In Vitro and In Vivo Effects of the Urokinase Plasminogen Activator Inhibitor WX-340 on Anaplastic Thyroid Cancer Cell Lines.

Increased expression of the urokinase-type plasminogen activator (uPA) system is associated with tumor invasion, neo-angiogenesis, and metastatic spread, and has been shown to positively correlate with a poor prognosis in several cancer types, including thyroid carcinomas. In recent years, several uPA inhibitors were found to have anticancer effects in preclinical studies and in some phase II clinical trials, which prompted us to evaluate uPA as a potential therapeutic target for the treatment of patients affected by the most aggressive form of thyroid cancer, the anaplastic thyroid carcinoma (ATC). In this study, we evaluated the in vitro and in vivo effects of WX-340, a highly specific and selective uPA inhibitor, on two ATC-derived cell lines, CAL-62 and BHT-101. The results obtained indicated that WX-340 was able to reduce cell adhesion and invasiveness in a dose-dependent manner in both cell lines. In addition, WX-340 increased uPA receptor (uPAR) protein levels without affecting its plasma membrane concentration. However, this compound was unable to significantly reduce ATC growth in a xenograft model, indicating that uPA inhibition alone may not have the expected therapeutic effects.

Management of concomitant hyperparathyroidism and thyroid diseases in the elderly patients: a retrospective cohort study.

BACKGROUND: Thyroid disease and hyperparathyroidism are the most common endocrine disorders. The incidence of thyroid disease in patients with hyperparathyroidism ranges in the different series from 17 to 84%, and thyroid cancer occurs with an incidence ranging from 2 to 15%. AIM: The aim of our study was to analyze the management of elderly patients with concomitant thyroid and parathyroid disease in order to define the best surgical therapeutic strategy and avoid reoperations associated with a higher risk of complications. METHODS: All consecutive patients (64 patients, age range 60-75 years), undergoing surgery for hyperparathyroidism, from January 2011 to June 2014, were retrospectively evaluated. Enrolled patients were divided into two study groups of patients affected by hyperparathyroidism with or without a concomitant thyroid disease. RESULTS: Out of 64 patients enrolled in our study (24 men, age range 60-75 years), affected by hyperparathyroidism, 34 had an associated thyroid disease and were treated with total thyroidectomy and parathyroidectomy. The group, who underwent parathyroidectomy associated with thyroidectomy, had no greater complications than the group receiving only parathyroidectomy. CONCLUSIONS: Thyroid disease must be excluded in patients affected by hyperparathyroidism. It is difficult to determine whether hyperparathyroidism can be considered a risk factor for thyroid disease, but an accurate preoperative study is essential for a surgery able to treat both thyroid and parathyroid disease. In this way, we avoid the elderly patient, with associated morbidity and increased surgical risk, to undergo a reoperation for thyroid disease, burdened with major complications.

Irreversible electroporation for locally advanced pancreatic cancer through a minimally invasive surgery supported by laparoscopic ultrasound.

INTRODUCTION: Pancreatic cancer is one of the most lethal cancers worldwide, with 5-years survival rate as low as 6%. The majority of pancreatic cancer patients present locally advanced or metastatic disease at diagnosis. Typically, patients affected by locally advanced pancreatic cancer (LAPC) do not undergo radical surgery but are treated with focal ablative therapies. However, a high rate of morbidity due to the heat sink effect has limited the application of ablative techniques on a routine basis in LAPC patients. Irreversible electroporation (IRE) has proved to be a new method of LAPC ablation. PRESENTATION OF THE CASE: A 69-year-old woman affected by LAPC with good response to systemic chemotherapy with FOLFIRINOX and residual 35 mm mass in the neck of the pancreas underwent to IRE through a minimally invasive surgical approach under laparoscopic ultrasound guide. The post-operative course was uneventful and the patient was discharged after 5 days. Six months after surgery she had no evidence of distant or recurrent disease. DISCUSSION: IRE has previously shown promising results in the treatment of LAPC, with relatively acceptable morbidity rates and improvement of survival. We report on the application of IRE through a minimally invasive surgical approach supported by laparoscopic ultrasound. CONCLUSION: In conclusion, we propose a novel technical approach that combines the benefits of IRE on the treatment of patients affected by LAPC with the advantages of laparoscopic surgery.

Worldwide burden of colorectal cancer: a review.

Colorectal cancer is a major public health problem, being the third most commonly diagnosed cancer and the fourth cause of cancer death worldwide. There is wide variation over time among the different geographic areas due to variable exposure to risk factors, introduction and uptake of screening as well as access to appropriate treatment services. Indeed, a large proportion of the disparities may be attributed to socioeconomic status. Although colorectal cancer continues to be a disease of the developed world, incidence rates have been rising in developing countries. Moreover, the global burden is expected to further increase due to the growth and aging of the population and because of the adoption of westernized behaviors and lifestyle. Colorectal cancer screening has been proven to greatly reduce mortality rates that have declined in many longstanding as well as newly economically developed countries. Statistics on colorectal cancer occurrence are essential to develop targeted strategies that could alleviate the burden of the disease. The aim of this paper is to provide a review of incidence, mortality and survival rates for colorectal cancer as well as their geographic variations and temporal trends.

Chievitz' juxtaparotid organ, free from cancer.

INTRODUCTION: Up to the half of twentieth century, Chievitz organ was considered an embryonal organ, disappearing with growth. But Zenker, in 1953, demonstrated the existence of this organ in adult life, too4. REVIEW: In this article we review the embryology, the macroscopic and microscopic anatomy, the ultrastructure, the functional significance and the pathology of the Chievitz'Juxtaparotid Organ (CJO). The CJO is not a macroscopic apparent organ, but it looks like a nerve. The CJO takes connections with buccinator muscle, at the level of the parotid duct, and the medial pterygoid muscle. The cell parenchyma is enveloped by the connective tissue, that is divided into three layers15, 16: the inner layer -"stratum fibrosum internum"-, composed of collagenous and elastic microfibrils; the middle layer - "stratum nervosum" - containing a lamellar inner core and Ruffini SNF5; the external layer - "stratum fibrosum externum", that is a collagen capsule. The parenchymal cells show a rich enzyme activity. The parenchymal cells may play the same role as glomus cells of the 1st type and Merkel cells20, 21. When a surgical resection is performed for an oral carcinoma, the CJO may be present in the specimen25. The CJO may be wrongly diagnosed as perineural invasion by carcinoma26, 27, 28. CONCLUSION: We report that Chievitz' organ is the only organ in which the cancer does not occur. KEY WORDS: Chievitz' organ, Juxtaoral organ, Parotid gland.

Bloodless surgery in geriatric surgery.

In bloodless surgery a series of measures has to be implemented to reduce the perioperative need for transfusion of whole blood or its components. Jehovah's Witness are the most representative group of patients opting for bloodless surgery as their faith follows strict believes that prohibits receiving blood. Geriatric patients requiring bloodless surgery are even more delicate and represent a challenge for surgeons. The physiological response of the over 65 year population to decreased hemoglobin level is slower and less effective than in young and adult patients. Herby we describe the perioperative protocol implemented in our surgical Department offered to geriatric Jehovah's Witness patients. Preoperative optimization of the patients is the key step in the preparation period. Intraoperative anesthetic and surgical measures are also required along with a strict postoperative follow-up. From our experience, bloodless surgery is feasible in the geriatric population as long as it is performed in specialized centers where a multidisciplinary team is prepared to specifically manage this scenario. Rigorous patients selection and preparation are mandatory.

Association between Pituitary Langerhans Cell Histiocytosis and Papillary Thyroid Carcinoma.

Here we report a case of panhypopituitarism caused by pituitary Langerhans cell hystocitosis (LCH) in a 22-year-old woman affected by papillary thyroid carcinoma (PTC). Although several cases of the coexistence of PTC and LCH within thyroid tissue have been described in relative literature, in this case, the patient presented a unique suprasellar retrochiasmatic histocytosis localization which, to the best of our knowledge, had never been described before in association with PTC. Even if this aspect is not addressed in the present case report, it is worth noting that about 50% of the patients affected either by LCH or PTC are characterized by activating mutations of the proto-oncogene BRAF. This, along with other clinical studies, may warrant further biomolecular large-scale case study investigations in order to evaluate a possible connection between the 2 conditions and shed light on the etiology of these diseases, which are still largely unknown.