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Breast metastasis originating from a primary lung tumor is exceedingly rare and can present challenges in distinguishing it from primary breast cancer. This case report discusses the management of a 64-year-old woman who initially presented with a nodule in her left breast. A biopsy revealed an infiltrating ductal carcinoma. Despite negative BRCA genetic testing, her significant family history of cancer and the presence of a newly detected right breast lesion led to a bilateral mastectomy. Post-operative imaging identified multiple hypodense nodules and a spiculated pulmonary nodule, necessitating further investigation. An endoscopic lung biopsy confirmed a primary pulmonary carcinoma with histological features similar to the breast carcinoma, suggesting the lung as the primary source. This case highlights the complexity of differentiating breast metastasis originating from a lung tumor and primary breast cancer. It underscores the importance of comprehensive diagnostic evaluations and the consideration of extramammary origins in metastatic cases. The findings emphasize the role of multidisciplinary teams in managing such rare and challenging cases and highlight the necessity for thorough and repeated assessments in atypical breast cancer presentations.

Locally advanced breast cancer (LABC) is a complex disease that requires a multidisciplinary approach. Neoadjuvant chemotherapy (NAC) is usually performed in order to achieve loco-regional radical resection; although its importance in the multidisciplinary approach to LABC is well recognized, a small number of patients show Progressive Disease (PD). No standard salvage treatment (ST) has been defined and different strategies can be adopted, such as second-line systemic therapies, radiation therapy, and surgery. Herein, a case of LABC in PD during NAC is reported with a literature review, with the aim of highlighting the importance of a tailored multidisciplinary treatment for each patient.

Oncoplastic breast-conserving surgery (OBCS) is increasingly used to treat breast cancer with the dual purpose of performing a radical oncological resection while minimizing the risk of post-operative deformities. The aim of the study was to evaluate the patient outcomes after Level II OBCS as regards oncological safety and patient satisfaction. Between 2015 and 2020, a cohort of 109 women consecutively underwent treatment for breast cancer with bilateral oncoplastic breast-conserving volume displacement surgery; patient satisfaction was measured with BREAST-Q questionnaire. The 5-year overall survival and disease-free survival were 97% (95%CI 92, 100) and 94% (95%CI 90, 99), respectively. In two patients (1.8%), mastectomy was finally performed due to margin involvement. The median patient-reported score for "satisfaction with breast" (BREAST-Q) was 74/100. Factors associated with a lower aesthetic satisfaction index included: location of tumour in central quadrant (p = 0.007); triple negative breast cancer (p = 0.045), and re-intervention (p = 0.044). OBCS represents a valid option in terms of oncological outcomes for patients otherwise candidate to more extensive breast conserving surgery; the high satisfaction index also suggests a superiority in terms of aesthetic outcomes., (© 2023. The Author(s).)

Background/Aim-Twenty patients had corrective reconstruction surgery by means of a reduction mammaplasty or mastopexy after a previous BCS (Breast Conserving Surgery) and RT (Radiation Therapy); the risk factors and post-operative complications were reported in order to define a safe and effective technique for reduction mammaplasty in previously irradiated breast cancer patients. Materials and Methods-From June 2011 to December 2019, 20 pts. were operated on at the Breast Surgery Clinic of San Martino Policlinic Hospital, Genoa, Italy. Pre- and post-operative parameters included clinic-pathological features of the primary tumor; a lapse of time from primary radio-surgery; the extent of follow-up; the rate of post-operative wound infections; the persistence of breast asymmetry, and a post-operative patient satisfaction index by means of a BREAST-Q questionnaire. Results-Three patients (15%) developed minor complications in the irradiated breast, but no complication was observed into the non-irradiated breast. No statistically significant correlation was found between the post-operative complications and the risk factors. The statistical analysis of BREAST-Q questionnaire responses gave an average patient's satisfaction index that was equal to 90.8/100 (range: 44 to 100). Conclusions-Inferior pedicle reduction mammoplasty is an effective reduction mammoplasty technique in regard to the extent of breast tissues that are to be removed both in irradiated and contralateral breast; moreover, the incidence of post-operative complications is clearly limited when a careful technique is adopted, and it can be reasonably applied also in patients with co-morbidity factors.

Background: Tissue regeneration is a complex process that allows wounds to heal. Many options are currently available to help human skin repair and to reduce the recurrence of hernias. The aim of this study is to analyze the best decellularization protocol for allogenic human dermal tissues. Methods: Dermal flaps from donors were used and compared with a control group. Each flap was subjected to seven different decellularization protocols and washed with a sequence of five solutions. The samples were then subjected to four control tests (such as Nile Red), and long-term contacts were analyzed to assess whether the decellularized dermis samples could support the growth of human fibroblasts. Results: All the samples had an average residual viability of 60%. Except for one sample, the decellularization treatments were able to reduce cell viability significantly. The Nile Red test showed a significant reduction in phospholipid content (mean 90%, p-value < 0.05) in all treatments. The cell growth increased in a linear manner. As described in the literature, sodium-dodecyl-sulfate (SDS) caused an interference between the test and the detergent. Conclusions: This paper shows the first step to finding the best decellularization protocol for allografting human dermal tissues. Further biocompatibility tests and DNA quantification are necessary.

Background/Aim: Patients with Stage I-II breast cancer undergoing breast-conserving surgery after neoadjuvant chemotherapy (BCS-NAC) were retrospectively assessed in order to evaluate the extent of a safe excision margin. Materials and Methods: Between 2003 and 2020, 151 patients underwent risk-adapted BCS-NAC; margin involvement was always assessed at definitive histology. Patients with complete pathological response (pCR) were classified as the RX group, whereas those with residual disease and negative margins were stratified as R0 < 1 mm (margin < 1 mm) and R0 > 1 mm (margin > 1 mm). Results: Totals of 29 (19.2%), 64 (42.4%), and 58 patients (38.4%) were included in the R0 < 1 mm, R0 > 1 mm, and RX groups, respectively, and 2 patients with margin involvement had a mastectomy. Ten instances of local recurrence (6.6%) occurred, with no statistically significant difference in local recurrence-free survival (LRFS) between the three groups. A statistically significant advantage of disease-free survival (p = 0.002) and overall survival (p = 0.010) was observed in patients with pCR. Conclusions: BCS-NAC was increased, especially in HER-2-positive and triple-negative tumors; risk-adapted BCS should be preferably pursued to highlight the cosmetic benefit of NAC. The similar rate of LRFS in the three groups of patients suggests a shift toward the “no ink on tumor” paradigm for patients undergoing BCS-NAC.

Background/aim: Clinicopathological features of patients undergoing margin enlargement after lumpectomy for early breast cancer with positive/close excision margins were analyzed in order to define whether a re-operative procedure could have been avoided. Furthermore, a standardized protocol of specimen orientation was adopted in order to optimize both the widening procedure as well as the oncologic outcome., Patients and Methods: A retrospective analysis was performed including pre-, peri-, and post-operative parameters, and a predictive score by means of a multivariate model was developed using all clinically and statistically significant variables associated with residual disease (RD)., Results: RD was significantly related to positive tumor margins, hormone receptor negative, HER2-positive, and tumors with high Ki67 proliferation index (p<0.001); the corresponding contribution to the prognostic score was as follows: close margins, 3 points; hormone receptor positive disease, 2 points; low Ki67, 2 points; HER2 negativity, 1 point. In 102 patients with a score >3, only 2 patients (2.0%) had RD, while in 81 patients with a score ≤3, 55 patients (67.9%) had RD (p<0.001)., Conclusion: This predictive model might aid in clinical-decision making of patients with positive margins who actually require a widening procedure after intraoperative and/or definitive histology., (Copyright© 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Breast-conserving surgery (BCS) is the standard of care for early-stage breast cancer. We retrospectively enrolled 530 patients (mean age: 62.96 ± 12.69 years) undergoing BCS between January 1, 2018, and December 31, 2019. During the COVID-19 pandemic, all patients with at least 1 year of follow-up were telephonically asked after surgery to provide clinical signs and symptoms attributable to postoperative breast cancer-related lymphedema of the breast (BCRL-B). Thirty-one (5.8%) patients reported breast edema and were visited to measure the tissue dielectric constant (TDC) and to assess the induration of the skin. There was a difference seen in treatment with lumpectomy + ALND performed more frequently in patients with (29%) than without (12%) BCRL-B. In the subgroup of patients with BCRL-B (n=31), significantly higher values of local total water were calculated in the nine patients who underwent Lump + ALND procedure (1.86 ± 0.48 vs. 1.48 ± 0.38; p = 0.046). Among patients with BCRL-B (n=31), in eight patients (25.8%) tissue induration measured with SkinFibroMeter was >0.100 N, thus suggesting tissue fibrosis. Cumulative survival probability at 1-year after surgery was 0.992. No statistical differences in 1-year survival after surgery were found for type of surgery (p = 0.890) or absence/presence of BCRL-B (p = 0.480). In univariate logistic regression, only lumpectomy + ALND surgery (p = 0.009) and any subsequent axillary lymph node removal surgery (p = 0.003) were associated with BCRL-B. Both of these variables were also found to be statistically significant in the multivariate regression model. Further prospective research is warranted to analyze potentential predictors of BCRL-B and to reduce/ prevent this complication., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright by International Society of Lymphology.)

Competing Interests: None

Aim: We report a particular case study of the unexpected death of a 70-year-old caucasian man (affected by crohn's disease) due to the laceration of the ileocolic mesentery and its blood vessels following a colonoscopy procedure carried out only a few hours previously., Material of the Study: The autopsy showed that the lacerated blood vessels (i.e. the collateral and terminal branches of the superior mesenteric artery), which run along the section of the intestines between the end of the ileum and the ascending cecum, had led to a severe intra-abdominal hemorrhage and, consequently, fatal hemorrhagic shock., Results: In such cases, both an autopsy and complete histological analysis are essential in order to determine the exact point responsible for the intestinal hemorrhage and to better understand the pathological mechanism involved., Discussion: The unexpected death due to severe peritoneal hemorrhaging following a minimally invasive diagnostic clinical procedure, such as a colonoscopy, is particularly rare in Literature. In fact, amongst the several endoscopy procedures commonly used today, it is one of the safest procedures with the lowest recorded rate of complications. Furthermore, it is an even rarer event that a routine diagnostic colonoscopy can result in a fatality, with only two cases reported., Conclusions: In the case of sudden death following such a routine diagnostic clinical procedure, the forensic scientist should not disregard the fact that also damage, which appears negligible (caused by the normal procedures used in carrying out a colonoscopy) can actually also result in severe and fatal hemorrhaging., Key Words: Colonoscopy, Fatal hemorrhage, Forensic pathology.

Background/aim: A notable re-allocation of healthcare resources and specific clinical and organizational measures have been required to prevent COVID-19 infection among hospitalized patients and healthcare workers., Patients and Methods: From March 9th to May 9th 2020 we performed colorectal cancer elective surgery on 25 patients: a pre-hospital screening was carried out in order to avoid hospitalization of patients suspected of COVID-19 infection., Results: All patients (median age=76 years; range=37-88 years) were considered suitable for admission after telephone triage; the median interval between primary diagnosis and hospital admission was 23.1 days (range=1-55 days). The median hospitalization was 7.8 days (range=4-18 days). One COVID-19-associated death was reported., Conclusion: Our experience demonstrates that safe colorectal cancer elective surgery can be performed during the pandemic COVID-19. Further consensus and guidelines to prevent diffusion of pandemic diseases among hospitalized patients and healthcare workers still need to be implemented., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The perspective validation of a selective approach in patients undergoing breast cancer surgery was performed in order to assess whether patients as well as Health Care Workers (HCWs) were exposed to any undue risk of COVD-19 infection., Patients and Methods: From March 9 th to June 9 th 2020, 207 patients were phone-triaged by a dedicated Breast Care Nurse; a patient-tailored program was adopted with the aim of avoiding hospitalization of SARS-CoV-2 symptomatic patients, with a careful prioritization of surgical procedures according to specific disease features., Results: Two hundred and three out of 207 patients underwent operation; seven patients were temporarily excluded because they tested positive at phone triage (n=3), or in-hospital triage (n=3); another asymptomatic patient with negative NP swab tested IgM Ab-positive so that surgery was re-scheduled two weeks later. Four patients had no surgery; one of them was reconsidered for neoadjuvant chemotherapy (NAC) after testing positive at phone triage; three patients were excluded because they were already hospitalized for COVID-19. Overall, mean in-hospital stay was 2.2 days (±SD, 0.7) and, after hospital discharge, no patient required readmission., Conclusion: This preventive program avoided any COVID-19 infection among patients and HCWs, so that an elective breast cancer surgical procedure can be safely and timely pursued without affecting the oncologic outcome., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: COVID-19 pandemic required a marked re-allocation of healthcare resources, including at Breast Units. A patient-tailored program was developed to assess its efficacy regarding prevention of COVID-19 infection among patients with breast cancer undergoing surgery and healthcare workers (HCWs)., Patients and Methods: From March 9th to April 9th 2020, 91 patients were selected for elective surgery by means of: i) Pre-hospital screening aimed at avoiding hospitalization of symptomatic or suspicious COVID-19 patients, and ii) prioritisation of surgical procedure according to specific disease features., Results: Eighty-five patients (93.4%) were fit for surgery, while five patients (5.5%) were temporarily excluded through 'telephone triage'; another two patients were excluded at in-hospital triage. A total of 71 out of 85 patients (83.5%) were diagnosed with invasive cancer, most of whom were undergoing breast-conserving surgery (61 out of 85 patients, 71.8%). The mean in-hospital stay was 2.2 days (SD=0.7 days). After hospital discharge, no patient needed re-admission due to post-operative complications; moreover, no COVID-19 infection among patients or HCWs was detected., Conclusion: Safe breast cancer surgery was accomplished for both patients and HCWs by means of a careful preoperative selection of patients and in-hospital preventative measures. This screening program can be transferred to high-volume Breast Units and it may be useful in implementing European Community recommendations for prevention of COVID-19 infection., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: A retrospective study was performed in 246 breast cancer patients to define whether tumor-to-nipple distance (TND) assessment by breast MRI may select patients eligible to nipple-sparing mastectomy (NSM) as compared to permanent section assessment of retroareolar margin., Patients and Methods: Pre- and post-operative parameters including imaging data, histology of the primary tumor, biologic prognostic factors, and adjuvant regimens were retrieved; patients with close/positive retroareolar margins underwent nipple or NAC excision. The primary endpoint was loco-regional recurrence (LRR)., Results: Patients with TND ≤2 cm had a significantly higher rate of invasive ductal carcinoma (p<0.003) and excision margins less than 2 mm (p<0.000). Eleven retroareolar specimens were positive at definitive pathology; final re-excision specimen examination showed residual disease in seven patients (63.6%). At a median follow-up of 31 to 33 months, no NAC recurrence did occur; disease-free survival was more than 96%, and LRR was homogeneously distributed among TND subgroups., Conclusion: Therapeutic NSM is a safe procedure independently of TND assessed at preoperative breast MRI. Permanent section assessment of retroareolar tissue is more accurate and cost-effective than frozen section. Furthermore, delayed nipple and/or NAC excision did not impair local disease control., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The histopathological assessment of the B5c category may sometimes be hampered by simple artifacts that may lead to over- or underestimation of that particular breast cancer so that its management is still controversial, especially with regard to the decision to proceed immediately to sentinel lymph node (SLN) biopsy. Hence, a retrospective study was performed in 174 patients undergoing breast-conserving surgery with a preoperative diagnosis of B5c in order to assess the usefulness of axillary node staging by means of SLN biopsy., Patients and Methods: Pre- and post-operative parameters including imaging data, histology of the primary tumor and SLN biopsy, biological prognostic factors, type of operation, and adjuvant regimens were computed., Results: Invasive carcinoma and carcinoma in situ were diagnosed in 46 (26.5%) and 128 patients (73.5%), respectively. Preoperative tumor size was significantly related to post-operative diagnosis of invasive carcinoma (p=0.020), retaining its predictive value at logistic regression analysis (p=0.046). Post-operative predictive factors of invasion were represented by tumor stage (p=0.008) and grading (p=0.008)., Conclusion: B5c preoperative diagnosis in patients undergoing breast conservative surgery would suggest an immediate wide local excision avoiding any further preoperative histologic assessment. Conversely, one-stage SLN biopsy might be suggested for patients eligible to mastectomy, similar to patients with carcinoma in situ, although its impact on the therapeutic and prognostic assessment seems negligible., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background Influence of tumor subtype, radiological sign and prognostic factors on tumor size discrepancies between DBT and final histology has not been completely investigated so far. Purpose To study the influence of tumor subtype, radiological sign and prognostic factors on tumor size discrepancies between digital breast tomosynthesis and final histology. Material and methods This is a retrospective study conducted between January 2015 and December 2016. After IRB approval, 130 consecutive patients with breast cancer diagnosed with digital breast tomosynthesis (DBT) were evaluated. A discrepancy between DBT and final histology was considered present if the difference was above the cut-off of 5 mm. Tumor subtype, radiological sign and prognostic factors were evaluated in patients with discrepancies. Descriptive statistic and non-parametric tests were used. Results A total of 105 cases of cancer, in 96 patients, all female, were included. Mean age was 61 years (range: 35-82 yrs). In 19 (18.1%) cases, discrepancies were found: 13 (68.4%) were underestimated by DBT. For tumor subtype, 10 (52.6%) were infiltrating lobular carcinomas (ILC) (p < 0.01). Fourteen (73.7%) discordant cases were architectural distortions (p < 0.01). Prognostic factors did not affect tumor size discrepancies. Conclusion ILC or an architectural distortion represents the majority of cases of tumor size discrepancies between DBT and final histology., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Garlaschi et al.)

Background/aim: This retrospective study was performed in patients undergoing Stapled Haemorrhoidopexy (SH) who were post-operatively treated with Proctonorm® with the aim of assessing its effect on early and late haemorrhoidal-related symptoms., Patients and Methods: Forty-six males and 54 females received Proctonorm® (one tablet twice daily for 14 days) and Ketoprofene R (200 mg, one tablet twice daily, as requested)., Results: "Early Complication Score" (0-12) two days after surgery was 2.02±1.03; pain VAS (Visual Analogue Scale) (0-10) was 1.21±0.89, and the number of anti-inflammatory tablets was 4.24±1.06. At 40-day post-operative assessment, seven patients had post-operative complications with "Late Complication Score" (0-20) of 0.34±0.68. At six-month follow-up, a high index of patient satisfaction (VAS=9.39±0.24) was self-reported with 75% reduction in CSS (Constipation Scoring System) (1.95±2.58) compared to preoperative scores; "Late Complication Score" was 0., Conclusion: The specific target activity of Proctonorm® at the microcircular level may be effective in patients undergoing SH in order to reduce the inflammatory response of residual haemorrhoids while waiting for stable resolution of symptoms within one or two weeks., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: A retrospective analysis of 388 patients with pure ductal carcinoma in situ (DCIS) was performed in order to test the correlation of clearance margin of resection and other host-, tumor- and treatment-related factors with ipsilateral breast tumor recurrence (IBTR)., Materials and Methods: The pathological analysis was performed according to a standardized protocol: positive margins had DCIS at the inked margin; close margins had tumor between 0.1 to 0.9 mm, or 1 to 1.9 mm, and negative margins were ≥2 mm., Results: At a median follow-up of 90 months there were 26 IBTR (10 invasive and 16 DCIS). Both in univariate and multivariate analysis a significant difference was observed in IBTR by comparing positive versus close/negative margins of excision (p=0.05) and the number of re-operations (p=0.000). Moreover, the actuarial IBTR rates were significantly different in patients with a positive compared to close/negative margins (log-rank test, p=0.042) while the stratification by the margin width (0.1-0.9 mm; 1.0-1.9 mm; ≥2 mm) was not significant (log-rank test, p=0.243)., Conclusion: The policy of "no ink on the tumor" can be translated from invasive to DCIS, because the actuarial IBTR rates were significantly different only in patients with a positive, compared to close/negative margins., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Hyperthermic isolated limb perfusion (HILP) represents a limb-sparing treatment for unresectable soft tissue sarcoma (STS) of the extremities with substantial complete response rates. HILP often provides good functional limb preservation, hence a significant improvement also in terms of quality of life of the patient. Notwithstanding these clear advantages, the traditional technique is still hindered by relatively high post-operative morbidity., Method: We treated a 78-year-old female with unresectable angiosarcoma of the left leg using a new surgical approach: an entirely laparoscopic HILP., Results: No conversion from laparoscopic to "open" surgery was necessary. Since no abdominal muscle section was performed, post-operative pain was low and easily manageable; early mobilisation and early discharge were achieved. Patient developed moderate toxicity, which resolved spontaneously within 3-4 weeks, with complete return to normal daily activities after 30 d. Complete clinical response with preservation of leg function was obtained., Conclusions: We describe for the first time an entirely laparoscopic HILP. Demonstration of this technique's efficacy and safety on a large series of patients is clearly necessary but its therapeutic efficacy appears to be comparable to the standard technique. Furthermore, laparoscopic HILP has shown low post-operative morbidity: no wound complications, mild and easily manageable post-operative pain and early discharge from the hospital and early resuming of daily activities.

Background: The tumescent mastectomy technique has been used to facilitate dissection of subcutaneous tissue and mammary gland in order to reduce intraoperative bleeding and speed the operation., Patients and Methods: A prospective clinical study was performed on 30 female patients undergoing immediate breast reconstructions after skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) in order to assess early postoperative complications, pain, and final esthetic outcome of skin flaps related to tumescent anesthesia (TA)., Results: TA significantly speeded-up the operative procedure (131±49.99 vs. 180.5±67.15 min; p=0.03) achieving less skin damage compared to patients who did not have TA (p=0.045); moreover, no significant difference occurred with regard to the length of in-hospital stay and overall lymphatic drainage., Conclusion: The length of the operation as well as the final cosmetic outcome of skin flaps was significantly improved due to TA, with no appreciable side-effects., (Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: A prospective observational clinical study was undertaken to assess the accuracy of preoperative Axillary Ultrasound (AUS) plus Fine-Needle Aspiration Cytology (FNAC) as well as and its clinical utility, that is the capacity of the information supplied by the test to guide the clinical decision-making., Materials and Methods: from January 2013 to August 2015, 400 female patients with pT1-3 cN0 operable breast cancer underwent AUS with FNAC at the Breast Unit of the "IRCCS San Martino-IST" in Genoa (Italy)., Results: 127 out of 400 patients (31.7%) had axillary lymph node metastases; in 69 out of 127 node-positive patients (54.3%) AUS detected at least one abnormal lymph node, and in 56 out of 127 patients (44.1%) the abnormal sonographic pattern of the lymph node was coupled with a positive FNAC finding. No false-positive finding by both AUS-alone or combined AUS/FNAC was observed. AUS-alone had sensitivity of 54.3% (69/127), specificity of 100% (273/273), PPV of 100% (69/69), NPV of 82.5% (273/331), and accuracy of 85.5% (342/400). Combined AUS/FNAC had sensitivity of 44.1% (56/127), specificity of 100% (273/273), PPV of 100% (56/56), NPV of 79.4% (273/344), and accuracy of 82.2% (329/400)., Conclusions: AUS-alone or combined AUS/FNAC had a high accuracy rate coupled with a more than satisfactory efficiency due to their low costs and easy access for the preoperative staging of the axilla. Notably, AUS-alone might be suggested for the preoperative staging of patients with early stage breast cancer because FNAC did not increased the specificity but reduced the sensitivity of the technique. Patients with negative findings might undergo either SLNB or close observation while waiting for the definitive results of ongoing SOUND randomized clinical trial., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aim: The feasibility of videoscopic inguinal-iliac-obturator lymphadenectomy (VIIOL) was assessed in 20 patients with melanoma and compared with a retrospective sample of 24 patients undergoing standard 'open' technique (IIOL)., Results: No postoperative death occurred; the mean operative time was lower in the IIOL series (190 min vs. 302 min) but the quality of life was greatly improved in the VIIOL group thanks to earlier bladder catheter removal, no nasogastric suction, less pain, earlier mobilization, lower in-hospital stay, and earlier resumption of daily activities (27.6 vs. 83.2 days, p<0.001). Six out of 20 patients in the IIOL series had wound complications (30%) as compared to one in the VIIOL series (4%) (p=0.035)., Conclusion: Staging and therapeutic efficacy of VIIOL were similar to the standard technique; the longer operative time of VIIOL was greatly compensated by less pain, lower wound complication rate, and earlier discharge from hospital and recovery of daily activities., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The clinical chart of 621 patients with III-IV haemorrhoids undergoing Stapled Hemorrhoidopexy (SH) with CPH34 HV in 2012-2014 was consecutively reviewed to assess its safety and efficacy after at least 12 months of follow-up. Mean volume of prolapsectomy was significantly higher (13.0 mL; SD, 1.4) in larger prolapse (9.3 mL; SD, 1.2) (p < 0.001). Residual or recurrent haemorrhoids occurred in 11 of 621 patients (1.8%) and in 12 of 581 patients (1.9%), respectively. Relapse was correlated with higher preoperative Constipation Scoring System (CSS) (p = 0.000), Pescatori's degree (p = 0.000), Goligher's grade (p = 0.003), prolapse exceeding half of the length of the Circular Anal Dilator (CAD) (p = 0.000), and higher volume of prolapsectomy (p = 0.000). At regression analysis, only the preoperative CSS, Pescatori's degree, Goligher's grade, and volume of resection were significantly predictive of relapse. A high level of satisfaction (VAS = 8.6; SD, 1.0) coupled with a reduction of 12-month CSS (Δ preoperative CSS/12 mo CSS = 3.4, SD, 2.0; p < 0.001) was observed. The wider prolapsectomy achievable with CPH34 HV determined an overall 3.7% relapse rate in patients with high prevalence of large internal rectal prolapse, coupled with high satisfaction index, significant reduction of CSS, and very low complication rates.

Background: Fine-needle aspiration cytology (FNAC) is a simple and reliable technique to assess breast lesions, although a definitive differential diagnosis (benignity vs. cancer) is achieved approximately in 60-70% of cases because an inadequate (C1), atypical (C3) or suspicious (C4) category is otherwise reported., Patients and Methods: A retrospective analysis of 763 cases with C3 or C4 reports was performed to define their positive predictive value (PPV), as well as the practical implications of clinical and imaging findings as for clinical decision-making. FNACs were collected from January 2003 to September 2012 at the Breast Unit of IRCCS "A.O.U. San Martino-IST" Genoa, with each being received later to definitive histology. The PPV for cancer of C3/C4 categories were computed to measure the accuracy of FNAC; moreover, the PPV was also stratified according to clinical, mammography and sonography data alone or by their combination., Results: The PPV of C3 and C4 was 21.1% (80/380) and 84.1 % (322/383), respectively. Within each C3/C4 category, a significant direct correlation (p<0.001) between the suspicion index of clinical, mammography and sonography data and cancer detection rate was always observed. The PPV of C3/C4 stratified by the combination of clinical and imaging findings showed satisfactory values in the C3 category only when there was an agreement between clinical and imaging findings, whereas the PPV of the C4 category was always remarkably high (ranging from 92.3% to 100%)., Conclusion: the diagnostic work-up in C4 reports or in patients with a C3 report but with an high suspicion index at clinical or imaging examination should be preferably implemented by means of a core biopsy to optimize the therapeutic planning; given a C3 report with dubious clinical and/or imaging findings, an excisional biopsy (or in alternative vacuum-assisted breast biopsy with complete removal of the nodule) should be preferably performed in order to reach a definitive histological dia gnosis with no further delay., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: Standard stapled transanal rectal resection (STARR) with two PPH-01™ poses some questions regarding the completeness of prolapse resection in patients with obstructed defecation syndrome (ODS) since 20% to 30% of patients have persistent rectocele or rectal intussusception that may impair the physiological recovery of rectal sensitivity. New high-volume (HV) devices, such as CPH34 HV™ and CPH36 SMS™, allow for wider prolapsectomy to be performed and we herein assessed the possibility and safety of a STARR mono-stapler., Materials and Methods: On May 30th-31st 2011, 13 pigs were selected to undergo standard STARR with two PPH-01™ (n=2) or STARR mono-stapler with one CPH34 HV™ (n=11) at the Experimental Center of Vila do Conde (Portugal); another set of 13 pigs was selected on January 14th-17th 2014 to undergo standard STARR (n=2) or STARR mono-stapler by means of one CPH36 SMS™ (n=11). The length, height, square surface, and volume of resected specimens were intra-operatively assessed. Pigs were monitored for three days before undergoing transrectal sonography and autopsy to check for locoregional complications., Results: CPH36 SMS™ STARR mono-stapler achieved 57% higher volume of prolapsectomy compared to Standard STARR (p=0.008); moreover, surface measures of the specimens of CPH36 SMS™ STARR mono-stapler were significantly higher (length, p=0.003; height, p=0.004; square surface, p=0.002) compared to CPH34 HV™ STARR mono-stapler, with a 97.8% increase of prolapsectomy (p<0.001). No intra- or early postoperative complications occurred. Transrectal sonography and autopsy detected: two (50%) small intra-parietal and two (50%) extra-rectal haematomata after Standard STARR; five small intraparietal (45.5%) and one (9%) extra-rectal haematoma after CPH34 HV™ STARR mono-stapler; three (27.2%) small intraparietal and (27.2%) extra-rectal haematomata after CPH36 SMS™ STARR mono-stapler., Conclusion: CPH36 SMS™ STARR mono-stapler is quite feasible both from the technological and safety standpoint; most importantly, the higher volume of prolapsectomy achievable with CPH36 SMS™ compared to standard STARR with two PPH-01™ might reduce the risk of residual/recurrent prolapse and further improve the clinical efficacy of the STARR procedure., (Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

From January 2003 to March 2010, a prospective study was undertaken at the National Cancer Research Institute of Genoa in 15 patients with melanoma who had local recurrence (LR) or a few (≤ 3) in-transit metastases and clinically-negative regional lymph nodes with the aim of defining: i) the feasibility of sentinel node re-staging (r-sN) of the regional nodal basin; ii) the prognostic value of sentinel node status, and iii) the potential benefit in terms of disease-free survival and overall survival in patients with an histologically-positive sentinel node undergoing therapeutic regional lymph node dissection. Preoperative lymphoscintigraphy was performed to identify the r-sN: the radiotracer was intra-dermally injected around the LR or in-transit metastasis. Moreover, 10 min prior to the operative procedure, 0.5 ml intradermal injection of Patent-Blue-V dye was given around each LR or in-transit metastasis site, so that r-sN identification was achieved by both visualization of the nodal blue dye staining and the information supplied by gamma-detection probe. At least one sentinel node was intra-operatively identified in each patient, and a tumor-positive r-sN was required in four out of fifteen patients. The interval between the diagnosis of primary melanoma and the onset of recurrence was longer, although not significantly, in patients with tumor-negative r-sN, a compared to tumor-positive r-sN (49 ± 47 months vs. 25 ± 19 months, p=0.342). There was a trend toward an improved 1-, 3-, and 5-year disease-free survival and overall survival in patients with tumor-negative r-sN a compared to tumor-positive r-sN. Hence, the r-sN proved to be a feasible and accurate staging procedure even in patients with a few localizations of LR or in-transit metastases (≤ 3). r-sN identified those with a more favorable prognosis, supporting an aggressive therapeutic approach in the natural history of their disease; moreover, an unnecessary regional lymph node dissection was safely avoided in 11 out of 15 73.3% patients because they had a tumor-negative r-sN., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

CPH34 HV, a high volume stapler, was tested in order to assess its safety and efficacy in reducing residual/recurrent haemorrhoids. The clinical charts of 430 patients with third- to fourth-degree haemorrhoids undergoing SH in 2012-2013 were consecutively reviewed, excluding those with obstructed defecation (rectocele >2 cm; Wexner's score >15). Follow-up was scheduled at six and 12 months. Rectal prolapse exceeding more than half of CAD was reported in 341 patients (79.3%); one technical failure was reported (0.2%) without any serious untoward effect; and 1.3 stitch/patient (SD, 1.7) was required to achieve complete haemostasis. Doughnuts volume was higher (13.8 mL; SD, 1.5) in patients with a large rectal prolapse than with smaller one (8.9 mL; SD, 0.7) (P value <0.05). Residual and recurrent haemorrhoids occurred in 8 of 430 patients (1.8%) and 5 of 254 patients (1.9%), respectively. A high index of patient satisfaction (visual analogue scale = 8.9; SD, 0.9) coupled with a persistent reduction of constipation scores (CSS = 5.0, SD, 2.2) was observed. The wider prolapse resection well correlated with a clear-cut reduction of haemorrhoidal relapse, a high index of patient satisfaction, and clinically relevant reduction of constipations scores coupled with satisfactory haemostatic properties of CPH34 HV.

Patient-related, tumor-related, and sentinel node (SN)-related factors have been identified with the aim of predicting non-SN status in patients with SN micrometastases. According to our previous experience, primary tumor size (p=0.005) and the presence of lymphovascular invasion (LVI) (p=0.000) significantly predicted non-SN status in patients with SN micrometastasis; moreover, non-SN metastases were never detected in patients with pT1a-1b, G1, and no LVI. A prospective assessment was undertaken in a validation set of 126 patients to confirm these findings. Univariate analysis indicated that primary tumor size (p=0.05), Scarff-Bloom-Richardson (SBR) grade (p=0.008), LVI (p=0.001), and the number of mitoses/mm(2) (p=0.01) were significant predictors of non-SN status. By logistic regression analysis, tumor size (p=0.03), LVI (p=0.001), grade (p=0.003) and the number of mitoses/mm(2) (p=0.01) were the only variables remaining in the model. Three subsets of patients were identified: i) 18.3% of patients (pT1, G1, and no LVI) had tumor-negative non-SN (no risk group); ii) 37.3% of patients (number of mitoses/mm(2) <10, SBR grade II-III) had a rate of tumor-positive non-SN <15% (intermediate risk); iii) 44.4% of patients had a mean rate of non-SN involvement of 46% (high risk). By these parameters, more than 50% of patients could be selectively spared unnecessary axillary lymph node dissection without staging or therapeutic benefit, especially in patients with well-differentiated pT1 tumors without LVI.

Background: An evolution of CPH34 (CPH34 HV) for stapled transanal rectal resections was developed and tested to assess its safety and resection volume as compared to other staplers., Materials and Methods: A total of 16 pigs were randomly assigned to rectal prolapsectomy with CPH34 HV (n=4), CPH34 (n=4), PPH03-33 (n=4), HEEA (n=2) and PPH-01 (n=2). Measures and histological structure of specimens were assessed; transrectal echotomography (ETG) was performed on the third postoperative day, hence pigs were autopsied., Results: Significant differences of the volumes and weights of specimens were observed by type of stapler (p=0.0298 and p=0.0278, respectively) which were mainly due to CPH34 HV vs. PPH03-33 (p=0.0402 and p=0.0375, respectively). The average volumes were 17.1% lower for CPH34, 30.2% lower for HEEA, and 34.7% lower for PPH03-33 with respect to CPH34 HV. No significant increase of resection volume (7.5%) was observed between two PPH-01 units combined (two specimens together) vs. a single CPH34 HV unit. The highest percentage of muscularis propria was observed into the specimens collected with CPH34 HV and HEEA (50%). ETG detected three intra- and two extraparietal haematomata., Conclusion: The safety and higher volume of resection achievable with CPH34 HV correlated well with the specimen weight and percentage of muscularis propria.

Osteoradionecrosis (ORN) of the mandible is a major complication of radiation therapy of head and neck cancer with a potential of occurrence ranging from 5 to 15% of the irradiated patients. Due to the gradual necrotic process, the mandibular bone becomes necrotic and looses its spontaneous regeneration ability. Containing an elevated content of mitogenic and osteogenic growth factors, the use of platelet rich plasma (PRP) from autologous source has been suggested to re-activate the healing process of osteogenesis. Autologous PRP gel was introduced into the ORN necrotic defect of a 44-year old patient previously treated for squamous cell carcinoma of the tongue, subsequent to proper surgical debridement. We report post-operative two-year follow-up demonstrated by panoramic X-ray which showed regain of the mandibular bone continuity with a complete repair of the necrotic defects. We conclude that this case illustrates an incident of successful regeneration of ORN critical-sized defect of the mandible by autologous PRP gel.

Objective: A randomized clinical trial was performed in patients with chronic or recurrent pilonidal sinus (PS) comparing primary closure coupled with random application of in house autologous platelet gel or produced by means of Vivostat- in order to assess whether a standardized product had an impact on the wound healing process., Patients and Methods: Between June 2006 and June 2009, 100 patients (82 males, 18 females: median age 30 years; range, 16-51 years) underwent wide excision of the pilonidal area with midline tension-free closure and were randomly given either the in house autologous platelet gel (Group 1) or the Vivostat- gel (Group 2)., Results: Group 2 patients had shorter wound healing time (8 vs. 10 days; p<0.0001), time to return to full activity (11 vs. 16 days: p<0.0001), less uncomplicated fluid collections (120 vs. 190 ml: p<0.0001), and fewer postoperative wound complications (1/50=2% vs. 5/50=10%, p<0.001). After a median follow-up of 21 months (range: 4-40 months), two recurrences were detected in Group 1., Conclusion: The standardized production of platelet gel by means of the Vivostat- system guarantees the reproducibility of the procedure and its use was correlated with an improved outcome, with a high degree of patient satisfaction and better cosmetic results.

Purpose: A careful preoperative selection of patients was performed in order to identify those eligible for stapled transanal rectal resection to correct obstructed defecation syndrome. The aim was to assess the consequences of surgery on anorectal function and patient outcomes., Methods: From January 2004 to June 2007, 33 female patients (median age, 56.3 years; range, 27-77 years) eligible for stapled transanal rectal resection completed standardized questionnaires for the assessment of constipation (constipation scoring system), quality of life (Patient Assessment of Constipation-Quality of Life Questionnaire), and patient satisfaction (visual analogue scale). A complete clinical reassessment including anorectal manometry and defecography was performed after one year., Results: At a median follow-up of 18 months, significant improvement in constipation scoring system, quality of life, and visual analog scale (P < 0.0001) was observed. Postoperative defecography confirmed the correction of internal rectal prolapse (P < 0.01) and rectocele (P < 0.0001) with an increase in rectal sensitivity (P < 0.0001). Significant correlations were observed between rectocele correction and rectal sensitivity, as evidenced by a decrease in rectal sensory threshold volumes (P = 0.017; Phi = 0.7), increased rectal sensitivity, and patient's satisfaction index (P = 0.011; Phi = 0.64)., Conclusions: Stapled transanal rectal resection allowed for the correction of rectocele and intussusceptions. These corrections increased rectal sensitivity, diminished symptoms of obstructed defecation syndrome, and improved the quality of life of patients.

We reviewed our experience to assess the predictive role of preoperative lymphoscintigraphy with regard to the pathological status of sentinel lymph node (sN) in patients with cutaneous melanoma, to optimize the surgical treatment planning with regard to the use of intraoperative frozen section examination of sN. Eighty-eight patients with clinically node-negative cutaneous melanoma pT1b-T4 stage underwent preoperative lymphoscintigraphy for the lymphatic mapping of sN. A lymphoscintigraphic 'score' (from L1 to L5) was developed based on the ratio of radiotracer concentration within sN nodes as compared with the injection site. Our score allowed us to foresee that sN of patients with thick melanomas (T3 and T4) and a low preoperative score (L1-L2-L3) had a 90% expected likelihood (P<0.001) of harboring metastasis, whereas sN in patients with thin melanomas (T1b-T2) and high preoperative score (from L4 to L5) showed a 100% likelihood of being metastasis free. In conclusion, the sN is a reliable predictor of regional lymph node status in patients with cutaneous malignant melanoma. Moreover, we suggest that a low score (L1-L2-L3) associated with a thick melanoma is a good predictive factor of the positive sN involvement. This information could be useful in scheduling the intraoperative frozen-section examination with an expected benefit of a positive test in almost 90% of patients. Such patients might be selected for a 'one-stage' procedure with a more effective cost/benefit ratio and decreased hospitalization costs.

Background: Sentinel lymph node (SLN) staging is currently used to avoid complete axillary dissection in breast cancer patients with negative SLNs. Evidence of a similar efficacy, in terms of survival and regional control, of this strategy as compared with axillary resection is based on few clinical trials. In 1998, we started a randomized study comparing the two strategies, and we present here its results., Materials and Methods: Patients were randomly assigned to sentinel lymph node biopsy (SLNB) and axillary dissection [axillary lymph node dissection (ALND arm)] or to SLNB plus axillary resection if SLNs contained metastases (SLNB arm). Main end points were overall survival (OS) and axillary recurrence., Results: One hundred and fifteen patients were assigned to the ALND arm and 110 to the SLNB arm. A positive SLN was found in 27 patients in the ALND arm and in 31 in the SLNB arm. Overall accuracy of SLNB was 93.0%. Sensitivity and negative predictive values were 77.1% and 91.1%, respectively. At a median follow-up of 5.5 years, no axillary recurrence was observed in the SLNB arm. OS and event-free survival were not statistically different between the two arms., Conclusions: The SLNB procedure does not appear inferior to conventional ALND for the subset of patients here considered.

The authors report their clinical experience regarding an original method of surgical repair of oro-sinusal communications. From September 1999 to December 2003, 13 patients (7 male and 6 female patients; mean age: 52 years, range: 24-68 years) underwent surgical repair of an oro-antral fistula by means of cryoplatelet gel: in three patients, it was mixed with bioglass granules; in two, it was mixed with Bioss; in three, it was mixed with particulate bone extracted by means of a bone grafter from the oral cavity close to the operative site, with addition of demineralised bovine bone; in three, it was used together with porose hydroxyapatite, and in two patients the cryoplatelet gel was used only. No postoperative complication was reported; primary wound healing was achieved within seven to nine days. A bony orthopantoscintigraphy was performed a few months following the operative procedure, showing an active osteogenic process. In eight patients, a CT was performed after 8 to 12 months from the operation, showing a normal pneumatization with reconstruction of the floor of the maxillary sinus. Although preliminary, these findings seem to suggest that the use of bioengineered materials coupled with growth factors and osteoprogenitor cells may represent a valuable alternative to autologous bone transplantation for the reconstruction of the maxillary sinus.

Objective: A retrospective analysis of patients undergoing surgery for complex (> or =3 tracks) or recurrent pilonidal sinus (PS) was performed; the results of this clinical experience were compared with an original method of primary wound closure, coupling a "tension-free" technique of wound reconstruction with autologous cryoplatelet gel application, in order to improve the wound healing process and reduce the postoperative disability period., Patients and Methods: The retrospective analysis included 30 patients undergoing surgery for PS between January 2003 and May 2005: in the first group of 15 consecutive patients, the wound was left open to close secondarily while in the remaining 15 patients, primary closure by means of a "tension-free" technique of wound reconstruction was attempted. Between June 2005 and May 2006, another subset of 15 patients was prospectively recruited, coupling the "tension-free" technique of wound reconstruction with autologous cryoplatelet gel application., Results: In the first group of patients, median postoperative disability accounted for 65 days with one recurrence. In the second group, primary healing was achieved in 11 patients, with a median postoperative disability of 28 days; two recurrences did occur. In the third group of patients, primary healing was achieved in all patients within 14 to 29 days, and no recurrence has yet been detected., Conclusion: Short follow-up notwithstanding, the simplicity of the operation, the use of autologous products and the minimal postoperative disability with complete wound healing suggest that this new approach may represent a useful alternative to current surgical techniques for PS excision.

Aim: To identify by means of clinical and histopathological features a subset of breast cancer patients with sentinel lymph-node (sN) micrometastases and metastatic disease confined only to the sN in order to spare them an unnecessary axillary lymph node dissection (ALND)., Materials and Methods: From January 1998 to December 2004, 116 patients with sN micrometastases underwent standard ALND for early-stage (T1-2 N0 M0) invasive breast cancer; clinical and histopathologic parameters were prospectively collected and evaluated by means of univariate and logistic regression analysis in order to identify which patients with sN micrometastases were free of metastasis in axillary non-sN., Results: Sixteen of 116 patients with sN micrometastases had tumour involvement of non-sN, with six and 10 patients having non-sN micrometastases and macrometastases, respectively. None of 19 patients with primary tumour measuring

Background: Cryosurgery is safely employed for the treatment of skin precancerous and malignant lesions of the head and neck in selected patients. The case of a 101-year-old female patient with advanced malignant melanoma of the facial skin, undergoing cryosurgery, is reported in order to assess the feasibility and tolerability of the technique, as well as the biological implications of cryosurgical treatment in this specific neoplasm., Case Report: A 101-year-old woman, with a large (pT4b N0 M0) cutaneous melanoma of the facial skin on the right cheek, was treated at the Division of Surgical Oncology of the National Cancer Research Institute, Italy, from June to August 2003. The treatment was accomplished by means of serial cryosurgical applications which were performed within three months; the bulk of the lesion was cryotreated with a liquid nitrogen cryoprobe, while the residual disease was treated with a nitrous protoxide cryoprobe, by means of the insertion technique. The treatment was well tolerated, with a good aesthetic result, and the patient is recurrence- and distant-disease-free two years after the initial cryosurgical application., Conclusion: Cryosurgery is feasible in the treatment of head and neck melanoma, mostly for mucosal melanomas and cutaneous lesions in anatomically critical sites, as well as in high-risk surgical patients. Here, a good aesthetic result was obtained in a very elderly patient with a large cutaneous melanoma of the facial skin, avoiding skin flap transposition for tissue repair and postoperative complications (e.g., serious bleeding or postoperative pain), with a satisfactory functional and oncological outcome at two years.

Aim: To define the benefit of intraoperative frozen section examination of the sentinel lymph node (sN), and to assess its prognostic value in clinically node-negative melanoma patients., Materials and Methods: Between July 1993 and December 2001, 214 patients with Stage I-II cutaneous melanoma underwent sN biopsy; complete follow-up data are available in 169 of 175 patients who underwent preoperative lymphoscintigraphy, lymphatic mapping with Patent Blue-V and radio-guided surgery (RGS)., Results: In an initial subset, the sN was identified in 35 out of 39 patients; in the principal group of 169 patients, the sN was detected in all patients. The benefit of frozen section examination, that is the proportion of all patients having intraoperative histologic examination who tested positive, was 17.2% (29/169); notably, in patients with pT(1-2) vs pT(3-4) melanoma the corresponding values were 2.3 and 33.3%, respectively, (P=0.000). Cox regression analysis for overall survival indicated that sN-positive patients had a two-fold increased risk of death; the most significant predictors of relapse-free survival were sN status (P=0.004), age (P=0.015), and T stage grouping (P=0.033)., Conclusions: The sN is a reliable predictor of regional lymph node status in patients with cutaneous melanoma. Frozen section examination can be useful in avoiding a 'two-stage' operative procedure in patients with tumour-positive sN, but its greatest benefit seems to be restricted to patients with pT(3)-pT(4) primary melanoma.

A review of the clinical applications of sentinel lymph node (sN) biopsy has been performed with the aim of defining the rationale, the methods of detection, the accuracy, and the current indications to sN biopsy in different solid neoplasms. In melanoma patients, sN biopsy represents a standard procedure for staging purpose, although its therapeutic value is still under examination. The sN is an accurate method for the pathologic staging of the axilla in patients with early stage breast cancer, and it can be useful for the selection of patients with axillary metastasis who should undergo standard axillary dissection. In gynecologic malignancies, appreciable results are available in patients with vulvar and cervical cancer only. Patients with squamous cell vulvar cancer may benefit by sN biopsy because a complete bilateral inguino-femoral lymph-node dissection may be avoided whenever the sN is free of metastasis. As regards to cervical cancer, further studies are required with the combined technique (blue dye injection and gamma-probe guided surgery), which seems more promising, before abandoning pelvic lymphadenectomy in patients with histologically-negative sN. The experience in urologic cancer deals mainly with penile and prostate cancer; the modern procedures for the dynamic detection of sN are going to clarify its role in the surgical management of penile cancer; as regards to prostate cancer, very preliminary results suggest that the sN biopsy may enhance the pathologic staging of this neoplasm compared to modified pelvic lymphadenectomy, due to the individual variability of the lymphatic drainage of this cancer. In patients with clinically node-negative squamous head and neck cancer, the reliability of sN-guided neck lymph node dissection seems promising. The sN biopsy is also technically feasible in patients with differentiated thyroid cancer; however, the future role of this procedure in the clinical decision-making of these patients remains to be defined due to the questionable biological meaning of nodal metastases. Patients with non-small-cell lung cancer should be investigated by means of radiotracers injected at the time of thoracotomy or under CT-scan guidance in order to achieve a satisfactory identification rate (over 80%); the focused histopathologic staging of the sN improves current pathologic staging by conventional bi-valve assessment of all the lymph nodes of the surgical specimen; moreover, the prognostic role of isolated N2 metastasis can be better elucidated. In patients with gastrointestinal malignancies, the intraoperative lymphatic mapping with sN biopsy have suggested that the lymphatic drainage of the gastrointestinal tract is much more complicated than other sites, skip metastasis being rather frequent. In patients with gastric cancer, current data show that it can be detected by means of peritumoral injection of indocyanine green; the detection of tumor positive lymph nodes beyond the perigastric area could select patients amenable to D2 lymphadenectomy. As regards to colorectal cancer patients, the focused analysis of the sN may reveal disease that might otherwise go undetected by conventional surgical and pathological methods, and those patients which are upstaged can benefit by adjuvant chemotherapy. Finally, in patients with Merkel cell carcinoma, notwithstanding the limited experiences with sN biopsy, sN histology seems to predict regional lymph node status and may aid in selecting which patients are amenable to therapeutic lymph node dissection.

Background and Objectives: Literature review suggests that the sentinel lymph node (sN) represents a reliable predictor of axillary lymph node status in breast cancer patients; however, some important issues, such as the optimisation of the technique for the intraoperative identification of the sN, the role of intraoperative frozen section examination of the sN, and the clinical implications of sN metastasis as regards the surgical management of the axilla, still require further confirmation. The authors aimed (1) to assess the feasibility of sN identification with a combined approach (vital blue dye lymphatic mapping and radioguided surgery, RGS) and the specific contribution of either techniques to the detection of the sN, (2) to determine the accuracy and usefulness of intraoperative frozen section examination of the sN in order to perform a one-stage surgical procedure, and (3) to define how the sN might modulate the therapeutic planning in different stages of disease., Materials and Methods: From October 1997 to June 2001, 334 patients with early-stage (T(1-2) N(0) M(0)) invasive mammary carcinoma underwent sN biopsy; the average age of patients was 61.5 years (range, 39-75 years). In a subset of 153 patients, both vital blue dye (Patent Blue-V) lymphatic mapping and RGS were used to identify the sN, and the relative contribution of each of the two techniques was assessed., Results: In the whole group, the sN was identified in 326 of 334 patients (97.6%), and 105 of 326 patients (37.3%) had positive axillary lymph nodes (pN+). In 9 of 105 pN+ patients, the definitive histologic examination of the sN did not show metastases but these were detected in non-sN, thus giving an 8.6% false-negative rate, a negative predictive value of 94.5% (156/165), and an accuracy of 96.5% (252/261). As regards the specific contribution of the two different techniques used in the identification of the sN, the detection rate was 73.8% (113/153) with Patent Blue-V alone, 94.1% (144/153) with RGS alone, and 98.7% (151/153) with Patent Blue-V combined with RGS (P < 0.001). Noteworthy, whenever the sN was identified, the prediction of axillary lymph node status was remarkably similar (93-95% sensitivity; 100% specificity; 95-97% negative predictive value, and 97-98% accuracy) whichever of the three procedures was adopted (Patent Blue-V alone, RGS alone, or combined Patent Blue-V and RGS). Intraoperative frozen section examination was performed in 261 patients, who had at least one sN identified, out of 267 patients who underwent complete axillary dissection; 170 patients had histologically negative sN (i.o. sN-) and 91 patients histologically positive sN (i.o. sN+). All 91 i.o. sN+ were confirmed by definitive histology, whereas in 14 of 170 i.o. sN- patients (8.2%) metastases were detected at definitive histology. As regards the correlation between the size of sN metastasis, the primary tumour size, and the status of non-sN in the axilla, micrometastases were detected at final histology in 23 patients and macrometastases in 82 patients. When only micrometastases were detected, the sN was the exclusive site of nodal metastasis in 20 of 23 patients (86.9%) while in 3 patients with tumour size larger than 10 mm micrometastases were detected also in non-sN. Macrometastases were never detected in pT(1a) breast cancer patients; the sN was the exclusive site of these metastases in 30 patients (36.6%), while in 52 patients (63.4%) there were metastases both in sN and non-sN., Conclusions: Sentinel lymphadenectomy can better be accomplished when both procedures (lymphatic mapping with vital blue dye and RGS) are used, because of the significantly higher sN detection rate, although the prediction of axillary lymph node status remains remarkably similar whichever method is used. The intraoperative frozen section examination proved to be rather accurate in predicting the actual pathologic status of the sN, with a negative predictive value of 91.8%; in 35% of patients it allowed sN biopsy and axillary dissection to be performed in a one-stage surgical procedure. Finally, specific clinical and histopathologic features of the primary tumour and sN might be used to tailor the loco-regional and systemic treatment in different clinical settings, such as in ductal carcinoma in-situ (DCIS), early-stage invasive breast cancer, and patients with large breast cancer undergoing neo-adjuvant CT for breast-saving surgery as well as elderly patients with operable breast cancer.

Sentinel lymph node (sN) biopsy has gained special attention among surgical and medical oncologists as it represents an accepted technique for detecting occult nodal disease in regional lymph nodes of patients with melanoma and breast cancer. The histopathologic examination of the sN may well predict regional lymph node status in order to define the most suitable loco-regional and systemic treatment. Recently, this technique has also been applied to other solid tumor types such as gynecologic and urologic malignancies, squamous head and neck cancer, thyroid cancer, non-small-cell lung cancer, Merkel cell carcinoma, and gastric cancer. The aim of this literature review is to define the rationale of sN biopsy in these tumor sites, the most effective procedure for sN detection, and the accuracy of the sN in predicting regional nodal status, as well as the surgical perspectives of sN biopsy application., (Copyright 2004 Wiley-Liss, Inc.)

With the advent of sentinel node (sN) biopsy in melanoma patients, elective lymph node dissection (ELND) can be considered an exceeded procedure. Regardless of the possible therapeutic benefits, sN biopsy efficiently predicts prognosis avoiding the morbidity rate of ELND. The importance of the sN is underlined by multivariate analyses, which show that the sN status represents the most important prognostic factor influencing disease-free and distant disease-free survival in patients with stage I and II melanoma. Moreover, sN biopsy provides a minimally invasive method for identifying those patients with subclinical nodal metastasis who actually have stage III disease, with a very high risk of occult distant metastases and who may benefit by adjuvant therapy., (Copyright 2004 Wiley-Liss, Inc.)

As for other solid tumors, malignant cutaneous melanoma drains in a logical way through the lymphatic system, from the first to subsequent levels. Therefore, the first lymph node encountered (the sentinel node) will most likely be the first to be affected by metastasis, and a negative sentinel node makes it highly unlikely that other nodes in the same lymphatic basin are affected. Sentinel lymph node biopsy distinguishes patients without nodal metastases, who can avoid nodal basin dissection with its associated risk of lymphedema, and those with metastatic involvement who might benefit from additional therapy. This procedure represents a significant advantage as a minimally invasive procedure, considering that only an average 20% of melanoma patients with Breslow thickness between 1.5 and 4 mm harbour metastasis in their sentinel node(s) and are therefore candidates to elective lymph node dissection procedures. The cells that originate cutaneous melanomas are located between dermis and epidermis, a zone that drains to the inner lymphatic network in the reticular dermis, in turn to larger collecting lymphatics in subcutis. Therefore, the optimal modality of interstitial administration of radiocolloids for lymphoscintigraphy and subsequent radioguided sentinel lymph node biopsy is through intradermal/subdermal injection. (99m)Tc-labeled colloids in various size ranges are equally adequate for radioguided sentinel lymph node biopsy in patients with cutaneous melanoma, depending on local experience and availability. For melanomas located in the midline area of the head, neck, and trunk, particular consideration should be given to ambiguous lymphatic drainage, which frequently requires interstitial administration virtually all around the tumor or surgical scar from prior excision of the melanoma. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy because images are used to direct the surgeon to the sites of the node(s). The sentinel lymph node should have a significantly higher count than that of background (at least 10:1 intraoperatively). After removal of the sentinel node, the surgical bed must be reexamined to ensure that all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in melanoma patients is about 98% in institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. The procedure is becoming the standard of care for patients with cutaneous melanoma because of its high prognostic value that has led to include the procedure in the most recent version of the TNM staging system., (Copyright 2004 Wiley-Liss, Inc.)

Background: The sentinel lymph node (sN) represents one of the most powerful predictors of the outcome of patients with Stages I and II cutaneous melanoma, and may be relevant for the therapeutic planning of early-stage melanoma patients. Since adopting the technique of lymphatic mapping with vital blue dye (Patent Blue-V) in July 1993, we have periodically up-dated the methodology and revised our results in order to define the contribution of radio-guided surgery (RGS) to the detection of the sN as well as the role of intraoperative frozen section examination of the sN., Materials and Methods: Between July 1993 and December 1997, 180 patients with clinically node-negative primary cutaneous melanoma (Stages I-II) underwent sN biopsy followed by "selective lymph node dissection" (SLND) whenever sN metastasis was detected. Presently, complete data are available in 165 patients who were divided into two consecutive subsets of 39 and 126 patients, based on the technique for the identification of the sN: Patent Blue-V only or Patent Blue-V associated to RGS. Moreover, in this second subset of patients intraoperative frozen section findings were compared with definitive pathologic examination., Results: As regards the first subset of 39 patients (17 males and 22 females; mean age 51.3 years), the sN was identified in 35 patients (89.7%); 8 patients (22.8%) were found to have metastatic melanoma cells in their sN, and they all underwent SLND of the affected basin. As regards the second set of 126 patients (54 males and 72 females; mean age 53.5 years), the sN was detected in every case by means of the combined technique (Patent Blue-V and RGS): in 4 of 126 patients (3.2%), the sN was detected by means of RGS only whereas in no patient was the sN detected by Patent Blue-V only. Frozen section examination was performed in 123 of 126 patients who had sN detection by Patent Blue-V and RGS, and the intraoperative examination had a sensitivity of 66.6% (22 of 33), specificity of 100% (90 of 90), negative predictive value of 89.1% (90 of 101), and accuracy of 91% (112 of 123). The benefit of frozen section examination in avoiding a two-stage procedure was 17.9% (22 of 123 patients). In patients with thicker lesions (pT(3)-pT(4)), the sensitivity and the benefit of intraoperative examination were 76% (19 of 25) and 32% (19 of 59 patients), respectively., Conclusions: Sentinel node lymphadenectomy can be better accomplished when both procedures (lymphatic mapping with Patent Blue-V and RGS) are used because the two methods look quite complementary. In fact, the use of the radiocolloid mapping allows to detect a hot spot in the regional basin prior to making the skin incision in order to perform a minimal invasive access, and it may also more accurately differentiate the true sN from a secondary echelon node (non-sN). The use of frozen section examination should be restricted to patients with pT(3)-pT(4) primary melanoma, due to the higher sensitivity and benefit in terms of avoiding a two-stage operative procedure., (Copyright 2004 Wiley-Liss, Inc.)

Background and Objectives: Over the last decade, lymphatic mapping and sentinel lymph node (sN) biopsy have greatly increased the possibility of identifying nodal metastasis in clinically node-negative patients with melanoma and breast cancer, thus improving the accuracy of pathologic staging. Recently, sN biopsy has been applied also in colorectal cancer. This prospective study aimed to assess its feasibility and accuracy in predicting regional lymph nodes metastases in colorectal cancer patients as well as the impact on treatment decision-making., Materials and Methods: Lymphatic mapping was accomplished by means of blue dye, which was intraoperatively injected into the subserosa overlying the tumor site in 26 patients undergoing colorectal cancer surgery. Following bowel resection, the operative specimen was inspected to identify each blue-stained node, the sN, which was sent separately to the pathologist. One half of each sN was examined by multiple 200 microm sections, while the second half was examined by standard bi-valving technique with hematoxylin-eosin (H and E) staining; all the other regional non-sentinel nodes were routinely examined by standard bi-valving technique and H and E staining., Results: At least one sN was detected in 24 of 26 patients (92.3%); two patients with rectal cancer had no sN identified. Overall, 70 sN were retrieved into the operative specimens, with a mean of 2.9 sNs/patient, and 19 sNs were tumor-positive. An agreement between sN and regional lymph-node status was observed in 20 of 24 patients (83.4%). The sN was histologically negative in two of nine patients with positive regional nodes (sensitivity = 77.8%; false-negative rate of 22.2%); in two of seven patients with tumor-positive sN (28.6%), the sN was the exclusive site of regional nodal metastasis. The negative predictive value was 88.2% (15 of 17 patients), and the overall accuracy was 91.7% (22 of 24 patients). As regards the contribution to the detection of nodal metastasis according to the pathologic technique, standard H and E bi-valving technique detected 16 of 19 tumor-positive sNs (84.2%) while, by means of serial sectioning, metastases were detected in the remaining 3 of 19 sNs (15.8%)., Conclusions: The sN biopsy proved feasible, with a rather short learning curve. The focused analysis of the sN by means of serial sectioning improved the detection rate of nodal metastasis compared to standard bi-valving examination, so that a more accurate nodal staging should be expected; finally, an elective localization of metastasis within the sN was observed in almost one third of regional node-positive patients., (Copyright 2004 Wiley-Liss, Inc.)

The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way via the lymphatic system, from the first to upper levels. Therefore, (1) the first lymph node met (the sentinel node) will most likely be the first one affected by metastasis, and (2) a negative sentinel node makes it highly unlikely that other nodes are affected. Sentinel lymph node biopsy would represent a significant advantage as a mini-invasive procedure, considering that, after operation, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Although the pattern of lymphatic drainage from a breast cancer can be very variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Considering that tumor lymphatics are disorganized and relatively ineffective, subdermal, and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. (99m)Tc-labeled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy, as images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than background. After removal of the sentinel node, the axilla must be re-examined to ensure all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94-97% in Institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. At present, there is no definite evidence that a negative sentinel lymph node biopsy is invariably correlated with a negative axillary status, except perhaps for T(1a-b) breast cancers, with size < or =1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection in patients with a negative sentinel lymph node on the long-term clinical outcome of patients., (Copyright 2004 Wiley-Liss, Inc.)