Laparoscopic pancreatectomy: Did the indications change? A review from literature.

Pancreatic Cancer (PC) is the fourth cause of death for tumors in Western countries. Symptoms are not specific, and can vary according to the tumor size and place. Diagnostic workup includes CA 19-9, CT and MRI. Surgery is the only treatment for PC, associated to radio-chemo therapy. Laparoscopic approaches are actually used for PC treatment in few specialized centers, and could be an alternative to laparotomic surgery. The aim of our study is to evaluate the efficacy of laparoscopy for PC treatment compared to laparotomy. We reviewed 19 articles in literature to assess the feasibility and efficacy of Laparoscopic Distal Pancreatectomy (LDP) and Laparoscopic Pancreaticoduodenectomy (LPD). The results have shown that LDP is nowadays a safe technique, and the outcomes are comparable to laparotomic surgery. Regarding to LPD instead, results are controversial and the data are still not sufficient to consider this technique as a valid alternative to laparotomic surgery.

BRAF and PIK3CA genes are somatically mutated in hepatocellular carcinoma among patients from South Italy.

Poor data have been previously reported about the mutation rates in K-RAS, BRAF, and PIK3CA genes among patients with hepatocellular carcinoma (HCC). Here we further elucidated the role of these genes in pathogenesis of primary hepatic malignancies. Archival tumour tissue from 65 HCC patients originating from South Italy were screened for mutations in these candidate genes by direct sequencing. Overall, oncogenic mutations were detected in 15 (23%) patients for BRAF gene, 18 (28%) for PIK3CA gene, and 1 (2%) for K-RAS gene. Using statistical analysis, BRAF mutations were significantly correlated with the presence of either multiple HCC nodules (P=0.021) or higher proliferation rates (P=0.034). Although further extensive screenings are awaited in HCC patients among different populations, our findings clearly indicated that mutational activation of both BRAF and PIK3CA genes does contribute to hepatocellular tumorigenesis at somatic level in Southern Italian population.

Nanotech revolution for the anti-cancer drug delivery through blood-brain barrier.

Nanotechnology-based drug delivery was born as a chance for pharmaceutical weapons to be delivered in the body sites where drug action is required. Specifically, the incorporation of anti-cancer agents in nanodevices of 100-300 nm allows their delivery in tissues that have a fenestrated vasculature and a reduced lymphatic drainage. These two features are typical of neoplastic tissues and, therefore, allow the accumulation of nanostructured devices in tumours. An important issue of anti-cancer pharmacological strategies is the overcoming of anatomical barriers such as the bloodbrain- barrier (BBB) that protects brain from toxicological injuries but, at the same time, makes impossible for most of the pharmacological agents with anti-cancer activity to reach tumour cells placed in the brain and derived from either primary tumours or metastases. In fact, only highly lipophilic molecules can passively diffuse through BBB to reach central nervous system (CNS). Another possibility is to use nanotechnological approaches as powerful tools to across BBB, by both prolonging the plasma half-life of the drugs and crossing fenestrations of BBB damaged by brain metastases. Moreover, modifications of nanocarrier surface with specific endogenous or exogenous ligands can promote the crossing of intact BBB as in the case of primary brain tumours. This aim can be achieved through the binding of the nanodevices to carriers or receptors expressed by the endothelial cells of BBB and that can favour the internalization of the nanostructured devices delivering anti-cancer drugs. This review summarizes the most meaningful advances in the field of nanotechnologies for brain delivery of drugs.

Everolimus is an active agent in medullary thyroid cancer: a clinical and in vitro study.

Everolimus, an mTOR inhibitor, which has been demonstrated to induce anti-tumour effects in different types of neuroendocrine tumours, has never been evaluated in patients with medullary thyroid cancer (MTC). The aim of this study was to evaluate the in vitro and in vivo effects of everolimus in combination with octreotide in MTC. Two patients with progressive metastatic MTC and high calcitonin levels were treated with everolimus 5-10 mg/day. Both patients were under treatment with octreotide LAR at the study entry. An in vitro study was also performed to assess everolimus effects on MTC cell lines (TT and MZ-CRC-1 cells). A tumour response was observed in both patients. Serum calcitonin decreased by 86% in patient 1 and by 42% in patient 2. In TT and MZ-CRC-1 cells, everolimus induced a significant dose-dependent inhibition in cell proliferation. This effect seems to be related to a cell cycle arrest in G(0) /G(1) phase in both cell lines and to the induction of cellular senescence in TT cells. Everolimus in combination with octreotide may be active as anti-tumour therapy in patients with progressive metastatic MTC, suggesting to further evaluate this agent in MTC patients in a large prospective study.

Two Case Reports of Biliary Tract Injuries during Laparoscopic Cholecystectomy.

Background and Study Aims. Biliary tract injuries (BTI) represent the most serious and potentially life-threatening complication of cholecystectomy occurring also during laparoscopic approaches. Patients and Methods. We describe and discuss two different cases of BTI occurring during laparoscopic cholecystectomy (LC). Results. Two patients developed BTI during LC and one evidenced the complication during the LC itself and was treated during the same LC in real time. The other patient evidenced BTI only after the primary intervention and was successfully reoperated in laparotomy after 10 days from the LC. Conclusions. The factors that predispose to the occurrence of BTI during cholecystectomy and the cautions to be used to prevent BTI are discussed.

Oxidative stress and ERK1/2 phosphorylation as predictors of outcome in hepatocellular carcinoma patients treated with sorafenib plus octreotide LAR.

We reported a relevant activity of the combination between sorafenib and octreotide long-acting release (LAR) in advanced hepatocellular carcinoma (HCC) patients. In this work, we have studied if oxidative stress in both serum and peripheral blood mononuclear cells (PBMC) and pERK activation status in PBMC could be predictive of response. In the 20 responsive patients, the decrease of reactive oxygen species levels was already detectable after 10 days (T10) from the beginning of sorafenib administration, and this effect was enhanced by the combined treatment with sorafenib+octreotide LAR (T21). This effect correlated with the modulation of superoxide dismutase (SOD) activity (physiological scavenger of O(2-)) and of serum nitric oxide (NO) levels. Sorafenib alone induced an increase of about 40% of NO levels and of about two-fold of SOD activity in responsive patients, and both effects were significantly potentiated by the combined treatment. We found a gradual reduction of Erk1/2 activity, as evaluated by cytofluorimetric analysis, in 15 responsive patients reaching about 50% maximal decrease at T21. On the other hand, in 17 resistant patients, Erk1/2 activity was about 80% increased at T21. The determination of both the oxidative stress status and pERK activity in PBMC has high value in the prediction of response to sorafenib+octreotide therapy in HCC patients.

Ablation of large HCCs using a new saline-enhanced expandable radiofrequency device().

PURPOSE: Evaluation of a new device designed to achieve large volumes of necrosis in hepatocellular carcinoma (HCC) nodules by application of radiofrequency ablation (RFA). MATERIALS AND METHODS: 29 consecutive patients with 31 HCC nodules ≥3 cm in diameter (range 3-7.5 cm; mean diameter 5.5 cm) underwent ultrasound (US) guided percutaneous RFA using an expandable electrode with 7 active arrays and saline injection designed to create tissue ablation in areas of up to 7 cm (Starburst XLi-enhanced RFA device). Treatment was performed in general anesthesia (6 patients) or deep sedation (23 patients). Treatment efficacy was assessed by three-phase contrast-enhanced computed tomography (CT) and bimonthly US follow-up. RESULTS: One to three electrode insertions (mean number 1.6) were performed in each patient. CT showed complete necrosis in 23/31 HCC nodules (74%) in 22 patients. Follow-up of these 22 patients ranged from 2 to 15 months (mean time 8.3 months). In 6/22 patients (28%) intrahepatic recurrence occurred within 5-10 months (mean time 8.3 months). Major complications were post-ablation syndrome in 7/29 (24%), peritoneal effusion in 4/29 (14%), pleural effusion in 2/29 (7%) and transient obstructive jaundice in 1/29 (3.4%) patients. One patient died 6 months after treatment because of tumor progression. CONCLUSIONS: In the treatment of large HCC nodules, Starburst XLi-enhanced is an effective and safe device.

Surgical treatment of differentiated thyroid carcinoma: a retrospective study.

INTRODUCTION: We carried out a retrospective analysis of our experience in the management of Differentiated Thyroid Carcinoma (DTC), in order to better define prognostic factors (age, gender, histological type, stage) and outline a standard procedure, where it's possible, for surgical treatment. PATIENTS AND METHODS: Patient population consisted of 432 cases, operated from 1978 to 2003. We carried out 285 operations of total thyroidectomy of which 39 associated to some kind of lymphadenectomy, 66 totalization (21 pts had been operated in other institutes), 60 subtotal thyroidectomies and 21 lobo-isthmectomies. Survival and mortality curves for age, sex, histological type, grading and staging have been calculated. Kaplan-Meyer statistical elaboration for disease-free interval and Mann-Whitney test for the comparison of different clinical and pathological data have been employed. RESULTS: The statistical analysis puts in evidence that on 432 cases examined, with a follow-up from 1 to 25 ys (median = 6.33 ys) and with a drop-out of 60 cases (13.8 %), total mortality for cancer has been of 24 cases (6,4%), with a median interval free by disease of 4.2 ys (range 5 months to 25 ys), and a probability to stay free by disease at 12 and 24 months respectively of 95.1% and 91.6%. The median survival is resulted of 5.8 ys (range 1 to 25 ys) with a probability of survival at 24 and 48 months respectively of 97.5% and 94.3%. The multivariate analysis evidences the most important variables, i.e. age > 45 ys, tumor of intermediate malignancy, with size 1.5 cm, operative M+, significantly condition the prognosis, noticeably getting worse it, independently by the kind of carried out operation. CONCLUSION: Our present therapeutic choices are: 1. total thyroidectomy in the treatment of the apparently benign pathology when bilaterally with spread; the checking at the final histological exam of a cancer makes however think adequate the carried out operation; 2. lobo-isthmectomy in the treatment of unilateral benign pathology or with suspect FNAB for follicular neoplasm; the histological checking of a cancer makes think the operation adequate only in presence of favourable prognostic parameters, but in presence even of just one unfavourable variable, we consider necessary the totalization; 3. total thyroidectomy in presence of a certain or strongly suspected preoperative diagnosis of cancer.

[Is extrauterine endometriosis confined to the gynecological sphere? A critical review of the experience in a general surgery unit]. / Endometriosi esterna: patologia di esclusivo interesse ginecologico? Il punto di vista del chirurgo generale.

Extrauterine or external endometriosis (e.e.) describes ectopic localization of functional endometrial tissue, a finding whose incidence is increasing due to the diffusion of laparoscopic procedures. The clinical presentation of such disease is often non-specific, even in those cases with a definite surgical indication, depending on the site and pathology of the lesions. Surgical planning is therefore difficult at times, specifically regarding the extent of resection in patients--as young women--willing to maintain fertility. The Authors report on 7 cases observed in their own experience (inguinal endometriosis--1 case, umbilical endometriosis--1 case, abdominal wall endometriosis--3 cases, intestinal endometriosis--1 case, diaphragmatic endometriosis associated with pneumothorax--1 case), representing the wide range of clinical settings related to e.e. Based on literature data, an analysis of clinical and diagnostic issues is carried out. Specifically, the problems related to extent of surgical resection in multifocal cases, possible malignant degeneration and localization on abdominal wall scars are discussed.

[Surgical treatment of sinus pilonidalis by Dufourmentel's flap technique]. / Il trattamento chirurgico del sinus pilonidalis con trasposizione di lembo secondo Dufourmentel.

The present study reports the results of surgical treatment of 175 consecutive chronic pilonidalis sinus cases by excision alone, excision and primary closure, excision and Dufourmentel's flap technique. The analysis of hospital stay , average recovery time, patient compliance and percentages of failures and recurrences enables us to state that Dufourmentel's technique is the best choice, allowing fast recovery with minimal discomfort and lower rate of recurrence. Moreover the good compliance of the technique and the use of recently introduced more effective local anaesthetics have allowed us to plan the treatment in a day-surgery setting with good clinical results.

Surgical treatment with Ligasure Precise of schwannoma of brachial plexus: case report.

English version We present a case of bulky schwannoma arising from the brachial plexus treated by a new surgical device. A 38-year-old man presented with a slow-growing left-sided supraclavicular mass and complained paresthesia of the third and forth fingers of the hand and forearm weakness. Physical examination revealed Tinel's sign. A CT-scan revealed a solid mass situated in the left profound supraclavicular fossa. The tumour was resected with the utilization of bipolar vessel sealing system (Ligasure Precise). This device is very useful in sutureless removal of masses localized in deep supraclavicular fossa. During the operation, care was taken to preserve the nerve function.

[Male breast cancer. Five years experience and literature review]. / Il cancro della mammella maschile. La nostra esperienza di 5 anni e confronto con la letteratura internazionale.

Male breast cancer is an uncommon disease and its aetiology, clinical behaviour and treatment is not well-known . Retrospective studies show that age and stage-matched breast cancer in men and women are compared. Nevertheless, the poor mammary tissue in man allow a rapid local infiltration, late diagnosis and poor survival rate. The Authors report their five years experience and with a short literature review they summarise what is currently known about this uncommon neoplasm in terms of prognostic factors, therapy and survival.

Diagnosis of benign and malignant portal vein thrombosis in cirrhotic patients with hepatocellular carcinoma: color Doppler US, contrast-enhanced US, and fine-needle biopsy.

BACKGROUND: We assessed the role of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant portal vein thrombosis in patients who had cirrhosis with hepatocellular carcinoma (HCC). METHODS: Fifty-four consecutive patients who had cirrhosis, biopsy-proved HCC, and thrombosis of the main portal vein and/or left/right portal vein on US were prospectively studied with color Doppler US (CDUS) and CEUS. CEUS was performed at low mechanical index after intravenous administration of a second-generation contrast agent (SonoVue, Bracco, Milan, Italy). Presence or absence of CDUS signals or thrombus enhancement on CEUS were considered diagnostic for malignant or benign portal vein thrombosis. Twenty-eight patients also underwent percutaneous portal vein fine-needle biopsy (FNB) under US guidance. All patients were followed-up bimonthly by CDUS. Shrinkage of the thrombus and/or recanalization of the vessels on CDUS during follow-up were considered definitive evidence of the benign nature of the thrombosis, whereas enlargement of the thrombus, disruption of the vessel wall, and parenchymal infiltration over follow-up were considered consistent with malignancy. CDUS, CEUS, and FNB results were compared with those at follow-up. RESULTS: Follow-up (4 to 21 months) showed signs of malignant thrombosis in 34 of 54 patients. FNB produced a true-positive result for malignancy in 19 of 25 patients, a false-negative result in six of 25 patients, and a true-negative result in three of three patients. CDUS was positive in seven of 54 patients. CEUS showed enhancement of the thrombus in 30 of 54 patients. No false-positive result was observed at CDUS, CEUS, and FNB. Sensitivities of CDUS, CEUS, and FNB in detecting malignant thrombi were 20%, 88%, and 76% respectively. Three patients showed negative CDUS and CEUS and positive FNB results; follow-up confirmed malignant thrombosis in these patients. One patient showed negative CDUS, CEUS, and FNB findings. However, follow-up of the thrombus showed US signs of malignancy. Another FNB confirmed HCC infiltration of the portal vein. CONCLUSION: CEUS seems to be the most sensitive and specific test for diagnosing malignant portal vein thrombosis in patients with cirrhosis.

[Thyroid microcarcinoma: our experience]. / Microcarcinoma tiroideo: nostra esperienza.

Differentiated thyroid cancer had an excellent prognosis; the diagnosis of sub-centimetric differentiated cancer (microcarcinoma) is more and more frequently. Clinical evolution of microcarcinoma could be various: microcarcinoma can represent an autoptic finding or can evolve with locoregional lymph node involvement or metastasis. Various clinical and genetic factors have been considered to predict the aggressiveness of this neoplasm. From 2001 to 2004, 74 patients with diagnosis of thyroid microcarcinoma underwent surgical treatment. By a retrospective survey we evaluated risk factors and the choice of surgical treatment. The aggressiveness appear to be related mainly to multifocality and size. Our therapeutic strategy is to perform total thyroidectomy for benign pathologies, total thyroidectomy with lymphadenectomy in cases with preoperative diagnosis of microcarcinoma.

Breast surgery and sentinel node biopsy. Our experience.

Massive campaigns of screening of breast pathologies improved early diagnosis of breast cancers. Most of these cancers are small-sized (T1) and seldom show intraoperative nodal involvement. Sentinel node biopsy is the elective choice in the above mentioned cases because, if negative, it avoids axillary dissection. International literature reports rates of false negative sentinel node biopsy ranging among 4.5 and 12%; results in our experience account for almost 6%. As a consequence, there is the definite risk of potentially positive axilla that will not be dissected with subsequent risk of axillary recurrence within 24 months. The reason of that could be related to the fact that in Referral Centers this technique is performed in strictly selected patients, so as to gain a diagnostic accuracy of 98%. The rate of axillary recurrences does not justify the routine axillary dissection, since this is just a staging, not a therapeutic procedure. In case of doubt, it can be recommended a close and careful follow-up of the axilla.

Seeding from hepatocellular carcinoma after percutaneous ablation: color Doppler ultrasound findings.

BACKGROUND: We describe the clinical and color Doppler ultrasound findings in a series of cases of seeding from hepatocellular carcinoma (HCC) observed in patients treated with percutaneous ablation therapy (PAT) over a 15-year period. METHODS: We reviewed the clinical and imaging records of 12 patients with cirrhosis (nine men and three women, age range 51-82 years, mean age 63 years) that showed neoplastic seeding from HCC occurring after one or more PAT procedures. Five of 12 cases of seeding were observed as a complication of 1080 PAT procedures (0.46%) performed in 545 patients (0.96%) by two of the authors (L.T., G.F.) over a long period (15 years) at different institutions. The other seven patients had been treated with PAT procedures at other institutions and had come to our attention during post-treatment follow-up. RESULTS: The 12 patients who had seeding nodules had undergone the following PAT procedures: multisession conventional percutaneous ethanol injection (PEI) without anesthesia (four patients), single-session PEI with general anesthesia (three patients), single-session PEI with general anesthesia plus multisession conventional PEI (four patients), and single-session PEI plus radiofrequency ablation (one patient). Seeding nodules ranged from 0.9 to 6.0 cm (mean 1.7 cm). Eleven of 12 seeding nodules appeared as hypervascular hypoechoic nodules with smooth and regular margins and multiple intralesional vascular signals. CONCLUSIONS: Clinical and imaging findings of seeding from HCC should be recognized by physicians who perform follow-up ultrasound examinations of patients who are treated with PAT. Early diagnosis of seeding can be reliably made by scanning the abdominal wall with small probes in the area where the previous PAT has been performed. Hypoechoic hypervascular pattern of the seeding nodule allows definitive diagnosis.

[Bile leakage after laparoscopic cholecystectomy: report of three cases in our experience]. / Coleperitoneo dopo colecistectomia laparoscopica: descrizione di tre casi nella nostra esperienza.

Laparoscopic cholecystectomy (LC) is associated with an higher incidence of bile duct injury than open cholecystectomy. There has been concern and the reason why bile leakages are more frequent with LC is yet unclear. Bile collections can occurr because of major about (75%) or minor (about 25%) injuries. Anyway, external biliary decompression is a key factor in the treatment, in order to avoid an emergency intervention. The Authors report their experience concerning 3 cases of bile leakages among a series of 458 LC. Only in one of the three cases the subhepatic space was not drained and an emergency laparotomy was performed. The Authors, on the basis of their own experience and of the data reported in literature, suggest the routinary intraoperative placement of a drainage into the subhepatic space, to be removed, if no complications occur, one day after surgery.

[Interstitial laser photocoagulation in liver tumours: our experience]. / Laserterapia interstiziale nell'epatocarcinoma su cirrosi: nostra esperienza.

Interstitial lasertherapy (ILT) is one of the percutaneous thermal procedures allowing the ablation of primary or secondary hepatic lesions. This technique can be performed without general anaesthesia, since the patient is completely painless, in spite of the high temperatures reached, because there are no sensitive fibers around the lesion. This study includes patients with small hepatocarcinomas (< 2 cm) non peripherically sited, far from the gallbladder and the hepatic hilum. Twenty patients suffering from 24 cirrhotic hepatocarcinomas (two patients showed two nodules) have been enrolled for the present study. Mean diameter of lesions was 1.8 cm (1.3-2 cm). One or more 21 G (length 20 cm) Chiba's needles were inserted under sonographic view into the lesions. The laser energy was switched on at 4 Watts for 4-6 minutes, until an amount of energy of 900-1800 Joule was reached. All the patients were discharged 48 hours after the procedure. Triphasic CT-scan with contrast were performed 7 to 14 days after ILT, in order to check its efficacy. CT-scan showed complete necrosis in all the nodules ranging from 1.5 to 3 cm. All the patients received only one IL T session, whose longest duration was 20 minutes. No major complications occurred. ILT of small hepatocarcinomas is a safe, efficient procedure, also feasible without anaesthesia. Differently from percutaneous radiofrequency, in fact, it shows the advantage of less pain, that can avoid the need for general anaesthesia.

Which therapy to prevent post-thyroidectomy hypocalcemia?

Hypocalcemia is one of the most frequent complications after total extracapsular thyroidectomy (TET). In most of cases it is a transient phenomenon. The aim of this study is to evaluate if and how the oral administration of calcium or calcium combined with D-vitamin could effectively prevent post-thyroidectomy hypocalcemia. A randomized prospective study was performed, recruiting 120 patients who underwent total thyroidectomy. The patients in our series were randomly assigned to one of two groups: group A--patients who received calcium lactogluconate/calcium carbonate (mg 300 per day); group B--patients who received calcium carbonate/cholecalciferol therapy (calcium carbonate: 1500 mg per day; cholecalciferol 400 UI per day). The groups were well matched for age, sex and pathologies. Patients of both A and B groups were divided in two subgroups: those operated on for benign thyroid diseases (A1 and B1) and those operated on for malignancy (A2, B2). Serum calcium assays, performed 24, 48 and 72 hours after surgery, showed mean values of calcemia higher in patients of the B1 and B2 group. Statistical analysis was performed using a Student's t test. Mean serum calcium concentrations on post-operative day one, two and three were higher in patients of the group B (p<<0.01). Early and combined oral administration of both calcium and vitamin D seemed to prove major efficacy in preventing and treating post-operative hypocalcemia, showing mean serum calcium levels higher than those of patients who received only oral calcium administration. Nevertheless, further studies are necessary to validate these data.