Molecular testing in indeterminate thyroid nodules: an additional tool for clinical decision-making.

Thyroid nodules are commonly encountered in clinical practice, affecting up to 50% of the population. The large majority of thyroid lumps are benign incidental findings detected by imaging, while approximately 5-15% harbor malignancy. For a target patient's care, it is of paramount importance to identify and treat thyroid malignancy, while preventing unnecessary invasive surgery in patients with benign lesions. Although fine needle aspiration (FNA) associated with cytological examination provides malignant risk information, 20-30% of diagnoses fall into the "indeterminate thyroid nodule" (ITN) category. ITN clinical management remains a challenging issue for physicians since the ITN risk of malignancy varies from 5% to 40% and most thyroid nodules undergo overtreatment with surgery procedures. ITN molecular testing may better define malignant risk in the single nodule and is able to discriminate with accuracy benign from malignant nodules. Nowadays there are different technologies and different molecular panels, each with its own specificity, sensitivity and predictive values. In view of widespread introduction of molecular testing , some outstanding questions remain and are addressed in the present review such as the presence of molecular panels acting as "rule in" or "rule out" tools, the effective impact of testing results in the clinical decision-making process, and the prohibitive cost of commercial assays associated with the lack of test reimbursement in national health systems.

Gastric neuroendocrine tumor with Helicobacter pylori-associated chronic gastritis.

INTRODUCTION: Development of gastric neuroendocrine neoplasms in subjects infected with Helicobacter pylori is rare and it occurs through pathogenetic mechanisms related to gastrin. PRESENTATION OF CASE: We report a case of gastric neuroendocrine tumor in a patient infected with Helicobacter pylori and normal gastrin levels. He was treated by endoscopic mucosal dissection after eradication of Helicobacter pylori infection. Histologically the tumor was consistent with a grade 2 well differentiated neuroendocrine tumor. It was characterized by the presence of lymphoid aggregates around and inside the neoplasia. DISCUSSION: Helicobacter pylori-associated chronic gastritis can rarely cause the development of gastric neuroendocrine tumors through mechanisms unrelated to gastrin. CONCLUSION: The one related to a chronic Helicobacter pylori infection may be considered a distinct type of gastric neuroendocrine tumor.

Multifocal early gastric cancer in a patient with atrophic gastritis and pernicious anemia.

INTRODUCTION: Pernicious anemia (PA) caused by vitamin B12 deficiency is associated with Autoimmune Metaplastic Atrophic Gastritis (AMAG). Patients with AMAG have threefold risk of the development of gastric cancer. PRESENTATION OF CASE: We describe a case of a 66 year old man with a history of PA and atrophic antral-corpus gastritis. After endoscopic and chromoendoscopic evaluation the patient was treated with subtotal gastrectomy plus D2 lymphadenectomy. The tumor was diagnosed as Stage Ia; pT1a pN0 pM0 G2 with multiple foci of high grade dysplasia and intramucosal adenocarcinoma. DISCUSSION: Multifocal Early Gastric Cancer can be a problem for minimally invasive treatment such as endoscopic excision. Surgical management where it is not possible Endoscopic Mucosal Resection or Submucosal Resection (EMR/ESD) should include D1 or more type of lymphadenectomy because of the risk of nodes metastases. The chromoendoscopic evaluation may be helpful in the preoperative work-up and during the follow-up period. CONCLUSION: Multidisciplinary approach is very important to reduce the under-treatment risk in multifocal early gastric cancer. Further studies will be needed to evaluate the safety of Subtotal vs Total Gastrectomy in this kind of disease.

Activated-cytotoxic TCRαß+CD4+ peripheral T-cell lymphoma with hypodermal localization: Case report of a lymphoproliferative disorder probably evolved from the CD4+ cytotoxic T-cell subpopulation.

The World Health Organization (WHO) classification of hematopoietic and lymphoid tumors identifies distinctive subtypes of peripheral T-cell lymphoma (PTCL), and, additionally, some PTCLs involving mostly extranodal sites like the skin. The difficulty of classifying PTCLs according to the normal stages of T-cell differentiation and the lack of definitive diagnostic markers for most of the subtypes make the diagnosis of these diseases challenging. PTCL cases which do not fit into any of the specifically defined entities are categorized as PTCL not otherwise specified (PTCL-NOS). PTCLs-NOS represent less than 2% of the total cases of T-cell lymphoma involving the skin. This article illustrates a case of a PTCL-NOS in which tumor cells have an activated cytotoxic TCRαß+CD3+CD4+CD56+ T-cell phenotype and histopathologic features of subcutaneous panniculitis-like T-cell lymphoma, leading to a fatal outcome.

Correction to: Surgical and oncological outcomes after complete mesocolic excision in right-sided colon cancer compared with conventional surgery: a retrospective, single-institution study.

The publisher regrets that some errors were introduced during the production process. The errors are now presented correctly in this article.

Surgical and oncological outcomes after complete mesocolic excision in right-sided colon cancer compared with conventional surgery: a retrospective, single-institution study.

PURPOSE: The aim of the study was whether complete mesocolic excision (CME) with central vascular ligation (CVL) is associated with a survival benefit compared with traditional procedure in right-sided colon cancer. METHODS: Overall, 251 consecutive patients underwent surgery for right colon cancer between 2007 and 2012. After exclusion, 95 subjects received non-CME surgery before 2010, and 97 subjects received CME surgery after January 2010, when we started to perform CME systematically. The number of lymph nodes, morbidity, and mortality was analyzed. Overall survival (OS) and disease-specific survival (DSS) were investigated. RESULTS: The median number of examined lymph nodes was 33.28 in the CME group and 26.92 in the non-CME group, p < 0.001. Postoperative complications were 21.6% in the CME group and 17.8% in the non-CME group, without significant difference. One out of 192 patients died. Three-year OS was 88% in the CME group and 71% in the non-CME group (p = 0.003). In stage II, 3-year DSS was 97% in the CME group and 86% in the non-CME group. In stage III, the 3-year DSSs in the CME and in the non-CME groups were 86 and 67%, respectively (p < 0.001). Cox's regression showed that CME (p = 0.0012), the number of lymph nodes (p = 0.029), and TNM stage (p < 0.001) were significant independent predictors of DSS at 3 years. CONCLUSION: Surgical standardization of CME with CVL for right-sided colon cancer is associated with better staging and prognosis, particularly in UICC stage II and III. This study shows that CME is safe and reproducible with acceptable morbidity.

Single-Agent Pixantrone as a Bridge to Autologous Stem Cell Transplantation in a Patient with Refractory Diffuse Large B-Cell Lymphoma.

Aggressive non-Hodgkin lymphoma is associated with poor long-term survival after relapse or resistance to chemotherapy. We report a case of aggressive non-Hodgkin lymphoma refractory to first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and second-line R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) chemotherapy treatments. The patient achieved remission with single-agent pixantrone, and received a consolidation with high-dose BEAM (BCNU, etoposide, cytarabine, and melphalan) chemotherapy and autologous stem cell transplantation. He received consolidation radiotherapy on the site of bulky disease. At 20 months from transplant, the disease is in continuous complete remission. The successful use of pixantrone as a bridge to transplant is highlighted, together with the absence of serious side effects.

Small-bowel myeloid sarcoma: Report of a case with atypical presentation.

INTRODUCTION: Small-bowel myeloid sarcoma is rare. Acute bowel obstruction is its usual clinical presentation. PRESENTATION OF CASE: We report a case of small-bowel myeloid sarcoma that occurred in a 64-year-old woman who presented chronic secretory diarrhoea, hypokalaemia, and weight loss. Immature white blood cells in a peripheral smear and small-bowel capsule endoscopic features were the main diagnostic clues. The patient experienced capsule retention and developed acute bowel obstruction. Urgent laparotomy showed a stricturing ileal mass and pathology of the resected bowel specimen unveiled a CD34+, CD117+, and myeloperoxidase-positive myeloid sarcoma. The diarrhoea promptly resolved after surgery, and the patient is now undergoing chemotherapy. DISCUSSION: Secretory diarrhoea can be the first manifestation of small-bowel myeloid sarcoma. Capsule endoscopy may provide a diagnostic clue, but it can trigger an acute bowel obstruction. Differential diagnosis of the pathologic specimen may be difficult and a high suspicion index of is mandatory to perform immunophenotyping to determine the correct management. CONCLUSION: Chronic diarrhoea with alarm features can be the first manifestation of small-bowel myeloid sarcoma.

Neurofibromatosis 1 presenting with multiple duodenal GISTS associated with a somatostatin-producing D cell neoplasm.

The co-existence of a duodenal somatostatin-producing D cell neoplasm and multiple duodenal gastrointestinal stromal tumours (GISTs) in a 61-year-old woman with neurofibromatosis type 1 is reported. Histologically, the D cell neoplasm showed a glandular pattern with psammoma bodies and was metastatic to regional lymph nodes and liver at the time of surgery. Tumour cells were monomorph and showed intense and diffuse immunoreactivity for somatostatin, focal positivity for calcitonin, while were negative for other gastroenteropancreatic hormones including insulin, glucagon, pancreatic polypeptide, serotonin and gastrin. Four submucosal and subserosal GISTs, ranging from 5 to 15 mm in diameter, were composed of uniform spindle-shaped cells lacking mitoses and contained numerous skeinoid fibres. The tumours were positive for CD117, DOG1, vimentin and CD34 and did not have KIT or PDGFRA mutations. The clinical and pathological importance of this unusual association is discussed.

Castleman's disease with numerous mantle zone lymphocytes with clear cytoplasm involving the skin: case report.

Castleman's disease (CD) is an unusual lymphoid hyperplasia occurring in the mediastinal lymph nodes and, less frequently, in the neck lymph nodes. CD is classified clinically into a unicentric and a multicentric type, whereas three histomorphological variants are recognized: the hyaline vascular type, the intermediate type and the plasma cell type. We report the clinical and pathological features of a 54-year-old female suffering with multiple sclerosis and developing a lymph node hyaline-vascular type CD relapsing in the skin after 24 months. Histological features showed a nodular dermatitis with atrophic germinal centers and an 'onion skin' rimming of lymphocytes in the mantle zone with numerous mantle zone lymphocytes with clear cytoplasm, with a CD20+, CD79a+, IgM+, IgG-, IgA-, CD5-, CD10-, CD43-, CD45RO-, bcl-2+ and bcl-6- phenotype with polytypic nature supporting the diagnosis of lymphoid variant of hyaline-vascular CD. This case shows that skin CD recapitulates all the histological variants of lymph node CD. Considering the many similarities between the present case and the primary cutaneous marginal zone lymphoma, it is important to bear in mind this atypical lymphoproliferative disorder in order to avoid overdiagnosis and overtreatment.

Adenocarcinoma of the ampulla of Vater: T-stage, chromosome 17p allelic loss, and extended pancreaticoduodenectomy are relevant prognostic factors.

OBJECTIVE: To evaluate the prognostic significance of different clinico-pathological and molecular factors, and to compare survival after standard and extended pancreaticoduodenectomy (PD) in ampulla of Vater adenocarcinoma (AVAC). There are discordant data on factors affecting prognosis, and hence therapeutic choices, in AVAC. PATIENTS AND METHODS: Clinical-pathological factors were evaluated in 59 patients, subjected to PD for AVAC; in 42 subjects information on chromosome 17p and 18q allelic losses (LOH) and microsatellite instability (MSI) was also available. The association between survival and type of PD was investigated in the 25 patients operated between 1990 and 2001 (16 standard and nine extended). RESULTS: The overall 5- and 10-year tumor-related survival rates were 46% and 33%, respectively. Sixteen patients had T-stages 1-2, 14 T-stage 3, and 29 T-stage 4 cancers. Chromosome 17p and 18q LOH were detected in 23 (55%) and 15 cases (36%), respectively, and in 12 cases (29%) coexisted. Five cases were MSI-positive (12%). At univariate analysis, poor survival was associated with cancer ulceration (P = 0.051), poor differentiation (P = 0.008), T-stage 4 (P < 0.001), nodal metastases (P = 0.004), chromosome 17p (P < 0.001) and 18q LOH (P = 0.002), and absence of MSI (P = 0.009). At multivariate analysis, only T-stage (P = 0.002) and 17p LOH (P = 0.001) were independent predictors of survival. All patients with MSI-positive cancers were long-survivors (>12 yrs), whereas only 30% of MSI-negative cancer patients survived at 5 years. Extended pancreaticoduodenectomy was associated with a 3-year disease-related survival higher than standard resection (83% vs 31%; P = 0.018). CONCLUSION: MSI and chromosome 17p status allow to better define prognosis within ampullary cancers at the same stage. Surgery alone resulted curative in MSI-positive cancer patients, whereas it was inadequate in patients showing allelic losses, who might benefit from adjuvant therapy. In this observational study, extended PD was associated with increased survival compared to standard procedures.

Adjuvant intra-arterial 5-fluoruracil, leucovorin, epirubicin and carboplatin with or without systemic gemcitabine after curative resection for pancreatic adenocarcinoma.

BACKGROUND: The role of adjuvant therapy in pancreatic cancer remains controversial. Gemcitabine given systemically seems to be effective; intra-arterial chemotherapy (IAC) has a deep rationale. PATIENTS AND METHODS: The goal was to evaluate the impact of postoperative IAC followed or not by systemic gemcitabine in patients after curative resection for pancreatic adenocarcinoma. 5-fluoruracil 750 mg sq m(-1), leucovorin 75 mg sq m(-1), epirubicin 45 mg sq m(-1), carboplatin 225 mg sq m(-1) were administered every 3 weeks into celiac axis for three cycles (FLEC regimen), then gemcitabine at the dosage of 1 g sq m(-1) on days 1, 8 and 15 every 4 weeks for 3 months (FLECG regimen). RESULTS: Forty-seven patients entered the study. The first 24 received only IAC (FLEC regimen), the other 23 received the same intra-arterial regimen followed by systemic gemcitabine (FLECG regimen). After a median follow-up of 16.9 months, 29 patients recurred (61.7%). Median disease free survival (DFS) was 18 months and median overall survival (OS) was 29.7 months. One-year DFS was 59.4% and 1-year OS was 75.5%. Main grade 3 toxicity related to IAC was only nausea/vomiting in 4%; regarding gemcitabine, grade 3 toxicities were anaemia 8%, leukopenia 8%, thrombocitopenia 17%, nausea/vomiting 4%. CONCLUSIONS: FLEC regimen with or without gemcitabine is active with a very mild toxicity and results are very encouraging in an adjuvant setting.

Indications and technique of central pancreatectomy-early and late results.

BACKGROUND AND AIM: Central pancreatectomy (CP) is an operation that allows one to resect benign or low grade malignant tumours located in the pancreatic isthmus that are not suitable for enucleation. The main advantage of this operation compared with major resections is that it permits to spare normal pancreatic parenchyma. PATIENTS AND METHODS: The operation is carried out by exposition of the pancreatic neck involved by the lesion. Thereafter, the gland is dissected from the splenic artery and porto-mesenteric axis and divided with a 1 cm clear margin. The cephalic stump is sutured, and the distal stump is anastomosed end-to-end or end-to-side with a Roux-en-Y jejunal loop. We treated 20 patients with this technique. The indications for CP were: serous cystadenoma in seven patients, mucinous in three, solid cystic papillary tumour in one, metastasis from renal cancer in one and endocrine tumour in eight patients. RESULTS: Mortality rate was 0% and morbidity rate was 35%; pancreatic fistulas occurred in 25% of the cases and were treated conservatively. Results of postoperative endocrine and exocrine function tests were normal in all controlled patients. All the patients are alive without evidence of local recurrence. CONCLUSION: CP is a safe technique for benign or low-grade malignant tumours of the pancreatic neck that allows one to cure the tumour with evident functional results without increasing the risk to the patient.

An unusual case of Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia.

We report a case of Cushing's syndrome due to ACTH-independent macro-nodular adrenal hyperplasia (AIMAH). The patient, a 51-year-old man, had been suffering from poorly controlled arterial hypertension for the previous 6 years and he complained of progressive weight gain, gynecomastia and impotence. Physical examination revealed classic cushingoid features. Endocrine basal assessment showed increased urinary free cortisol (264-600 micrograms/24 hr). Urinary steroid profile showed an increase of total 17-hydroxycorticosteroids (17-OHCS: 23 mg/24 hr), with a threefold increase of tetrahydrocortisol (THF:9.66 mg/24 hr) and of tetrahydrocorticosterone (THB: 1.35 mg/24 hr). Tetrahydrodesossicortisol was only slightly elevated (THS:0.67 mg/24 hr) and tetrahydrodesossicorticosterone was at the inferior limit of the normal range (THDOC: 0.03 mg/24 hr). Total 17-ketosteroids were decreased (17-KS: 3 mg/24 hr). Plasma cortisol level was elevated and without circadian rhythm (26-29 micrograms/dl in the morning, 26-28 micrograms/dl at 24:00 h). DHEAs and free testosterone levels were significantly reduced (106 ng/dl and 3.9 pg/ml respectively). ACTH was undetectable and unresponsive to CRH. Both dexamethasone and octreotide failed to suppress plasma cortisol levels. Abdomen computed tomography scan demonstrated bilaterally enlarged multinodular adrenal glands. Cerebral magnetic resonance revealed no alteration of the pituitary gland. The patient underwent bilateral adrenalectomy. On macroscopic examination, adrenal glands were occupied by multiple yellow nodules and their compressive weight was 190 g, with left adrenal heavier than the right one (120 g and 70 g respectively). Histologically, nodular lesions were predominantly composed of large clear cells, with small foci of "hybrid" cells and adipose tissue metaplasia. Reticularis zone was atrophic. In the immediate post-operatory course pulmonary embolism occurred, despite prophylaxis with low molecular weight heparin. After having recovered from this complication, the patient showed progressive regression of cushingoid status. The findings of increased THF/THS and THB/THDOC ratios were in agreement with a relative hyperfunction of 11-beta-hydroxylase "in vivo", which might have contributed to the hypercortisolism, in addition to the marked increase of secernent adrenal mass.

[Current trends of artificial enteral nutrition in acute pancreatitis]. / Attuali indirizzi di nutrizione artificiale enterale nella pancreatite acuta.

During recent years, there has been considerable debate as to the nutritional supply that needs to be established for a patient with acute pancreatitis. The main problem is still infection of the pancreatic necrosis, which has a decisive bearing on the indication for surgery and is the main cause of mortality. Infection stems from bacterial translocation from the patient's gut. Enteral nutrition with its known potential for reducing this type of infection constitutes an attempt to prevent it by preserving the enteric mucosal barrier. Today, the concept of pancreatic rest is no longer considered mandatory in the guidelines of many Surgical and Nutritional Societies, whilst enteral nutrition is the gold standard for acute pancreatitis. Assuring an integrated parenteral and enteral supply before reaching the full regimen of enteral nutrition is the most reliable policy during the early days of the disease. Moreover, outcomes being equal, enteral nutrition is cheaper than parenteral nutrition, as has been extensively demonstrated in many clinical trials in severe acute pancreatitis.

Results of pancreaticoduodenectomy for pancreatic cancer: extended versus standard procedure.

In Western experience, the long-term survival benefit after extended pancreaticoduodenectomy (EPD) in patients with pancreatic ductal adenocarcinoma is still controversial. The aim of this work was to evaluate weather EPD for pancreatic ductal adenocarcinoma prolongs long-term survival compared to standard pancreaticoduodenectomy (SPD). From November 1992 to September 1996, we performed pancreatic resections in 30 patients affected by stage I-III pancreatic ductal adenocarcinoma: 13 patients underwent SPD and 17 patients underwent EPD, consecutively. The two groups of patients were similar for all the demographic, clinical, and pathological characteristics, and all the intraoperative factors considered except the number of resected lymph nodes (mean number per case = 34.2 +/- 15.5 in the EPD group versus 12.8 +/- 3.6 in the SPD group, p <0.001) and the operative time (median time per case = 375 minutes in the EPD group versus 270 minutes in the SPD group, p = 0.009). Patients in the two groups experienced a similar postoperative course. The estimated survival probability at 1 and 3 years after operation was 0.76 (95% confidence interval [CI]: 0.49 to 0.90) and 0.24 (95% CI: 0.07 to 0.45) in the EPD group; 0.31 (95% CI: 0.09 to 0.55) and 0.08 (95% CI: 0.00 to 0.29) in the SPD group (p = 0.014). According to a Cox model, the treatment was associated with R0 patients' long-term survival (SPD versus EPD: hazard ratio (HR) = 4.82, 95% CI: 1.66 to 14.00, p = 0.004). Grading of tumor differentiation was confirmed to be a relevant prognostic factor (poor versus moderate: HR = 4.33, 95% CI: 1.49 to 12.61, p = 0.007), whereas type of resection had no significant effect (pylorus-preserving versus hemigastrectomy: HR = 1.49, 95% CI: 0.56 to 3.95, p = 0.42). The proportion of R0 patients with local recurrence was lower in the EPD group (20.0% versus 70.0%, p = 0.034).

Gastroduodenal artery stump haemorrhage following pylorus-sparing Whipple procedure: treatment with covered stents.

BACKGROUND/AIMS: To report a case of bleeding after pancreatoduodenectomy in a patient with pancreatic leak and portal thrombosis who was successfully treated with an endovascular approach. METHODS: A 58-year-old male, suffering from neoplasm of the distal bile duct, underwent a pylorus-preserving Whipple procedure. On the 18th day, following a sudden drop in pressure and low haematocrit values, the patient underwent surgery. The source of the bleeding was not found. Six days later, following the appearance of bleeding from the abdominal drainage and haematemesis with shock, the patient had an immediate angiography. Bleeding from the gastroduodenal artery stump was evident, the portography showed no portal flow. With respect to the shortness of the stump, safe embolisation with coils, while preserving the common hepatic artery patency, was difficult to obtain. RESULTS: By transcatheter placement of covered stents into the hepatic artery and thereby occluding the origin of the gastroduodenal artery, the bleeding was stopped. After 2 months, CT angiography showed patency of both the common and proper hepatic arteries. Nine months after the procedure the patient is in good health. CONCLUSIONS: Percutaneous placement of covered stents can be the solution in cases where transcatheter embolisation is not recommendable because of portal vein thrombosis.