Ultrasound scissors versus electrocautery in axillary dissection: our experience.

The ultrasound scissors are recently emerging as an alternative surgical tool for dissection and haemostasis and have been extensively used in the field of minimally invasive surgery. We studied the utility and advantages of this instrument compared with electrocautery to perform axillary dissection. The operative and morbidity details of thirty-five breast cancer patients who underwent axillary dissection using the ultrasound scissors were compared with 35 matched controls operated with electrocautery by the same surgical team. There was no significant difference in the operating time between the ultrasound scissors and electrocautery group (36 and 30 mins, p>0.05). The blood loss (60 +/- 35 ml and 294 +/- 155 ml, p<0.001) and drainage volume (200 +/- 130 ml and 450 +/- 230 ml, p<0.001) were significantly lower in the ultrasound scissors group. There was a significant reduction of draining days in ultrasound scissors group (mean one and four days, respectively p<0.05). There was significant difference in the seroma rate between the two groups (10% and 30%, respectively). Axillary dissection using harmonic scalpel is feasible and the learning curve is short. Ultrasound scissor significantly reduces the blood loss and duration of drainage as compared to electrocautery.

New trends on fibrin glue in seroma after axillary lymphadenectomy for breast cancer.

BACKGROUND: Axillary lymphadenectomy remains an integral part of breast cancer treatment, yet seroma formation occurs in 15-85% of cases. Among methods to reduce seroma magnitude and duration, fibrin glue has been proposed in several studies with controversial results. PATIENTS AND METHODS: Ninety patients underwent quadrantectomy or mastectomy with level I/II axillary lymphadenectomy; a suction drain was fitted in all patients. Fibrin glue spray were applied to the axillary fossa in 45 patients; the other 45 patients were treated conventionally. RESULTS: Suction drainage was removed between post-operative (p.o.) days 3 and 4. Seroma magnitude and duration were significantly reduced (p 0.004 and 0.02, respectively), and there were fewer evacuative punctures, in patients receiving fibrin glue compared with the conventional treatment group. CONCLUSIONS: Use of fibrin glue does not always prevent seroma formation, but does reduce seroma magnitude, duration and evacuative punctures.

Ductal carcinoma in situ of the breast: our experience.

AIM: The ductal carcinoma in situ (DCIS) is a more and more frequent neoplasia, representing over 25% of diagnosed breast cancer in recent surveys.It is particularly interesting as concerns several aspects of which the most important are issues linked to clinical diagnosis and the difficulties of histopathological classification, with evident and important therapeutic implications. PATIENTS AND METHODS: The authors report their experience about 161 ductal carcinoma in situ of the breast. Guidelines for surgical treatment are: radiological or clinical diagnosis, tumor's extension, histological classification, grading and margin status. At the present the authors prefer breast conserving surgery with tumor margin's study. They report their experience in the last seven years about sentinel lymph node biopsy. RESULTS: The most frequent histotype resulted comedocarcinoma (61,8%) followed by non comedo (38,2%). Local recurrence after DCIS therapy is 6,1%. CONCLUSIONS: 80-90% of the patients currently treated for DCIS present non-palpable breast lesions at diagnosis. Breast conserving surgery is the first choice and radiotherapy and endocrine therapy are indicated for selected patients.

Secondary breast angiosarcoma: A multicentre retrospective survey by the national Italian association of Breast Surgeons (ANISC).

BACKGROUND: Breast angiosarcoma is a malignant mesenchymal neoplasm, which accounts for approximately 2% of all soft tissue sarcomas. Secondary breast angiosarcoma (SBA) may be related to chronic lymphedema after a mastectomy with lymph node dissection (Stewart Treves syndrome) and previous radiotherapy for complications from breast radiation treatment. It is a very rare condition; therefore, diagnosis and management are still a challenge. METHODS: The ANISC collected SBA data by means of a survey sent to all Italian breast centres in the ANISC. The clinicopathological characteristics and the management of this disease were analysed. RESULTS: Twenty-four centres participated in this survey in which 112 cases of SBA were analysed. The median age of the women with SBA was 68.9 years and it appeared approximately 90 months after the first irradiation for breast cancer. In 92% of cases, a mastectomy was performed without axillary dissection for those patients having a high grade of SBA (74.2%). The prognosis was worse in the high-grade cases (overall survival-OS: 36 months) as compared with the low-grade cases (OS: 48 months). After a follow-up of 5 years, 50.5% of the patients were still alive. Disease-free survival (DFS) was 35 months, and there were no differences between the groups of patients with either high- or low-grade histology. CONCLUSIONS: Secondary breast angiosarcoma is a very aggressive disease associated with a short survival outcome. The surgical approach still remains an important step in the course of treatment; furthermore, an accurate histological examination is helpful in establishing the prognosis of the patient. A mastectomy is mandatory. A longer OS was observed in patients with low-grade angiosarcoma as compared to high-grade angiosarcoma (C.I. 40-57 vs. 31-41 months).

Serum vascular endothelial growth factor (VEGF) levels correlate with tumor VEGF and p53 overexpression in endocrine positive primary breast cancer.

Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, associated with unfavorable clinical characteristics in breast cancer. The aim of this study was to evaluate different angiogenic markers in endocrine-positive breast cancer patients. The authors analyzed serum and tumor samples from 71 patients with endocrine-positive operable primary breast cancer to determine the expression and the possible relationship between circulating serum VEGF levels, tumor VEGF expression, microvessel density (MVD), and other immunohistochemical parameters. Basal VEGF serum levels were significantly higher in breast cancer patients than in healthy controls. A significant correlation was observed between basal VEGF serum concentrations, microvessel density (p = 0.01) and p53 status (p = 0.004). Intratumoral VEGF expression was significantly associated with neoplastic embolization (p = 0.041) and circulating VEGF levels (p = 0.047). The results confirm that in primary endocrine-positive breast cancer serum VEGF levels are elevated and show a positive relationship with tumor VEGF and p53 overexpression.

Fibrin glue to reduce seroma after axillary lymphadenectomy for breast cancer.

UNLABELLED: Axillary lymphadenectomy remains an integral part of breast cancer treatment, yet seroma formation occurs in 15-85% of cases. Among the methods employed to reduce seroma magnitude and duration, fibrin glue has been proposed in numerous studies with controversial RESULTS: Sixty patients underwent quadrantectomy or mastectomy with level I/II axillary lymphadenectomy; a suction drain was fitted in all patients. Fibrin glue spray was applied to the axillary fossa in 30 patients; the other 30 patients were treated conventionally. Suction drainage was removed between postoperative days III and IV. Seroma magnitude and duration were significantly reduced (P=0.004 and 0.02, respectively), and there were fewer evacuative punctures, in patients receiving fibrin glue compared with the conventional treatment group. The authors conclude that the use of fibrin glue does not always prevent seroma formation, but does reduce seroma magnitude, duration and necessary evacuative punctures.

Plurifocal breast cancer and double lymphatic spread.

BACKGROUND: Sentinel node (SN) has been proved to be a reliable technique in predicting the lymph nodes state of the axilla in breast cancer. For the majority of the authors the intradermal and peritumoral injection is the best way. PATIENTS AND METHODS: Our experience, from 1997, includes 587 cases of SN in women with resectable breast cancer less than 3 cm of diameter. We performed the lymphoscintigraphy after a peritumoral injection of radioactive tracer and, if the lesion was superficial, we associated an intradermal injection on the skin above the lesion itself. Two patients had multifocal right breast cancer. We did two separate injections around each tumor. RESULTS: The radioactive tracer spread towards the internal mammary chain and homolateral axillary nodes. CONCLUSIONS: We consider the peritumoral injection as essential in tumors located deeply in the breast (under ultrasound guide if not palpable) together with intradermal injection in superficial ones. Using this technique the possibility of a mis-identification of the SN is reduced.

Three dimensional primary cultures for selecting human breast cancers that are sensitive to the anti-tumor activity of ipatasertib or taselisib in combination with anti-microtubule cytotoxic drugs.

Two inhibitors of phosphatidylinositol 3-kinase (PI3K) pathway taselisib, targeting the mutant PI3K-subunit-alpha (PI3KA) and ipatasertib, AKT-inhibitor, are currently under clinical investigation in breast cancer (BC) patients. We have previously demonstrated the anti-tumor efficacy of these anti-PI3K/AKT-inibitors in combination with anti-microtubule drugs in human BC cell lines, through a complete cytoskeleton disorganization. In this work, we generated ex-vivo three-dimensional (3D) cultures from human BC as a model to test drug efficacy and to identify new molecular biomarkers for selection of BC patients suitable for anti-PI3K/AKT-inibitors treatment. We have established 3D cultures from 25/27 human BC samples, in which the ability of growth in vitro replicates the clinical and biological aggressiveness of the original tumors. According to the results of next generation sequencing analysis, a direct correlation was found between PI3KA mutations and the sensitivity in 3D models in vitro to taselisib and ipatasertib alone and combined with anti-microtubule agents. Moreover, mutations in HER and MAPK families related genes, including EGFR, KRAS and BRAF, were found in resistant samples, suggesting their potential role as negative predictive factors of response to these agents. Thus, we demonstrated that ex vivo 3D cultures from human BC patients allow a rapid and efficient drug screening for chemotherapies and targeted agents in genetically selected patients and represent an innovative model to identify new biomarkers of drug resistance.

Sentinel lymph node biopsy in the treatment of breast cancer. Experience in 527 cases.

AIM: Knowledge of axillary lymph node status is a key aid to staging and prognosis and it represents a guideline for adjuvant therapy in breast cancer. Despite the morbidity it causes, complete axillary dissection was long the mainstay of treatment. Sentinel lymph node biopsy has proved so reliable in the evaluation of node involvement that axillary node dissection is now generally performed when sentinel node biopsy tests negative. METHODS: In this 3-phase study, 50 patients were enrolled to evaluate the learning curve of sentinel node biopsy (phase 1, September 1997-January 1998); 256 patients (age range 27-81 years) with infiltrative breast cancer (T <3 cm, clinical N0) underwent level 1 lymph node dissection when the sentinel node tested negative at histopathology (phase 2, February 1998-March 2001); 221 patients with T <3 cm underwent dissection of the sentinel node when it tested negative for metastasis (phase 3, April 2001-March 2005). RESULTS: The sentinel node was preoperatively detected in 98.6% of cases after peritumoral and intradermic injection of the radionuclide tracer and intraoperatively in 99% (90% with radio-guided surgery, 10% with vital staining). The sentinel node was positive in 15% of patients with T1 and metastatic in 65%. CONCLUSIONS: Our results are in line with the published data; therefore, the study will go forward to examine the role of the micrometastasis in the sentinel node and of in-transit tumoral cells.

[Ductal carcinoma in situ of the breast]. / Il carcinoma duttale in situ della mammella.

The Authors report their experience about 127 ductal carcinoma in situ (DCIS) of the breast. Guidelines for surgical treatment are: radiological or clinical diagnosis, tumor's extension, histological classification, grading and margin status. At the present the Authors prefer breast conserving surgery with tumor margin's study. They report their experience in the last seven years about sentinel node biopsy. Radiotherapy and endocrine therapy are indicated for selected patients; local recurrence after DCIS therapy is 8,1% on a 6,1 years follow-up.

[Breast-conserving surgery in breast cancer]. / La chirurgia conservativa nel cancro della mammella.

Breast-conserving surgery is the treatment of choice for the breast cancer T < 3 cm. The local recurrence is a problem of diagnosis and consequent treatment. We enrolled, from 1987 to 2004, 1504 breast cancer. In 803 (53.4%) tumor with T < 3 cm we performed conserving surgery. The sentinel lymph node (SN) technique induce to limit the axillary dissection in patients T1a-b to the SN only if non metastatic and located to the first level, the dissection of the 1st level of the axilla in patients T1c-T2 < 3 cm and SN negative, complete axillary dissection in patients with metastatic SN or located to the 2nd level. Our percentage of local recurrence in the follow-up was 3.5% at 5 years and 6% at 10 years.

Troglitazone prevents insulin dependent diabetes in the non-obese diabetic mouse.

Troglitazone has recently been introduced in the treatment of Type 2 diabetes. In addition to its anti-diabetic effects it acts as a perixosome proliferator activated receptor-gamma (PPAR-gamma) agonist and has anti-inflammatory properties by inhibiting macrophage tumour necrosis factor-alpha (TNF-alpha) secretion. It also inhibits the production of endothelial selectin (e-selectin). Troglitazone also reduces interleukin-1alpha induced nitric oxide production in pancreatic beta-cells, which may be relevant in preventing nitric oxide mediated damage to these cells in the Type 1 diabetes process. We tested troglitazone in the spontaneous model of autoimmune diabetes, the non-obese diabetic (NOD) mouse, to determine its effect on the disease process. When administered by gavage from weaning at a dose of 400 mg/kg body weight (n = 32), troglitazone reduced the incidence of diabetes by 16 weeks compared to controls (n = 32) in a pattern that was maintained up to the conclusion of the experiment at 31 weeks of age (p < 0.05). Insulitis was unaltered (index = 1.05 +/- 0.71 vs. 1.13 +/- 0.82, treated vs. controls, p = 0.78). The study was repeated using troglitazone in the diet of NOD mice (n = 24) to give a dose of approximately 200 mg/kg body weight in order to provide a more consistent level of troglitazone during the time course of the experiment. There was a reduction of diabetes incidence in this group but it did not reach significance. Insulin levels were reduced in gavage treated mice although such reduction did not reach significance (p < 0.07). We conclude that, in view of its effect on this model of autoimmune diabetes and because of its known function as an insulin sensitiser, troglitazone might be considered for potential use in those patients with Type 1 masquerading as Type 2 diabetes.

The effect of a heparin analogue, ITF-5005, on diabetes incidence and insulitis in the non-obese diabetic mouse.

It has been suggested that heparin and its analogues may have a suppressive effect on the immune response by interfering with T-lymphocyte heparinase activity, thus altering the ability of T-lymphocytes to penetrate the extracellular matrix and migrate to target tissues. We have investigated whether a heparin analogue (ITF-5005) can alter lymphocytic infiltration of the endocrine pancreas (insulitis) and/or diabetes incidence in the non-obese diabetic (NOD) mouse. Sixty-four NOD mice were divided at weaning and injected subcutaneously five times per week with either 18, 36 or 72 micrograms/kg body weight of ITF-5005 or saline as a control. At 12 weeks of age, the animals were culled and their pancreata sectioned, stained and assessed 'blind' for insulitis and insulin containing cells. Insulitis was similar in all groups as was the proportion of insulin-containing cells. To determine the effect on diabetes incidence, two groups of mice were injected with either saline or 140 micrograms/kg body weight of ITF-5005 from weaning until 30 weeks of age. No difference was found in overall diabetes incidence; however, disease onset was significantly accelerated in the treated group. We conclude that ITF-5005, at the doses employed, has no effect on insulitis or the proportion of treated group. We conclude that ITF-5005, at the doses employed, has no effect on insulitis or the proportion of insulin-containing cells found in the pancreas, but that it can accelerate the course of diabetes in the NOD mouse.

The effect of metformin on liver blood flow in vivo in normal subjects and patients with non insulin dependent diabetes.

We previously reported that metformin improves insulin-mediated glucose liver metabolism in patients with non insulin dependent diabetes (NIDDM). It is not clear whether this is a direct effect of metformin on liver metabolism or mediated by other mechanisms such as increased liver blood flow. In this respect it has recently been reported that metformin increases hepatic blood flow (HBF) in diabetic rats. The aim of this study was to evaluate whether the administration of metformin is associated with modifications in HBF in humans. Patients affected by NIDDM (n = 11) and normal subjects (n = 6) were studied. In the first protocol HBF was investigated in six overweight (BMI 27 +/- 2 Kg/m2) NIDDM patients and six normal subjects (age and BMI matched) already on metformin treatment before and 2 h after the administration of 500 mg metformin. In the second protocol HBF was investigated in obese (BMI 32 +/- 1 Kg/m2) NIDDM patients (n = 5) in good metabolic control before and after 15 days of metformin at the dose of 1 g daily. HBF was measured by intravenous injection of 3 mCi 99mTc-phytate. In both protocols no significant changes in HBF were observed following metformin administration either in NIDDM patients or normal subjects. No significant differences were observed in HBF between diabetic patients and normal subjects. These data indicate that metformin has no effect on HBF in man. The previously reported improvement of insulin mediated liver metabolism induced by metformin is likely to be a consequence of the direct effect of the drug at hepatocyte level which is independent of HBF modifications.

Phaeomelanin versus eumelanin as a chemical indicator of ultraviolet sensitivity in fair-skinned subjects at high risk for melanoma: a pilot study.

It is now generally agreed that solar exposure is a major external factor in the causation of cutaneous melanoma in light skinned populations with red hair and a marked susceptibility to the acute effects of ultraviolet (UV) radiation. In the present study, we investigated the existence of a possible relationship between hair melanin composition and minimal erythema dose (MED), as an indicator of UV sensitivity, in a group of 15 healthy red-haired subjects aged 20-46 years. In spite of comparable skin and hair colour, marked variations were observed in the MED values as well as in the hair melanin composition. Phaeomelanin levels varied in the range 0.026-0.53% w/w and were generally comparable to or higher than eumelanin levels (0.042-0.17% w/w). No significant relationship was found between MED values and phaeomelanin, eumelanin or total melanin (eumelanin plus phaeomelanin) content. Notably, however, a gross positive correlation was found between the eumelanin/phaeomelanin ratio and the MED values. These results would suggest that a high UV sensitivity is associated with high phaeomelanin and low eumelanin levels, and point to the eumelanin/phaeomelanin ratio as a novel chemical parameter that could be used for predicting individuals at high risk for skin cancer and melanoma.

In vivo measurement of immunoglobulin accumulation in the pancreas of recent onset type 1 diabetic patients.

OBJECTIVE: The possibility to quantify in vivo the severity of the inflammatory process in the pancreas of patients with recent onset insulin dependent diabetes mellitus (IDDM) could be of great relevance for follow-up studies involving immunotherapy. Scintigraphy with radiolabelled human polyclonal immunoglobulins (99mTc-HIG) is currently used for the diagnosis and follow-up of several acute and chronic inflammatory diseases. In this longitudinal study we have investigated to what extent 99mTc-HIG accumulate in the pancreas of patients with recent onset IDDM and in subjects at risk to develop IDDM. METHODS: Combined computerised tomography and gamma camera imaging were used to measure the radioactivity in the pancreatic region, as the pancreas/bone radioactivity ratio (P/B). Patients with IDDM (n = 15) were investigated at the time of diagnosis and after 1 year. Five pre-diabetic ICA+ve subjects and 8 age and sex matched normal subjects were also investigated. RESULTS: Eight out of 15 newly diagnosed IDDM patients and 2/5 ICA+ve subjects showed a significant accumulation of radiolabelled HIG in the pancreas (P/B higher than the upper 1st centile of normal subjects). One year after the diagnosis a significant accumulation of immunoglobulins was still detectable in the pancreas of IDDM patients positive who were positive at diagnosis. CONCLUSIONS: These results suggest that immunoglobulins home and bind to the pancreas of patients with recent onset IDDM and also in some ICA+ve individuals. This may reflect an increased vascular permeability of pancreatic capillaries as a consequence of the inflammatory process involving the islets. Thus, this technique may be useful for monitoring the efficacy of immune intervention at diagnosis.

Laparoscopy in acute biliary pancreatitis.

BACKGROUND: The high mortality rates (20-30%) still occurring in some forms of acute pancreatitis demands adequate clinical and instrumental protocols in order to establish the most suitable therapeutic option to employ. The use of laparoscopic surgery can reduce hospital stay and time for functional recovery. METHODS: The study enrolled 73 patients referring for acute biliary pancreatitis in whom staging with clinical, laboratory and instrumental criteria was performed. According to Ranson classification 63 patients (86.3%) had a mild-moderate acute biliary pancreatitis, 10 (13.6%) a severe one. In the first group laparoscopic cholecystectomy with retrograde cholangiography was performed within seven days of admission, in the second group surgical procedure followed medical treatment between eight and 30 days after the onset of the disease. No preoperative ERCP was performed. RESULTS: The rate of main biliary tract calculosis was 8.2% in group A: six cases all treated through laparoscopy. Two switches (2.7%) due to intolerance to the pneumoperitoneum, eight major postoperative complications (10.9%), and two deaths (2.7%) occurred and a mean hospital stay of 7.4 days was observed in group A versus 8.2 days in group B. CONCLUSIONS: The management suggested in this study for mild-moderate acute biliary pancreatitis showed consistent results with those of the recent literature, as far as morbidity (6.3%) and mortality (1.5%) are concerned. A higher number of severe biliary pancreatitis (10 cases) should be observed to assess the role of ERCP with endoscopic sphincterotomy rather than laparoscopic or combined treatment.

The contribution of laparoscopy to the treatment of gastric cancer.

BACKGROUND: Laparoscopy plays a role in the preoperative diagnosis of gastric cancer, particularly in determining the location and extent of the neoplasia. In addition to its use in staging, laparoscopy is indicated for the gastric resection of T1-T2, and its middle- and long-term results are comparable to those obtainable with open surgery. Herein we describe our experience with the laparoscopic resection of gastric carcinomas, including the dissection of lymph nodes and the Billroth II reconstruction of digestive continuity with gastrojejunostomia. METHODS: We carried out laparoscopic gastric resections in 25 patients with adenocarcinomas. Our method involved installing five trocars, tying the left and right gastric vessels and the right gastro-epiploic vessels, sectioning the duodenum 3 cm from the pylorus, sectioning the remaining portion of the stomach obliquely 3 cm from the cardias, and performing Billroth II reconstruction. RESULTS: The average duration of the operation was 4 h 45 min. The average number of removed lymph nodes was 30.5 (range, 22-41). Five patients were converted to laparotomy. Significant complications were observed in four cases (16%). Hospitalization ranged from 5 to 16 days. The average follow-up was 38 months (range, 7-63), without evidence of relapse. CONCLUSION: In terms of morbidity, our results were similar to those obtained with open surgery. Lymphectomy according to the extent and number of lymph nodes is acceptable in the treatment of tumors of the lower third of the stomach. More case studies are needed to provide further indications of the applicability of the technique (which is currently used only in a few centers) and long-term results.

Breast cancer detection with Tc-99m tetrofosmin.

Myocardial SPECT imaging was performed with Tc-99m tetrofosmin. Intense focal uptake at the level of the left breast was observed. At mammography a breast carcinoma was suspected, which was confirmed after surgery. This may be the first report of neoplastic mammary uptake of Tc-99m tetrofosmin.

[Role of the subfascial endoscopic perforating veins surgery in the treatment of venous ulceration: physiopathology and diagnosis]. / Ruolo della interruzione sottofasciale delle vene perforanti per via endoscopica nella terapia delle ulcere flebostatiche: fisiopatologia e diagnostica.

Chronic venous insufficiency is a recurrent pathology, but affected patients often undergo clinical observation at a most severe and clearly symptomatic stage of the disease. In this late stage, therapy can only relieve symptoms of the disease which often lead to disability. In the clinical course of chronic venous insufficiency, phlebostatic ulceration constitutes a recurrent finding and it is responsible of compromising patients quality of life. The role of perforating veins, made refluxive by various pathogenic noxa, in the genesis of ulcerative lesions has been known since long time. For many years the interest in perforating veins surgery has been limited because of the several negative consequences of the operations. The possibility of modifying the hemodynamics of perforating veins compartment without causing post-operation complications by video-supported surgery, led to the debate on the role of these vessels in the chronic venous insufficiency. The phlebostasis non-invasive diagnosis uses imaging techniques consisting in tests which mostly are cheap, simple and easy to perform, thus representing the best early approach to the patient. It is widely thought that even though complex examinations are available, most precious information can be obtained by only two examinations: color-Doppler ultrasonography and, limitedly, plethysmography. By these diagnostic directions it is possible to better identify the site and the hemodynamic origin of the venous insufficiency.