Rapid reversal of severe lactic acidosis after thiamine administration in critically ill adults: a report of 3 cases.

BACKGROUND: Thiamine plays a critical role in energy metabolism. Critically ill patients may have thiamine deficiency and increased mortality due to potentially irreversible consequences. The aim of this study was to show the impact of thiamine deficiency in a series of patients and the rapid response to thiamine replacement, showing the changes in clinical and metabolic conditions over time. METHODS: We described 3 cases of hospitalized patients who had received parenteral nutrition (PN) without vitamin supplementation. All the patients were admitted to the ICU between 2010 and 2011 with a severe form of lactic acidosis, an unstable circulatory state, and a different neurological disorder (a lethargic state, a severe form of impaired near-coma consciousness, and Wernicke encephalopathy). RESULTS: Intravenous (IV) administration of thiamine was associated with a rapid and marked restoration of acid-base balance, hemodynamic stability and the disappearance of neurological disturbances, and normalization of the clinical and biochemical conditions of all the patients within the following hours. CONCLUSIONS: The 3 cases demonstrated the rapidity of the reversal of severe thiamine deficiency, achieved by appropriate replacement in different hospitalized patients. The regression of clinical and biochemical disorders requires a prompt diagnosis and treatment based on the IV administration of thiamine and magnesium sulfate. In hospitalized patients at risk, thiamine deficiency is prevented by the integration of thiamine supplementation into PN and other forms of nutrition support.

Presence in the pre-surgical fine-needle aspiration of potential thyroid biomarkers previously identified in the post-surgical one.

Fine-needle aspiration biopsy (FNA) is usually applied to distinguish benign from malignant thyroid nodules. However, cytological analysis cannot always allow a proper diagnosis. We believe that the improvement of the diagnostic capability of pre-surgical FNA could avoid unnecessary thyroidectomy. In a previous study, we performed a proteome analysis to examine FNA collected after thyroidectomy. With the present study, we examined the applicability of these results on pre-surgical FNA. We collected pre-surgical FNA from 411 consecutive patients, and to obtain a correct comparison with our previous results, we processed only benign (n=114), papillary classical variant (cPTC) (n=34) and papillary tall cell variant (TcPTC) (n=14) FNA. We evaluated levels of five proteins previously found up-regulated in thyroid cancer with respect to benign nodules. ELISA and western blot (WB) analysis were used to assay levels of L-lactate dehydrogenase B chain (LDHB), Ferritin heavy chain, Ferritin light chain, Annexin A1 (ANXA1), and Moesin in FNA. ELISA assays and WB analysis confirmed the increase of LDHB, Moesin, and ANXA1 in pre-surgical FNA of thyroid papillary cancer. Sensitivity and specificity of ANXA1 were respectively 87 and 94% for cPTC, 85 and 100% for TcPTC. In conclusion, a proteomic analysis of FNA from patients with thyroid nodules may help to distinguish benign versus malignant thyroid nodules. Moreover, ANXA1 appears to be an ideal candidate given the high sensitivity and specificity obtained from ROC curve analysis.

Proteomic approach used in the diagnosis of Riedel's thyroiditis: a case report.

INTRODUCTION: Riedel's thyroiditis, a rare thyroid disease, can be difficult to diagnose prior to surgical removal and can be confused with malignancy both clinically and cytologically. CASE PRESENTATION: We report the case of a 72-year-old Caucasian woman who presented with a goiter, which showed a rapid increase in size at ultrasound check, suggesting malignancy. Because of inconclusive cytology, a total thyroidectomy was performed. Fine-needle aspiration of the removed thyroid was processed by two-dimensional electrophoresis, and the proteome was compared with both anaplastic cancer and control samples. Significant differentially expressed protein spots were identified by Western blot analysis by using specific antibodies. CONCLUSIONS: The protein pattern of Riedel's fine-needle aspiration revealed a superimposition with that of the control samples. The comparison of the protein pattern of Riedel's thyroiditis fine-needle aspiration with that of anaplastic cancer showed evidence of a different expression of ferritin heavy chains, ferritin light chains, and haptoglobins, as previously reported in thyroid cancers. Therefore, we performed Western blot analysis of these proteins and validated that their expression levels were low or absent in Riedel's thyroiditis and control samples despite the high concentrations present in fine-needle aspiration anaplastic samples. The concurrent absent or low expression levels of haptoglobin, ferritin light chain, and ferritin heavy chain in Riedel's thyroiditis fine-needle aspiration samples strongly indicate the benign nature of the thyroid lesion. These results suggest the potential applicability of fine-needle aspiration proteome analysis for Riedel's thyroiditis diagnosis.

A proteomic profile of washing fluid from the colorectal tract to search for potential biomarkers of colon cancer.

Washing fluid (WF) from the colon rectal tract after surgical resection might represent a first step in obtaining a mixture of proteins derived from the secretion of tumoral epithelial cells potentially involved in the pathological progression of tissue. In this study, we performed a proteomic analysis of colorectal WF to search for potential biomarkers of colon cancer. The outcome of this approach might open the possibility of using WF to screen for the precancerous and early stages of colorectal cancer (CRC). Samples of WFs were obtained during surgery from 35 patients submitted to colon resection for suspicious adenocarcinoma or carcinoma, while the respective controls were obtained by washing the healthy sections. WFs were immediately centrifuged, concentrated and trichloroacetic acid (TCA) was added to obtain protein pellets. After two-dimensional gel electrophoresis (2DE), the protein patterns of malignant samples were compared with respective normal samples. Forty-one protein spots were found to be differentially expressed exhibiting ≥2 fold-change of mean value spot intensities. After mass spectrometry, these protein spots collapsed into 38 different proteins. Interestingly, 19 of the differentially expressed proteins identified in the study corresponded to those suggested as being potential biomarkers of CRC. In accordance with the literature, these proteins showed the same direction of change (up or down for all proteins). Our results suggest that WF has the potential of being a method for the exploration of clinical samples for biomarker and drug target discovery.

Laparoscopic transcystic exploration for single-stage management of common duct stones and acute cholecystitis.

BACKGROUND: Common bile duct (CBD) stones are found in 10% of patients who undergo elective laparoscopic surgery for gallstone disease and in 10-20% of patients who present with acute cholecystitis (AC). For the latter, the role of laparoscopic transcystic exploration of the common duct (LTCE) as part of a single-stage procedure is still unknown. METHODS: This study, based on a "laparoscopy first" policy, included 201 subjects with cholecystocholedocholithiasis: 104 underwent a scheduled laparoscopic surgery (group A), and 97 where admitted for AC and had urgent laparoscopy (group B). Group B patients were significantly older (68.4 vs. 62.1 years; P = 0.0045), had a higher proportion of women (56% vs. 41%; P = 0.0345), and included more patients in the ASA III-IV class (39% vs. 21%; P = 0.0006). LTCE was performed by using basket-wired catheters. CBD clearance, operating time, conversion rate, morbidity and mortality, postoperative hospital stay, readmission, and residual CBD stones were the main outcome measures. RESULTS: Clearance of CBD was obtained in 84% of patients of group A and in 80% of patients of group B (P = not significant). Time spent in the operating room was longer for group B (175 vs. 141 min; P = 0.0003). There were no significant differences for postoperative hospital stay (group A 4.9 vs. group B 5.2 days), readmission rate (3.7% vs. 3.7%), and residual CBD stones (2.8% vs. 3.1%). Need to convert and morbidity occurred more frequently in group B (11.7% vs. 4.6% and 28.7% vs. 16.8%, respectively), but differences were not significant. In group A, one patient died from MOFS. CONCLUSIONS: LTCE has proved to be a simple technique with a high yield of CBD clearance in the acute setting. Courses are comparable to those observed for the same procedure in elective surgery despite the fact that patients with AC are more at risk for drawbacks.

Fine-needle aspiration for proteomic study of tumour tissues.

Fine-needle aspiration (FNA) is a technique largely applied in the diagnosis of tumours. FNA is a safe diagnostic procedure that is widely employed in the examination of masses at relatively low cost and minimal risk to the patient. In this review, we report on the state-of-the-art and the potential role of FNA to search for protein biomarkers by the proteomic approach.

Massive upper gastrointestinal bleeding from a pancreatic pseudocyst rupture: a case report.

INTRODUCTION: Bleeding from pancreatic pseudocyst's rupture into adjacent organs is a rare, but potentially fatal, complication of chronic pancreatitis requiring quick management. Timing of the rupture is unpredictable; early diagnosis and correct management is essential in preventing the bleeding. CASE PRESENTATION: We describe the case of a 53 years old male patient successfully treated with emergency surgery for massive hematemesis due to a rupture of a bleeding pseudocyst into the stomach. Patient underwent emergency laparotomy and suture of the bleeding vessel. At 5 years follow-up patient is in healthy condition. CONCLUSION: This case shows to surgeons that pancreatic pseudocyst cannot be managed strictly with one rule and prompt surgical treatment is mandatory in case of haemodinamic instability.

Fine-needle aspiration of thyroid nodules: proteomic analysis to identify cancer biomarkers.

At present, the clinical and pathological analysis used in the diagnosis of papillary thyroid cancer (PTC) are insufficient to discern tumor behavior, and new diagnostic and prognostic markers need to be identified. In this study, we performed a comparative proteome analysis to examine the global changes of fine needle aspiration fluid (FNA) protein patterns of two variants of malignant PTC (classical variant PTC (cPTC) and tall cell variant PTC (TCV)) with respect to the controls. Changes in protein expression were identified using two-dimensional electrophoresis (2DE) and peptide mass fingerprinting via MALDI-TOF mass spectrometry (MS), as well as Western blot analysis. A statistical significant up-regulation of 17 protein spots in cPTC and/or TCV with respect to controls was demonstrated. These proteins included transthyretin precursor (TTR), ferritin light chain (FLC), proteasome activator complex subunit 1 and 2, alpha-1-antitrypsin precursor, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase chain B (LDH-B), apolipoprotein A1 precursor (Apo-A1), annexin A1, DJ-1 protein and cofilin-1. In addition, 12 protein spots were found exclusively in cPTC and three exclusively in TCV. These latter proteins (ferritin heavy chain (FHC), peroxiredoxin 1 (PRX1) and 6-phosphogluconate dehydrogenase (6-PDGH)) correspond to stress response proteins and, until now, had not been described in thyroid tumors. These findings illustrate the potential use of FNA proteomics to identify protein changes associated with thyroid cancer and to advance potential protein biomarkers in the diagnostic classification of the disease.

Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders.

The survival rate of patients with medullary thyroid carcinoma (MTC) is significantly better in patients diagnosed and treated when the tumor is limited to the thyroid. In a pioneer study carried out in 1991, we demonstrated that routine measurement of serum calcitonin (CT) in nodular thyroid disease allowed the preoperative diagnosis of unsuspected sporadic MTC with better accuracy than routine fine needle aspiration cytology (FNAC). This finding has been confirmed in subsequent studies. In the present study we report the results of CT screening in 10,864 patients with thyroid nodular disease seen in the years 1991-1998 (group 1). We analyzed the prevalence of MTC and compared their outcomes with those of a historical group of patients (group 2) diagnosed before the introduction of CT screening (1970-1990). The prevalence of MTC found by CT screening in group 1 was 0.40% (44 patients). A positive CT test had a higher diagnostic sensitivity and specificity compared with FNAC. CT screening allowed the diagnosis of MTC at an earlier stage compared with group 2 (P = 0.004). Normalization of serum CT levels (undetectable) after surgery was more frequently observed in group 1. At the end of follow-up, complete remission was observed in 59% of group 1 and in 2.7% of group 2 (P = 0.0001). Our study confirms that MTC is not an infrequent finding among patients with thyroid nodules (nearly 1 in 250 patients). In addition, screening thyroid nodules with serum CT measurement allows the diagnosis and treatment of MTC at an earlier stage, resulting in a better outcome compared with MTC not detected by serum CT measurement. One of the reasons for this finding is that increasing the preoperative diagnostic accuracy of MTC prompts the surgeon to perform a more radical and possibly curative treatment. On this basis, routine measurement of basal serum CT levels should be considered an integral part of the diagnostic evaluation of thyroid nodules.

Prevalence of cancer in follicular thyroid nodules: is there still a role for intraoperative frozen section analysis?

The optimal surgical management of follicular thyroid nodules and the effectiveness of frozen section (FS) analysis in planning the operation are still controversial. In this study, we reviewed the prevalence of cancer in 309 consecutive patients (230 females, 79 males, aged 42 +/- 13 years) with follicular nodules at fine-needle aspiration cytology (FNAC) and the efficacy of FS evaluation in selecting cancers. On the whole, the prevalence of cancer was 20.1%; the occurrence of follicular variants of papillary cancer (14.9%) was threefold higher than follicular cancers (5.2%). The presence of atypical features at FNAC selected nodules with a significantly higher prevalence of cancer (46.7%, p = 0.01). FS analysis was performed in 142 patients and recognized only 8 of 27 (30%) cancers, one fourth of them with atypia at FNAC. In conclusion, this study confirms a 20% overall prevalence of malignancy in patients with follicular thyroid nodules. The association of cell atypia with a follicular pattern may define a subgroup of nodules more likely to be malignant. FS was seldom effective in recognizing cancer confirming the doubt on its cost effectiveness in planning the surgical approach. Protocols aimed at a better cytologic identification of follicular variants of papillary cancer should be considered.

Anthropometric, haemodynamic, humoral and hormonal evaluation in patients with incidental adrenocortical adenomas before and after surgery.

OBJECTIVE: To compare clinical and humoral parameters before and after surgery in patients with incidental adrenocortical adenomas. DESIGN: Six patients with subclinical Cushing's syndrome and nine with non-functioning adenomas were investigated before and 12 Months after removal of the mass. METHODS: Anthropometric (body weight, body mass index and waist to hip ratio), haemodynamic (blood pressure and heart rate), metabolic (lipids and oral glucose tolerance test (OGTT)), hormonal (cortisol, plasma renin activity, aldosterone, androgens and catecholamines) and bone metabolism (hydroxyproline, parathyroid hormone, osteocalcin and ostase) parameters were evaluated. RESULTS: In the whole group, a significant decrease in body weight (69.7+/-3.5 vs 70.8+/-3.5 kg, P<0.03), in systolic (135.3+/-5.1 vs 145.6+/-4.9 mmHg, P<0.009) and diastolic (83.7+/-1.9 vs 91.0+/-3.5 mmHg, P<0.03) blood pressure and in glucose levels in response to OGTT (106.4+/-9.6 vs 127.5+/-6.5 mg/dl, P<0.05) was observed after surgery. All other parameters examined did not change significantly. This trend was also found in both groups separately. Analytical data showed a high frequency of overweight/obesity (66.6%), hypertension (66.6%) and impaired glucose profile (26.6%) in our patients, with a greater prevalence of these cardiovascular risk factors in the subclinical Cushing's syndrome group. After surgery, values normalized or improved in eight out of ten hypertensive patients and in three out of four patients with impaired glucose profile. CONCLUSIONS: Solid adrenocortical incidentalomas are associated with some cardiovascular risk factors which may be corrected after removal of the mass. Therefore, surgery may be an appropriate choice in patients with subclinical Cushing's syndrome but also in those with solid non-functioning adenomas and coexistent cardiovascular risk factors.