Antioxidant Defense Capacity Is Reduced in Thyroid Stem/Precursor Cells Compared to Differentiated Thyrocytes.

There is much evidence linking oxidative stress to thyroid cancer, and stem cells are thought to play a key role in the tumor-initiating mechanism. Their vulnerability to oxidative stress is unexplored. This study aimed to comparatively evaluate the antioxidant capacity of stem/precursor thyroid cells and mature thyrocytes. Human stem/precursor cells and mature thyrocytes were exposed to increasing concentrations of menadione, an oxidative-stress-producing agent, and reactive oxygen species (ROS) production and cell viability were measured. The expression of antioxidant and detoxification genes was measured via qPCR as well as the total antioxidant capacity and the content of glutathione. Menadione elevated ROS generation in stem/precursor thyroid cells more than in mature thyrocytes. The ROS increase was inversely correlated (p = 0.005) with cell viability, an effect that was partially prevented by the antioxidant curcumin. Most thyroid antioxidant defense genes, notably those encoding for the glutathione-generating system and phase I detoxification enzymes, were significantly less expressed in stem/precursor thyroid cells. As a result, the glutathione level and the total antioxidant capacity in stem/precursor thyroid cells were significantly decreased. This reduced antioxidant defense may have clinical implications, making stem/precursor thyroid cells critical targets for environmental conditions that are not detrimental for differentiated thyrocytes.

Heavy Metals in the Environment and Thyroid Cancer.

In recent decades, the incidence of thyroid cancer has increased more than most other cancers, paralleling the generalized worldwide increase in metal pollution. This review provides an overview of the evidence supporting a possible causative link between the increase in heavy metals in the environment and thyroid cancer. The major novelty is that human thyroid stem/progenitor cells (thyrospheres) chronically exposed to different metals at slightly increased environmentally relevant concentrations show a biphasic increase in proliferation typical of hormesis. The molecular mechanisms include, for all metals investigated, the activation of the extracellular signal-regulated kinase (ERK1/2) pathway. A metal mixture, at the same concentration of individual metals, was more effective. Under the same conditions, mature thyrocytes were unaffected. Preliminary data with tungsten indicate that, after chronic exposure, additional abnormalities may occur and persist in thyrocytes derived from exposed thyrospheres, leading to a progeny population of transformation-prone thyroid cells. In a rat model predisposed to develop thyroid cancer, long-term exposure to low levels of metals accelerated and worsened histological signs of malignancy in the thyroid. These studies provide new insight on metal toxicity and carcinogenicity occurring in thyroid cells at a low stage of differentiation when chronically exposed to metal concentrations that are slightly increased, albeit still in the "normal" range.

Thyroid Stem Cells But Not Differentiated Thyrocytes Are Sensitive to Slightly Increased Concentrations of Heavy Metals.

Thyroid cancer incidence is markedly increased in volcanic areas where residents are biocontaminated by chronic lifelong exposure to slightly increased metals in the environment. Metals can influence the biology of living cells by a variety of mechanisms, depending not only on the dose and length of exposure but also on the type and stage of differentiation of target cells. We explored the effect of five heavy metals (Cu, Hg, Pd, W and Zn) at nanomolar concentrations (the biocontamination level in residents of the volcanic area in Sicily where thyroid cancer is increased) on stimulating the proliferation of undifferentiated (thyrospheres) and differentiated human thyroid cells. Thyrosphere proliferation was significantly increased after exposure to each individual metal and a greater stimulating effect was observed when a mixture of the examined metals was used. No effect was seen in differentiated thyrocytes. For all metals, the dose-response curve followed a biphasic pattern that is typical of hormesis. Thyrosphere growth concerned the size rather than number, except with the metal mixture. An altered morphology was also observed in metal-treated thyrospheres. Metal-induced proliferation was due to activation of the ERK1/2 pathway, as confirmed by growth inhibition when ERK1/2 signaling was blocked. These studies show that stem/precursor thyroid cells are sensitive to small increases in environmental metal concentrations that are harmless for differentiated thyrocytes.

Safe introduction of ancillary trocars in gynecological surgery: the "yellow island" anatomical landmark.

AIM: This technical note aims to suggest a safe introduction of ancillary trocars in gynaecological surgery, in order to prevent inferior epigastric artery damage. MATERIAL OF STUDY: We performed a narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: Among the different techniques, the identification of the "yellow island" as anatomical landmark seems to be a useful aid to avoid complication. This particular landmark is identified taking the lateral third of a line between the anterior superior iliac spine and the umbilicus as reference points, by a subperitoneal accumulation of adipose tissue located in that area. DISCUSSION: "Yellow island" could be considered a safe place for trocars introduction because epigastric artery never runs there, even in patients with particular anatomical variants. This technique is particularly useful in obese patients, in which "yellow island" appears to be more evident respect to lean ones. Furthermore, the use of "open" trocars insertion may reduce the possibility of epigastric artery lesions respect to "Verres needle technique". CONCLUSION: The identification of the "yellow island" anatomical landmark could be considered an useful aid for the safe introduction of ancillary trocars in gynaecological surgery. KEY WORDS: Gynaecology, Laparoscopic surgery, Trocars placement.

Full-Thickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating Endometriosis: Rationale and Potential Treatment Options.

Endometriosis is defined as the presence of endometrial mucosa (glands and stroma) abnormally implanted in locations other than the uterine cavity. Deep infiltrating endometriosis (DIE) is considered the most aggressive presentation of the disease, penetrating more than 5 mm in affected tissues, and it is reported in approximately 20% of all women with endometriosis. DIE can cause a complete distortion of the pelvic anatomy and it mainly involves uterosacral ligaments, bladder, rectovaginal septum, rectum, and rectosigmoid colon. This review describes the state of the art in laparoscopic approach for DIE with a special interest in intestinal involvement, according to recent literature findings. Our attention has been focused particularly on full-thickness excision versus shaving technique in deep endometriosis intestinal involvement. Particularly, the aim of this paper is clarifying from the clinical and methodological points of view the best surgical treatment of deep intestinal endometriosis, since there is no standard of care in the literature and in different surgical settings. Indeed, this review tries to suggest when it is advisable to manage the full-thickness excision or the shaving technique, also analyzing perioperative management, main complications, and surgical outcomes.

Prognostic Factors for Adrenocortical Carcinoma Outcomes.

PURPOSE: Adrenocortical carcinoma (ACC) is an aggressive tumor characterized by a high recurrence rate and poor response to treatment. This study analyzes a consecutive series of ACC patients to evaluate the prognostic value of various clinical and pathological characteristics. METHODS: We retrospectively evaluated 32 ACC patients followed at our Medical Center from 1997 to 2015 and evaluated the prognostic value of age at diagnosis, gender, tumor functional status, stage, and type of treatment with respect to overall survival (OS) and disease-free survival (DFS), as determined by Kaplan-Meier curves. RESULTS: ACC was associated with hormonal overproduction in 50% of cases, and patients with isolated hyperandrogenism had a better prognosis. Recurrence was observed in 12/26 (46.2%) patients with no evidence of disease after surgery. Tumor size [hazard ratio (HR) 1.32, 95% confidential intervals (CI) 1.12-1.64; p = 0.007], ki-67 (HR 1.06, 95% CI 1.02-1.11; p = 0.009) and advanced stage at diagnosis (III-IV) (HR 6.51, 95% CI 1.65-24.68; p = 0.006) were associated with recurrence in the 26 R0 patients in the univariate analysis. Advanced stage was an independent risk factor for recurrence in the multivariate analysis (HR 8.10, 95% CI 1.55-41.35; p = 0.01). Five-year survival was 40.0%. Positive resection margins (HR 10.61, 95% CI 3.02-38.31; p = < 0.001), ki-67 (HR 1.04, 95% CI 1.01-1.07; p = 0.01) and advanced stage (HR 11.31, 95% CI 1.45-87.76; p = 0.02) were associated with poor survival in all 32 patients, but only positive resection margins were an independent predictor of mortality in the multivariate analysis (HR 6.22, 95% CI 1.44-26.05; p = 0.01). CONCLUSION: ACC has a poor prognosis with a high recurrence rate. Tumor stage at diagnosis and the completeness of surgical excision are the most relevant prognostic factors.

The BRAF(V600E) mutation influences the short- and medium-term outcomes of classic papillary thyroid cancer, but is not an independent predictor of unfavorable outcome.

INTRODUCTION: The prognostic usefulness of BRAF(V600E) evaluation in papillary thyroid cancer (PTC) has been analyzed in many studies, with controversial conclusions. AIM: To analyze the clinical relevance of BRAF(V600E) measurement in a homogenous series of PTC patients followed in a single institution. METHODS: One hundred three classical variant PTC patients who underwent total thyroidectomy in the 3-year period between 2005 and 2008 were retrospectively selected, and BRAF(V600E) assessment was performed using paraffin-embedded archival specimens in 2013. All patients were actively followed at our medical center, with an average follow-up of 55±13 months. RESULTS: BRAF(V600E) mutation-positive cancers (55.3%) were more frequently associated with lymph node metastasis (p=0.01) and advanced TNM stage (III-IV) (p=0.03). These findings were also confirmed in the subset of 42 microcarcinomas. BRAF(V600E)-positive patients were also at a higher risk of persistent disease (OR 3.5 [95% confidence interval {CI} 1.2-10.3], p=0.03) in univariate but not multivariate analysis (OR 2.8 [CI 0.7-11.8], p=0.2). Lymph node involvement was an independent predictor of persistent disease (OR 30.9 [CI 6.0-159.0], p<0.0001). Kaplan-Meier curves confirmed a higher percentage of persistent/recurrent disease in BRAF(V600E)-positive patients (p=0.02). However, the BRAF(V600E) mutation did not change the recurrence rate of PTC in subgroup analyses on the basis of other established risk factors (p=0.2). CONCLUSIONS: BRAF(V600E)-positive tumors were at higher risk of developing more aggressive behavior and were associated with less favorable outcomes in the short and medium term, but the BRAF(V600E) mutation was not an independent predictor of unfavorable outcome. Therefore, its use as a prognostic marker in clinical practice is not advisable.

Is BCLC algorithm useful in clinical practice? Study on 164 HCC patients.

BACKGROUND/AIMS: The Barcelona Clinic Liver Cancer (BCLC) classification has been recently validated as the best system for treatment guidance for hepatocellular carcinoma (HCC). The aim of this retrospective study is to evaluate the usefulness of BCLC in the treatment of HCC comparing our treatment decision and the BCLC algorithm indications. METHODOLOGY: In 102 patients affected by HCC observed from 1991 to 2002 a retrospective analysis was performed. The choice of treatment was compared with the treatment schedule proposed by BCLC. Whereas the second group of 62 patients observed from 2008 to 2010 was analysed both retrospectively in comparison with the BCLC classification. RESULTS: We found a disagreement in between our decision making and the choices suggested by BCLC. We only found a statistical significance for age and performance status test. In surgical patients the median age and the PST class were lower with a statistically significant p value (0.04 and 0.03, respectively). CONCLUSIONS: The BCLC system would not have changed our decision either in the past, or in present days, especially in surgical indications. Even if the decision making is affected by BCLC, actually that process still needs the support of the experience of each clinical centre involved.

Colorectal cancer treatment and follow-up in the elderly: an inexplicably different approach.

The incidence of colorectal cancer increases as age progresses. At present, elderly patients have received substandard cancer treatment not supported by "evidence." Geriatric assessment should be performed preoperatively and selected elderly patients must be offered standard surgical treatment receiving the same complementary therapies as a younger patient. It should be stressed that elderly patients should not be deprived of their decision-making role. In our experience, more than 43% of patients with colorectal cancer are ≥70 years of age, and we believe that they should receive the same type of follow-up. This would allow for the detection and removal of polyps, treatment of malignant tumors, and psychological support similarly to younger patients. Significantly, in our experience, the incidence of reoperation for neoplastic disease is similar in the two patient populations.

Gastrointestinal carcinoid tumor and chylous ascites, a rare association with a poor prognosis. A case report.

Gastrointestinal carcinoid is a rare tumor. The association of this tumor with chylous ascites is uncommon. A review of the English-language literature carried out in 2002 identified only 15 cases. We report a case of chylous ascites, gastrointestinal carcinoid tumor and elevated blood levels of CA-125 in a patient who did not respond to chemotherapy.