Rates of re-excision and conversion to mastectomy after breast-conserving surgery with or without oncoplastic surgery: a nationwide population-based study.

BACKGROUND: There is no consensus regarding the impact of oncoplastic surgery (OPS) on rates of re-excision and conversion to mastectomy following breast-conserving surgery (BCS). Here these two outcomes after BCS and OPS were compared in a nationwide population-based setting. METHODS: In Denmark, all OPS is registered and categorized into volume displacement, volume reduction or volume replacement. Patients who underwent BCS or OPS between 2012 and 2018 were selected from the Danish Breast Cancer Group database. Multivariable analyses were performed to adjust for confounders, and propensity score matching to limit potential confounding by indication bias. RESULTS: A total of 13 185 patients (72·5 per cent) underwent BCS and 5003 (27·5 per cent) OPS. Volume displacement was used in 4171 patients (83·4 per cent), volume reduction in 679 (13·6 per cent) and volume replacement in 153 (3·1 per cent). Re-excision rates were 15·6 and 14·1 per cent after BCS and OPS respectively. After adjusting for confounders, patients were less likely to have a re-excision following OPS than BCS (odds ratio (OR) 0·80, 95 per cent c.i. 0·72 to 0·88), specifically after volume displacement and reduction. The rate of conversion to mastectomy was similar after OPS and BCS (3·2 versus 3·7 per cent; P = 0·105), but with a lower risk in adjusted analysis (OR 0·69, 0·58 to 0·84), specifically after volume displacement and reduction procedures. Findings were similar after propensity score matching. CONCLUSION: A modest decrease in re-excision rate and less frequent conversion to mastectomy were observed after OPS compared with BCS.

ANTECEDENTES: No existe consenso con respecto al impacto de la cirugía oncoplástica (oncoplastic surgery, OPS) en las tasas de re-exéresis y conversión a mastectomía tras la cirugía conservadora de la mama (breast conserving surgery, BCS). En este estudio se compararon los dos resultados después de BCS y OPS en una base de datos poblacional de ámbito nacional. MÉTODOS: En Dinamarca, todas las OPS se registran y clasifican en procedimientos que incluyen 1) desplazamiento (o remodelación) de volumen, 2) reducción de volumen o 3) restitución de volumen. Todas las pacientes sometidas a BCS o OPS entre 2012 y 2018 fueron seleccionadas de la base de datos del Grupo de Cáncer de Mama Danés. Se realizaron análisis multivariables para ajustar por factores de confusión y un emparejamiento por puntaje de propensión para limitar las variables de confusión potenciales por el sesgo en la indicación. RESULTADOS: Un total de 13.185 (72,5%) pacientes fueron sometidos a BCS y 5.003 (27,5%) a OPS. Se utilizó el desplazamiento de volumen en 4.171 (83,4%) pacientes, reducción de volumen en 679 (13,6%) pacientes y restitución de volumen en 153 (3,1%) pacientes. Las tasas de re-exéresis fueron del 15,6% y 14,1% tras BCS y OPS, respectivamente. Tras ajustar por factores de confusión, las pacientes tuvieron menos probabilidad (razón de oportunidades, odds ratio, OR 0,80, i.c. del 95%. 0,72-0,88) de requerir re-exéresis tras OPS, específicamente después de desplazamiento y reducción de volumen, en comparación con BCS. La tasa de conversión a mastectomía fue inferior (3,2% versus 3,7%, P = 0,04) y menos probable (OR 0,71, i.c. del 95% 0,58-0,87) tras OPS, específicamente en el desplazamiento y reducción de volumen, en comparación con BCS. Los resultados fueron similares después del emparejamiento por puntuación de propensión. CONCLUSIÓN: Se observó un descenso modesto en las tasas de re-exéresis y una menor frecuencia de conversiones a mastectomía después de la cirugía oncoplástica cuando se comparó con la cirugía conservadora de la mama.

Breast-contour preserving procedures for early-stage breast cancer: a population-based study of the trends, variation in practice and predictive characteristics in Denmark and the Netherlands.

PURPOSE: Breast-contour preservation (BCP) is possible for most women treated for early-stage breast cancer. BCP can be defined as primary breast-conserving treatment (BCT), neoadjuvant chemotherapy (NAC) followed by BCT and immediate postmastectomy breast reconstruction (IBR). This study provides insight in current BCP strategies in Denmark and the Netherlands and aims to identify opportunities for improvement within both countries. METHODS: A total of 92,881 patients with early-stage breast cancer who were operated in Denmark and the Netherlands between 2012 and 2017 were selected from the Danish Breast Cancer Group and the Dutch National Breast Cancer Audit databases. BCP procedures and predictive factors were analyzed within and between both countries. RESULTS: BCP was achieved in 76.7% (n = 16,355) of the Danish and in 74.5% (n = 53,328) of the Dutch patients. While BCP rate did not change significantly over time in Denmark (p = 0.250), a significant increase in BCP rate from 69.5% in 2012 to 78.5% in 2017 (p < 0.001) was observed in the Netherlands. In both countries, variation in BCP rates between hospitals decreased over time. NAC followed by BCT and postmastectomy IBR was substantially more often used in the Netherlands compared to Denmark, specifically in patients younger than 50 years. CONCLUSIONS: In more than 75% of all Danish and Dutch patients, surgically treated for early-stage breast cancer, the breast-contour was preserved. The different use of BCP strategies within Denmark and the Netherlands and the differences observed between hospitals in both countries emphasize the need for more (inter)national consensus on treatment modalities.

Breast cancer recurrence after reoperation for surgical bleeding.

BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from the DNPR. Follow-up began 14 days after primary surgery and continued until breast cancer recurrence, death, emigration, 10 years of follow-up, or 1 January 2013. Incidence rates of breast cancer recurrence were calculated and Cox regression models were used to quantify the association between reoperation and recurrence, adjusting for potential confounders. Crude and adjusted hazard ratios according to site of recurrence were calculated. RESULTS: Among 30 711 patients (205 926 person-years of follow-up), 767 patients had at least one reoperation within 14 days of primary surgery, and 4769 patients developed breast cancer recurrence. Median follow-up was 7·0 years. The incidence of recurrence was 24·0 (95 per cent c.i. 20·2 to 28·6) per 1000 person-years for reoperated patients and 23·1 (22·5 to 23·8) per 1000 person-years for non-reoperated patients. The overall adjusted hazard ratio was 1·06 (95 per cent c.i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence.

Failure pattern and survival after breast conserving therapy. Long-term results of the Danish Breast Cancer Group (DBCG) 89 TM cohort.

UNLABELLED: Based on the results from the DBCG 82 trial, breast conserving therapy (BCT) has been implemented as standard in Denmark since 1989, and today constitutes more than 70% of the primary treatment. Our aim was to evaluate the implementation of BCT as a routine procedure in patients treated according to the DBCG 89 program and compare recurrence pattern and survival both overall and when separated in age groups, with the results from the randomized DBCG 82 TM trial. MATERIAL AND METHODS: A total of 1847 patients treated between 1989 and 1999 were included in a retrospective population-based cohort study. Data from the DBCG database were completed via search through the Danish Pathology Data Bank and medical records. RESULTS: Median follow-up time was 17 years. At 20 years the cumulative incidences of local recurrence (LR) and disease-specific mortality (DSM) were 15.3% and 25.8%, respectively. Twenty-year overall survival (OS) and recurrence-free survival were 63.7% and 43.1%, respectively. Subdivided by age groups cumulative incidences at 20 years were LR: 18.9%, 10.5% and 12.4%, and DSM: 28.9%, 18.9% and 28.4% in young (≤45 years), middle-aged (46-55 years) and older (≥56 years) women, respectively. In an adjusted analysis age maintained a significant and independent effect on both LR and DSM. CONCLUSION: The DBCG 82 TM program was successfully implemented. The women treated with BCT in the DBCG 89 program displayed equal failure pattern and improved survival in comparison with women from the DBCG 82 TM protocol. Occurrence of first failure and mortality varied with age; demonstrated by increased risk of LR, DM and DSM in the young patients and increased risk of DM and DSM in the older patients, compared to the middle-aged patients.

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.

[Cohort study of fracture risk before and after surgery of primary hyperparathyroidism]. / Kohortestudie af frakturrisiko før og efter operation for primaer hyperparatyreoidisme.

We studied the risk of fracture in 674 patients operated on for primary hyperparathyroidism compared to 2,021 age- and gender-matched controls, matched for age and gender, randomly drawn from the background population. Before surgery, there was an increased risk of fracture (relative risk 1.8, 9% confidence interval 1.3-2.3), but after surgery the relative risk was normalised (RR = 1.0, 0.8-1.3). The increased risk began ten years before surgery and peaked five to six years before surgery. After surgery, there was a temporary increase in the first year, but in the following years the fracture risk was normalised, with a small rise in distal forearm fractures more than ten years after surgery. Primary hyperparathyroidism may have started up to ten years before surgery, and the fracture risk is normalised after surgery.

[Complications of cholecystectomy before and after introduction of laparoscopic surgery]. / Komplikationer til kolecystektomi før og efter indførelse af laparoskopisk kirurgi.

OBJECTIVES: In the University Department of Surgical Gastroenterology, Arhus University Hospital, the frequency of complications to acute and elective cholecystectomy was investigated before and after introduction of laparoscopic cholecystectomy. MATERIAL AND METHODS: A retrospective survey turned up 1768 patients in the period of conventional open surgery (1974-1985) and 1432 patients in the laparoscopic period (1991-1998). All patients with exploration of the common bile duct were excluded. RESULTS: In the open period 12 patients (0.68%) had lesions of the common bile duct requiring reconstruction. In patients operated on with laparoscopic cholecystectomy, lesions of the common bile duct were found in three patients (0.21%) (p = 0.06). Lesions of the cystic duct or an aberrant bile duct occurred in 14 patients (0.79%) during the open period and in 24 patients (1.7%) (p < 0.05) operated on with the laparoscopic technique. Infectious and cardiopulmonary complications were seen in significantly more patients operated on with the open technique. DISCUSSION: It is concluded that laparoscopic cholecystectomy offers a safe procedure, although the technique can still be improved, especially with respect to decreasing leakage from the cystic duct.

Muscular performance and fatigue in primary hyperparathyroidism.

The purpose of this study was to evaluate changes in muscular strength and endurance, work capacity, and subjective fatigue following surgical treatment of primary hyperparathyroidism (pHPT), and to assess whether changes in muscular function were due to changes in activation of the muscles. A prospective consecutive study design was used, and patients surgically treated for nontoxic goiter served as controls. Nineteen female patients with mild to moderate pHPT and 20 controls were included. Maximal isometric handgrip and quadriceps strength, quadriceps endurance (intermittent stimulation), and quadriceps activation (superimposed twitch technique) were used for evaluation of muscular function. All patients were operated on successfully. Knee extension strength increased by 17 +/- 17% (mean +/- SD; p = 0.0004) in the patients, whereas no change was observed in the controls. The relative strength increase correlated positively to patient age at operation (r = 0.52, p = 0.02). Handgrip strength, quadriceps endurance, and general work capacity did not change in any group after operation. Subjective fatigue was preoperatively higher in patients than in controls (p = 0.01), and decreased postoperatively to the level of controls. In conclusion, women with pHPT increase knee extension force after parathyroidectomy as a result of increased force generation capacity of the muscle. If change in physical performance is a determinant for change in subjective fatigue in pHPT after operation, then change in strength of the quadriceps muscle seems to be of primary importance, whereas handgrip strength, muscular endurance, and work capacity do not seem to be important. The cause of the increasing strength benefit with increasing age at operation as found in this study needs further investigation.

[Laparoscopic adrenalectomy. An alternative to open surgery of minor adrenal tumors]. / Laparoskopisk adrenalektomi. Et alternativ til åben operation ved mindre binyretumorer.

In the period February 1994 to November 1995 11 laparoscopic adrenalectomies were performed at our institution (seven women, four men). A transperitoneal approach was used in both right- and left-sided operations. Results were collected retrospectively. Indications for surgery were: Conn's syndrome (four), Cushing's syndrome (two), phaecromocytoma (four), and incidentaloma (one). The operations took median 170 minutes (range 105-250 minutes). Median size of the tumour was 4 cm range 1(1/2)-5 cm). No significant peri- or postoperative complications were recorded. The patients were discharged from the surgical unit median two days after surgery. Laparoscopic operation emerges as an alternative to open operation when dealing with smaller adrenal tumours. Because of the small number of patients, these operations have to be restricted to a few centres where both internists, anaesthesiologists and surgeons with expertise in this field are found.

The effect of ranitidine on postoperative infectious complications following emergency colorectal surgery: a randomized, placebo-controlled, double-blind trial.

OBJECTIVE AND DESIGN: To study the potential effect of ranitidine on postoperative infectious complications following emergency colorectal surgery. A randomized, placebo-controlled, double-blind trial was carried out in three university clinics and two county hospitals in Denmark. PATIENTS AND TREATMENT: One hundred and ninety-four consecutive patients undergoing acute colorectal surgery for perforated and/or obstructed large bowel were randomized in a double-blind fashion to receive ranitidine 100 mg i.v. twice a day commencing at induction of anesthesia and continued for five days (group I) or i.v. placebo (group II). All patients were given 1.5 g metronidazole plus 3.0 g cefuroxime at the time of surgery. Patients with perforation of the colon or rectum were given metronidazole and cefuroxime for further 3 days. All patients were assessed daily until discharge from the hospital. Thirty patients were withdrawn from the study (for reasons such as other diagnosis, refused to continue, medication not given as prescribed). MAIN OUTCOME MEASURES: Patients were observed for signs of infectious complications; such as wound infection, intra-abdominal abscess, septicemia, and pneumonia. RESULTS: Both groups were similar with respect to age, sex, weight, duration of surgery, blood transfusions, and site of the procedure, as well as the histologic nature of the underlying disease process. However, the Mannheim Peritonitis Index (MPI) was significantly higher in group I compared with group II (p < 0.05). Wound infection, intraabdominal abscess, septicemia, and pneumonia were 12.9%, 5.2%, 3.8% and 14%, respectively in group I. In group II, the infectious complications were 16.1%, 6.8%, 6.9% and 22%, respectively. Twelve patients (13.8%) in the placebo group developed more than one complication compared with 5 patients (6.5%) in the ranitidine group. CONCLUSION: Ranitidine may have a beneficial effect on postoperative infectious complications in patients following acute colorectal surgery.

Long-lasting functional abdominal pain and duodenal ulcer are associated with stress, vulnerability and symptoms of psychological stress. A controlled study including healthy and patient controls.

OBJECTIVE: To assess psychological differences between patients with functional abdominal pain (FUNC) and three separate control groups comprising patients with duodenal ulcer (DU), patients with gallstone or urinary tract stone (STONE), and healthy non-patient controls (HEALTH). METHODS: All participants completed a self-administered questionnaire including questions about the relationship between symptoms and certain life events and psychometric tests for psychological distress (SCL-90) and vulnerability. PARTICIPANTS: The FUNC group consisted of 27 hospital outpatients with long-lasting abdominal pain without demonstrable abnormalities (ten men and 17 women; mean age 38 years). The DU group consisted of 13 untreated outpatients with endoscopically proven duodenal ulcer (nine men and four women; mean age 42 years) while the STONE group comprised 13 untreated patients with gallstone (n = 7) or urinary calculi (n = 6) (six men and seven women; mean age 43 years). The HEALTH group consisted of five men and nine women (mean age 36 years). RESULTS: Significantly more FUNC and DU patients compared with STONE patients experienced an association with at least one of 14 life events (74%, 77%, and 31%, respectively; p = 0.02). The FUNC and DU groups showed significantly higher scores on the depression subscale of the SCL-90 than the HEALTH group (p < 0.05), and on the anxiety subscale compared with the STONE and HEALTH groups (p < 0.05). The FUNC group scored significantly higher on the somatization subscale compared with all the other groups (p < 0.05). As an overall measure of psychological distress the Global Severity Index (GSI) was calculated. GSI was significantly higher in the FUNC group compared with the HEALTH group (p < 0.01) and tended to be higher in the DU group (p = 0.06). The FUNC and DU groups had significantly higher scores for vulnerability than the STONE and HEALTH groups (p < 0.05). CONCLUSION: FUNC as well as DU outpatients seem to be more psychologically distressed and vulnerable than healthy controls or outpatients suffering from pain caused by stones in the gallbladder or urinary tract. As opposed to the STONE group, a high proportion of the FUNC and DU patients experienced that the onset or aggravation of abdominal pain was associated with certain life events. The similarities between the FUNC and DU group demonstrate that it is important to separate DU patients from other "organic" patients in such investigations.

[Reduced concentration of beta-endorphin in cerebrospinal fluid and reduced pain tolerance in patients with functional dyspepsia]. / Nedsat koncentration af beta-endorfin i spinalvaeske og nedsat smertetolerance ved funktionel dyspepsi.

It was investigated whether central pain mechanisms including the endogenous antinociceptive system were involved in functional dyspepsia defined as: abdominal pain without abnormal findings. Pain sensitivity was measured by an ischaemic pain test comparing 21 functional dyspepsia patients with two control groups: 1) 24 patients with organic abdominal pain, and 2) 13 healthy pain-free controls. The endogenous opioids beta-endorphin, met-enkephalin immunoreactivity, and dynorphin immunoreactivity were measured in cerebrospinal fluid (CSF) from nine patients with functional dyspepsia and pain-free controls undergoing minor surgery while under spinal analgesia. There was no significant difference between the groups in pain sensitivity, but subdivision of the functional dyspepsia group showed that individuals with pain and no symptoms of irritable bowel syndrome (IBS) were significantly more sensitive to ischaemic pain than functional dyspepsia patients with IBS. The CSF beta-endorphfin concentration was significantly decreased in the functional dyspepsia group as compared with the controls. There were no significant group differences regarding met-enkephalin immunoreactivity and dynorphin immunoreactivity. Because of post-lumbar-puncture headache, this part of the investigation was suspended after nine patients. Functional dyspepsia is probably a pain syndrome with decreased central antinociceptive activity.

[Blood transfusion increases the risk of surgical infection]. / Blodtransfusion øger den kirurgiske infektionsrisiko.

In a prospective randomized trial the frequency of infectious complications and natural killer cell function were investigated in 197 patients undergoing elective colorectal surgery and having either no blood transfusion (n = 93), transfusion with whole blood (n = 56), or filtered blood free from leucocytes (n = 48). Postoperative infections developed in 13 patients transfused with whole blood (23%), in one patient transfused with blood free from leucocytes (2%) and in two non-transfused patients (2%) (p < 0.01). Natural killer cell function was significantly (p < 0.001) impaired up to 30 days after surgery in patients transfused with whole blood. These data provide a strong case against the use of whole blood transfusion in patients undergoing elective colorectal surgery.

Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery.

The frequency of infection in 197 patients undergoing elective colorectal surgery and having either no blood transfusion, transfusion with whole blood, or filtered blood free from leucocytes and platelets was investigated in a prospective randomized trial. Natural killer cell function was measured before operation and 3, 7 and 30 days after surgery in 60 consecutive patients. Of the patients 104 required blood transfusion; 48 received filtered blood and 56 underwent whole blood transfusion. Postoperative infections developed in 13 patients transfused with whole blood (23 per cent, 95 per cent confidence interval 13-32 per cent), in one patient transfused with blood free from leucocytes and platelets (2 per cent, 95 per cent confidence interval 0.05-11 per cent) and in two non-transfused patients (2 per cent, 95 per cent confidence interval 0.3-8 per cent) (P less than 0.01). Natural killer cell function was significantly (P less than 0.001) impaired up to 30 days after surgery in patients transfused with whole blood. These data provide a strong case against the use of whole blood transfusion in patients undergoing elective colorectal surgery.

[Hemithyroidectomy. A consecutive series of 100 patients]. / Hemityreoidektomi. En konsekutiv serie på 100 patienter.

Treatment of isolated, scintigraphically cold thyroid nodules in the thyroid gland by means of hemithyroidectomy ensures that, in patients with thyroid carcinoma, it is possible subsequently to carry out total thyroidectomy by means of an intervention limited to the contralateral surgically intact side. The object of the present investigation to assess whether this therapeutic strategy was rational and safe. Hemithyroidectomy was carried out in 67 patients on account of a "cold nodule" while the remaining 33 patients were submitted to operation on other indications. Out of the 67 patients, one (2%) had a papillary carcinoma, 53 (79%) had follicular adenomata, 12 (18%) had nodular goitre and one (2%) had Hashimoto's thyroiditis. In the entire material, one case (1%) of permanent hypocalcaemia was encountered. None of the patients developed paresis of the recurrent laryngeal nerve. Reoperation proved necessary in one patient (1%) on account of postoperative heamorrhage. It is concluded that hemithyroidectomy is a rational primary method of treatment in cases with suspected malignant disease in the thyroid gland. Non-neoplastic conditions may be excluded with reasonable certainty by preoperative clinical assessment and thyroid scintigraphy and ultrasound scanning. The intervention is safe and every thyroid surgeon should be capable of performing the operation.

The impact of unilateral ureteral obstruction on pelvic and parenchymal transit times in the pig kidney.

In 10 female pigs a partial unilateral ureteral obstruction was investigated for 3 weeks. The pigs were monitored with 131I-iodo-hippuran scintigraphies before obstruction and once a week during the course of obstruction. Parenchymal and pelvic mean transit times were calculated by deconvolution analysis. Before the pigs were killed, pelvic pressure and volume were measured. During the course of obstruction there was a slight, but significant (P less than or equal to 0.05) difference in renographical split function between the 2 sides. Parenchymal transit times increased moderately ipsilaterally during the 1st and 2nd week after obstruction and a significant difference (P less than 0.02) appeared in the 2nd week compared to the contralateral side, which was unchanged during the course of obstruction. Pelvic transit times increased steadily ipsilaterally during the course of obstruction and the opposite took place contralaterally. A fair correlation (r = 0.65) was found between parenchymal transit time and pelvic baseline pressure. Pelvic transit times were prolonged at any time after obstruction and significantly correlated to the presence of obstruction. The study suggests that interpretation of the obstructed renogram will encounter analysis of both parenchymal and pelvic transit times in cases where renal function is moderately reduced.

The personality pattern of duodenal ulcer patients in relation to spontaneous ulcer healing and relapse.

One hundred consecutive out-patients with duodenal ulceration from a hospital and a gastroenterological clinic were tested with the Minnesota Multiphasic Personality Inventory (MMPI). This was carried out in order to investigate whether neuroticism or other personality disorders were characteristics of duodenal ulcer patients, and whether the presence of such possible personality disorders might influence the prognosis of the disease. Neuroticism occurred in 53% of the patients, but only in 5% of controls (P less than 0.0001). Overall, personality disorders were present in 69% of the patients compared with 30% of the controls (P less than 0.0001). Neuroticism was connected with a high frequency of relapse (P less than 0.05) whereas failure of spontaneous ulcer healing had no certain relation to personality disorders. Patients with non-neurotic personality disorders had more frequently suffered stressful life events before entrance to the study (P less than 0.05) and, like the neurotic patients, they had lower ego-strength to cope with such events (P less than 0.05). The results indicate that personality assessments make it possible to distinguish between subgroups of duodenal ulcer patients with different course of the disease.

Plasma concentrations of pituitary and peripheral hormones during ranitidine treatment for two years in men with duodenal ulcer.

The effects of treatment for 2 years with the histamine H2-receptor antagonist ranitidine (100 or 200 mg b.d. for 6 weeks followed by 100 or 200 mg daily) on plasma concentrations of pituitary and peripheral hormones in ten men with duodenal ulcer have been investigated. Stimulation tests with TRH 200 micrograms i.v. and LHRH 100 micrograms i.v. were performed before, during (6 and 24 months), and at least 6 months after treatment. Basal and TRH-stimulated prolactin (PRL) secretion was marginally reduced after treatment for 6 months, but not for 24 months. The LH response to LHRH was slightly increased after treatment for 6 months and 24 months and after the end of treatment. The plasma concentrations of TSH, FSH, cortisol, androgenic hormones, and thyroid hormones did not change significantly during treatment. No adverse effects were reported during the observation period. The few, minor changes in pituitary hormone concentrations were all within the reference range. They may be related to ranitidine treatment, but are more likely to be due to age-dependent alterations in hormone secretion. It is concluded that long-term treatment with ranitidine does not cause major changes in circulating hormone concentrations.

Temporal responses of cutaneous blood flow and plasma catecholamine concentrations to histamine H1- or H2-receptor stimulation in man.

We have studied the effect of histamine and H1- or H2-receptor antagonists on cutaneous blood flow and catecholamine release in man. Histamine was infused alone or in combination with mepyramine, an H1-antagonist or cimetidine, an H2-antagonist for 2 h. Cutaneous blood flow was measured continuously with a laser Doppler flowmeter, and noradrenaline and adrenaline concentrations were determined in blood samples drawn every 15 min. The infusion of histamine caused an immediate and sustained vasodilatation. The Concomitant infusion of mepyramine prevented the immediate vasodilatation, but had no effect on the sustained response. The Concomitant infusion of cimetidine was without effect on the immediate vasodilatation, but abolished the sustained response. Infusion of the antagonists alone had no effect on cutaneous blood flow. Histamine caused a rapid and sustained increase in plasma noradrenaline, while the increase during concomitant H1-receptor blockade was delayed but achieved the level observed during the histamine infusion. The response to histamine during H2-receptor blockade was small and transient. The rise in plasma adrenaline was not significant. These findings suggest that histamine causes an immediate cutaneous vasodilatation through H1-receptors and a more sustained response through H2-receptors. The vasodilatation is accompanied by an increase in plasma catecholamine concentrations. Despite the continuous infusion of histamine, blood flow decreased during the last hour of histamine infusion, while the plasma noradrenaline concentration was still elevated.