Andrea Polistena

Impact of prophylactic central compartment neck dissection on locoregional recurrence of differentiated thyroid cancer in clinically node-negative patients: A retrospective study of a large clinical series

BACKGROUND In clinically node-negative patients with differentiated thyroid cancer (DTC), indications for routine central lymph node dissection (RCLD) are the subject of intensive research, and surgeons are divided between the pros and cons of this surgery. To better define the role of neck dissection in the treatment of DTC, we analyzed retrospectively the results in three centers in Italy. METHODS The clinical records of 752 clinically node-negative patients with DTC who underwent operative treatment between January 1998 and December 2005 in three endocrine surgery referral units were evaluated retrospectively. The complications and medium- and long-term outcomes of total thyroidectomy (TT) alone (performed in 390 patients: group A) and TT combined with bilateral RCLD (362 patients: group B) were analyzed and compared. RESULTS The incidence of permanent hypoparathyroidism and permanent unilateral vocal folds was 1% and 0.8% in group A and 3.6% and 1.7% in the group B, respectively. Bilateral temporary recurrent nerve palsy was observed in one of the 362 patients in group B. After a follow-up of 9.5 ± 3.5 years (mean ± SD), the locoregional recurrence rate with positive cervical lymph nodes was not substantially significantly different between the two groups. CONCLUSION In our series, TT combined with bilateral RCLD was associated with a greater rate of transient and permanent complications. Similar incidences of locoregional recurrence were reported in the two groups of patients. Considering the recent trend toward routine central lymphadenectomy, further studies are needed to evaluate the benefits of these different approaches.

Gastrointestinal and Retroperitoneal Manifestations of Type 1 Neurofibromatosis

BackgroundType 1 neurofibromatosis (NF1) is a genetic disease characterized by neoplastic and not neoplastic disorders, involving tissues of neuroectodermal or mesenchymal origin. The mainly involved districts are skin, central nervous system, and eye, and there is a wide range of severity of clinical presentations.Data sourcesAbdominal manifestations of NF1 comprehend five categories of tumors: neurogenic with neurofibromas, malignant peripheral nerve sheath tumors and ganglioneuromas, neuroendocrine with pheochromocytomas and carcinoids, non-neurogenic gastrointestinal stromal tumors, i.e., GISTs, and embryonal tumors and miscellaneous.ConclusionsEarly diagnosis of these abdominal manifestations is very important given the risk of malignancy, organic complications such as in the case of pheochromocytomas or hemorrhagic-obstructive complications such as in the case of the tumors of the gastrointestinal tract (GISTs and neurofibromas). The importance of an annual clinical evaluation on the part of a multidisciplinary pool of clinicians in highly specialized centers allows early detection of complications and of neoplastic transformation.

Local radiotherapy of exposed murine small bowel: Apoptosis and inflammation

BackgroundPreoperative radiotherapy of the pelvic abdomen presents with complications mostly affecting the small bowel. The aim of this study was to define the features of early radiation-induced injury on small bowel.Methods54 mice were divided into two groups (36 irradiated and 18 sham irradiated). Animals were placed on a special frame and (in the radiated group) the exteriorized segment of ileum was subjected to a single absorbed dose of 19 or 38 Gy radiation using 6 MV high energy photons. Specimens were collected for histology, immunohistochemistry (IHC) and ELISA analysis after 2, 24 and 48 hours. Venous blood was collected for systemic leucocyte count in a Burker chamber.ResultsHistology demonstrated progressive infiltration of inflammatory cells with cryptitis and increased apoptosis. MIP-2 (macrophage inflammatory protein) concentration was significantly increased in irradiated animals up to 48 hours. No significant differences were observed in IL-10 (interleukin) and TNF-α (tumour necrosis factor) levels. IHC with CD45 showed a significant increase at 2 hours of infiltrating leucocytes and lymphocytes after irradiation followed by progressive decrease with time. Caspase-3 expression increased significantly in a dose dependent trend in both irradiated groups up to 48 hours.ConclusionAcute small bowel injury caused by local irradiation is characterised by increased apoptosis of crypt epithelial cells and by lymphocyte infiltration of the underlying tissue. The severity of histological changes tends to be dose dependent and may affect the course of tissue damage.

Surgical morbidity of cervical lymphadenectomy for thyroid cancer: A retrospective cohort study over 25 years.

INTRODUCTION Prognosis of thyroid cancer is strictly related to loco-regional metastases. Cervical lymphadenectomy has a specific oncologic role but may lead to significant increase of morbidity. Aim of the study is the analysis of surgical morbidity in cervical lymphadenectomy for thyroid cancer. METHODS We retrospectively analyzed 1.765 thyroid cancers operated over a period of 25 years at S. Maria University Hospital, Terni, University of Perugia, Italy. Type of lymphadenectomy, histology and complications were analysed. RESULTS A prevalence of differentiated and medullary cancers was observed (respectively 88% and 7.2%). Central lymphadenectomy was carried out in 425 patients, lateral modified and radical lymphadenectomy respectively in 651 and 17 cases. Following central neck dissection we observed: bilateral and unilateral temporary recurrent nerves palsy respectively of 0.7% and 3.5%, unilateral permanent palsy in 1.6% of cases, temporary and permanent hypoparathyroidism respectively in 17.6% and 4.4%. After lateral neck dissection we observed: intra and post-operative haemorrhage respectively in 2% and 0.29%, respiratory distress in 0.29%, lesions of facial nerve in 0.44%, of vagus in 0.14%, of phrenic nerve in 0.14%, of hypoglossal nerve in 0.29%, of the accessory nerve, transient in 1.34% and permanent in 0.29%, permanent lesion of cervical plexus in 0.29%, salivary fistula in 0.14% and chylous fistula in 1.04% of patients. Students t test was used to compare groups when appliable. CONCLUSION Central and lateral cervical lymph node dissection are associated to severe morbidity. Correct indication, surgical expertise, high volume of patients and early multidisciplinary management of complications is the key of an acceptable balance between oncologic benefits and surgical morbidity.

Role of Desmoplasia in Recurrence of Stage II Colorectal Cancer within Five Years after Surgery and Therapeutic Implication

Background: Colorectal cancer (CRC) metastasis is enhanced in patients with venous embolization increasing the risk of recurrence and therefore mortality rate. Several evidences indicate that stage II patients have an abrupt recurrence within five years from surgery. This fact, led us to investigate the role played by different histological variables on CRC invasiveness. Aim: To demonstrate if quantitative and qualitative desmoplastic response and lymphocytic infiltration are prognostic factor involved in the recurrence of CRC within five years from surgery, considering possible clinical and therapeutical implications. Methods: Thirty-four patients with CRC underwent colectomy and the UICC-TNM classification was applied for disease staging. Histological variables were semi-quantitatively evaluted. Qualitative evaluation of desmoplasia was obtained with the hematoxillin-eosin method. Results: Survival rate arose 88% at stage II, at five years of follow-up, and the 12% not treated with adiuvant chemotherapy developed metastasis. Desmoplasia is strongly associated with venous neoplastic invasiveness (OR: 21.93; 95%CI: 1.012-475.26, p = 0.02), and therefore, with mortality rate (OR: 14.33; 95%CI: 0.67-304, p = 0.04). Moreover, mortality rate was significantly higher in patients with immature desmoplasia compare to mature stromal tissue (OR: 15.61, 95%CI: 0.69-343.38, p = 0.04). Conclusions: These observations should prompt a future evaluation of desmoplasia to extent more suitably the use of adjuvant chemotherapy in II stage patients. Further clinical trials are needed to determine if these findings will be able to reduce mortality rate, in stage II CRC patients.

Necrotizing pancreatitis: A review of the interventions

Acute pancreatitis may have a wide range of severity, from a clinically self-limiting to a quickly fatal course. Necrotizing pancreatitis (NP) is the most dreadful evolution associated to a poor prognosis: mortality is approximately 15% and up to 30-39% in case of infected necrosis, which is the major cause of death. Intervention is generally required for infected pancreatic necrosis and less commonly in patients with sterile necrosis who are symptomatic (gastric or duodenal outlet or biliary obstruction). Traditionally the most widely used approach to infected necrosis has been open surgical necrosectomy, but it is burdened by high morbidity (34-95%) and mortality (11-39%) rates. In the last two decades the treatment of NP has significantly evolved from open surgery towards minimally invasive techniques (percutaneous catheter drainage, per-oral endoscopic, laparoscopy and rigid retroperitoneal videoscopy). The objective of this review is to summarize the current state of the art of the management of NP and to clarify some aspects about its diagnosis and treatment.

Genetics of medullary thyroid cancer: An overview

Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved. In MEN2A, Codon 634 in exon 11 (Cys634Arg), corresponding to a cysteine in the extracellular cysteine-rich domain, is the most commonly altered codon. Many other mutations include codons 611, 618, 620. In the genetical testing of RET mutations in MTCs, Next-Generation Sequencing (NGS) is taking an increasingly important role. One of the most important benefit is the comprehensive analysis of molecular alterations in MTC, which allows rapidly to select patients with different risk levels. There is a difference in miRNA expression pathway between sporadic and hereditary MTCs. Among sporadic cases, expression of miR-127 was significantly lower in those who harbor somatic RET mutations than those with wild-type RET. CDKN1B mutations are associated with many clinical pictures of cancers, such as MEN4. V109G polymorphism is associated with sporadic MTCs negative for RET mutations, and might influence the clinical course of the patients affected by MTC. Although surgery (i.e. total thyroidectomy with neck lymph node dissection) is the elective treatment for MTCs, about 80% of patients have distant metastases at diagnosis and in this cases surgery is not enough and an additional treatment is needed. Interesting results come from two large phase III clinical trials with two targeted tyrosine kinase inhibitors (TKIs), vandetanib and cabozantinib. CONCLUSIONS New genetical testings and therapeutical approaches open new perspectives in MTC management.

Inability of University of Wisconsin Solution to reduce postoperative peritoneal adhesions in rats

OBJECTIVE To examine the effect of University of Wisconsin solution (UWS) on the formation of postoperative peritoneal adhesions. DESIGN Laboratory experiment. SETTING University hospital, Italy. ANIMALS 42 Sprague-Dawley rats. INTERVENTIONS A standard lesion was made consisting of serosal trauma of the caecum and a parietal peritoneal defect. Rats were randomly divided into seven groups (n = 6 each): the first group acted as controls; the second had instilled normal saline 6 ml; the third Ringers lactate 6 ml; the fourth UWS 6 ml; the fifth normal saline 12 ml; the sixth Ringers lactate 12 ml; and the seventh UWS 12 ml. MAIN OUTCOME MEASURES Adhesions were scored two weeks later for extent (0 to 4) and type (0 to 4). Adhesion strength was measured by a tensiometer. RESULTS The mean (SEM) scores for extent and type of adhesions were significantly lower (p < 0.05) after instillation of Ringers lactate 12 ml [1.0 (0.4) and 1.2 (0.4), respectively] than controls [3.5 (0.3) and 2.7 (0.2), respectively]. Adhesions were also significantly weaken (p < 0.05) [101 (33) g] than in controls [207 (6) g]. CONCLUSIONS Intraperitoneal instillation of normal saline and UWS were ineffective in reducing the extent and type of adhesions. Although Ringers lactate produced a significant reduction in severity, the effect was strongly volume related. This amount of fluid may be detrimental to a patients postoperative course.

Laparoscopic adrenal-sparing surgery: personal experience, review on technical aspects

Partial adrenalectomy is usually performed for the treatment of bilateral pheochromocytomas and in case of sporadic, monolateral tumors, to minimize the risk of adrenal failure, especially in younger patients. Due to the lack of consistent series, many issues such as correct surgical indications and technical aspects still need to be debated. From 2007 to 2010 we performed four unilateral partial adrenalectomies (3 aldosterone-producing adenomas and 1 cortisol-producing adenoma), and three bilateral subtotal adrenalectomies, consisting in total adrenalectomy on one side and partial adrenalectomy on the contralateral gland (3 bilateral pheochromocytomas in MEN IIa). In case of single tumor, partial adrenalectomy was carried out without adrenal vein ligation and the results were similar to total adrenalectomy both in terms of surgical and functional outcome, with normalization of hormone levels and control of hypertension. Operating time and postoperative stay were not significantly different from unilateral total adrenalectomy. In case of bilateral subtotal adrenalectomy our results demonstrate effectiveness in terms of surgical outcome and control of hypertension, but one patient needed steroid replacement therapy due to post-operative adrenocortical failure. Care must be taken when giving indication to adrenal sparing surgery, because this procedure can be technically difficult, and due to the risk of recurrence, especially in case of bilateral tumors, it can affect both surgical and functional outcomes.

MULTIPLE CATECHOLAMINE-SECRETING PARAGANGLIOMAS: DIAGNOSIS AFTER HEMORRHAGIC STROKE IN A YOUNG WOMAN

OBJECTIVE To describe a case of multiple catecholamine-secreting paragangliomas, with a hemorrhagic stroke as the main clinical manifestation. METHODS We present a case report with clinical, laboratory, histologic, and genetic details. RESULTS A 23-year-old woman with a history of hypertension treated with orally administered medications presented to our emergency department because of sudden onset of hemiplegia of the left side of the body. A computed tomographic scan of the brain showed a right frontoparietal hematoma, and her blood pressure was 185/115 mm Hg. She was admitted to the Department of Neurosurgery, and an external drain was inserted to evacuate the hematoma. She was then referred to the Department of Clinical Sciences, where a search for possible secondary causes of hypertension was undertaken. Substantially elevated urinary levels of vanillylmandelic acid and metanephrines were found, and a pheochromocytoma was suspected. Abdominal computed tomographic scans revealed a large retroperitoneal mass (3.6 by 4 cm) and similar smaller lesions in the right adrenal gland, between the aorta and the vena cava, and in the left paraaortic area. Iodine I 123 metaiodobenzylguanidine scintigraphy showed high uptake in those same areas, consistent with the diagnosis of multiple catecholamine-secreting paragangliomas. After adequate control of the patients hypertension was achieved with an alpha1-adrenergic receptor blocker, a Ca2+ antagonist, and a beta-adrenergic blocking agent, the tumors were excised in the Department of Surgery. The histopathologic findings confirmed the diagnosis of multiple paragangliomas. The genetic analysis demonstrated an exon 4 mutation in codon 109 (CAA>TAA, Gln>Stop) of the SDHD gene. CONCLUSION Although cerebral hemorrhage is an unusual complication of pheochromocytomas or paragangliomas, early recognition of the characteristic symptoms of headache, palpitations, and diaphoresis in a patient with hypertension and prompt appropriate intervention can minimize the morbidity associated with such tumors and prevent a potentially fatal outcome.