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Medullary thyroid cancer (MTC) is typically associated with multiple endocrine neoplasia type 2 syndrome (MEN 2), but not with multiple endocrine neoplasia type 1 (MEN 1). We report a very rare case of MTC in a patient with MEN 1 syndrome. A 60-year-old Caucasian woman with sporadic MEN 1 syndrome was admitted in October 2018 for recurrent hyperparathyroidism unresponsive to medical therapy. Her medical history included the diagnosis of a non-functioning pancreatic neuroendocrine tumor (NF-pNET) of the head of the pancreas 1.5 cm in size in 2001, and subtotal parathyroidectomy for uncontrolled hyperparathyroidism due to bilateral parathyroid hyperplasia in the same year. This history prompted genetic studies, and MEN 1 syndrome was confirmed. Family screening was performed in first-degree relatives, with negative results. Other typical clinical manifestations of MEN 1 syndrome were ruled out. In November 2018, the patient underwent excision of the residual left inferior parathyroid, extended to include the left thyroid lobe, for recurrent uncontrolled hyperparathyroidism. The pathologist identified MTC and adenoma of the parathyroid gland. Genetic tests were performed to identify any RET mutation, with negative results. The patient underwent total thyroidectomy about 6 months later, and the subsequent histological report showed only focal reactive C-cell hyperplasia of the thyroid. A literature review identified only three previously published cases of MTC coexisting with MEN 1 syndrome. This association may have two etiological hypotheses: either a sporadic MTC arising in a patient with MEN 1 syndrome, or a rare case of medullary cancer linked to a MEN 1 gene mutation.

Purpose The study aimed to evaluate the feasibility and safety of a new trans-anal rectoscopic-assisted minimally invasive surgery (ARAMIS) platform to treat rectal lesions. Methods ARAMIS was first compared with two transanal minimally invasive surgery platforms (SILS Port and GelPOINT Path) on human cadavers. Surgeons with different experience performed running sutures at different distances, at four quadrants, using the three platforms and gave a score to visibility, safety, and maneuverability. ARAMIS was then utilized on patients affected with rectal neoplasia who met the inclusion criteria. Patients and tumor characteristic and results were prospectively collected. The follow-up examinations included proctoscopy at 3, 6, and 12 months. Results According to surgeons’ scores, ARAMIS improves visibility and safety with respect to other platforms for distances beyond 10 cm. The procedure, which lasted an average of 59 min, was successfully carried out in 14 patients. No intraoperative or postoperative complications were reported. The mean tumor size was 3 cm; they were located a mean of 11 cm from the anal verge. Complete removal of the lesion was possible in 13/14 patients. There was one case of adenoma recurrence at follow-up. Conclusion Study results showed that ARAMIS, which is equipped with an adjustable rectoscope, can be considered a safe, effective platform for transanal surgery. The rectoscope protects the rectum during the procedure, a particularly important consideration when proximal rectal lesions are being treated. Further clinical studies are warranted to confirm these encouraging results.

Background: The potassium channel encoded by the ether-a-gogo-related gene 1A (erg1a) has been detected in the atrophying skeletal muscle of mice experiencing either muscle disuse or cancer cachexia and further evidenced to contribute to muscle deterioration by enhancing ubiquitin proteolysis; however, to our knowledge, ERG1A has not been reported in human skeletal muscle. Methods and Results: Here, using immunohistochemistry, we detect ERG1A immunofluorescence in human Rectus abdominis skeletal muscle sarcolemma. Further, using single point brightness data, we report the detection of ERG1A immunofluorescence at low levels in the Rectus abdominis muscle sarcolemma of young adult humans and show that it trends toward greater levels (10.6%) in healthy aged adults. Interestingly, we detect ERG1A immunofluorescence at a statistically greater level (53.6%; p < 0.05) in the skeletal muscle of older cancer patients than in age-matched healthy adults. Importantly, using immunoblot, we reveal that lower mass ERG1A protein is 61.5% (p < 0.05) more abundant in the skeletal muscle of cachectic older adults than in healthy age-matched controls. Additionally, we report that the ERG1A protein is detected in a cultured human rhabdomyosarcoma line that may be a good in vitro model for the study of ERG1A in muscle. Conclusions: The data demonstrate that ERG1A is detected more abundantly in the atrophied skeletal muscle of cancer patients, suggesting it may be related to muscle loss in humans as it has been shown to be in mice experiencing muscle atrophy as a result of malignant tumors.

Objective Immune thrombocytopenia (ITP) is an acquired disorder, characterized by immune-mediated platelet destruction. The spleen plays a key pathogenic role in ITP and splenectomy is a valuable second-line therapy for this disease. Little is known on ITP spleen histology and response to splenectomy is unpredictable. This study aims to characterize ITP spleen histology and assess possible predictors of splenectomy outcome. Methods A series of 23 ITP spleens were retrospectively assessed for the following histological parameters: density of lymphoid follicles (LFs), marginal zones (MZs), T helper and cytotoxic T cells; presence of reactive germinal centers (GCs); width of perivascular T cell sheaths; and red pulp features. Clinical and histological data were matched with postsplenectomy platelet counts to assess their prognostic relevance. Results Three histological patterns were documented: a hyperplastic white pulp pattern, a non-activated white pulp pattern (lacking GCs), and a white pulp-depleted pattern. Poor surgical responses were associated with presplenectomy high-dose steroid administration, autoimmune comorbidities and low T follicular helper cell density. The combination of such parameters stratified patients into different splenectomy response groups. The removal of accessory spleens was also associated with better outcome. Conclusion ITP spleens are histologically heterogeneous and clinical-pathological parameters may help predict the splenectomy outcome.

Background: The ERG1a potassium channel has been detected in the atrophying skeletal muscle of mice experiencing either muscle disuse or cancer cachexia and further evidenced to contribute to muscle deterioration by enhancing ubiquitin proteolysis; however, to our knowledge, ERG1 has not been reported in human skeletal muscle. Methods and Results: Here, using immunohistochemistry, we detect ERG1 immunofluorescence in human Rectus abdominis skeletal muscle sarcolemma. Further, using single point brightness data, we report detection of ERG1 immunofluorescence at low levels in the Rectus abdominis muscle sarcolemma of young adult humans and show that it trends toward greater levels (10.6%) in healthy aged adults. Interestingly, we detect ERG1 immunofluorescence at a statistically greater level (53.6%; p

Surgical training in virtual, animal and cadaver models is essential for minimally invasive surgery. Thiel cadavers are suitable for laparoscopy, but there are few data about the use of embalmed (Tutsch method) and slightly embalmed (Thiel method) cadavers in procedures of Natural Orifice Transluminal Endoscopic Surgery (NOTES), which are usually developed and learned on swine models and fresh frozen cadavers. The aim of this study was thus to assess the use of these cadavers for NOTES approaches. The following surgical procedures were evaluated: transanal total mesorectal excision (four cadavers: one Tutsch, two Thiel, one fresh frozen), transanal ileorectal bypass (five cadavers: one Tutsch, three Thiel, one fresh frozen), and transvaginal appendectomy (two Tutsch cadaver). The Thiel method ensured tissue flexibility and consistency suitable for performing the above surgical procedures with good results and without complications, with only a small increase in rigidity with respect to fresh specimens. Cadavers embalmed with higher formalin concentrations (Tutsch method) were more difficult to use, due to high tissue rigidity and resistance of the abdominal wall to pneumoperitoneum, although NOTES accesses were possible. Thiel cadavers are suitable for transanal/transrectal and transvaginal NOTES approaches, for training surgical residents/specialists and also for surgical research. In minimally invasive surgery (and particularly in NOTES), integration between cadaver (fresh frozen and/or Thiel) and animal models would represent the gold standard, allowing guaranteed knowledge of and respect for human surgical anatomy and correct management of surgery on living subjects. NOTES approaches to human cadavers may also be proposed for the anatomical education of medical students.

e15696Background: GEM still represents one of the mostly adopted treatments for PC. Combination treatments provided some improvement in response rate (RR) and progression free survival (PFS), although almost invariably associated to increased toxicity. Aiming to find a complementary therapy to GEM in advanced PC, we tested a preparation of curcumin complexed with phospholipids (Meriva) to increase bioavailability. Curcumin has antinflammatory, antioxidant and potential antitumor properties, seemingly, descending from the activation of nuclear factor Nrf2 and inhibition of NFkB. From this pattern of nutraceutical effects of Curcumin, Meriva emerges as a good candidate for complementary therapy, while also improving quality of life (QoL). Methods: This was a single centre, single arm prospective phase II trial. Inclusion criteria were: previously untreated patients with histologically confirmed metastatic or locally advanced PC, ECOG performance status (PS) of 0-2, adequate organ function and written inform...

Introduction Pour les tumeurs de l’hypopharynx et de l’œsophage cervical, une premiere ligne radiochimio est de plus en plus utilisee, la chirurgie etant reservee aux tumeursrecurrentes ou qui ne repondent pas. Methodes Nous rapportons une etude retrospective sur 190 patients avec un carcinome epidermoide de l’hypopharynx et de l’œsophage cervical, traites dans notre Service de 1992 a 2012. Le stade clinique etait T3–4 dans 164 (86,3 %) patients, et N + dans 129 (67,9 %). 26 patients (14 %) ont eu une chirurgie premiere, et 164 (86 %) ont ete traites avec une radiochimio premiere. Resultats Pour la chirurgie premiere la mortalite postoperatoire etait de 15,4 % (4 sur 26) et la survie a 3 et 5 de 23 % et 19 %. Dans le groupe radiochimio premiere (164 patients) la reponse clinique etait : complete (CR) chez 58 patients (41 %), et partielle (PR) chez 40 patients (28 %). La mortalite postop. apres traitement radiochimio etait de 4 %. Le taux de survie a 3 ans et 5 ans des patients avec un CR clinique etait de 57 % et 41 %, et pour les patients avec une PR clinique, il a ete de 39 % et 33 %. Discussion Les patients ayant subi une chirurgie primaire avaient un plus mauvais pronostic que les patients qui ont eu une premiere ligne radiochimio malgre le fait qu’ils avaient des tumeurs de stade precoce. Conclusion La radiochimio premiere devrait etre le traitement de choix pour le cancer de l’hypopharynx et de l’œsophage cervical, et la chirurgie premiere seulement pour les tumeurs que ne repondent pas.

A new manometric classification of esophageal achalasia has recently been proposed that also suggests a correlation with the final outcome of treatment. The aim of this study was to investigate this hypothesis in a large group of achalasia patients undergoing laparoscopic Heller-Dor myotomy.We evaluated 246 consecutive achalasia patients who underwent surgery as their first treatment from 2001 to 2009. Patients with sigmoid-shaped esophagus were excluded. Symptoms were scored and barium swallow X-ray, endoscopy, and esophageal manometry were performed before and again at 6 months after surgery. Patients were divided into three groups: (I) no distal esophageal pressurization (contraction wave amplitude30 mmHg); (II) rapidly propagating compartmentalized pressurization (panesophageal pressurization30 mmHg); and (III) rapidly propagating pressurization attributable to spastic contractions. Treatment failure was defined as a postoperative symptom score greater than the 10th percentile of the preoperative score (i.e.,7).Type III achalasia coincided with a longer overall lower esophageal sphincter (LES) length, a lower symptom score, and a smaller esophageal diameter. Treatment failure rates differed significantly in the three groups: I = 14.6% (14/96), II = 4.7% (6/127), and III = 30.4% (7/23; p = 0.0007). At univariate analysis, the manometric pattern, a low LES resting pressure, and a high chest pain score were the only factors predicting treatment failure. At multivariate analysis, the manometric pattern and a LES resting pressure30 mmHg predicted a negative outcome.This is the first study by a surgical group to assess the outcome of surgery in 3 manometric achalasia subtypes: patients with panesophageal pressurization have the best outcome after laparoscopic Heller-Dor myotomy.

Background Skeletal muscle is the major reservoir of body proteins and it can be affected in conditions associated to altered protein turnover and metabolism such as cancer. Although severe wasting is seen primarily in patients with advanced malignancy, some of them present degree of wasting at the onset of disease. Autophagy has been recently described to play a relevant role inmuscle wasting.Materials andMethodsWeperformedmorphometric studies and immunohistochemical analyses on intraoperative rectus abdominis muscle biopsies from 50 consecutive weight stable colorectal patients and 25 weight-stable patients operated for non-inflammatory benign diseases with no clinical signs of myopathies. Biochemical and molecular analyses have been performed in order to evaluate protein profile, the presence of autophagy induction and their correlation with clinical outcome. Results In cancer patients, we observed a subclinical myopathy characterized by an abnormal distribution of myonuclei relocated from the periphery inside themyofiber. The percentage ofmyofibers with abnormally located myonuclei was significantly higher in patients (median= 9%) compared to controls (median= 2.7%) (p=0.0002). Analyses on serum samples showed that, in the absence of systemic inflammation, in the prevalence of cancer patients the levels of albumin and prealbumin were below the normal range and the mean value was significantly lower compared to that detected in controls (albumin: 34.82 ± 5.8 g/L vs 45.2 ± 5.3, p< 0.01; prealbumin: 174.38±57.86 mg/L vs 264.00±69.73, p

Background Skeletal muscle is the major reservoir of body proteins and it can be affected in conditions associated to altered protein turnover and metabolism such as cancer. Although severe wasting is seen primarily in patients with advanced malignancy, some of them present degree of wasting at the onset of disease. Autophagy has been recently described to play a relevant role in muscle wasting. Materials and Methods We performed morphometric studies and immunohistochemical analyses on intraoperative rectus abdominis muscle biopsies from 50 consecutive weight stable colorectal patients and 25 weight-stable patients operated for non-inflammatory benign diseases with no clinical signs of myopathies. Biochemical and molecular analyses have been performed in order to evaluate protein profile, the presence of autophagy induction and their correlation with clinical outcome. Results In cancer patients, we observed a subclinical myopathy characterized by an abnormal distribution of myonuclei relocated from the periphery inside the myofiber. The percentage of myofibers with abnormally located myonuclei was significantly higher in patients compared to controls. Analyses on serum samples showed that, in the absence of systemic inflammation, in the prevalence of cancer patients the levels of albumin and prealbumin were below the normal range and the mean value was significantly lower compared to that detected in controls. Molecular analyses showed an accumulation of p62, a typical marker of autophagy induction, significantly higher in cancer patients compared to controls. We found an inverse correlation between the number of abnormally nucleated myofibers and the presence of lymph node metastasis. Cancer relapse was correlated with low serum levels of prealbumin and high levels of p62 in myofibers of cancer patients. Conclusions Colorectal cancer patients have a subclinical myopathy characterized by myofibers with internally located myonuclei. In the absence of inflammation, cancer patients show low levels of prealbumin and albumin as markers of altered protein turnover and persistent high levels of p62 in myofibers as expression of autophagy induction with an impairment in physiological autophagic flux. Up to now our data indicate that skeletal muscle fibers show nuclear abnormalities that seems to be associated to a better prognosis, while the presence of an altered protein turnover at an early stage of disease, with an impairment in the physiological autophagic flux, that could be predictive of cancer relapse and onset of cancer cachexia.