A renewed insight into Barrett's esophagus: comparative histopathological analysis of esophageal columnar metaplasia.

Specialized intestinal metaplasia (SIM) is considered as a premalignant condition of the esophagus, but other types of esophageal metaplasia are commonly neglected. A standardized histopathological analysis was focused not only on SIM but also on the presence of metaplastic processes typical of additional glands. A morphological study using standardized histopathological tests was carried out between 2004 and 2007, with biopsies taken from esophageal mucosa of 826 consecutive patients. Mean age and male : female ratio of patients were 55.6 ± 14.7 and 1.1 : 1, respectively. Only 4.1% (n = 34) of all cases proved to have SIM. The remainder of the cases (n = 615; 74.4%) contained cardiac-fundic mucosa without SIM. Some samples exhibited superficial mucous glands, pancreatic acinar metaplasia (PAM), and ciliated metaplasia accounting for 24% (n = 198), 14.9% (n = 123), and 0.2% (n = 2), respectively. SIM was colocalized with superficial mucous glands (103/198 superficial mucous gland cases; P < 0.001). Low-grade dysplasia (n = 51; 6.2%) and high-grade dysplasia (n = 9; 1.1%) were found mainly in SIM (37/51; 9/9; P = 0.071) with male preponderance (3 : 1 at low-grade and 2 : 1 at high-grade dysplasia). PAM was found mainly in cases without dysplasia (103 of 123 pancreatic metaplasias; P < 0.001). SIM alone in the esophagus is rare, and its frequent association with cardiac mucosa-type metaplasia testifies to transition of mucinous-goblet cell through pseudogoblet cells. PAM rather indicates absence of dysplasia, but superficial mucous glands predicts that SIM follows dysplasia.

Detailed esophageal function and morphological analysis shows high prevalence of gastroesophageal reflux disease and Barrett's esophagus in patients with cervical inlet patch.

Although the pathogenesis of cervical inlet patch (CIP) is not fully understood, most authors consider it as a congenital abnormality, whereas others surmise it to be related to gastroesophageal reflux disease (GERD). We aimed to evaluate esophageal function and the prevalence of GERD and Barrett's esophagus in patients with CIP. GERD is defined by the presence of erosive esophagitis or an abnormal pH monitoring. Seventy-one consecutive patients with endoscopic and histological evidence of CIP were prospectively evaluated. Esophageal symptom analysis, 24-hour simultaneous biliary reflux and double-channel pH-monitoring, and esophageal manometry were carried out in 65/71 (92%) patients and in 25 matched controls. Six patients were not suitable for testing and were, therefore, excluded. The histological evaluation of the heterotopic islands showed cardia and/or oxyntic mucosa in 64/65 (98%) patients and specialized intestinal metaplasia (SIM) in one patient (2%). The cardia and/or oxyntic mucosa was accompanied by focally appearing pancreatic acinar metaplasia and pancreatic ductal metaplasia in 7/64 (11%) and in 1/64 (2%), superficial mucous glands in 6/64 (9%), and SIM in 2/64 (3%) cases. In total, SIM was present in three patients (5%), and one of them had low-grade dysplasia. At the gastroesophageal junction, 28 (43%) patients had columnar metaplasia, including nine (14%) patients with SIM. Erosive esophagitis was present in 37 (57%) cases. Thirty-two patients (49%) had abnormal acid reflux in the distal and 25 (38%) in the proximal esophagus. Abnormal biliary reflux was present in 25 (38%) cases. On the basis of endoscopic and pH studies, GERD was established in 44/65 (68%) patients. Typical reflux symptoms were common (33/65, 51%). The combined 24-hour biliary and double-channel pH-monitoring detected significantly more significant acidic reflux at both measurement points and significantly longer bile exposure time in the distal esophagus in patients with CIP. Acid secretion in the CIP was detected in three (5%) cases. Esophageal manometry revealed decreased LES pressure and prolonged relaxation with decreased peristaltic wave amplitude, and an increased number of simultaneous contractions in the esophageal body. The detailed evaluation of the esophageal morphology and function in subjects with CIP showed a high prevalence of GERD and Barrett's esophagus. Further studies are needed to evaluate whether combined acidic and biliary reflux is able to promote similar histomorphological changes in the CIP, as it is shown distally in patients with Barrett's esophagus.

Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity.

OBJECTIVES: Diarrhoea-predominant irritable bowel syndrome (IBS-D) is characterised by elevated colonic lumenal serine protease activity. The aims of this study were (1) to investigate the origin of this elevated serine protease activity, (2) to evaluate if it may be sufficient to trigger alterations in colonic paracellular permeability (CPP) and sensitivity, and (3) to examine the role of the proteinase-activated receptor-2 (PAR-2) activation and signalling cascade in this process. PATIENTS AND METHODS: Faecal enzymatic activities were assayed in healthy subjects and patients with IBS, ulcerative colitis and acute infectious diarrhoea. Following mucosal exposure to supernatants from control subjects and IBS-D patients, electromyographic response to colorectal balloon distension was recorded in wild-type and PAR-2(-/-) mice, and CPP was evaluated on colonic strips in Ussing chambers. Zonula occludens-1 (ZO-1) and phosphorylated myosin light chain were detected by immunohistochemistry. RESULTS: The threefold increase in faecal serine protease activity seen in IBS-D patients compared with constipation-predominant IBS (IBS-C) or infectious diarrhoea is of neither epithelial nor inflammatory cell origin, nor is it coupled with antiprotease activity of endogenous origin. Mucosal application of faecal supernatants from IBS-D patients in mice evoked allodynia and increased CPP by 92%, both of which effects were prevented by serine protease inhibitors and dependent on PAR-2 expression. In mice, colonic exposure to supernatants from IBS-D patients resulted in a rapid increase in the phosphorylation of myosin light chain and delayed redistribution of ZO-1 in colonocytes. CONCLUSIONS: Elevated colonic lumenal serine protease activity of IBS-D patients evokes a PAR-2-mediated colonic epithelial barrier dysfunction and subsequent allodynia in mice, suggesting a novel organic background in the pathogenesis of IBS.

Transforming growth factor beta regulates thyroid growth. Role in the pathogenesis of nontoxic goiter.

The production and growth regulatory activity of transforming growth factor beta were studied in human thyroid tissue. As estimated by its mRNA expression in fresh tissue samples, transforming growth factor beta was produced in normal and in diseased thyroid glands. Transforming growth factor beta mRNA was mainly produced by thyroid follicular cells and in lesser quantities by thyroid infiltrating mononuclear cells. The concentrations of transforming growth factor beta mRNA were lower in iodine-deficient nontoxic goiter than in Graves' disease and normal thyroid tissue. Transforming growth factor beta protein secretion by cultured thyroid follicular cells was also low in nontoxic goiter, but could be increased by addition of sodium iodide (10 microM) to the culture medium. Recombinant transforming growth factor beta did not affect basal tritiated thymidine incorporation in cultured thyroid follicular cells, but inhibited, at a concentration of 10 ng/ml, the growth stimulatory influence of insulin-like growth factor I, epidermal growth factor, transforming growth factor alpha, TSH, and partly that of normal human serum on cultured thyroid follicular cells. This inhibition was greater in Graves' disease than in nontoxic goiter. These results suggest that transforming growth factor beta may act as an autocrine growth inhibitor on thyroid follicular cells. Decreased transforming growth factor beta production and decreased responsiveness to transforming growth factor beta may be cofactors in the pathogenesis of iodine-deficient nontoxic goiter.

Colonic luminal proteases activate colonocyte proteinase-activated receptor-2 and regulate paracellular permeability in mice.

Luminal activation of protease-activated receptors-2 (PAR(2)) on colonocytes by trypsin or PAR(2)-activating peptide increases colonic paracellular permeability (CPP). The aim of this study was to evaluate the role of proteases from endogenous and bacterial origin in the modulation of CPP and colonocyte PAR(2) expression in mice. CPP was assessed with (51)Cr-EDTA after intracolonic administration of different protease inhibitors. After 12 days of oral antibiotic treatment, measurements of colonic luminal serine protease activity (CLSPA), CPP, mucosal mouse mast cell proteinase-1 (MMCP-1) content, immunochemistry of PAR(2) and assessment of effects of PAR(2) agonist (SLIGRL) and mast cell degranulator (C48/80) on CPP in Ussing chambers were performed. Immunochemistry was repeated after intracolonic trypsin administration. Colonic infusion of protease inhibitors significantly reduced CPP. In antibiotic-treated mice, CLSPA was reduced coupled with a decrease in PAR(2) expression, but with no change in CPP and MMCP-1 content. Trypsin administration restored PAR(2) expression. The increase in CPP induced by SLIGRL and C48/80 was reduced after antibiotic treatment. Protease activity of colonic content plays an important role in the regulation of mucosal barrier through activation of PAR(2).

Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients.

OBJECTIVE: Obesity is closely linked to the insulin resistance syndrome (IRS), type 2 diabetes, and cardiovascular disease, the primary cause of morbidity and mortality in these patients. Elevated levels of C-reactive protein (CRP) and interleukin-6 (IL-6), indicating chronic subclinical inflammation, have been associated with features of the IRS and incident cardiovascular disease. METHODS AND RESULTS: We studied the cross-sectional and longitudinal relation of CRP, IL-6, and tumor necrosis factor-alpha (TNF-alpha) with features of the IRS in 37 morbidly obese patients with different stages of glucose tolerance before and 14 months after gastric surgery. Weight loss after gastric surgery induced a significant shift from diabetes (37% vs 3%) to impaired glucose tolerance (40% vs 33%) and normal glucose tolerance (23% vs 64%). The baseline concentration of IL-6 was correlated with TNF-alpha (r=0.59, P<0.01) and CRP (r=0.44, P<0.05) levels. TNF-alpha, IL-6, and CRP were significantly correlated with insulin resistance estimated by the homeostatic model assessment (r=0.48, P<0.05; r=0.56, P<0.01; and r=0.35, P<0.05, respectively). Concentrations of CRP and IL-6 decreased after weight loss (median, 8.6 and interquartile range, 2.7/14.5 vs 2.5 and 1.2/4.1 mg/L; P<0.006, and 5.13 and 2.72/12.15 vs 3.95 and 1.97/5.64 pg/mL, P<0.02, respectively), whereas serum levels of TNF-alpha remained unchanged (8.6 and 6.3/18.8 vs 11.7 and 5.8/17.2 pg/mL; NS.). Multiple regression analysis revealed that the decrease in insulin resistance remained independently and significantly correlated with the decrease in IL-6 concentrations (P<0.01) and the decrease in body mass index with the decrease in CRP (P<0.05), respectively. CONCLUSIONS: Weight loss in morbidly obese patients induces a significant decrease of CRP and IL-6 concentrations in association with an improvement of the IRS.

Radiation of jejunal interposition in T3-T4 upper aerodigestive tumours.

30 patients with T3 and T4 tumours of the upper aerodigestive tract had their tumours resected by pharyngolaryngectomy. This was followed by reconstruction of a gullet or creation of a siphon as a tracheohypopharyngeal shunt for voice restoration with a free jejunal autograft. All patients were treated postoperatively with 60Co gamma radiation, 6 MeV photons or 7.5 to 10 MeV electrons of a beta-tron, with a dose of 50-65 Gy in the area of the primary tumour and 50-65 Gy to the neck. 4 patients refused further treatment after a depth dose of between 16 and 32 Gy. Local recurrence occurred in 40% of cases. The survival rate was 36.6% (11/30) after a mean follow-up time of 21.5 months, although 2 patients died of intercurrent diseases without recurrence of their tumours. The results obtained justify active surgical intervention with postoperative irradiation even at an advanced stage of the tumour.

Autotransplanted jejunum in patients with carcinomas of the head and neck: transport of immunosurveillance against tumor cells?

Autologous jejunum, transplanted as a functional replacement immediately after radical dissection of advanced stages of squamous cell carcinomas of the head and neck and subsequently irradiated, was examined by immunohistochemistry (APAAP/PAP-technique). Biopsies from 9 patients were taken at the time of transplantation and up to 24 months thereafter (group 1) and from 5 patients only once after transplantation (group 2). Twenty-six monoclonal antibodies (mAbs) were used as surface markers to give an overview about phenotypical changes with respect to T-, B- and M phi-antigens. 1) B cells: a general increase of CR2+ (CD21, p less than 0.01) could be noticed after transplantation, immunoglobulin positive cells remained unchanged expect for a significant decrease of IgM+ (p less than 0.01) and IgA1+ (p less than 0.01) cells. 2) The number of T cells (CD3+) showed no significant differences although TcR gamma/delta+ cells decreased (p less than 0.01) in the autotransplant. ICAM-1 (CD54) and IL-2R (CD25) were found on a significant (p less than 0.01) higher number of cells after transplantation. 3) Cells with M/M phi morphology showed increased expression of the Fc gamma receptors (CD64, p less than 0.001; CD32, n.s.; CD16, p less than 0.001), of the complement receptors CR1 (CD35, (p less than 0.001) and CR3 (CD11b, p less than 0.02), of HLA-DQ (p less than 0.01), and of the antigens 25F9 (mature M phi; p less than 0.01) and CD4 (p less than 0.02). Correlation analyses of data obtained from the biopsies of the 14 autotransplanted jejunum cases revealed a CD35+ and a 25F9+ subpopulation of M/M phi. Our findings indicate that despite irradiation autotransplanted jejunum contained cells with immunological capacities. Therefore, the replacement of larynx by autologous jejunum may facilitate not only mechanical but also immunological functions.

Dietary changes after vertical banded gastroplasty.

BACKGROUND: Gastric restriction surgery relies on obstruction to oral intake by formation of a gastric pouch. Therefore, the therapeutic effect is closely related to intolerance for different types of food, and an ingestion of an unbalanced diet. We investigated dietary changes after VBG and their associations with therapeutic success. METHODS: 70 patients (4 men, 66 women, median age 32) with a median preoperative BMI of 44.6 were examined > or =3 years after VBG. Weight reduction, nutritional changes (type of diet, number of daily meals, amount of food that could be ingested, intolerance for different types of food, frequency of vomiting), satisfaction with results, and willingness to undergo the operation once again were investigated. RESULTS: The average reduction of the BMI was 13, with sufficient weight loss in 80%. 36% were eating a solid, 43% a soft, and 21% a liquid diet. Weight reduction did not depend on the type of diet eaten but on the ingestion of sweets. 93% indicated they could take only small amounts of food. The average number of daily meals was 3.76% reported an intolerance for some type of food (most often meat, fruit, or vegetable). Vomiting was the most common problem and occurred in 71%. 71% indicated a high level of satisfaction with the results of the operation, and 96% said they would undergo the operation again. CONCLUSIONS: The investigation demonstrated successful weight reduction despite dietary changes in 80% of patients after VBG. Weight reduction was not influenced by type of, diet but depended on consumption of sweets.

Transsternal operations in thyroid cancer.

Large thyroid carcinomas extending into the anterior mediastinum were removed from six patients by a transsternal surgical approach (partial median sternotomy). Transcervical mediastinal dissection offers obscure exposure and therefore entails the risk of the operation not being radical. The transsternal procedure was used as an alternative to remove affected lymphatic and fatty tissue from an additional nine patients. Sternal metastases were extirpated from 10 patients. Irrespective of the stage of the tumor, the indications for a transsternal approach to onocologically radical extirpation of tumors and mediastinal lymphatic fatty tissue should be more liberal, particularly with differentiated and medullary thyroid carcinomas. The prognosis for differentiated carcinomas is improved by radioiodine treatment, and optimal conditions for this therapy are ensured by the most radical possible removal of the tumor with its affected lymph nodes and sternal metastases. In the case of mixed differentiated/anaplastic and medullary carcinomas, this operative procedure ensures favorable conditions for other adjuvant forms of therapy. Although it was not possible to extend the life expectancy of patients suffering from anaplastic carcinomas, their quality of life was at least improved by the prevention of mechanical dyspnea caused by the mediastinal tumor.

Early relapse after operation for Graves' disease: postoperative hormone kinetics and outcome after subtotal, near-total, and total thyroidectomy.

BACKGROUND: The relative merit of operation in the treatment of Graves' disease has been questioned, and the extent of surgical resection is still a matter of debate. METHODS: We have analyzed retrospectively the incidence of recurrent hyperthyroidism (frequency and time point) in 215 consecutive patients subjected sequentially to subtotal thyroidectomy (n = 63; remnant mass 6 to 8 g, based on surgeons' estimates and dimensions measured during operation), extensive subtotal thyroidectomy (n = 106; remnant mass approximately 4 g), and near-total (n = 27; unilateral capsular remnant of < 2 g) or total thyroidectomy (n = 19). In addition, we have evaluated the postoperative kinetics of thyroid hormone elimination (free triiodothyronine and free thyroxine) in 14 selected patients with hyperthyroidism who underwent operation under beta-adrenergic blockade but without any thyrostatic pretreatment. RESULTS: The size of the remnant significantly (P < .05) affected the relapse rate (23.8%, 9.4%, and 0% in subtotal, extensive subtotal, and near-total/total thyroidectomy, respectively). However, the time point at which the relapse occurred did not differ in subtotal and extensive subtotal thyroidectomy. All relapses occurred within the first 70 weeks. The incidence of complications (permanent recurrent nerve paresis and persistent hypocalcemia) was comparable in all groups. The elimination of fT3 was biphasic and rapid such that the levels were within the normal range on the second day. In contrast, 15 days were required until the fT4 level had declined below the upper limit in all patients. CONCLUSIONS: We propose that the therapeutic goal in thyroid operations is to avoid recurrent hyperthyroidism. This is not reliably achieved by subtotal thyroidectomy; in contrast, near-total and total thyroidectomy are effective and safe. On the basis of the postoperative elimination kinetics, hormone replacement is to be instituted within 2 weeks after operation.

Thyroid surgery in untreated severe hyperthyroidism: perioperative kinetics of free thyroid hormones in the glandular venous effluent and peripheral blood.

BACKGROUND AND METHODS: It is generally believed that thyroid surgery in Graves' disease requires a euthyroid state to avoid thyrotoxic reactions. We carried out a prospective study on 23 patients who had severe hyperthyroidism with free thyroid hormone concentrations (fT3 or fT4) exceeding the upper normal boundary by 300% or more and who were not pretreated with thyrostatic agents. We determined hormone levels during operation in the thyroid venous effluent before and after surgical trauma and monitored their postoperative elimination kinetics. RESULTS: The concentration of fT3 and fT4 in the venous effluent of the hyperactive gland did not exceed the peripheral levels. Surgery did not induce any intraoperative or postoperative increase in fT4 or fT3, whereas thyroglobulin concentrations rose sharply. Both fT4 and fT3 followed biphasic elimination kinetics, and a significant decline of circulating free hormone concentrations was measurable within the first postoperative hour. CONCLUSIONS: Contrary to widely held assumptions, the surgical trauma does not stimulate the release of thyroid hormones. Hence this mechanism cannot account for the postoperative development of thyroid storm. Our observations imply that immediate operation should generally be considered for the emergency treatment of an imminent thyroid storm.

Morphologic and functional studies to prevent graft-dependent recurrence in renal osteodystrophy.

The cross sections of hyperplastic glands removed during total parathyroidectomy in patients with renal osteodystrophy were classified on the basis of macroscopic and functional criteria. Diffuse (type 1) and nodular (type 2) glands could be distinguished macroscopically. Functional in vitro studies showed no significant difference in suppressibility and basal parathyroid hormone (PTH) secretion (61% and 74%, respectively). In both types of glands A, B, C, and D regions could be distinguished with use of a stereo magnifier (magnification, x10 to x16). In diffuse A regions containing stroma fat cells, PTH secretion could be suppressed optimally (more than 50% of maximum secretion) in more than 90% of all specimens in vitro. In diffuse B regions containing no fat cells, hormonal secretion could be suppressed in only 17% and 25%, respectively. Confined (oxyphilic or chief cell) nodules (C regions), only found in type 2 glands, could be suppressed in 18%. Nodules of "degenerating" oxyphilic cells (D regions), only found in type 2 glands, were suppressible, but the low PTH secretion indicated degenerative processes. Thus only fragments from A regions should be selected for autotransplantation.

Reoperation as treatment of relapse after subtotal thyroidectomy in Graves' disease.

BACKGROUND AND METHODS: In Graves' disease radioiodine is the recommended treatment for relapses after subtotal thyroidectomy. If patients reject radioiodine, hyperthyroidism is managed with antithyroid drugs; surgery is generally not considered as an alternative. Here we retrospectively analyzed 30 consecutive patients with Graves' disease who had recurrent hyperthyroidism after subtotal thyroidectomy. RESULTS: On relapse after the first operation, the patients were initially treated by medication; 25 opted for definitive treatment (19 for reoperation and 6 for radioiodine). Operations consisted of 10 unilateral and 8 bilateral resections (total or near-total with capsular remnants of < 1 g) and 1 transsternal approach (because of dystopic intrathoracic thyroid tissue). The decision between a unilateral and a bilateral reintervention was based on the ultrasonographic determination of remnant volumes. These size estimates were valid because they were significantly correlated to the weight of the resected remnants (r = 0.92, slope = 0.95). Eighteen of the 19 patients were adequately treated by this approach. Unilateral resection was performed in 1 patient with a remaining contralateral remnant of 5.4 mL; this patient had a second relapse. The complication rate was low (2 cases of transient recurrent nerve injury and 1 of transient hypocalcemia). CONCLUSION: Provided that no contraindication is present, reoperation is safe, effective, and expeditious in recurrent hyperthyroidism. Because the likelihood of a recurrence depends on the total remnant size, the goal is to keep it below 2 g. Preoperative ultrasonography can effectively guide the decision between a unilateral and a bilateral resection.

Surgical treatment of distant metastases in differentiated thyroid cancer: indication and results.

A total of 45 patients have received surgical treatment for distant metastases in 41 follicular and four papillary carcinomas. Fifty-four metastatic lesions were removed. In the majority of cases (n = 25, 46%), surgical intervention was indicated on the basis of oncologic data (reduced administration of radioiodine). Sixteen patients (30%) underwent surgery to relieve pain, and 13 other patients (24%) had surgical treatment of pathologic fracture. At the time of surgery, 29 patients (64%) had only one resectable metastasis, while 16 patients (36%) had further nonresectable metastases (six in the bone, 10 in the bones and lungs). In the course of 53 operations, metastases were resected from bone in 46 cases, from the lungs and greater omentum in two cases, and from the skin, suprarenal gland, pleura, and intra-abdominal lymph node in one case each. A total of 25 metastases (17 bone, eight soft tissue) could be removed by resection. In 16 patients, the resulting bone defect was filled with bone cement after resection of the metastases. Osteosynthesis was necessary in another six cases, while seven required the implantation of an endoprosthesis. Thirty-eight patients died between 1 and 136 months after surgical treatment. Twenty-six (58%) died of their primary disease after an average 49.3 months, seven (15%) died with their carcinomas of other causes after an average of 12 months, and five (11%) died intercurrently after an average of 16 months. Seven patients (15%) are still alive after 12 to 264 months (average, 99.3 months); four of them are without recurrence and three have metastases. Five of these patients exhibit normal activity, while the activity of the other two is limited by the progress of the carcinoma or as a result of surgical treatment. The estimated cumulative survival rate (Kaplan-Meier) was 44.8 +/- 11.2% for 5 years and 32.7 +/- 11.0% for 10 years after removal of a solitary metastasis. Analysis of these patients shows that the surgical removal of resectable metastases can be a valuable complement to nuclear medical therapy. The complicated surgical treatment of metastases is justified by the favorable effect it has on prognosis and on the patient's quality of life.

Successful parathyroidectomy in primary hyperparathyroidism: a clinical follow-up study of 212 consecutive patients.

The long-term clinical courses of 212 "cured" (normocalcemic) patients were analyzed for 1 to 25 years (mean, 6.8 +/- 5.4 years). Preoperatively, 181 patients (85%) were classified as having typical symptoms, 22 patients (11%) as having minimal symptoms, and nine patients (4%) as having no symptoms of primary hyperparathyroidism (PHP). Although the formation of urinary calculi was stopped in 91% of patients, deteriorated renal function and hypertension were seen in patients with symptoms (14% and 8%, respectively) and patients with minimal symptoms of PHP (6% and 15%, respectively). Renal function changes and hypertension were unpredictable despite normalization of the hyperactive parathyroid metabolism and had decisive results: 7% of the patients died of uremia or of the consequences of hypertension (stroke). Large, multiple bone lesions healed functionally and were of no prognostic significance. In the majority of patients with symptoms of PHP, gastrointestinal manifestations healed postoperatively, but two patients who had no preoperative gastrointestinal complaints died of acute pancreatitis. Almost all symptoms of the hypercalcemia syndrome disappeared immediately and permanently in patients with symptoms and patients with minimal symptoms of PHP. Neither deterioration of renal function nor elevation of blood pressure were observed postoperatively in "cured" patients who showed no symptoms of PHP preoperatively. Even in these patients, immediate surgical treatment may have avoided the complications of chronic renal failure or hypertension. As soon as organic manifestations, even in mild form, have been established, it seems impossible to predict the course and to prevent an unfavorable clinical outcome.

Cardiac calcific deposits in patients with primary hyperparathyroidism: preliminary results of a prospective echocardiographic study.

To explain the incidence and significance of mitral and aortic valve calcification and calcific deposits in the myocardium, a prospective echocardiographic study was performed with 21 consecutive patients who had primary hyperparathyroidism (PHP) and with 21 age- and sex-matched control subjects with normocalcemia. Calcific deposits in the myocardium were seen in 13 patients (62%) with PHP, mainly in the interventicular septum, and in one control subject. Aortic valve calcification was observed in 12 patients (57%) with PHP and in one control subject. Calcification of the mitral valve was found in seven patients with PHP (33%) and three controls (14%). Calcification led to mild or moderate stenosis of the aortic valve in three patients with PHP and of the mitral valve in two patients with PHP. No stenosis was found in the subjects in the control group. Both calcification of the aortic and mitral valves and calcific deposits in the myocardium are common in patients with PHP and can be detected noninvasively by echocardiography. Because of the potential relationship of elevated calcium, calcification, and valvular heart disease, clinical evaluation of PHP should include echocardiographic studies before surgery is performed and during follow-up examination.