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.

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.

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.

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.

Catheter-induced ascites--an unusual complication of parenteral feeding.

A nearly fatal complication of parenteral feeding is reported. An emaciated infant with severe Shigella dysentery was treated with intravenous feeding through a catheter in the inferior vena cava. After three days severe ascites developed acutely. Venocavography revealed effusion into the peritoneal cavity due to the catheter having penetrated the wall of the inferior vena cava.

Determination of pepsin (EC 3.4.23.1) and gastricsin (EC 3.4.23.3) in gastric juice by rocket immunoelectrophoresis.

Antisera were raised in rabbits against chromatographically purified preparations of pepsin and gastricsin. With these antisera the contents of pepsin and gastricsin in gastric juice were determined by rocket immunoelectrophoresis. The potential content of pepsin and gastricsin of a secondary standard of gastric mucosal extract was calibrated against the chromatographically purified enzymes. This secondary standard was used for routine analyses. The intra-assay and between-assay precision was 3-4% and 6-9%, respectively. Ten healthy volunteers underwent a standard pentagastrin test. The amounts of pepsin and gastricsin determined by rocket immunoelectrophoresis corresponded to the amounts observed by ion exchange chromatography of gastric juice. After stimulation with pentagastrin the secretion of both pepsin and gastricsin was increased about 10 times.

Solid-phase double-antibody radioimmunoassay of pepsinogen I in serum.

A solid-phase radioimmunoassay for the determination of pepsinogen I in serum has been developed. The antibody was raised in rabbits with pepsinogen I isolated from urine as previously described. Radioiodination was carried out with a chloramine-T procedure resulting in a tracer with excellent shelf life. In the standard procedure with a 24-h incubation time, followed by 2-h incubation with a second antibody coupled to a solid phase, 50 microliter serum was analyzed, standard range 1.88-60 ng PG I. An eight times more sensitive method was also developed using sequential saturation techniques. Specificity studies demonstrated 0.6% crossreactivity with PG II. The immunoreactivity of PG I purified from urine was nearly identical with the immunoreactivity of PG I purified from gastric mucosa. The levels of PG I in serum from 121 control subjects were similar to those obtained with conventional phase separation methods. It is concluded that the method is simple, precise and free from non-specific serum interference.

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.

Clinical implications of serum pepsinogen and progastricsin in man.

The serum pepsinogens in man have been reviewed with respect to clinical and physiological significance. The many places of synthesis of pepsinogen (PG A) and progastricsin (PG C) are described. The major part of serum pepsinogen and progastricsin is synthezized in the stomach, and the findings after antrectomy indicate that the majority of the pepsinogens in serum originates from the corpus of the stomach. The concentrations of pepsinogen and progastricsin in serum in relation to stomach diseases, e.g. ulcer disease, gastritis, and cancer of the stomach, are described. Despite typical findings, i.e. hyperpepsinogenemia in duodenal ulcer disease, or hypopepsinogenemia in atrophic gastritis or stomach cancer, there is a big overlap in serum concentrations between the groups reducing the clinical value of routine measurements of pepsinogens. Most promising are the findings in stomach cancer disease, where the combined measurement of pepsinogen levels and the isozymogen Pg5 is found to be highly indicative for the presence of a gastric carcinoma. Reports state that pepsinogens are excellent markers of recurrence of gastric cancer somewhere in the body after total gastrectomy. Genetical studies have--concerning pepsinogen--proved the multiple gene/multiple loci model. There is only a single progastricsin gene in humans and no genetic heterogenity has been found. Finally, the relationship between gastric infection with the bacterium Helicobacter pylori, and elevated pepsinogen and progastricsin levels in the blood, and the search for serologic markers of gastric diseases is discussed.

[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.

[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.

[Urease test for rapid demonstration of Helicobacter pylori in biopsies from the pyloric antrum]. / Ureasetest til hurtig påvisning af Helicobacter pylori i biopsier fra antrum ventriculi.

Helicobacter pylori (HP) is an important etiological factor in chronic gastritis and duodenal ulceration. Demonstration of HP by means of culture and histological examination is relatively time-consuming. The object of this investigation was to assess the validity of two rapidly read chemical tests: the buffered urease reagent (BR) and the unbuffered urease reagent (UBR) in demonstration of HP among patients referred for gastroscopy on account of upper abdominal dyspepsia. In 230 sets of biopsies investigated for HP by culture and histology, the following results were obtained by reading of the BR test three hours later at room temperature: Nosographic sensitivity 0.54, nosographic specificity 0.97, PVpos 0.93 and PVneg 0.71. In another material consisting of 57 sets of biopsies, both BR and UBR were performed. Reading of UBR after 15 minutes yielded the following results: Nosographic sensitivity 0.56, nosographic specificity 1.00, PVpos 1.00 and PVneg 0.61. It is concluded that positive results of the urease tests indicate the presence of HP. If the urease tests are negative, supplementary culture and/or histological examination for HP should be performed. UBR is preferable rather than BR.

[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.

[Adjuvant endocrine treatment of postmenopausal patients with breast cancer with high risk of recurrence. 5. Results from the DBCG (Danish Breast Cancer Cooperative Group) 77C randomized trial]. / Adjuverende endokrin behandling af postmenopausale brystkraeftpatienter med høj risiko for recidiv. 5. Resultater fra DBCG 77C, en randomiseret undersøgelse.

The role of antiestrogen treatment of postmenopausal breast cancer patients with high risk of recurrent disease is evaluated in a nationwide, prospective trial conducted by the Danish Breast Cancer Cooperative Group (DBCG). After total mastectomy and postoperative radiotherapy (RT), 840 patients were randomized to treatment with tamoxifen (RT + TAM) for one year, and 824 were randomized to no further therapy (RT). The recurrenceree survival (RFS) after ten years of lifeable analysis is 31% in the RT + TAM treated group, and 28% in the RT group (p = 0.01). Survival is 38% and 34% in the two treatment groups, respectively (p = 0.04). The data were further analyzed with respect to prognostic factors such as age, number of positive nodes, tumour size, and degree of anaplasia. Survival is prolonged in nearly all subgroups of patients treated with RT + TAM. However, the prolongation is only significant in patients with four or more positive nodes, with tumours of less than 5 centimeters or with tumours of anaplasia grade II. Estrogen (ER) and progesterone receptor (PgR) concentrations were measured in tumours from 309 and 219 patients, respectively. Only patients with ER and PgR values above 100 fmol/mg cytosol protein seemed to have a prolongation of survival. In conclusion, a modest survival benefit is achieved with one year of adjuvant tamoxifen treatment. Nevertheless, this is the first example of a systemic treatment approach being able to change the fatal course of breast cancer in postmenopausal patients. By means of endocrine therapy, and in the context of a new randomized trial, the DBCG will try to improve the survival in these patients even further.

[Rationalization profits of radiographic diagnosis with systematic follow-up DBCG (Danish Breast Cancer Cooperative Group) programs. 1]. / Rationaliseringsgevinster inden for billeddiagnostik ved systematiske opfølgningsprogrammer i DBCG's regi. 1.

In the follow-up programme of the DBCG-77 control and treatment protocols for primary operable breast cancer, bone scintigraphy and chest X-ray were performed 6 months after surgery and thereafter yearly until the diagnosis of any recurrence or another cancer. In the present study, the value of the two examinations was examined to the 6th year control. As a result of a low incidence of primary recurrence to the bone (0.6-3.9%) and to the chest (0.0-3.0%) the value was found to be low. About two thirds of the patients with primary chest recurrence addressed themselves with or had at the time of control pulmonary symptoms. About one half of those patients, in whom (during a 12-month period after the scheduled bone scintigraphy) bone metastases were diagnosed by another method, had a normal scheduled bone scintigraphy. False positive changes were not infrequent, especially at the bone scintigraphies. The diagnosis of asymptomatic chest recurrence did not reduce the mortality among stage II patients, among whom the greatest value of the control examination was found. It is concluded, that systematic use of bone scintigraphy and chest X-ray is not justified in a follow-up programme for stage I and II breast cancer patients.

[Prognosis after surgical treatment of breast cancer. 3. The low-risk group of the DBCG (Danish Breast Cancer Cooperative Group)]. / Prognosen efter kirurgisk behandling af cancer mammae. 3. DBCG's lavrisikogruppe.

The two therapeutic protocols of The Danish Breast Cancer Cooperative Group (DBCG) DBCG 77a (1977-1982) and 82a (1982-1990) comprise patients who were classified as low risk patients after operation for cancer of the breast, a total of 7,315 women. Treatment consisted of mastectomy and dissection of the lower and middle axillary levels. The median period of observation for DBCG 77a was 9 1/2 years and for DBCG 82a 3 1/3 years. The curves for recurrence-free survival and survival were found to be congruent in the two protocols. The recurrence-free survival after five years was 70% and 55% after ten years. Survival was 87% after five years and 70% after ten years. Local recurrence developed in 12.7% and 1.1% had distant recurrences simultaneously. Local recurrence was distributed with 60% in the scar or thoracic wall, 33% in the axilla and 7% in the clavicular lymph nodes. Distant recurrence alone developed in 11.4%. The time curves for development of local or distant recurrences were practically congruent. Local recurrence developed in 3.8% of the patients per annum during the first four years and after that in 1.5% per annum. Distant recurrence was found in 3.5% per annum in the first four years and after that in 1.8% per annum. The survival was significantly different after local and distant recurrence. Patients with tumours of grade 1 anaplasia had better prognoses than patient with grade 2 og 3 tumours as regards recurrence-free survival and survival. Multivariate analysis revealed that age under 40 years and anaplasia grad were significant prognostic variables for the parameters: distant recurrence and local recurrence. In addition, the number of lymph nodes in the operation specimen was a prognostic variable for local recurrence.

[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.

[Adjuvant chemotherapy in premenopausal and menopausal high-risk patients with breast cancer. 4. Results of the DBCG (Danish Breast Cancer Cooperative Group) 77B study]. / Adjuverende kemoterapi af praemenopausale og menopausale højrisikopatienter med cancer mammae. 4. Resultater fra DBCG 77B undersøgelsen.

From October 1977 to November 1982 premenopausal and menopausal high-risk breast cancer patients were included in a randomized trial (DBCG 77B). The primary surgical treatment was total mastectomy with axillary dissection. In the trial, a total of 1,034 patients were enrolled and received postoperative radiotherapy (RT) and were further randomized to 1) no systemic treatment, 2) cyclophosphamide, or 3) cyclophosphamide + methotrexate + 5-fluorouracil. The chemotherapy was given for one year. With a median observation time of ten years, the survival was 45, 60 and 62%, respectively. Retrospectively, the survival benefit was observed to be most pronounced in the age group less than 40 years, in patients with tumour size less than or equal to 5 cm or with less than or equal to 3 positive lymph nodes. In high-risk premenopausal and menopausal patients adjuvant chemotherapy combined with RT thus resulted in a more than 25% relative reduction in mortality at ten years of observation compared with RT alone.