Postoperative hypocalcemia: analysis of factors influencing early hypocalcemia development following thyroid surgery.

BACKGROUND: Early Hypocalcemia is the most frequent complication after thyroid surgery. Several studies have tried to identify factors (patient caracteristics or surgical technique variations) affecting hypocalcemia following thyroid surgery. This studiy evaluates the role of several factors in postoperative hypocalcemia development. METHODS: A retrospective study conducted on 2108 patients that underwent thyroid surgery in a single center (1669 women and 439 men). Postoperative early hypocalcemia was defined as serum calcium levels lower than 8,0 mg/dl measured 24 h after surgery. Following factors were evaluated in the study: sex, age, glandular hyperfunction, preoperative diagnosis, preoperative serum calcium levels, preoperative serum PTH levels, type of surgery performed (total thyroidectomy vs. lobectomy); minimally invasive video assisted thyroidectomy (MIVAT); number of parathyroid preserved in situ, postoperative serum calcium levels, changes in perioperative calcium levels (difference between preoperative values ​​and postoperative calcium levels), presence of carcinoma in the surgical specimen, presence of thyroiditis based on histopatology reports. RESULTS: Among evaluated factors only gender and surgical procedure revealed to be significantly correlated to early hypocalcemia development. In fact female patients experienced postoperative hypocalcemia in 42% (701/1669) of cases, which was signicantly higher than the 21.4% (94/439) identified in men. We also noticed a greater hypocalcemia incidence in patient undergoing total thyroidectomy (38.8%) than in patient undergoing lobectomy group (13.8%). Early hypocalcemia development didn't appear to be related to preoperative serum calcium levels but it showed a statistically significant correlation with perioperative serum calcium level drop. CONCLUSION: This findings suggest that sex (female gender is a strong risk factor),surgical procedure and perioperative changes in serum calcium are the only factors (among all variables examined) that influence early hypocalcemia development.

Is there a correlation between thyroiditis and thyroid cancer?

BACKGROUND: In the past few decades, the incidence of thyroid cancer has increased significantly all over the world. In the same period, there also seems to have been an increase in the incidence of Hashimoto's Thyroiditis-the most common inflammatory autoimmune thyroid disease. Several studies have linked thyroiditis to thyroid cancer. METHODS: In our study, we examined 2304 cases of thyroid surgery collected over a 12-year period starting from 2004. In 2090 cases (90.7%) out of our sample, it has been possible to compare the presence, or lack thereof, of thyroiditis by means of a histological diagnosis post-surgery; 214 (9.3%) cases were excluded from our study due to insufficient data. We then divided the different histological classifications into two groups. Group A included all the benign histological classifications and Group B included all the malignant histological classifications. In each group, we then assessed the presence, or lack thereof, of thyroiditis in order to evaluate if thyroiditis can be linked to a higher incidence of thyroid cancer. RESULTS: Data analysis showed a higher incidence of thyroiditis in Group B, 36.4% (malignant pathology report), than in Group A, 32.4% (benign pathology report), but no statistically significant difference emerged between those two groups (P > 0.05). CONCLUSIONS: Our conclusion was that a correlation between thyroiditis and a higher incidence of thyroid cancer is still undefined.

Relationship between postoperative complications and survival after gastrectomy for cancer.

BACKGROUND: Surgical resection remains the main curative treatment for gastric cancer but is still affected by high postoperative morbidity and mortality rates, especially in Western countries. MATERIALS AND METHODS: We've analyzed patients treated for gastric cancer at our Operative Unit of ent, extent of lymphadenectomy and survival. General Surgery and Organ Transplantation of the University Hospital of Parma from January 2006 till December 2010, relating the occurrence of eventual complications to sex, age at diagnosis, definitive histological examination, type and duration of surgical treatment. RESULTS: The surgically treated cases were 152 (30.4 gastrectomies per year on average). 62 patients developed at least one adverse event during the postoperative period, reaching 108 total events. Among these, 71 were minor complications (grade I-II in Clavien-Dindo's classification), while 26 were major ones (grade III). Postoperative mortality affected 8 patients (5.3%). Data analysis did not stress any statistically significant correlation between the valued variables and the global incidence of complications. For severe ones, some risk factors emerged such as the type of gastrectomy, the execution of a multi-visceral resection and the operative time. Five-year overall survival has been 36.7%, lower in patients with severe complications (29%) when compared to patients without severe complications (38%). Radicality of operation, the lymph node involvement and the occurrence of severe complication emerged as significant prognostic factors for five-year overall survival. CONCLUSIONS: Surgery is still the mainstay of treatment for gastric cancer and the only one able to grant a curative therapy. When performed in high-volume centres, with more than 20 gastrectomies per year, it represents a safe treatment, affected by low mortality. Attention must be paid to careful preoperative selection, to treatment of pre-existent comorbidities, to plan a therapeutical strategy to minimize surgical stress, to postoperative monitoring and to managing complications', as they're able to impact not only low-term outcomes but also overall and disease-free survival. The poor prognosis for these patients is mainly related to advanced stage at presentation, thus confirming the need to increase early diagnosis in order to detect in larger percentages the tumor in its early stage. KEY WORDS: Complications, Gastrectomy, Gastric Cancer, Survival.

The surgical approach to nodule Thyr 3-4 after the 2.2014 NCCN and 2015 ATA guidelines.

BACKGROUND: The incidence of palpables thyroid nodules in general population is 5% and the prevalence of non -palpable nodules is higher (35-60%) in the endemic goiter area. In the last years the new guidelines and new classification related to thyroid nodule have changed the indication to treat it. MATERIAL AND METHOD: We analyzed the patients treated from January 2013 to June 2016 for Thyr 3 and Thyr 4 thyroid nodule sec. Bethesda system. We have divided in I and II period related to the 2.2014 and 2015 ATA guidelines and we have evaluated the indication to treat, the type of surgical procedure, the incidence of thyroid carcinoma and the adverse events. RESULTS: We selected from 909 cases, 252 cases surgically treated with preoperative diagnosis of Thyr 3(80 cases) and Thyr 4(172 cases); carcinoma was found in 21/80 (26.2%) and in 62/172 (26.05%). The period was divided from January 2013 to December 2014 and from January 2015 to june 2016 (first and second period). In II period we found carcinoma in 8/40 Thyr3 and in 26/88 Thyr 4. The incidence of lobectomy in II period was higher than I period (p < 0.0001) sec.guidelines indications. No difference in adverse events. The number of cancer is lower in patients treated with lobectomy than those who underwent total thyroidectomy (12,5%vs 21,8% in Thyr 3; 15,3% vs 32% in Thyr 4). CONCLUSIONS: The indications to treat related to Thyr 3 and Thyr4 are changed in the two periods. The number of cancer is lower in patients treated with lobectomy. The new guidelines have changed the surgical approach to thyroid nodule.

Thyroid micro-carcinoma: only a diagnostic epidemic?

BACKGROUND: The incidence of thyroid carcinoma ranges from 0.5 to 10 cases every 100,000, depending on the country, the context and purpose of the study. The high incidence of differentiated thyroid tumor is continuously growing. While most malignant pathologies affect the adults, a proportion of 1-2% of pediatric population is affected by solitary nodule, of which some are malignant cancers. Studying thyroid malignant cancer, the most sensitive and accurate imaging technique is color Doppler ultrasonography. Fine needle aspiration cytology (FNAC), if correctly performed, is the key to a correct diagnosis. METHODS: This prospective study analyzes 1726 cases of total thyroidectomy and lobectomy performed between January 2004 and December 2013. The cytology sampling has been done following standard FNAC or capillary aspiration. Results have been classified in five classes, following the Italian SIAPEC-AIT system (2008). Sensibility, specificity, accuracy, negative predictive value and positive for the evaluation of FNAC technique are the statistical parameters considered. RESULTS: The outcome is aligned with what already known in literature, that FNAC has sensibility between 60-98% and specificity between 72-100%. Considering Tir3 as a low malignancy risk category therefore not suitable for surgery, those values decrease. CONCLUSIONS: Micro-carcinoma is a more represented entity than apparently suspected. Nowadays, cytology is the most precise diagnostic support to the therapeutic management of thyroid node, yet it is still charged with false negatives. The evaluation of data records, combined with some molecular biology techniques and applied to cytology, could help in giving more appropriate surgical indication, allowing the surgery to be therapeutic more than diagnostic.

Minimally invasive thyroidectomy: a ten years experience.

BACKGROUND: The conventional thyroidectomy is the most frequent surgical procedure for thyroidal surgical disease. From several years were introduced minimally invasive approaches to thyroid surgery. These new procedures improved the incidence of postoperative pain, cosmetic results, patient's quality of life, postoperative morbidity. The mini invasive video-assisted thyroidectomy (MIVAT) is a minimally invasive procedure that uses a minicervicotomy to treat thyroidal diseases. METHODS: We present our experience on 497 consecutively treated patients with MIVAT technique. We analyzed the mean age, sex, mean operative time, rate of bleeding, hypocalcemia, transitory and definitive nerve palsy (6 months after the procedure), postoperative pain scale from 0 to 10 at 1 hour and 24 hours after surgery, mean hospital stay. RESULTS: The indications to treat were related to preoperative diagnosis: 182 THYR 6, 184 THYR 3-4, 27 plummer, 24 basedow, 28 toxic goiter, 52 goiter. On 497 cases we have reported 1 case of bleeding (0,2%), 12 (2,4%) cases of transitory nerve palsy and 4 (0,8%) definitive nerve palsy. The rate of serologic hypocalcemia was 24.9% (124 cases) and clinical in 7.2% (36 cases); 1 case of hypoparathyroidism (0.2%). CONCLUSIONS: The MIVAT is a safe approach to surgical thyroid disease, the cost are similar to CT as the adverse events. The minicervicotomy is really a minimally invasive tissue dissection.

FOXE1 and SYNE1 genes hypermethylation panel as promising biomarker in colitis-associated colorectal neoplasia.

BACKGROUND: Colitis-associated colorectal cancer affects individuals with inflammatory bowel disease (IBD) more often and earlier than cancer in the general population. Colonoscopy provides the surveillance gold standard. Changes to the surveillance intervals depending on endoscopic activity have been made, given data demonstrating that this is an important predictor of future dysplasia or cancer, but adjuvant, noninvasive clinical tools are still warranted to improve surveillance outcomes and to assist in management and interpretation of dysplasia. Methylation markers may be able to do this. METHODS: SYNE1, FOXE1, NDRG4, and PHACTR3 genes were screened using methylation-specific PCR that permit the methylation status of the genes to be determined directly on biopsies. Ninety-three patients with long-standing IBD undergoing a cancer surveillance program, and 30 healthy controls were studied. These included colorectal adenocarcinomas on a background of IBD of various stages (n = 25), IBD-associated dysplastic lesions (n = 29), adenomas arising on a background of ulcerative colitis (n = 8), samples from patients with no evidence of dysplasia or cancer but long-standing IBD (n = 31), and symptomatic patients found to have normal colonoscopy (controls) (n = 30). RESULTS: Gene promotor hypermethylation of SYNE1 and FOXE1 genes varied significantly between the groups and was increasingly likely with increased disease severity. Neither occurred in controls, whereas promotor hypermethylation was detected in biopsies of 60% of patients with colitis-associated colorectal cancer for FOXE1 and 80% for SYNE1. Promotor hypermethylation of either gene was highly significantly different between the groups overall. CONCLUSIONS: FOXE1 and SYNE1 hypermethylation markers demonstrated significantly increased expression in neoplastic tissue. Promoter methylation analysis of these genes might be a useful marker of neoplasia in long-standing IBD.

Sensitivity and specificity of magnetic resonance enterography in the clinical management of fistulizing Crohn's disease.

BACKGROUND: High diagnostic accuracy is reported for magnetic resonance enterography (MRE) in Crohn's disease (CD), but few studies have evaluated its role in abdominal fistulae. The primary aim of this study was to assess the reliability of MRE in the identification of internal fistulae in CD. METHODS: One hundred and eighty-six patients with moderate CD (CD Activity Index : 250-400) were prospectively selected from the inflammatory bowel disease clinic of Parma University Hospital. Eligible patients had already undergone nutritional screening, pancolonoscopy, and computed tomography enterography (CTE) in the month before enrollment. MRE was performed according to the study protocol. Additional fluoroscopic contrast-enhanced studies or surgical evaluation were used for discordance between CTE and MRE results. A consensus committee resolved equivocal findings. Surgical findings and/or fluoroscopic contrast-enhanced studies together with the clinical data were considered the composite "reference standard" to which the results of MRE were compared. RESULTS: MRE identified 22 internal fistulae in 21 patients (11%), of whom 4 (19%) also had perianal fistulae and found 7 abscesses (33%). Forty-one (22%) additional patients with perianal fistulae were identified. Thirteen patients (57%) with internal fistulae required enteral nutrition support. No statistically significant differences were found between MRE and CTE in fistula detection. There was also no significant difference between MRE and the composite diagnosis in those who underwent surgery (n = 8) and/or contrast-enhanced studies (n = 7). CONCLUSIONS: CTE and MRE accurately detect internal fistulae in CD. MRE is preferable because it avoids radiation. Reliable identification of internal fistulae by MRE should permit earlier and improved treatment.

Altered expression of type-1 and type-2 cannabinoid receptors in celiac disease.

Anandamide (AEA) is the prominent member of the endocannabinoid family and its biological action is mediated through the binding to both type-1 (CB1) and type-2 (CB2) cannabinoid receptors (CBR). The presence of AEA and CBR in the gastrointestinal tract highlighted their pathophysiological role in several gut diseases, including celiac disease. Here, we aimed to investigate the expression of CBR at transcriptional and translational levels in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also biopsies from treated celiac patients cultured ex vivo with peptic-tryptic digest of gliadin were investigated. Our data show higher levels of both CB1 and CB2 receptors during active disease and normal CBR levels in treated celiac patients. In conclusion, we demonstrate an up-regulation of CB1 and CB2 mRNA and protein expression, that points to the therapeutic potential of targeting CBR in patients with celiac disease.

Impact of lymph node ratio in the colorectal cancer staging system.

AIM: Some researchers have proposed the Lymph Node Ratio (LNR) as a prognostic index for post-surgical colorectal cancer follow up. MATERIAL AND METHOD: Two hundred patients with colorectal cancer (ratio F/M of 2:1) were studied. Patients were divided in subgroups according to N-stage and LNR score, subgroups of LNR were made on quartiles. For each subgroup 5 year survival rate was calculated and comparison between groups was carried out. RESULTS: There were 104 patients on N0, 38 on N1 and 58 on N2 stage. Survival rate at 5 years was 61.30% for the NO subgroup, 18.70% for the N1 subgroup, and 12.31% for the N2 subgroup (Fig. 1). The most significant p value, was reported between N0 and N1 as well as between N0 and N2 subgroup (p=0.001). Nodes positive were 44 a LNR ranging from 1% to 25% (1% < LNR < 25%); 24 patients from 26% to 50% (26% < LNR < 50%). In 6 patients LNR was ranging from 51% to 75% (51% < LNR 75%) and in 8 patients from 76% to 100% (76% < LNR 100%); overall survival rate in different quartiles was respectively 27.12%, 9.38%, 16.67% and 1.56%. CONCLUSION: LNR is a reliable prognostic index in post surgical colorectal cancer staging.

Abnormal anandamide metabolism in celiac disease.

The endocannabinoid system has been extensively investigated in experimental colitis and inflammatory bowel disease, but not in celiac disease, where only a single study showed increased levels of the major endocannabinoid anandamide in the atrophic mucosa. On this basis, we aimed to investigate anandamide metabolism in celiac disease by analyzing transcript levels (through quantitative real-time reverse transcriptase-polymerase chain reaction), protein concentration (through immunoblotting) and activity (through radioassays) of enzymes responsible for anandamide synthesis (N-acylphosphatidyl-ethanolamine specific phospholipase D, NAPE-PLD) and degradation (fatty acid amide hydrolase, FAAH) in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also, treated celiac biopsies cultured ex vivo with peptic-tryptic digest of gliadin were investigated. Our in vivo experiments showed that mucosal NAPE-PLD expression and activity are higher in untreated celiac patients than treated celiac patients and controls, with no significant difference between the latter two groups. In keeping with the in vivo data, the ex vivo activity of NAPE-PLD was significantly enhanced by incubation of peptic-tryptic digest of gliadin with treated celiac biopsies. On the contrary, in vivo mucosal FAAH expression and activity did not change in the three groups of patients, and accordingly, mucosal FAAH activity was not influenced by treatment with peptic-tryptic digest of gliadin. In conclusion, our findings provide a possible pathophysiological explanation for the increased anandamide concentration previously shown in active celiac mucosa.

Is CD10 a reliable marker of invasive colorectal cancer?

AIM: Previous studies reported that CD10 positive Colorectal Cancer Cells (CRC) characterized by deeply invasive neoplasia. MATERIALS AND METHODS: We have examined 50 pts surgically treated for colorectal cancer on at least 5 years follow up. TNM, grading score and survival have been compared to CD10 expression. RESULTS: Thirty-four out of fifty cases have been analyzed (18 males and 16 female) of whom nineteen were CD10 positive and fifteen were CD10 negative. The remaining 16 cases were droping out. No difference in survival rate between CD10 positive and negative in N0, N1, N2. No difference on survival rate and grading 1, 2, 3. We have then analyzed CD10 positive and CD10 negative cases, according to neoplasia grading, in patients with positive linphonodes N1 and N2. We showed a statistical difference between the CD10 positive/N2 (grading 1.66 +/- 0.5) and the CD10 negative/N2 (grading 3) (p < 0.005). CONCLUSIONS: We can hypothesize that CD10 positive neoplasia display a more invasive behaviour, independently from the N score and the G score, compared to CD10 negative neoplasia.