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).

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.

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.

[Non recurrent inferior laryngeal nerve: our surgical experience]. / Il Nervo Laringeo Inferiore Non Ricorrente. Nostra esperienza chirurgica.

AIM: Iatrogenic damage to the recurrent laringeal nerve is the most feared complication in thyroid surgery and the main cause for vocal cord palsy. Prevention of such a lesion is based upon the thorough search for the nerve along its anatomic pathway. In the present study the Authors discuss an important anatomic variation: non-recurrent inferior laryngeal nerve, emphasizing the aspects of surgical anatomy, on the basis of their own experience in neck surgery. MATERIALS AND METHODS: The study takes into conideration 301 surgical interventions on the thyroid gland, in 268 women and 33 men; consisting in 256 total thyroidectomies and 45 loboisthmectomies, as follows: 186 for nodular goiter, 48 for follicular nodule, 34 for papillifer carcinoma, 33 for toxic goiter. The identification and exposure of inferior laryngeal nerve was performed according to the principles and technique by Lahey. RESULTS: The overall prevalence of non recurrent inferior laryngeal nerve was equal to 0.33% (1/301 operations). The anomaly is prevailing on the right side, being due by an anomalous reabsorption of the IV ventral arch. This is the cause of the formation of a subclavian artery that is responsible for dysphagia lusoria. CONCLUSIONS: The rationale for the preservation of recurrent nerve is its systematic identification and exposure along all its course from its laryngeal entry. Diagnosis of non recurrent inferior laryngeal nerve is exclusively intra-operative. The anomaly is clinically asymptomatic and its suspicion can be posed in case of vascular anomalies or dysphagia. In such a circumstance the golden diagnostic tool is the angio Tc-RMN, while both the EGDS and baritate esophagous can be of some diagnostic help.

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.

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.

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.

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.

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.

[Modulation of the axillary lymph node dissection in breast cancer]. / La modulazione della dissezione linfonodale dell'ascella nel carcinoma mammario. Nostra esperienza.

UNLABELLED: Several studies showed the reliability of the sentinel lymph node (SN) technique in the evaluation of the N parameter in breast cancer so much to induce surgeons to limit the axillary dissection to the biopsy of the SN alone (SNB) in case this is negative to the extemporaneous examination. After a period of focusing on the identification technique, biopsy and histological examination of the SN (October 97-January 98) always followed by a complete dissection of the three axillary node levels (ALND), we started a study to evaluate the reliability of a limited dissection of the 1st level of the axilla (FLND) in women with T < 3 cm, N0-1a, M0, that did not undergo any neoadjuvant treatment and in which the SN resulted free from metastases. We started this phase of the study in February 1998 till May 2001. In the present paper we show the results related to this period. MATERIALS AND METHODS: We enrolled 256 women with T < 3 cm, N0-1a, M0. In 49 cases we used vital dye, in 23 dye + radioguided surgery (RGS) and in 184 RGS only. The extemporaneous histological examination of the SN has been performed with thin sections, dyed with EE. When SN was negative to the intraoperative examination, we limited the dissection to the 1st level of the axilla, except that in 3 patients, with SN located to the 2nd level, in which we did an ALND. The FLND has been performed in 17 cases with a minimally invasive technique. The definitive histological examination of the SN always included the immunohistochemistry. If the SN was positive, usually underestimated to the intraoperative examination, the patients had an adjuvant chemotherapy. RESULTS: In 203/207 patients (98.1%) SN was found to the pre-operative lymphoscintigraphy. During surgery the SN was identified in 46/49 (94%) using the vital dye, in 22/23 (96%) using the vital dye + RGS and in 176/179 (98.3%) using RGS. To the extemporaneous histological examination SN was negative in 140, metastatic in 101; to the histological definitive results of the SN we noticed 6 false negative, since others lymph nodes than SN were positive (4 cases) or for evidence of micrometastases at the immunohistochemistry which were not detected at the extemporaneous examination (2 cases). On 107 cases of N+ the SN was the only metastatic lymph node in 42 (39.3%). The false negative percentage was 5.6% and the diagnostic accuracy of the SNB was 97.5%. In the group treated with FLND we only noticed two cases of light lymphedema (1.4%). CONCLUSIONS: Our results are in concordance with the international literature and they induced us, from June 2001, to begin a new phase of the study in which we limit the dissection of the axilla to the SN only, if not metastatic, in women with T1 breast carcinoma.

Non-ionizing electromagnetic radiations, emitted by a cellular phone, modify cutaneous blood flow.

BACKGROUND: Our surroundings are full of non-ionizing electromagnetic radiation (EMR) of different frequency and power. The non-ionizing EMRs emitted by television, computer and cellular phone (CF) sets have been increasing over the past few years. OBJECTIVE: The aim of our study was to assess the effects of non-ionizing EMRs (frequency 3 x 10(8) to 3 x 10(11) Hz), emitted by CFs, on cutaneous blood flow in healthy volunteers. METHODS: Thirty healthy volunteers (14 male and 16 female; age: 18-53 years) entered the study. Measurements of cutaneous blood flow were taken under standard conditions (temperature and humidity), using a laser Doppler He-Ne flowmeter that was applied to the ear skin by an optical fibre probe. Microflow values were recorded without CF contact with the skin (T0), with the CF turned off but in contact with the ear skin (T1), with CF contact and turned on (T2), with CF contact, turned on and receiving (T3). The microflow values were also recorded backwards: with CF contact and set turned on (T4), with CF contact and turned off (T5), without CF contact (T6). RESULTS: The mean value of basal microflow (T0), expressed as perfusion units (PU), was 51.26+/-11.93 PU. During the T1 phase, the microflow increase was 61.38%; in T2 it was 131.74%, in T3 157.67%, in T4 139.21% and in T5 122.90%; in T6, the microflow value was 57.58+/-10 PU (similar to the basal microflow). Statistically significant cutaneous microflow values (p<0.050) were observed comparing the T1 to T5 values with basal microflow (T0). Furthermore, in comparison with T1 values (CF turned off in contact with the ear skin), the T2, T3 and T4 data were statistically significant (T2 vs. T1: t=7.763 with p<0.050; T3 vs. T1: t=9.834 with p<0.050; T4 vs. T1: t=8.885 with p<0.050).

Laparoscopic procedures in patients who have previously undergone laparotomic operations.

BACKGROUND: Patients who have undergone laparotomy can undergo laparoscopic procedures and thus benefit from the advantages that the technique offers without significantly increasing the risk of the operation. METHODS: We present the results of 240 patients, chosen at random who underwent laparoscopic procedures and who had already had 1 or more laparotomic abdominal operations. We carried out 180 cholecystectomies, 12 of which for acute inflammation of the gall bladder, 10 for acute biliary pancreatitis, 3 with exploration of the common bile duct, 45 Nissen fundoplication procedures, of which 16 with removal of the gall bladder, 4 subtotal gastrectomies, 2 GEAs, 2 left colectomies, 4 adhesiolyses. RESULTS: The duration of the procedure varied from 40 to 300 minutes, and hospitalization time after the operation from 1 to 15 days, depending on the previous operation and on the laparoscopic procedure used. A traditional operation (conversion) became necessary in 1.35% of patients. Complica-tions arose in 4% of cases: 4 hematomas, 1 infected wound, 2 bile leaks and 2 bowel fistulas at low flow. CONCLUSIONS: Laparoscopic surgery in pa-tients who have previously undergone abdominal operations is difficult. The extent of conversions and complications can be contained within acceptable limits by choosing carefully the insertion point of the first trocar and dissecting the bowel with great precision.

[Sarcoma of the breast. Two clinical cases and review of the literature]. / I sarcomi della mammella. Due casi clinici e revisione della letteratura.

BACKGROUND: Sarcomas of the breast are rare neoplasm. Wide discordances exist about prognostic factors, therapy and life expectancy. METHODS: Two women affected by sarcoma of the breast; prognostic aspects and therapy are analyzed. RESULTS: After radical mastectomy one patient, with neoplasm of 4.5 cm in diameter, is still alive one year after the surgical procedure. CONCLUSIONS: Diagnosis of the sarcomas of the breast is very difficult with the common radiological imaging, specially in the early phases when the sarcomas often can simulate absolutely benign lesions. Prognostic factors are histological type and degree, mytosis number for field and, probably, dimensions of the neoplasm. Sarcomas less than 3 cm in diameter can be admitted to conservative surgical procedure, but radical mastectomy is unavoidable when dimensions exceed this limit.

[Intraoperative cholangiography in videolaparoscopic cholecystectomy: indications, advantages, and limitations]. / Colangiografia intraoperatoria in corso di colecistectomia videolaparoscopica: indicazioni, vantaggi, limiti.

Consensus doesn't exist about the intraoperative cholangiography specially if is need in every one laparoscopic cholecystectomy either exclusively in case of anatomical doubts or suspect of injures or stones of the common duct. We have considered 450 patient subjected to laparoscopic cholecystectomy during 1992-2000. Patients suspicious to be affected by common duct lithiasis (28 cases) are subjected to ERCP with cleaning of the biliary tree. In 18 patients (4%) it has been necessary the laparotomic conversion; 176 patients (39%) have been subjected to intraoperative cholangiography, selected on anatomical regional disposition or anamnesis and biochemical and instrumental results (history of jaundice or gallstones pancreatitis, abnormal serum level of the biliary stasis biochemistry, common bile duct major of 8 mm, michrolitiasis of the gallbladder). In 7 cases (4%) we have discovered common bile duct stones. We don't attempt intraoperative cholangiography in every one laparoscopic cholecystectomy, but only in cases where we suspect presence of common bile duct stones either iatrogenic injuries or when we retain it necessary to clarify the regional anatomy. Unlikely just in patients where would be more useful, causes major risk of intra- and post-operative complications, it is very difficult, often impossible, to attempt the intraoperative cholangiography. Routinary employing of the intraoperative cholangiography could be useful just for a little number of patients, while selective employing reduce 60% the X-ray. Collaboration with the radiologist is able to reduce the mistaken on the interpretation of the radiograms.

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.