse revealed no difference between the treatments. There was no significant difference between treatments with respect to the proportion of patients in whom endoscopic and/or symptomatic relapse was reported (lansoprazole 12/126 (9.5%), omeprazole 11/122 (9.0%)). No difference between the treatments in either the number or severity of adverse events was reported. CONCLUSIONS: Continuous treatment with either lansoprazole 30 mg or omeprazole 20 mg is effective in preventing the relapse of oesophagitis over a 48-week period in a majority of patients. Both treatments exhibit a similar side-effect profile.

Does interpleural bupivacaine blockade reduce arterial hypoxemia and pain in endoscopic retrograde cholangiopancreatography? A prospective randomized trial.

BACKGROUND AND STUDY AIMS: Interpleural blockade with bupivacaine has been used in operations and for the treatment of pain with promising results. Endoscopy may be followed by serious complications associated with the use of intravenous drugs. Drug-induced hypoxemia has an important role in the pathophysiology. PATIENTS AND METHODS: A randomized study to assess whether interpleural bupivacaine blockade compared with a standard procedure reduced the risk of hypoxemia and the need of medication in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Other variables studied were its acceptability to patients and morbidity. RESULTS: Ninety patients were included. Interpleural blockade (n = 43) was followed by minor complications. The blockade itself induced mild hypoxemia in four patients (9%). Overall, eight patients (27%) developed hypoxemia. There were correlations between age, drugs given and hypoxemia in the total series and in the two study groups individually. During ERCP eight (19%) in the blockade group and 16 (34%) in the standard procedure group developed hypoxemia. During the recovery period the opposite pattern was observed: (26%) compared with four (9%) (p = 0.05). Drug requirements did not differ. Procedure-related discomfort did not differ. More patients in the blockade group would prefer another sedative procedure. CONCLUSIONS: Interpleural bupivacaine blockade did not contribute to patients' comfort or safety during ERCP.

[Clinics for counseling on cancer genetics. Experiences with genetic studies and counseling on familial breast cancer and colorectal cancer]. / Cancergenetisk rådgivningsklinik. Erfaringer med genetisk udredning og rådgivning ved familiaer cancer mammae og familiaer cancer colorectalis.

Five to ten percent of cases of breast cancer and colorectal cancer are familial. These families can be divided into high-risk families and moderate-risk families. Cancer in high-risk families can often be explained by dominant inheritance of a gene causing increased susceptibility to cancer. There is a great demand for genetic counseling in these families, and the structure of and experiences from a familial cancer clinic at Odense University Hospital is described. The establishment of a familial cancer clinic involves three steps: 1) Identification of families with increased cancer susceptibility; 2) Molecular tests to identify gene carriers; 3) Clinical examinations for early detection of tumors. Achievement of these three steps requires the involvement of several medical specialties to ensure patient care. Experience with familial cancer clinics is still limited and the involvement of genetic testing and clinical examination programs at risk individuals are insufficiently examined. The rapidly improving techniques for genetic testing make it urgent that it is implemented as part of already established clinical programs.

[Thyroid gland surgery in a teaching department of parenchymal surgery. Quality control and perspectives based on a 10-year material]. / Thyreoideaoperationer i en organkirurgisk uddannelsesafdeling. Kvalitetskontrol og perspektiver på basis af et tiårsmateriale.

The complications after surgery for benign thyroid disease in a non-specialized department were evaluated in a retrospective study. Furthermore it was evaluated whether the new recommendations of The National Board of Health for referral of patients in need of thyroid surgery would influence the rate of operations and complications in the ward. Three hundred and seventy-four patients were operated on. The complication rate was at the same level as in earlier Danish reports. Permanent unilateral palsy of the recurrent laryngeal nerve was registered in 2.1% of the patients (i.e. in 1.4% of "nerves at risk") in patients with primary benign goitre. The complication rate was slightly, but not significantly, higher after operations for recurrent goitre. Hypoparathyroidism occurred in 1.8%, infection in 3% and haemorrhage in 5.3% of the patients. If the recommendations of The National Board of Health for referral of patients were applied the complication rate would decrease, but not to a level of statistical significance. The number of operations would decrease by 20%. From the findings it is argued that not more than one or two hospitals in a county should perform thyroid operations and that not every surgeon should be trained in thyroid surgery.

Helicobacter pylori-associated gastritis and dyspepsia. The influence on migrating motor complexes.

Twenty-five patients with dyspepsia were included. In 19 patients with a median age of 48 (range, 20-72) years endoscopy and histologic examination of biopsy specimens from the antrum and corpus of the stomach showed Helicobacter pylori-positive gastritis as the only pathologic finding. In six patients with a median age of 42 (range, 32-56) years H. pylori-negative gastritis was found. After an overnight fast the patients underwent an ambulatory duodenal motility study for 6-8 h. Twenty-five young healthy men served as the control group. In patients with H. pylori-positive gastritis the duration of phase I of the migrating motor complex (MMC) was significantly shorter than in the control group. The median value was 33 min (quartiles, 24-49), and in controls 56 min (40-136 min). Phase II was of significantly longer duration, with a median value of 88 min (51-121 min) in the patient group and 39 min (22-89 min) in the control group. The duration of phase III and the whole MMC cycle was similar in the two groups. However, in the patients with H. pylori-negative gastritis the values of the duration of the different phases of the MMC were similar to those of the patients with H. pylori-positive gastritis. Nine patients were reexamined after eradication of the H. pylori infection, and the motility pattern had changed to the characteristics found in normals. In conclusion, the patients with dyspepsia and gastritis showed a disturbed motility pattern. The disturbance was similar whether there was colonization of H. pylori or not.(ABSTRACT TRUNCATED AT 250 WORDS)

The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG).

In primary, operable breast cancer, the Nottingham Prognostic Index (NPI) based on tumour size, lymph node stage and histological grade can identify three prognostic groups (PGs) with 10-year survival rates of 83%, 52%, and 13%. With the aim of defining a subset of patients having so good prognosis that adjuvant therapy can be withhold, the NPI was applied to a Danish population-based study group comprising 9,149 patients. As opposed to the British study, we used conventional axillary lymph-node staging. Histological grading was in both studies done by means of a similar slight modification of the Bloom and Richardson procedure, but in the Danish study only ductal carcinomas were graded. The 10-year crude survival was 68.1% for 4,791 patients with tumour size < or = 2 cm and 70.0% for 2,900 patients with grade I tumours. For 4,761 node-negative patients, the 10-year survival was also 70.0%, the expected survival being 89.3%. The relative mortality (observed:expected) was even at 10 years 2.1 demonstrating that more than 10 years observation time is necessary to estimate cumulated mortality. By application of the NPI, the Danish good PG comprising 27.3% of the patients had a 10-year survival of 79.0%. Thus, the index defined a subset with better survival than could be defined individually by each of its three components, but it did not succeed in defining a subset with survival similar to the expected; additional prognostic factors are therefore needed. The somewhat poorer survival of the Danish good PG may be ascribed to the British inclusion of non-ductal carcinomas, to interobserver variation present only in the Danish study, and to poorer expected survival of the Danish patients. The 10-year survival of the Danish moderate PG and poor PG was 56% and 25%, respectively. These improved survival rates are attributed to the administration of adjuvant therapies. There were virtually no node-positive patients in the good PG and no node-negative patients in the poor PG. Patients should therefore still be stratified initially by lymph-node status, but tumour size and histological grade are significant prognostic factors primarily within the node-negative group, and they should be included in future prognostication procedures.

Pepsinogen A and C serum levels in relation to acute NSAID-associated mucosal lesions in healthy volunteers.

Serum pepsinogen has been suggested as a risk marker for the development of gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs). The relation between serum levels of pepsinogen A (PGA) and pepsinogen C (PGC) and endoscopic findings in association with short-term NSAID use was investigated in two double-blind, crossover studies in healthy volunteers. Thirty-two male subjects with a median age of 23 years were given naproxen, oxindanac, or piroxicam for 2 weeks. Upper endoscopy was performed by the same investigator before and after each treatment period, scoring mucosal injection and erosive and hemorrhagic lesions separately on 150-mm visual analogue scales. Blood samples for pepsinogen analyses were drawn before each endoscopy. PGA and PGC were analyzed by means of solid-phase radioimmunoassays. Significant amounts of gastroduodenal mucosal lesions were found in all treatment periods, whereas neither PGA nor PGC changed during treatment. Moreover, the initial levels of serum pepsinogen also failed to predict the subsequent development of gastroduodenal lesions. The risk of a type-II error was small in this study, and our results therefore do not support the use of PGA or PGC as a risk marker in this context.

[Axillary dissection in primary surgical treatment of breast cancer: risk of false-negative axillary status]. / Aksildissektion ved primaer kirurgisk behandling af cancer mammae: risiko for falsk-negativ aksilstatus.

The present study evaluates the extent of axillary dissection as part of the primary surgical treatment of operable breast cancer. Data are from the period January 1979 to August 1990 and were collected prospectively as part of the Danish Breast Cancer Cooperative Group protocols for low-risk mammary carcinoma. The series consists of 6774 breast cancer patients aged 69 years or younger. The number of axillary lymph nodes removed was related to the frequency of ipsilateral axillary recurrence, recurrence-free survival, and overall survival after a median of five years follow-up, respectively. The recurrence-free survival and overall survival rate were directly related to the number of axillary lymph nodes removed. The difference in outcome is believed to be caused by false-negative classification of axillary-positive high-risk patients in groups of patients where only a few axillary lymph nodes were removed.

Axillary dissection of level I and II lymph nodes is important in breast cancer classification. The Danish Breast Cancer Cooperative Group (DBCG).

In order to define the term "a node-negative patient", the axillary nodal status at the primary operation for breast cancer was evaluated in 13,851 patients registered by the Danish Breast Cancer Cooperative Group (DBCG). The determinants for node negativity in primary breast cancer were the number of lymph nodes removed and the tumour size. The number of lymph nodes removed should be at least 10 to exclude misclassification of node-positive patients as node negative. There was a strong relationship between tumour size and the percentage of node-negative patients. Another observation was that high rate of node negativity was associated with low histological grade. The age of the patients had no influence on node negativity. Where 10 or more negative lymph nodes were removed, significantly better axillary recurrence-free survival (P less than 0.0001), over-all recurrence-free survival (P less than 0.0001) and survival (P less than 0.005) were found.

Danish randomized trial comparing breast conservation therapy with mastectomy: six years of life-table analysis. Danish Breast Cancer Cooperative Group.

The Danish Breast Cancer Cooperative Group (DBCG) conducted a randomized trial comparing breast conservation with mastectomy in patients with invasive mammary carcinoma. From January 1983 to March 1989, the trial accrued a total of 1153 women. Of this number, 905 patients (79%) were randomly assigned to one of the two treatment options, whereas 248 patients (21%) did not accept randomization. Of the randomly assigned patients, 90% received the surgical option to which they had been originally assigned. In the breast conservation arm the tumor was excised with the intention of obtaining free margins determined at gross examination, and radiotherapy was subsequently administered to residual breast tissue. The axilla was dissected in all instances. Patient and tumor characteristics were similar in the two randomization arms. The median follow-up time was 40 months. At 6 years of life-table analysis the probability of recurrence-free survival was 70% in the breast conservation arm against 66% in the mastectomy arm. Survival figures were 79% against 82%, respectively.