Synchronous thyroid cancer on the edge: Incidentalomas of 18F-FDG PET/CT in clinical practice.

AIMS: The objective of this study was to discuss the outcomes of the oncology patients whose PET/CT scans show incidental focal thyroid 18F-FDG uptake. METHODS: This retrospective analysis examined 2575 18F-FDG PET/CT scans from 1803 patients with no known thyroid cancer history. The survival rates were analyzed for patients with and without cytopathological evaluation. RESULTS: Increased metabolic activity of the thyroid was detected in 96 patients. Of those, 72 were diagnosed with a focal uptake of 18F-FDG and 24 subjects had a diffuse uptake. All 72 patients with a focal uptake were referred for ultrasound (US) and fine-needle aspiration cytology (FNAC). Of those patients, 44 were admitted for US and 16 underwent FNAC. The mean SUVmax was 16.0 ± 7.97 for patients with malignant lesions and 3.24 ± 0.88 for patients with benign lesions (p = 0.023). The mortality rate was higher in the patients who were not evaluated with FNAC. CONCLUSION: Patients with incidental focally increased thyroid 18F-FDG accumulation on PET/CT are known to have a high risk of malignancy. These patients require additional diagnostic procedures to distinguish the underlying pathology. However, the clinical condition of these patients will be the primary concern when performing these procedures.

Oxidative stress status in congenital hypogonadism: an appraisal.

Patients with hypogonadism are at increased risk of cardiac and metabolic diseases. However, the pathogenesis of increased cardiometabolic risk in patients with hypogonadism is not clear. Oxidative stress plays an important role in the pathogenesis of cardiometabolic diseases. This study aimed to investigate possible differences in oxidative stress conditions between patients with hypogonadism and healthy controls. In this study, 38 male patients with congenital hypogonadotropic hypogonadism (CHH) (mean age: 21.7 ± 1.6 years) and 44 healthy male controls (mean age: 22.3 ± 1.4 years) with almost equal body mass index were enrolled. The demographic parameters, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total and free testosterone, homeostatic model assessment of insulin resistance (HOMA-IR) and oxidative stress parameters, such as superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA), were compared between both groups. Compared to the healthy controls, triglycerides (p = .02), insulin levels, HOMA-IR values, CAT activities and MDA levels (p < .001 for all) were significantly higher and HDL cholesterol (p = .04), total and free testosterone, FSH, LH levels and GPx activity were significantly lower (p < .001 for all) in patients with CHH. There were significant correlations between total testosterone levels and CAT activity (r = -.33 p = .01), GPx activity (r = .36 p = .007) and MDA (r = -.47 p < .001) levels. The results of this study showed that young and treatment-naïve patients with congenital hypogonadism had an increased status of oxidative stress.

An unusual presentation of primary hyperparathyroidism: multiple brown tumors and coexisting thyroid carcinoma / Presentación inusual de hiperparatiroidismo primario: múltiples tumores pardos y coexistencia de carcinoma tiroideo

We present a patient with a complex clinical picture of primary hyperparathyroidism with multiple destructive skeletal lesions suspicious of bone metastases and concomitant multifocal papillary thyroid carcinoma with a metastatic central lymph node. He presented with progressively worsening right hip pain and restricted motion. Magnetic resonance imaging revealed multiple lytic lesions involving predominantly the right trochanter minor and the left inferior and posterior pubic rami. Biochemical tests were consistent with primary hyperparathyroidism. Neck ultrasound and parathyroid scintigraphy revealed a single parathyroid adenoma and a thyroid nodule, preoperative cytology of which confirmed papillary thyroid carcinoma, as did the final surgical specimen. Biochemical results, regarding hyperparathyroidism, declined to normal levels and his complaints gradually decreased after surgery. Postoperative whole body bone scintigraphy showed increased tracer uptakes at multiple sites, but they were proved to be metabolically inactive by fluorodeoxyglucose positron emission tomography/computed tomography (AU)

Presentamos el caso de un paciente con un cuadro clínico de hiperparatiroidismo primario, con muchas lesiones óseas destructivas sospechosas de metástasis óseas y carcinoma tiroideo multifocal concomitante con un ganglio linfático metastásico central. Se presentó con agravamiento progresivo de dolor y restricción de movimiento en la cadera derecha. La resonancia magnética reveló múltiples lesiones líticas que implicaban principalmente al trocánter menor derecho y a las ramas púbicas izquierdas inferior y posterior. Las pruebas bioquímicas fueron consistentes con un hiperparatiroidismo primario. La ecografía cervical y la gammagrafía paratiroidea revelaron un único adenoma paratiroideo y un nódulo tiroideo, cuya citología preoperatoria confirmó un carcinoma papilar de tiroides, que fue confirmado también por la muestra final obtenida quirúrgicamente. Los resultados bioquímicos, en relación con el hiperparatiroidismo, descendieron a niveles normales tras la cirugía, y los dolores fueron remitiendo gradualmente. La gammagrafía ósea postoperatoria de cuerpo entero reflejó un incremento de captación del radiotrazador en múltiples localizaciones, que resultaron ser metabólicamente inactivas en la tomografía por emisión de positrones con fluorodesoxiglucosa/tomografía computarizada (AU)

Two-dimensional speckle tracking echocardiography is useful in early detection of left ventricular impairment in patients with Crohn's disease.

OBJECTIVE: Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract. Cardiac involvement is considered very rare. Pericarditis, myocarditis, endocarditis, cardiomyopathy and complete heart block are some of the cardiac extraintestinal manifestations of CD. The aim of this study was to explore the left ventricular (LV) functions with two-dimensional (2D) speckle tracking echocardiography (STE) in patients with CD with normal cardiac functions. PATIENTS AND METHODS: We enrolled 50 consecutive patients with CD and 50 age and sex matched healthy controls. All patients underwent a transthoracic echocardiogram with evaluation of LV functions with 2D STE. RESULTS: Baseline characteristics were similar between patients with CD (24 male, mean age: 41.0 ± 13.9 years) and controls (24 male, mean age: 40.1 ± 7.3 years). Although conventional echocardiographic parameters were similar between two groups, global longitudinal strain was significantly lower in patients with CD compared to controls (19.6 ± 3.3 versus 21.2 ± 2.9, p = 0.014). Correlation analysis revealed that Crohn's Disease Activity Index is inversely correlated with LV global longitudinal strain (r = -0.703, p < 0.001) in patients with CD. We also evaluated inflammatory parameters such as CRP, erythrocyte sedimentation rate, and complete blood counts in patients with CD. Correlation analysis revealed that only platelet value is weakly correlated with Crohn's Disease Activity Index (r = 0.311, p = 0.083). CONCLUSIONS: Crohn's disease is associated with impairment in LV global longitudinal myocardial function. Crohn's Disease Activity Index is also strongly correlated with LV global longitudinal strain. 2D-STE may be an useful method for early detection of LV impairment in patients with CD.

An unusual presentation of primary hyperparathyroidism: multiple brown tumors and coexisting thyroid carcinoma.

We present a patient with a complex clinical picture of primary hyperparathyroidism with multiple destructive skeletal lesions suspicious of bone metastases and concomitant multifocal papillary thyroid carcinoma with a metastatic central lymph node. He presented with progressively worsening right hip pain and restricted motion. Magnetic resonance imaging revealed multiple lytic lesions involving predominantly the right trochanter minor and the left inferior and posterior pubic rami. Biochemical tests were consistent with primary hyperparathyroidism. Neck ultrasound and parathyroid scintigraphy revealed a single parathyroid adenoma and a thyroid nodule, preoperative cytology of which confirmed papillary thyroid carcinoma, as did the final surgical specimen. Biochemical results, regarding hyperparathyroidism, declined to normal levels and his complaints gradually decreased after surgery. Postoperative whole body bone scintigraphy showed increased tracer uptakes at multiple sites, but they were proved to be metabolically inactive by fluorodeoxyglucose positron emission tomography/computed tomography.

Trace Element Levels in Congenital Hypogonadotrophic Hypogonadism.

Cardiometabolic diseases are prevalent in hypogonadism. The pathophysiologic mechanism of increased cardiometabolic risk in hypogonadal patients is not clear. Recently, trace elements have been linked to the development of chronic disease especially cardiovascular disease. We investigated the trace element levels in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and also searched for the relationship with metabolic risk factors. A total of 89 patients with CHH (mean age 21.8 ± 2.0 years) and 80 healthy control subjects (mean age 21.3 ± 1.1 years) were enrolled. The demographic parameters, homeostatic model assessment of insulin resistance (HOMA-IR) levels and plasma zinc, copper, and selenium levels, were measured in patients and healthy controls. The patients had higher waist circumferences (p = 0.014), triglyceride (p = 0.04), insulin (p = 0.004), HOMA-IR levels (p = 0.001), and lower selenium (p = 0.049), zinc (p = 0.004), and copper (p = 0.012) levels when compared to the healthy controls. There was a significant relationship between zinc levels and HOMA-IR levels (p = 0.015). In the regression analysis, zinc levels were independently associated with the calculated HOMA-IR levels (p = 0.015). The results of the present study show that plasma selenium, zinc, and copper levels are decreased in patients with CHH. Also, plasma zinc levels are independently associated with insulin resistance in patients with hypogonadism. Long-term follow-up studies are warranted to investigate the effect of trace elements on the increased cardiometabolic risk in hypogonadism.

A Very Rare Case -  Hairy Cell Leukemia in Patient with Sarcoidosis.

Although the coexistence of hairy cell leukemia with sarcoidosis has been reported in a few cases in the literature, in our case the patient had been diagnosed and followed about 10 years with sarcoidosis and massive splenomegaly. It has been demonstrated that T helper 1 cells exist in organs influenced by sarcoidosis. These cells produce IL-2 and IFN-γ and induce a nonspecific inflammatory response and granuloma formation. Also these cytokines may play a role in the development of hairy cell leukemia.Key words: hairy cell leukemia -  sarcoidosis - massive splenomegaly.

Evaluation of the response to treatment of psoriasis vulgaris with reflectance confocal microscopy.

BACKGROUND/OBJECTIVE: Reflectance confocal microscopy (RCM) is a noninvasive, objective imaging technique that provides in vivo, high-resolution skin imaging. We sought to assess epidermal and dermal changes associated with the psoriasis and its treatment with RCM before the treatment and at weeks 4 and 8 of the treatment. MATERIAL AND METHODS: This is an investigator-blinded, internal-controlled, follow-up study. A total of 25 patients with plaque psoriasis were included in the study. The RCM evaluation criteria were defined on the basis of the histopathological diagnostic criteria for psoriasis. The clinical severity of the psoriasis was evaluated using the Psoriasis Area Severity Index (PASI). RESULTS: The RCM findings which were correlated with the PASI can be used to follow up the patient's response to treatment have been identified as follows: the acanthosis, the number of spongiotic sites, the number of regular/irregular honeycomb-like sites, the number of epidermal inflammatory cells, the number of focal microabscesses, the total epidermal thickness, the number of nonedge dermal papillae, the length of the papillary dermis, the number of dermal inflammatory cells, and the vascularization in the papillary dermis (P < 0.05). CONCLUSION: This is the first study with a large group of patients to perform a noninvasive assessment with RCM of the response of psoriasis to different treatments: phototherapy, systemic and topical treatment. Micrometric and morphometric changes occurring in the psoriatic tissue during the 8-week treatment period were identified by in vivo RCM in a noninvasive manner. RCM is capable of monitoring of treatment response in psoriasis.

Predictive value of plasma asymmetric dimethylarginine, homocysteine, and high-sensitive CRP levels in occult coronary artery disease: A multidetector-row computed tomography study.

BACKGROUND: Multidetector-row computed tomography (MDCT) is an attractive noninvasive imaging modality for detecting coronary atherosclerotic plaques, which may be underestimated by conventional angiography. The aim of our study was to determine the predictive value of plasma asymmetric dimethylarginine (ADMA), homocysteine, and high-sensitivity C-reactive protein (hsCRP) levels for occult coronary artery disease (CAD). PATIENTS AND METHODS: Thirty-five patients with angiographically normal coronary arteries (NCA) were consecutively included in our study. They underwent MDCT including indications and were divided into an NCA group (18 subjects, 8 male, 46 ± 8 years) and an occult CAD group (17 subjects, 11 male, 48 ± 9 years), with respect to the presence of coronary plaque. Plasma ADMA, homocysteine, and hsCRP levels were measured in blood samples. RESULTS: Plasma ADMA and homocysteine levels of the occult CAD group were significantly higher than those of the NCA group. A nonsignificant trend was observed for higher serum hsCRP levels in the occult CAD group. Receiver operating characteristics analysis revealed that an ADMA level of > 0.71 µmol/l could predict patients with occult CAD (sensitivity, 76 %; specificity, 67 %). The discriminative power of ADMA in distinguishing the occult CAD group from the NCA group was high (area under the curve, 0.80; CI, 0.66-0.95, p = 0.002), while it was not sufficiently high for homocysteine and hsCRP (p > 0.05). CONCLUSION: Plasma ADMA is a useful parameter for predicting subclinical atherosclerosis, whereas homocysteine and hsCRP are not, and it may be complementary to the conventional cardiovascular risk factors for the selection of individuals at high risk for CAD before undertaking MDCT procedures in clinical practice.

Right ventricular and atrial functions in systemic sclerosis patients without pulmonary hypertension. Speckle-tracking echocardiographic study.

BACKGROUND: Systemic sclerosis (SSc) is a systemic connective tissue disease and cardiac involvement is one of the most important causes of death. Right ventricular (RV) systolic dysfunction is a poor prognostic finding in SSc patients. Assessment of RV function has some difficulties because of its crescent shape and extensive trabeculations. Two-dimensional (2D) speckle-tracking echocardiography (STE) is an angle-independent quantitative technique to evaluate myocardial function. The aim of this study was to assess the RV and right atrial (RA) functions of SSc patients without pulmonary hypertension by using 2D STE. PATIENTS AND METHODS: A total of 40 patients with SSc (mean age 48.5 ± 11.4 years, 28 female) and 40 healthy volunteers (mean age 45.9 ± 7.6 years, 21 female) were included in the study. All subjects underwent transthoracic echocardiography for evaluation of RV and RA functions with 2D STE. RESULTS: Although left ventricular systolic and diastolic functions, systolic pulmonary artery pressure (PAP), and RA measurements were similar in both groups, tricuspid annular plane systolic excursion (TAPSE) and maximum systolic myocardial velocity (S') were decreased in SSc patients. The RV free wall global longitudinal strain (GLS) of SSc patients was lower than the controls (- 18.5 ± 4.9 % vs. - 21.8 ± 2.4 %, p < 0.001) and the RA reservoir and conduit functions were also decreased in SSc patients compared with controls (34.4 ± 9.9 % vs. 39.7 ± 11.2 %, p = 0.027 and 15.0 ± 5.7 % vs. 18.7 ± 6.4 %, p = 0.009, respectively). Disease duration was inversely correlated with RVGLS and TAPSE (r: - 0.416, p = 0.018 and r: - 0.383, p = 0.031, respectively). CONCLUSION: The use of 2D STE can be helpful in the detection of impairment in RV and RA functions in SSc patients with normal PAP.

Osteoprotegerin, fibroblast growth factor 23, and vitamin D3 levels in male patients with hypogonadism.

Cardiometabolic disorders and osteoporosis are prevalent in patients with hypogonadism. Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF-23), are co-secreted from bones and vascular endothelium, regulating bone mineral metabolism and vascular functions. Vitamin D is another hormone with dual effects on bone and vascular metabolism. The aim of this study was to search for any difference between the serum levels of OPG, FGF-23, and vitamin D in patients with hypogonadism and the healthy controls. We also aimed to search for any relationship between these parameters and endothelial dysfunction or insulin resistance. Forty-nine male patients with congenital hypogonadotropic hypogonadism (CHH) (mean age 20.71 ± 1.75 years) and 43 BMI matched healthy male subjects (mean age 21.37 ± 1.04 years) were enrolled. OPG, FGF-23, vitamin D, and asymmetric dimethylarginine (ADMA) levels were measured from the fasting serum samples. The insulin sensitivity was estimated by homeostatic model assessment-insulin resistance (HOMA-IR) formula. Triglycerides, insulin, HOMA-IR, and ADMA levels in the patient group were significantly higher than the values of the control group (p = 0.014, p = 0.002, p = 0.003, p < 0.001, respectively). The OPG, FGF-23, and vitamin D levels of the patients were not significantly different from the healthy controls. In addition, these markers were not correlated to ADMA or HOMA-IR levels. The results show that young and treatment naive subjects with CHH have endothelial dysfunction and insulin resistance when compared to their healthy counterparts. However, the OPG, FGF-23, and vitamin D levels were similar in the 2 groups. In addition, these parameters are not significantly related to the endothelial functions or insulin resistance in these subjects.

HDL cholesterol subfractions and the effect of testosterone replacement in hypogonadism.

Metabolic disorders and cardiovascular events are increased in hypogonadism. Serum HDL composition is a better cardiovascular predictor than the HDL counts. However, there is no information about the HDL subfractions in patients with hypogonadism. We designed a prospective study to investigate the HDL subfractions in treatment naïve subjects with hypogonadism and the effects of 2 different testosterone replacement regimens on the HDL subfractions. Seventy young male patients with congenital hypogonadotropic hypogonadism (CHH) and 70 age and BMI-matched healthy males were enrolled in the present study. The patients were assigned to receive intramuscular injections of testosterone esters 250 mg every 3 weeks and transdermal testosterone applications 50 mg daily. Biochemical investigations including HDL subfractions and insulin resistance were done. Patients with CHH had higher levels of insulin, HOMA-IR, WC, triglyceride, and diastolic blood pressure. Although, the HDL cholesterol concentrations were similar in both groups, hypogonadal patients had lower HDL2 and higher HDL3 levels. The total testosterone levels were independent determinants of the HDL2 subfractions. During the follow-up, a significant increase in the BMI and WC values and a significant decrease in the levels of total cholesterol, HDL cholesterol, and HDL3 were observed. No difference was present between the 2 treatment arms. These results show that patients with hypogonadism have unfavorable HDL compositions in addition to the other dysmetabolic features. However, testosterone replacement for about six months neither improves the metabolic problems nor the HDL composition. Mechanistic studies are warranted to better understand the cardiovascular effects of unfavorable HDL compositions in hypogonadism.

Women with polycystic ovary syndrome have increased plasma chitotriosidase activity: a pathophysiological link between inflammation and impaired insulin sensitivity?

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low grade inflammation has been reported to participate in the pathogenesis of insulin resistance. Chitotriosidase (ChT), a protein secreted by activated macrophages, has been shown to be involved in chronic inflammatory responses. In the present study, serum chitotriosidase activity and its relationship with insulin resistance were determined in patients with PCOS.34 patients with PCOS and 44 age and body mass index (BMI) matched healthy controls were enrolled in the study. ChT activity was measured by the fluorescence method. High sensitivity C reactive protein (hs-CRP) and adiponectin levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula.Plasma ChT activity, hs-CRP level and HOMA-IR score were significantly higher (p=0.024, p=0.002, p=0.001, respectively) while plasma adiponectin concentration was significantly lower (p=0.018) in women with PCOS compared to healthy controls. Blood ChT activity correlated positively with age, waist-to-hip ratio (WHR), BMI, hs-CRP, HOMA-IR and negatively with blood adiponectin level. After adjustment for age and BMI, ChT activity, total testosterone level and WHR remained as the independent predictors of HOMA-IR score in logistic regression analysis.ChT activity is increased in patients with PCOS in concordance with insulin resistance. These findings may reflect the pronounced risk for metabolic syndrome and atherosclerotic diseases in this particular patient group.

The role of visfatin in the pathogenesis of gestational diabetes mellitus.

AIM: The objective of the present study was to evaluate the role of visfatin in gestational diabetes mellitus. MATERIALS AND METHODS: Forty-five pregnant women at 24 to 28 weeks' gestation were assigned to consume an initial screening test using a 1-h 50-g glucose load, and then a 3-h 100-g glucose load. The study group consisted of 23 patients who were diagnosed with gestational diabetes mellitus and the control group consisted of 22 healthy pregnant women. We studied the levels of visfatin and the other parameters of inflammation, glucose and lipid metabolism between the 24th and 28th week of gestation and also between the 6th and 10th week after delivery. RESULTS: Plasma visfatin and glucose levels at 60 min after a 50-g and a 100-g glucose load between the 24th and 28th week of gestation were significantly higher in the gestational diabetes group than in the control group. There were no statistical differences in visfatin levels between the groups at 6-10 weeks post-partum. CONCLUSION: Visfatin levels were significantly elevated in women with gestational diabetes mellitus and during the course of pregnancy and increased visfatin concentrations were reduced within 6 to 10 weeks after delivery.

Assessment of QT interval duration and dispersion in athlete's heart.

An athlete's heart is characterized by morphological and functional changes occurring as a consequence of regular physical exercise. We sought to determine if these physiological changes lead to ventricular repolarization abnormalities in trained athletes. Forty-four trained athletes and 35 sex- and age-matched healthy sedentary controls were included in the study. A 12-lead surface electrocardiogram (ECG) was obtained from all participants. Maximum QT (QTmax) and minimum QT (QTmin) interval durations, QT dispersion (QTd) and corrected QT dispersion (QTcd) were calculated for each ECG record. Heart rate, systolic and diastolic blood pressure values were found to be identical in both groups. QTmax and QTmin interval durations were not statistically different between the athletic and control groups. Similarly, QTd and QTcd did not differ significantly between the two groups. No association was observed between an athlete's heart and ventricular heterogeneity compared with healthy sedentary controls, despite physiological and structural changes.

Primary cardiac angiosarcoma.

Primary malignant cardiac tumors are extremely rare neoplasms. About three-quarters of all cardiac tumors are histologically benign. A 24-year-old man presented to the hospital with dyspnea and chest pain. A solid, dense, nonhomogeneous and rough-surfaced mass (89 x 90 x 36 mm) with protrusion into the right heart cavities was observed on transthoracic echocardiography. The findings were confirmed by transesophageal echocardiography and magnetic resonance imaging. The histopathology of the mass confirmed a diagnosis of angiosarcoma. No evidence of an extracardiac origin of the tumor was found by radiological body imaging. The patient died 2 months after presentation to the hospital.

Paravalvular leakage after mitral valve replacement: is left atrial enlargement an additional indication for reoperation?

BACKGROUND AND AIM OF THE STUDY: Prostheses used to treat heart valve disease improve patient survival, but have certain disadvantages. Paravalvular leakage (PVL) is a rare complication after mitral valve replacement (MVR), and can impair cardiac function and reduce the patient's functional capacity, depending on the degree of periprosthetic regurgitation. METHODS: Between 1985 and July 1999, 2,502 patients underwent MVR with or without concomitant cardiac procedures. Of these patients, 33 (18 males, 15 females; mean age 39.8+/-15.3 years; range: 12-62 years) had PVL of differing degree. The interval between MVR and observation of PVL was 30.5+/-31.5 months (range: 1-126 months), and the period after diagnosis was 22.6+/-31.5 months (range: 2-114 months). Fourteen patients (42.4%) underwent reoperation (RO group), and 19 (57.6%) were followed medically (ME group). Indications for reoperation were reduction of functional capacity, echocardiographically proven serious mitral regurgitation, and hemolysis. RESULTS: Reoperative mortality was 3.0% (1/33), and late mortality 3.1% (1/32) for all patients. Cumulative survival after PVL was 90.2+/-6.7% at both five and ten years. Annular calcification (33.0%) and infective endocarditis (18.2%) were important predictive factors for development of PVL. Only one patient required second re-do surgery. Univariate and forward stepwise logistic regression analyses showed that there was no predictor for the development of severe PVL requiring a second reoperation. No difference was observed between left ventricular dimensions before and after periprosthetic regurgitation. The only significant finding between groups was an increase in left atrial diameter in RO patients after the development of PVL (p <0.05). CONCLUSION: Among patients undergoing MVR there are no clinical features to distinguish who will develop severe PVL during follow up. If PVL reduces the patient's functional capacity or causes serious hemolysis, or if severe PVL is evaluated echocardiographically, then reoperation must be performed. Mild or moderate mitral regurgitation without impairment of functional capacity may be followed medically. In asymptomatic patients, enlargement (>5%) of the left atrial diameter following development of moderate PVL may be a valuable criterion for deciding when to reoperate.