Definitions matter: detection rates and perinatal outcome for infants classified prenatally as having late fetal growth restriction using SMFM biometric vs ISUOG/Delphi consensus criteria.

OBJECTIVES: Fetal growth restriction (FGR) is often secondary to placental dysfunction and is suspected prenatally based on biometric or circulatory abnormalities detected on ultrasound. The aims of this study were to compare the screening performance of the Society for Maternal-Fetal Medicine (SMFM) biometric criteria (estimated fetal weight (EFW) or abdominal circumference (AC) < 10th centile) with that of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)-endorsed Delphi consensus criteria for late FGR for delivery of a small-for-gestational-age (SGA) infant at term, emergency Cesarean section (CS) for non-reassuring fetal status (NRFS), perinatal mortality and composite severe neonatal morbidity. METHODS: We classified retrospectively non-anomalous singleton infants as having late FGR (diagnosed ≥ 32 weeks) according to SMFM and ISUOG/Delphi criteria in a cohort of women who had been referred to the Mater Mother's Hospital, Brisbane, Australia and who delivered at term between January 2014 and December 2020. The study outcomes were delivery of a SGA infant (birth weight (BW) < 10th or < 3rd centile), emergency CS for NRFS, perinatal mortality (defined as stillbirth or neonatal death within 28 days of a live birth) and a composite of severe neonatal morbidity. We assessed the screening performance of various ultrasound variables by calculating the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, false-positive and false-negative rates, positive likelihood ratio (LR+) and negative likelihood ratio. RESULTS: The SMFM and ISUOG/Delphi consensus criteria collectively classified 1030 cases as having late FGR. Of these, 400 cases were classified by both SMFM and ISUOG/Delphi criteria, whilst 548 cases were classified using only SMFM criteria and 82 cases were classified only by ISUOG/Delphi criteria. Prenatal detection of late FGR by SMFM and ISUOG/Delphi criteria was associated with increased odds of delivery of an infant with BW < 10th centile (SMFM: adjusted odds ratio (aOR), 133.0 (95% CI, 94.7-186.6); ISUOG/Delphi: aOR, 69.5 (95% CI, 49.1-98.2)) or BW < 3rd centile (SMFM: aOR, 348.7 (95% CI, 242.6-501.2); ISUOG/Delphi: aOR, 215.4 (95% CI, 148.4-312.7)). Compared with the SMFM criteria, the ISUOG/Delphi criteria were associated with lower odds (aOR, 0.5 (95% CI, 0.3-0.8)) of predicting a SGA infant with BW < 10th centile, but higher odds of predicting emergency CS for NRFS (aOR, 2.30 (95% CI, 1.14-4.66)) and composite neonatal morbidity (aOR, 1.22 (95% CI, 1.05-1.41)). Both SMFM and ISUOG/Delphi criteria were associated with high LR+, specificity, PPV and NPV for the prediction of infants with BW < 10th and BW < 3rd centile. However, both methods functioned much less efficiently for the prediction of composite severe neonatal morbidity or emergency CS for NRFS, with LR+ < 10. The SMFM biometric criteria alone, particularly AC < 3rd centile, had the highest LR+ values for the prediction of perinatal mortality. CONCLUSION: Both the SMFM and ISUOG/Delphi criteria had strong screening potential for the detection of infants with BW < 10th or < 3rd centile but not for adverse neonatal outcome. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Expanding functions of ADP-ribosylation in the maintenance of genome integrity.

Cell response to genotoxic stress requires a complex network of sensors and effectors from numerous signaling and repair pathways, among them the nuclear poly(ADP-ribose) polymerase 1 (PARP1) plays a central role. PARP1 is catalytically activated in the setting of DNA breaks. It uses NAD+ as a donor and catalyses the synthesis and subsequent covalent attachment of branched ADP-ribose polymers onto itself and various acceptor proteins to promote repair. Its inhibition is now considered as an efficient therapeutic strategy to potentiate the cytotoxic effect of chemotherapy and radiation or to exploit synthetic lethality in tumours with defective homologous recombination mediated repair. Still, efforts made on understanding the role of PARylation in DNA repair continues to yield novel discoveries. Over the last years, our knowledge in this field has been particularly advanced by the discovery of novel biochemical and functional properties featuring PARP1, by the characterization of the other PARP family members and by the identification of a panel of enzymes capable of erasing poly(ADP-ribose). The aim of this review is to provide an overview of these newest findings and their relevance in genome surveillance.

Colonic microbiota can promote rapid local improvement of murine colitis by thioguanine independently of T lymphocytes and host metabolism.

OBJECTIVE: Mercaptopurine (MP) and pro-drug azathioprine are 'first-line' oral therapies for maintaining remission in IBD. It is believed that their pharmacodynamic action is due to a slow cumulative decrease in activated lymphocytes homing to inflamed gut. We examined the role of host metabolism, lymphocytes and microbiome for the amelioration of colitis by the related thioguanine (TG). DESIGN: C57Bl/6 mice with or without specific genes altered to elucidate mechanisms responsible for TG's actions were treated daily with oral or intrarectal TG, MP or water. Disease activity was scored daily. At sacrifice, colonic histology, cytokine message, caecal luminal and mucosal microbiomes were analysed. RESULTS: Oral and intrarectal TG but not MP rapidly ameliorated spontaneous chronic colitis in Winnie mice (point mutation in Muc2 secretory mucin). TG ameliorated dextran sodium sulfate-induced chronic colitis in wild-type (WT) mice and in mice lacking T and B lymphocytes. Remarkably, colitis improved without immunosuppressive effects in the absence of host hypoxanthine (guanine) phosphoribosyltransferase (Hprt)-mediated conversion of TG to active drug, the thioguanine nucleotides (TGN). Colonic bacteria converted TG and less so MP to TGN, consistent with intestinal bacterial conversion of TG to so reduce inflammation in the mice lacking host Hprt. TG rapidly induced autophagic flux in epithelial, macrophage and WT but not Hprt-/- fibroblast cell lines and augmented epithelial intracellular bacterial killing. CONCLUSIONS: Treatment by TG is not necessarily dependent on the adaptive immune system. TG is a more efficacious treatment than MP in Winnie spontaneous colitis. Rapid local bacterial conversion of TG correlated with decreased intestinal inflammation and immune activation.

PARP-2 sustains erythropoiesis in mice by limiting replicative stress in erythroid progenitors.

Erythropoiesis is a tightly regulated process in which multipotential hematopoietic stem cells produce mature red blood cells. Here we show that deletion of poly(ADP-ribose) polymerase-2 (PARP-2) in mice leads to chronic anemia at steady state, despite increased erythropoietin plasma levels, a phenomenon not observed in mice lacking PARP-1. Loss of PARP-2 causes shortened lifespan of erythrocytes and impaired differentiation of erythroid progenitors. In erythroblasts, PARP-2 deficiency triggers replicative stress, as indicated by the presence of micronuclei, the accumulation of γ-H2AX (phospho-histone H2AX) in S-phase cells and constitutive CHK1 and replication protein A phosphorylation. Transcriptome analyses revealed the activation of the p53-dependent DNA-damage response pathways in PARP-2-deficient cells, culminating in the upregulation of cell-cycle and cell death regulators, concomitant with G2/M arrest and apoptosis. Strikingly, while loss of the proapoptotic p53 target gene Puma restored hematocrit levels in the PARP-2-deficient mice, loss of the cell-cycle regulator and CDK inhibitor p21 leads to perinatal death by exacerbating impaired fetal liver erythropoiesis in PARP-2-deficient embryos. Although the anemia displayed by PARP-2-deficient mice is compatible with life, mice die rapidly when exposed to stress-induced enhanced hemolysis. Our results pinpoint an essential role for PARP-2 in erythropoiesis by limiting replicative stress that becomes essential in the absence of p21 and in the context of enhanced hemolysis, highlighting the potential effect that might arise from the design and use of PARP inhibitors that specifically inactivate PARP proteins.

[The role of PARP2 in DNA repair].

The genome stability of higher eukaryotes is mainly dependent on the functioning of the DNA repair systems. In turn, the precise regulation of each step of repair processes is required for efficient DNA repair. While at present the most pathways of DNA repair have been established already, but the mechanisms of DNA repair regulation are required further investigation. Poly(ADP-ribose)polymerases (PARPs) are widely considered as potential regulators of a DNA repair. The role of most prominent member of this protein family--PARP1--in DNA repair is intensively studied, while the literature data on participation in repair processes of PARP2--the closestPARP1 homolog--are poorly Sum- marized although a great body of information concerning PARP2 participation in DNA repair has accumulated.. Using PARP2-deficient model organisms and cell lines, their increased sensitivity to several DNA damage agents was elucidated. The accumulation of PARP2 at the DNA damage sites in cells was shown. There are data demonstrating protein-protein interaction of PARP2 with several base excision repair/single strand break repair and non-homologous end joining proteins. Most of the data on PARP2 role have been obtained in experiments with model organisms and cell lines so it is difficult to project the attribution of PARP2 influence to specific process in vivo. In this review, we tried to summarize data on PARP2 participation in DNA repair processes, including our recent results.

Recurrent intrahepatic dislocation of ventriculoperitoneal shunt.

BACKGROUND: Dislocation of ventriculoperitoneal (VP) shunt catheters is a well known complication after treatment of cerebrospinal fluid disorders; however, secondary perforation of the liver capsule by the catheter is exceptional. The literature on VP shunt complications involving the liver, their possible pathomechanisms and minimally invasive recovery strategies in reference to our own experience is reviewed. CASE REPORT: We present a patient who suffered penetration of the liver by the peritoneal catheter of her VP shunt. Causing intermittent epigastric pain, the shunt tip was found to have progressively dislocated into the liver, as documented by CT scans. A laparoscopic approach was indicated to recover the shunt. The peritoneal catheter was found to be covered by widespread adhesions, consistent with peritoneal fibrosis. After local adhesiolysis, it was successfully recovered without shunt dysfunction, hemorrhage of the liver, or biliary fistula. After 4 months, dislocation recurred with formation of a subdiaphragmatic pseudocapsule. Early formation of fibrosis was detected during laparoscopic revision surgery. Although bacterial smears from both laparoscopic surgeries did not show any pathological findings, the patient presented with an abscess in the Douglas pouch 4 months later. Coagulase-negative staphylococci were found on ultrasound-guided insertion of a pigtail catheter. The VP shunt had to be replaced by a ventriculoatrial shunt. The infection was treated successfully with piperacillin. The subsequent 6 months follow-up period was without adverse events. CONCLUSION: The treatment of choice in this exceptional case of intrahepatic shunt dislocation was laparoscopic recovery of the catheter. Laparoscopy allowed good visualization during adhesiolysis, immediate exclusion of hemorrhage or bile fistula at the puncture site, as well as function control and safe deposition of the shunt tip. Chronic infection as an underlying cause of peritoneal fibrosis has to be ruled out.

No significant effect of orally administered chemokine receptor 1 antagonist on intercellular adhesion molecule-3 expression in relapsing--remitting multiple sclerosis patients.

We investigated the expression of intercellular adhesion molecules ICAM-1 and ICAM-3 on peripheral blood mononuclear cells in a subgroup of 34 patients with relapsing-remitting multiple sclerosis who were treated orally with the chemokine receptor 1 antagonist BX 471 in a 16-week, randomised, double-blind, placebo-controlled phase II study. ICAM-1 and ICAM-3 expression was measured by flow cytometry at different time points during and after therapy and compared using multivariate analysis of variance and non-parametric Mann Whitney test. ICAM-3 expression on CD14( +) peripheral blood mononuclear cells was increased in the verum group under therapy, but did not differ significantly between the verum and placebo groups. Most likely, this trend represents a small epiphenomenon only mediated by receptor cross-talk and feedback mechanisms.

Targeting of adenovirus vectors carrying a tumor cell-specific peptide: in vitro and in vivo studies.

Previously, we have identified a tumor cell-specific peptide, HEW, by panning of phage display libraries on the human colorectal cancer cell line WiDr. In this report we demonstrate that this peptide can modify the infection properties of adenovirus vectors. Increased infectivity of replication-deficient adenovirus 5 vectors in WiDr cells was observed upon genetic insertion of the HEW peptide in the HI loop of the fiber knob. Moreover, whereas the coxsackie and adenovirus receptor (CAR)-ablating fiber mutation S408E abolished apparent infection in CAR-positive WiDr cells, the insertion of HEW completely restored infectivity toward these cells in vitro. To assess whether the de- and re-targeted infection profile was maintained in vivo, the fiber-modified adenovirus vectors were injected intratumorally or intravenously in WiDr tumor-bearing Swiss nu/nu mice. No significant differences in efficiency of infection could be observed suggesting alternative viral uptake mechanisms in vivo. Next, we have included the fiber shaft mutation S(*) in our studies, which was described to confer a de-targeted phenotype in vivo. Reduced gene transfer due to the S(*) mutation both in vitro and in vivo could be confirmed. Insertion of HEW in the HI knob loop of shaft-mutated fiber, however, did not rescue infectivity in target cells neither in vitro nor in vivo. We demonstrate the efficient ligand-mediated re-targeting of adenoviral vector infection to the human cancer cell line WiDr. The lack of apparent re-targeting in the in vivo situation is described.

[Two 150 years anniversaries: Claude Bernard's internal environment and Addison disease]. / Dve stopadesátiletá výrocí: Claude Bernardovo vnitrní prostredí a Addisonova nemoc.

In 2005 two 150 years anniversaries, which essentially influenced the development of modern medicine will be celebrated. French physiologist Claude Bernard from College de France published his work "Lectures on Experimental Physiology, applied to medicine" and British medical doctor T. Addison described insufficiency of adrenal cortex, today known as Addison disease.

[Laparoscopic Janeway gastrostomy: an advantageous solution for self-sufficient enteral feeding]. / Gastrostomie tubulisée coelioscopique : une solution avantageuse pour une nutrition entérale autonome.

INTRODUCTION: Laparoscopic gastrostomy according to Janeway (LGJ) is an alternative to percutaneous gastrostomy techniques. METHODS: A series of 10 LGJ is reported. The laparoscopic technique involves an isoperistaltic tube of 6-7 cm of length and 10-12 mm of diameter is created by 2 applications of linear stapling and cutting device. The tube is led out, opened and fixed to the fascial and cutaneous planes and a Foley catheter is inserted. RESULTS: Mean operation time was 35 minutes. There was no complication. The LGJ was indicated in 9 patients with tumour of the pharynx and 1 patient with encephalopathy. CONCLUSION: The main drawback of the LGJ is the need of general anaesthesia. The main advantage is the creation by minimal invasive surgery of a permanent gastrostomy equipped with a removable catheter easily changeable by non specialized health professionals, and even by the patient himself.

Intraperitoneal chemohyperthermia and attempted cytoreductive surgery in patients with peritoneal carcinomatosis of colorectal origin.

BACKGROUND: Colorectal cancer with peritoneal carcinomatosis is usually considered incurable. The purpose of this study was to evaluate the efficacy of intraperitoneal chemohyperthermia (IPCH) following cytoreductive surgery in patients with colorectal carcinomatosis. METHODS: Between January 1989 and August 2002, 53 patients (mean age 48.6 years) were treated by IPCH with mitomycin C. IPCH was performed in 34 patients following extensive cytoreductive surgery (more than two peritonectomy procedures). Five patients underwent two operations and one patient three operations. RESULTS: Operative morbidity and mortality rates were 23 and 4 per cent respectively. At a median follow-up of 59.5 months, the overall median survival was 12.8 months. The extent of carcinomatosis, completeness of cytoreduction and histological differentiation were significant prognostic indicators by univariate analysis. The median survival was 32.9 months for patients whose resection was classified as completeness of cancer resection (CCR) 0 (complete cytoreduction), 12.5 months for those whose operation was CCR-1 (diameter of residual nodules 5 mm or less) and 8.1 months for patients who had a CCR-2 resection (diameter of residual nodules more than 5 mm) (P < 0.001). Completeness of cytoreduction was the only significant independent predictor of survival by multivariate analysis. CONCLUSION: IPCH combined with cytoreductive surgery seems to be an effective therapy for carefully selected patients with carcinomatosis from colorectal cancer. This strategy was most effective in patients with carcinomatosis of limited tumour volume or when cytoreductive surgery allowed sufficient downstaging (residual tumour nodules smaller than 5 mm).

Cytoreductive surgery and intraperitoneal chemohyperthermia for peritoneal carcinomatosis arising from gastric cancer.

HYPOTHESIS: The most common cause of palliative resection and recurrence in gastric cancer is peritoneal seeding. This study evaluates the efficacy of intraperitoneal chemohyperthermia after cytoreductive surgery in patients with peritoneal carcinomatosis arising from gastric cancer. DESIGN: Prospective clinical trial. SETTING: Surgical department at a university academic hospital. PATIENTS: Forty-nine consecutive patients with peritoneal carcinomatosis treated between January 1, 1989, and February 29, 2000. INTERVENTIONS: All patients underwent intraperitoneal chemohyperthermia with mitomycin C (40-60 mg); 21 patients had previously undergone extensive cytoreductive surgery. MAIN OUTCOME MEASURES: Clinicopathologic factors that affect overall survival rates. RESULTS: With median follow-up of 99 months, overall median survival was 10.3 months. Two factors were significant independent predictors of survival by multivariate analysis: preoperative ascites (P =.04) and completeness of cancer resection (CCR) by cytoreductive surgery (P<.001). Median survival was 21.3 months for patients with CCR-0 (macroscopic complete resection) or CCR-1 (diameter of residual nodules <5 mm) and 6.1 months for patients with CCR-2 (diameter of residual nodules >5 mm) (P<.001). Four patients survived longer than 5 years. CONCLUSIONS: An aggressive management strategy combining intraperitoneal chemohyperthermia with cytoreductive surgery is effective for patients with peritoneal carcinomatosis arising from gastric cancer. In highly selected patients (good general status, resectable primary tumor, resectable peritoneal carcinomatosis), this therapy may result in long-term survival.

Ghrelin -- a new endogenous growth hormone secretagogue.

Ghrelin is a new endogenous peptide, discovered in 1999 by Kojima et al., as the result of a search for an endogenous ligand for an orphan receptor of known structure and function. Ghrelin is composed of 28 amino acids and is produced mostly by cells of the stomach, hypothalamus, and hypophysis, but it has also been detected in other tissues. Its discovery is related to the development of a new hypothesis regarding the regulation of growth hormone secretion. It is an antagonist of somatostatin. Ghrelin activates the release of growth hormone from the somatotrophic cells of the hypophysis. It participates in the regulation of energy homeostasis, increases food intake, decreases energy output and exerts a lipogenetic effect. Its metabolic effects do not depend on the GH/IGF-I system, but are mediated by the NPY/Y1 and AGRP receptor system. Ghrelin influences the secretion and motility of the gastrointestinal tract, especially the stomach. The presence of ghrelin and its receptors has also been demonstrated in many other tissues. Its function in these tissues has not yet been studied, thus providing many possibilities for further research.

The role of dopamine in methylene blue-mediated inhibition of estradiol benzoate-induced anterior pituitary hyperplasia in rats.

Recently, we demonstrated that methylene blue partially inhibited estradiol-benzoate-induced anterior pituitary hyperplasia in rats. Since central dopaminergic systems participate in the regulation of estrogen-induced anterior pituitary growth and tumor transformation, this study examined whether a 3-week treatment with methylene blue could affect anterior pituitary levels of dopamine (DA), dihydroxyphenylalanine (DOPA), and dihydroxyphenylacetic acid and dopamine (D-2) receptors in male rats. Compared to controls, methylene blue significantly decreased anterior pituitary weight, increased basal anterior pituitary DA levels, and inhibited estradiol benzoate-induced decreases in anterior pituitary DA concentrations. Furthermore, we found that methylene blue alone decreased anterior pituitary D-2 receptor number. Methylene blue given in combination with estradiol benzoate partially inhibited estradiol benzoate-induced anterior pituitary growth and estradiol benzoate-induced increases in D-2 receptor number. Estradiol benzoate-treated rats had significantly lower anterior pituitary DOPA accumulation after intraperitoneal administration of 3,4-hydroxybenzyl-hydrazine dihydrochloride (NSD-1015), an irreversible inhibitor of L-aromatic amino acid decarboxylase whereas methylene blue did not affect anterior pituitary DOPA accumulation when compared to controls. Methylene blue decreased anterior pituitary prolactin levels and inhibited increases in anterior pituitary prolactin after estradiol benzoate administration. The present results suggest that anterior pituitary DA may play an important role in estrogen-induced anterior pituitary hyperplasia and tumor formation and that antioxidant drugs such as methylene blue may attenuate estrogen-induced pituitary growth. This may occur via increases in anterior pituitary DA levels associated with down-regulation of anterior pituitary D-2 receptors.

[Endocrinology 1999-2000]. / Endokrinologie 1999-2000.

Long-lasting problem on the differentiation of adenohypophyseal cell, which prepares them for their specific tasks (somatotropic, lactotropic ect.), becomes elucidated after recognition of the differentiational effect of transcription factor Pit-1. Expression of that factor in somatotrops results in STH secretion, contrary to lactotrops producing prolactin. Subclinical hypothyreosis (increased TSH with normal T3 and T4) endangers vessel not because of hypercholesterolemia, but because of changes in the dynamics of the blood flow. The idea of cardiotropic effect of thyroidal hormones is supported by the finding that administration of trijodthyronine to children after the surgical correction of heart malformations (cardiopulmonary bypass) improves myocardial function--it elevates cardiac output and decreases requirements on the intensive care. Receptors for hormones in tissues are flexible, they can be "heterooligomers" for dopamine and somatostatin. Mutations of mineralocorticoid receptor may cause hypertension in pregnancy and progesterone receptors have several isoforms. Receptors can be also activated by short exposition to a hormone. Glucocorticoids have probably also membrane receptors. Diabetes mellitus "type I" needn't to be immunogenic and DM type II not only results from down-regulation of receptors and subsequent insulin resistance, but it can be also caused by defects in insulin secretion. Insulin has receptors in the brain and participates in the appetite regulation. The attempt to use "desensibilisation" by peroraly administered insulin in patients with immunogenic DM had no effect. Stress affects memory mechanisms, heavy emotional stress during gravidity can bring congenital malformations. The decrease of mental functions in aged women depends on the level of free estradiol (the fraction, which is not bound to plasma proteins). Activation of dopaminergic neurons can be achieved by neurotropic growth factors. Nesiritide is a recombinant brain natriuretic hormone successfully tested in heart failure. The role of leptin in the appetite regulation in man is still not clear, other signalling molecules may have also an effect, e.g., ghrelin, which primarily stimulates STH secretion and brings about weight gain. Sildenafil influences nitrergic neurons elsewhere than in penis, for example it has positive effects in patients with oesophageal achalasia.

A bidirectional promoter connects the poly(ADP-ribose) polymerase 2 (PARP-2) gene to the gene for RNase P RNA. structure and expression of the mouse PARP-2 gene.

Poly(ADP-ribose) polymerase 2 (PARP-2) is a DNA damage-dependent enzyme that belongs to a growing family of enzymes seemingly involved in genome protection. To gain insight into the physiological role of PARP-2 and to investigate mechanisms of PARP-2 gene regulation, we cloned and characterized the murine PARP-2 gene. The PARP-2 gene consists of 16 exons and 15 introns spanning about 13 kilobase pairs. Interestingly, the PARP-2 gene lies head to head with the gene encoding the mouse RNase P RNA subunit. The distance between the transcription start sites of the PARP-2 and RNase P RNA genes is 114 base pairs. This suggested that regulation of the expression of both genes may be coordinated through a bi-directional promoter. The PARP-2/RNase P RNA gene organization is conserved in the human. To our knowledge, this is the first report of a RNA polymerase II gene and an RNA polymerase III gene sharing the same promoter region and potentially the same transcriptional control elements. Reporter gene constructs showed that the 113-base pair intergenic region was indeed sufficient for the expression of both genes and revealed the importance of both the TATA and the DSE/Oct-1 expression control elements for the PARP-2 gene transcription. The expression of both genes is clearly independently regulated. PARP-2 is expressed only in certain tissues, and RNase P RNA is expressed in all tissues. This suggests that both genes may be subjected to multiple levels of control and may be regulated by different factors in different cellular contexts.

[Jugular lymph node metastasis of papillary thyroid gland carcinoma 10 years later]. / Juguläre Lymphknotenmetastase von papillärem Schilddrüsenkarzinom vor zehn Jahren. Ein Fallbericht.

We present a patient with occult papillary thyroid carcinoma, in whom a single nodal metastasis had been excised. Ten years later a nodal recurrence was diagnosed by ultrasound and fine needle aspiration cytology. The diagnosis of recurrence was erroneous, and we discuss the differential diagnostic problems, the natural course, and the adequate treatment of occult papillary microcarcinoma.