Incidental cancer in patients surgically treated for benign thyroid disease. Our experience at a single institution

Increased incidence of incidental cancer in patients operated for benign thyroid disease has been reported. We report our experience about incidental thyroid cancer (ITC) in order to better characterize this nosologic entity. Between 2001 and 2009 a total of 568 patients underwent surgery for benign thyroid disease. Patients with preoperative cytology undetermined or positive for malignancy were excluded. The most frequent indication for surgery was multinodular or diffuse nontoxic goiter. We performed total thyroidectomy in 499 cases and emithyroidectomy in 69 cases. Final histology revealed ITC in 53 patients (9.3%): 44 had papillary carcinoma (20 classic variant and 24 follicular variant), 4 follicular carcinoma, 4 medullary carcinoma and 1 primitive thyroid paraganglioma. The preoperative diagnosis was multinodular or diffuse goiter in 45 cases of ITC and uninodular goiter in 8 cases. We performed total thyroidectomy in 46 case, emithyroidectomy in 4 patients with past history of lobectomy, emithyroidectomy in 3 patients with following radicalization and central neck dissection. In 14 patients the tumor was multifocal and in 12 of these patients the tumor foci were bilateral. The lesion was a microcarcinoma in 34 cases. Mean diameter of the ITC was 1.14 cm. We retrospectively reconsidered the results of preoperative ultrasound examinations in relation to the exact position of the tumor in the specimens and we found a statistically significant association between echogenicity and papillary histotype. Twenty-six patients were followed up at our Hospital. The mean follow-up period was 38.2 months. A relapse was observed in 3/26 patients. Incidental thyroid cancer in patients operated for benign disease has its own surgical and oncological relevance. A correct preoperative assessment, with a careful selection of nodules for fine-needle aspiration cytology on the basis of ultrasound pattern, could better address the choice of surgical procedure. The non irrelevant incidence of incidental thyroid cancer, the eventuality of multifocality and bilaterality and the possible occurrence of relapse, support that total thyroidectomy without residuum is a valuable option for treating benign thyroid conditions such as multinodular goitre. When an incidental cancer is diagnosed after emithyroidectomy, a radicalization with central neck dissection could be considered. We suggest that natural history of papillary microtumors and the correct surgical approach for these lesions could be better defined with a more extensive use of “Porto proposal” criteria. Incidental thyroid cancer, Papillary microcarcinoma, Papillary microtumors, Total thyroidectomy.

Whipple’s disease infection surgical treatment: presentation of a rare case and literature review

The Whipple’ Disease (W.D.) is a very rare disease with an incidence of 1 per 1.000.000 inhabitants; it is a systemic infection that may mimic a wide spectrum of clinical disorders, which may have a fatal outcome and affects mainly male 40-50 years old. The infective agent is an actinomycete, Tropheryma Whipplei (T.W.) that was isolated 100 years after first description by Wipple, and identified in macrophages of mucosa of the small intestine by biopsy which is characterized by periodic acid-Schiff-positive, products of the inner membrane of his polysaccharide bacterial cell wall. The multisystemic clinical manifestations evolve rapidly towards an organic decay characterized by weight loss, malabsorption, diarrhea, polyathralgia, opthalmoplegia, neuro-psychiatric disorders and sometimes associated to endocarditis. Early antibiotic treatment with trimethoprim and sulfometathaxazole reduces the fatal evolution of the disease. The authors present a rare experience about a female subject in which the clinical gastrointestinal signs were preceded by neuro-psychiatric disorders, and evolved into obstruction and intestinal perforation which required an emergency surgery with temporary ileostomy, recanalized only after adequate medical treatment with a full dose of antibiotic and resolution of clinical disease for the high risks of fistulae for the edema and lymphadenopathy of mucosa. The diagnosis was histologically examined by intestinal biopsy performed during surgery, which showed PAS-positive histiocytes, while PRC polymerase RNA was negative, which confirms the high sensibility of PAS positive and low specificity of RNA polymerase for T.W.

Pediatric ocular rosacea, a misdiagnosed disease with high morbidity: Proposed diagnostic criteria

Ocular rosacea is an important and underdiagnosed chronic inflammatory disorder observed in children. A clinical spectrum ranging from chronic eyelid inflammation, recurrent ocular redness, photophobia and/or hordeola/chalazions and conjunctival/corneal phlyctenules evolving to neovascularization and scarring may occur. Visual impairment and consequent amblyopia are frequent and corneal perforation although rare is the most feared complication. Ocular manifestations usually precede cutaneous lesions. Although few cases of pediatric ocular rosacea (POR) have been reported in the literature, many cases must have been underdiagnosed or misdiagnosed. The delay in diagnosis is greater than one year in the large majority of cases and may lead to serious ocular sequelae. This review aims to highlight the clinical features of POR, its epidemiology, easy diagnosis and effective treatment. We also propose new diagnostic criteria, in which at least three of the five clinical criteria must be present: (1) Chronic or recurrent keratoconjunctivitis and/or red eye and/or photophobia; (2) Chronic or recurrent blepharitis and/or chalazia/ hordeola; (3) Eyelid telangiectasia documented by an ophthalmologist; (4) Primary periorificial dermatitis and/ or primary features of rosacea; and (5) Positive familial history of cutaneous and/or ocular rosacea.

Capsule endoscopy in inflammatory bowel disease type unclassified and indeterminate colitis serologically negative

BACKGROUND: The value of capsule endoscopy in the setting of inflammatory bowel disease type unclassified (IBDU) and indeterminate colitis (IC) remains obscure. The aim was to evaluate the clinical impact of capsule endoscopy on IBDU/IC patients with negative serology. METHODS: Eighteen patients with long-standing IBDU (n = 14) and IC (n = 4) were enrolled to undergo a capsule endoscopy and then followed prospectively. Lesions considered diagnostic of Crohn's disease (CD) were 4 or more erosions/ulcers and/or a stricture. The median follow-up time after capsule endoscopy was 32 ± 11 months (23-54 months). RESULTS: Total enteroscopy was possible in all patients. In 2 patients the examination was normal (Group 1). In 9 patients subtle findings were observed (Group 2): focal villi denudation (n = 1) and fewer than 4 erosions/ulcers (n = 8). In 7 patients, 4 or more erosions/ulcers were detected (Group 3), leading to a diagnosis of CD. However, their treatment was not reassessed on the basis of the capsule findings. Until now, a definitive diagnosis has been achieved in 2 additional patients: 1 from Group 1 (ulcerative colitis) and another patient from Group 2 (CD), who began infliximab infusions. Nine patients remained indeterminate at follow-up. CONCLUSIONS: Although capsule endoscopy enabled the diagnosis of CD in 7 patients, in none of them was the clinical management changed. Moreover, a change in therapy due to a diagnosis of CD was made for only 1 patient, who presented nonspecific findings. Our results suggest that capsule findings are not helpful in the work-up of these patients

Non-Celiac Gluten Sensitivity and Autoimmunity. A Case Report

Introduction, objective: To present a case report in which the finding of non-coeliac gluten sensitivity was decisive for the treatment of a complex autoimmune disease. Materials and methods: A 43-year-old woman with polyarthritis, psoriatic features, anti-SSA/Ro and anti-cyclic citrullinated peptide antibodies, with refractory course, was evaluated for gluten sensitivity despite negative serology for coeliac disease. Results: The patient carried the HLA DQ2 haplotype and duodenal biopsy showed lymphocytic enteritis. A gluten-free diet resolved the clinical picture and permitted tapering of immunosuppressive therapy. Conclusion: Non-coeliac gluten sensitivity can be associated with autoimmunity despite the absence of the specific autoantibodies of coeliac disease.

Psychiatric manifestations of sporadic Creutzfeldt-Jakob disease simulate depressive disorder with psychotic symptoms

Creutzfeldt–Jakob disease (CJD) is a rare and fatal neurodegenerative disorder with a broad spectrum of early clinical manifestations, comprising neurological and psychiatric symptoms. The authors report the case of a patient admitted with a diagnosis of depressive disorder with psychotic symptoms, with post-mortem confirmation of CJD and discuss how CJD’s clinical heterogeneity can lead to misdiagnosis of the disease. Despite CJD’s unique pathogenesis, its kaleidoscopic presentation justifies the integrated investigation of patients with psychiatric symptoms, avoiding restrictive diagnosis.

Eosinophilic Fasciitis: an Atypical Presentation of a Rare Disease

Objectives: We report an atypical presentation of eosinophilic fasciitis and provide a concise overview of the literature. Materials and Methods: Clinical and laboratory findings in a patient presenting with fever and skin induration were recorded. A deep muscle biopsy was performed in order to confirm the diagnosis. Results: A spontaneous favourable clinical and radiological evolution was observed. Conclusion: The diagnosis of eosinophilic fasciitis is challenging due to the lack of pathognomonic signs and symptoms. As spontaneous resolution has been described, watchful waiting is defendable depending on the clinical presentation. Although magnetic resonance imaging (MRI) can be useful in establishing the diagnosis, a deep muscle biopsy remains the gold standard diagnostic tool.

Cardiac magnetic resonance imaging in the diagnosis and determination of outcome of pulmonary hypertension

Pulmonary hypertension (PH) is a rare but serious condition that causes progressive right ventricular (RV) failure and death. PH may be idiopathic, associated with underlying connective-tissue disease or hypoxic lung disease, and is also increasingly being observed in the setting of heart failure with preserved ejection fraction (HFpEF). The management of PH has been revolutionised by the recent development of new disease-targeted therapies which are beneficial in pulmonary arterial hypertension (PAH), but can be potentially harmful in PH due to left heart disease, so accurate diagnosis and classification of patients is essential. These PAH therapies improve exercise capacity and pulmonary haemodynamics, but their overall effect on the right ventricle remains unclear. Current practice in the UK is to assess treatment response with 6-minute walk test and NYHA functional class, neither of which truly reflects RV function. Cardiac magnetic resonance (CMR) imaging has been established as the gold standard for the evaluation of right ventricular structure and function, but it also allows a non-invasive and accurate study of the left heart. The aims of this thesis were to investigate the use of CMR in the diagnosis of PH, in the assessment of treatment response, and in predicting survival in idiopathic and connective-tissue disease associated PAH. In Chapter 3, a left atrial volume (LAV) threshold of 43 ml/m2 measured with CMR was able to distinguish idiopathic PAH from PH due to HFpEF (sensitivity 97%, specificity 100%). In Chapter 4, disease-targeted PAH therapy resulted in significant improvements in RV and left ventricular ejection fraction (p<0.001 and p=0.0007, respectively), RV stroke volume index (p<0.0001), and left ventricular end-diastolic volume index (p=0.0015). These corresponded to observed improvements in functional class and exercise capacity, although correlation coefficients between Δ 6MWD and Δ RVEF or Δ LVEDV were low. Finally, in Chapter 5, one-year and three-year survival was worse in CTD-PAH (75% and 53%) than in IPAH (83% and 74%), despite similar baseline clinical characteristics, lung function, pulmonary haemodynamics and treatment. Baseline right ventricular stroke volume index was an independent predictor of survival in both conditions. The presence of LV systolic dysfunction was of prognostic significance in CTD-PAH but not IPAH, and a higher LAV was observed in CTD-PAH suggesting a potential contribution from LV diastolic dysfunction in this group.

Hansen Neuropathy: Still a Possible Diagnosis in the Investigation of a Peripheral Neuropathy

INTRODUCTION: Leprosy is still one of the most frequent causes of peripheral neuropathy. Although regarded as eradicated in Portugal, is still documented in neuropathological study of patients with clinical peripheral neuropathy without proper diagnosis.

DNA Damage and Oxidative DNA Damage in Inflammatory Bowel Disease

Background and aims: Inflammation has long been regarded as a major contributor to cellular oxidative damage and to be involved in the promotion of carcinogenesis. Methods: We aimed to investigate the oxidative damage in inflammatory bowel disease [IBD] patients through a case–control and prospective study involving 344 IBD patients and 294 healthy controls. DNA damage and oxidative DNA damage were measured by comet assay techniques, and oxidative stress by plasmatic lipid peroxidation, protein carbonyls, and total antioxidant capacity. Results: Higher DNA damage [p < 0.001] was found both in Crohn’s disease [CD] (9.7 arbitrary units [AU]; interquartile range [IQR]: 6.2–14.0) and ulcerative colitis [UC] [7.1 AU; IQR: 4.4–11.7], when compared with controls [5.4 AU; IQR: 3.8–6.8], and this was also the case with oxidative DNA damage [p < 0.001] [CD: 3.6 AU; IQR: 1.8–6.8; UC: 4.6 AU; IQR: 2.4–8.1], when compared with controls: 2.3 AU; IQR: 1.2–4.2]. Stratifying patients into groups according to therapy (5-aminosalicylic acid [5-ASA], azathioprine, anti-TNF, and combined therapy [azathioprine and anti-TNF]) revealed significant between-group differences in the level of DNA damage, both in CD and UC, with the combined therapy exhibiting the highest DNA damage levels [11.6 AU; IQR: 9.5–14.3, and 12.4 AU; IQR: 10.6–15.0, respectively]. Among CD patients, disease behaviour [B1 and B2], and age at diagnosis over 40 years [A3] stand as risk factors for DNA damage. For UC patients, the risk factors found for DNA damage were disease activity, treatment, age at diagnosis under 40 years [A1 + A2] and disease locations [E2 and E3]. Conclusions: In IBD there is an increase in DNA damage, and treatment, age at diagnosis and inflammatory burden seem to be risk factors.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

FTIR, a potential tool to dementia diagnosis trough analysis of plasma

Nowadays it is still difficult to perform an early and accurate diagnosis of dementia, therefore many research focus on the finding of new dementia biomarkers that can aid in that purpose. So scientists try to find a noninvasive, rapid, and relatively inexpensive procedures for early diagnosis purpose. Several studies demonstrated that the utilization of spectroscopic techniques, such as Fourier Transform Infrared Spectroscopy (FTIR) and Raman spectroscopy could be an useful and accurate procedure to diagnose dementia. As several biochemical mechanisms related to neurodegeneration and dementia can lead to changes in plasma components and others peripheral body fluids, blood-based samples and spectroscopic analyses can be used as a more simple and less invasive technique. This work is intended to confirm some of the hypotheses of previous studies in which FTIR was used in the study of plasma samples of possible patient with AD and respective controls and verify the reproducibility of this spectroscopic technique in the analysis of such samples. Through the spectroscopic analysis combined with multivariate analysis it is possible to discriminate controls and demented samples and identify key spectroscopic differences between these two groups of samples which allows the identification of metabolites altered in this disease. It can be concluded that there are three spectral regions, 3500-2700 cm -1, 1800-1400 cm-1 and 1200-900 cm-1 where it can be extracted relevant spectroscopic information. In the first region, the main conclusion that is possible to take is that there is an unbalance between the content of saturated and unsaturated lipids. In the 1800-1400 cm-1 region it is possible to see the presence of protein aggregates and the change in protein conformation for highly stable parallel β-sheet. The last region showed the presence of products of lipid peroxidation related to impairment of membranes, and nucleic acids oxidative damage. FTIR technique and the information gathered in this work can be used in the construction of classification models that may be used for the diagnosis of cognitive dysfunction.

Endoluminal calprotectin measurement in assessment of pouchitis and a new index of disease activity: a pilot study

Pouchitis is the most common complication following proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis (UC). To provide a standardized definition of pouchitis clinical, endoscopic and histological markers were grouped and weighted in the pouch disease activity index (PDAI). However, the delay in the assessment of the final score due to the time requested for histological analysis remains the main obstacle to the index implementation in clinical practice so that the use of modified-PDAI (mPDAI) with exclusion of histologic subscore has been proposed. We tested the ability of calprotectin measurement in the pouch endoluminal content to mimic the histologic score as defined in the PDAI, the index that we adopted as gold standard for pouchitis diagnosis. Calprotectin was measured by ELISA in the pouch endoluminal content collected during endoscopy in 40 consecutive patients with J-pouch. In each patient PDAI and mPDAI were calculated and 15% of patients were erroneously classified by mPDAI. ROC analysis of calprotectin values vs. acute histological subscore ≥ 3 identified different calprotectin cut-off values with corresponding sensitivity and specificity allowing the definition and scoring of different range of calprotectin subscores. We incorporated the calprotectin score in the mPDAI obtaining a new score that shows the same specificity as PDAI for diagnosis of pouchitis and higher sensitivity when compared with mPDAI. The use of the proposed new score, once validated in a larger series of patients, might be useful in the early management of patients with symptoms of pouchitis.

Development and evaluation of the polymerase chain reaction (PCR) method for diagnosis of spring viremia of carp virus (SVCV)

Aquaculture has been expanded rapidly to become a major commercial and food-producing sector worldwide in recent decade. In parallel, viral diseases rapidly spread among farms causing enormous economic losses. The accurate detection of pathogens at early stages of infection is a key point for disease control in aquaculture. Spring Viraemia of Carp Virus (SVCV) is a very severe pathogen of carp fishes in different parts of the world and is categorized as a reportable listed disease in the annual published list of World Organization for animal Health (OIE). The objective of this study was to develop and evaluate RT- PCR test for detecting SVC virus and also the sensitivity and specificity of this test. A semi nested RT- PCR was designed using combination of three primers: two external (SVCF , SVCR) and one internal (SVCS) primers which based on conserved region of G gen. The specificity of designed primers (only external ones) by examination on Viral Hemorrhagic Septicemia Virus (VHSV) and Infectious Hematopoietic Necrosis Virus (IHNV) was confirmed. For optimizing of the PCR test, primer concentration, primer annealing temperature, cycle number and Mgcl2 concentration were surveyed. Also for validity test, prevention of false negative and Assurance of its accuracy, a competitive internal control (mimic) designed and its suitable concentration was defined. Evaluation of the sensitivity of designed test were conducted first by comparing the different commercially available RNA isolation guidelines, two guidelines: isotiocyanate phenol–chloroform based protocols (RNX–Plus Iran, Iq2000 kit Taiwan ) and two column based protocols (Cinna pure RNA Iran , high pure viral RNA kit, Roche Germany ). The results indicated that the column based protocols (Roche method and Cinna pure), yield 36.77 ng/μl and 16/47 ng/μl RNA concentration respectively, which were significantly higher than other protocols(P<0.05). Then for evaluation of extracted RNA sensitivity, Serial dilution of SVCV strain 56.70 grown in EPC (1.9×105 TCID50/ml) was examined To compare sensitivity. Extracted RNA from serial dilution with stone's primers and commercial IQ-2000 kit were examined simultaneously. The result indicated that designed semi- nested RT- PCR was able to recognize SVC virus to 10-4 dilution and stone's primer recognize to 10-3 dilution whereas Iq-2000 commercial kit did not recognized in any dilution. In high virus titer in designed test two DNA band (462 bp and 266 bp) produced, and by decreasing virus titer 462 bp was omitted. In low virus titer or lack of virus, just DNA band (mimic) 729 bp can propagate. After designing and optimizing PCR test, a total of 400 suspected cultured Cyprinus carpio with high mortality from 4 aquaculture zone of Khuzestan province were collected and tested for SVCV during 2012- 2013 using developed PCR method and IQ- 2000. The results indicated that SVC virus was not observed in samples using both methods.

Is renal medullary carcinoma the seventh nephropathy in sickle cell disease? A multi-center Nigerian survey.

Introduction: Previous studies had enlisted renal medullary carcinoma (RMC) as the seventh nephropathy in sickle cell disease (SCD). Clinical experience has contradicted this claim and this study is targeted at refuting or supporting this assumption. Objective: To estimate the prevalence of RMC and describe other renal complications in SCD. Materials and methods: 14 physicians (haematologists and urologists) in 11 tertiary institutions across the country were collated from patients’ case notes and hospital SCD registers. Results: Of the 3,596 registered sickle patients, 2 (0.056%) had been diagnosed with RMC over a ten year period, thereby giving an estimated prevalence rate of 5.6 per 100,000. The most common renal complication reported by the attending physicians was chronic kidney disease (CKD). The frequency of routine renal screening for SCD patients varied widely between centres – most were done at diagnosis, annually or bi-annually. Conclusion: The ten year prevalence of RMC in Nigerian SCD patients was determined to be 5.6 (estimated incidence of 0.56). RMC is not more common in SCD patients and therefore cannot be regarded as a “Seventh Sickle nephropathy”. Most of the managing physicians reported that the commonest nephropathy observed in their SCD patients was chronic kidney disease.