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Bacillus cereus is a ubiquitous spore-forming gram-positive bacterium. The antibacterial molecules or bacteriocins provide an ecological advantage to B. cereus and promote its proliferation in the bacterial communities and food contamination. The goal of the present work was to detect and identify the antimicrobial activity potential of 114 B. cereus food strains. It aimed at accessing the ecological status of B. cereus variants and characterizing the bacteriocins. An inhibitory activity was detected in 61.4% of the collection. Three selected isolates were found to be bacteriocin (cerein) producers and were identified as B. cereus by 16S rRNA gene sequencing. The cerein activities were inhibited by at least one protease treatment. They were stable within a wide range of pH, sustained heat treatments (up to 96°C for 30 min) and treatment with organic solvents and detergents. These cereins showed bactericidal and bacteriolytic effects. They belonged to class II of bacteriocins. The three cereins were produced at the early stationary phase and remained stable until 50 h of cultivation. The preparation trough SDS PAGE gave an inhibitory zone with an apparent molecular weight of about 10 kDa to the three cereins. The three selected bacteriocins produced by B. cereus dairy strains deserve further research of their potential in pathogen control. Bacteriocin production may play a key role in the ubiquitous distribution of B. cereus and his persistency in dairy products. [ABSTRACT FROM AUTHOR]

In this paper the directional hemispherical reflectivity and transmissivity of one-dimensional, randomly rough, dielectric surfaces are determined by the use of the integral method. This method is derived from electromagnetic theory without any restrictive hypotheses. Since this exact approach is computationally very intensive, a geometric optics approximation method is also developed. Curves displaying radiative properties versus the correlation length for a constant mean square deviation of the surface from flatness are presented. In this respect, the influence on the validity of the approximate method of multiple scattering, the shadowing effect and the real index of refraction of the dielectric have been investigated. Transverse electric and transverse magnetic polarized incident plane waves are considered. For the latter, our interest is focused on the influence of roughness on the reflected and transmitted intensities for an angle of incidence close to the Brewster angle. [ABSTRACT FROM AUTHOR]

Introduction: Perivascular epithelioid cell tumors are uncommon mesenchymal tumors. The genital tract is the most common extrarenal location. Preoperative diagnosis is rarely achieved owing to non-specific symptoms and imaging features. Consensus on treatment strategies remains elusive. Case presentation We report the case a 38 year-old north African woman with a primary sterility, who was diagnosed with a uterine Perivascular epithelioid cell tumor of uncertain malignant potential on a resection specimen of an intracavity polypoid mass. Immunohistochemistry confirmed the diagnosis and we opted for conservative surgery to preserve the patient's fertility desires., Conclusion: Uterine perivascular epithelioid cell tumor is a rare entity that warrants consideration in the differential diagnosis of uterine tumors. Treatment modalities, follow-up protocols, and prognosis remain ambiguous. Given their unpredictable behavior, accurate diagnosis and long-term monitoring are imperative., (© 2024. The Author(s).)

Purpose: In Italy, Lombardy was the first region to reimburse multigene assays (MGAs) for patients otherwise candidates for chemotherapy. This is a real-world experience of MGAs usage in six referral cancer centers in Lombardy., Methods: Among MGAs, Oncotype DX (RS) was used in 97% of cases. Consecutive patients tested with Oncotype DX from July 2020 to July 2022 were selected. The distribution of clinicopathologic features by RS groups (low RS: 0-25, high RS: 26-100) was assessed using chi-square and compared with those of the TAILORx and RxPONDER trials., Results: Out of 1,098 patients identified, 73% had low RS. Grade and Ki67 were associated with RS (p < 0.001). In patients with both G3 and Ki67 > 30%, 39% had low RS, while in patients with both G1 and Ki67 < 20%, 7% had high RS. The proportion of low RS in node-positive patients was similar to that in RxPONDER (82% vs 83%), while node-negative patients with low RS were significantly less than in TAILORx (66% vs 86%, p < 0.001). The distribution of Grade was different from registration trials, with more G3 and fewer G1 (38% and 3%) than in TAILORx (18% and 27%) and RxPONDER (10% and 24%) (p < 0.001). Patients ≤ 50 years were overrepresented in this series (41%) than in TAILORx and RxPONDER (31% and 24%, respectively) (p < 0.001) and, among them, 42% were node positive., Conclusions: In this real-world series, Oncotype DX was the test almost exclusively used. Despite reimbursement being linked to pre-test chemotherapy recommendation, almost 3/4 patients resulted in the low-RS group. The significant proportion of node-positive patients ≤ 50 years tested indicates that oncologists considered Oncotype DX informative also in this population., (© 2024. The Author(s).)

Background: Neurofibromatosis type 1 is a neurocutaneous genetic disorder caused by mutations in the NF1 gene, resulting in the formation of benign tumors called neurofibromas. The most common type of tumor seen in patients with neurofibromatosis type 1 is the slow-growing and benign neurofibroma, with a subtype called plexiform neurofibroma being particularly common and causing pain, functional impairment, and cosmetic disfigurement., Case Presentation: We report the case of a 20-year-old North African female patient with a history of neurofibromatosis type 1 who presented with a growing mass in her right gluteal region, which was later diagnosed as a giant cutaneous neurofibroma. Imaging studies revealed infiltration in several regions, including the urinary bladder wall, resulting in significant bilateral hydronephrosis. The patient is currently being monitored, and no excisional procedures are planned., Conclusions: Neurofibromatosis type 1 can cause a variety of clinical symptoms, including the development of large plexiform neurofibromas. It is important to closely monitor patients with neurofibromatosis type 1 for the early detection of neurofibromas. Early detection and prompt surgical intervention are essential for preventing complications., (© 2024. The Author(s).)

Introduction: The abdominal wall is an extremely rare location for malignant peripheral nerve sheath tumors (MPNSTs). Besides presenting a rare location of MPNST, the peculiarity of our case lies in its association with Lynch syndrome, which is to our knowledge the first reported case of its kind., Presentation of Case: We present a case report of a 39-year-old male with a personal history of colonic cancer. Genetic counseling revealed Lynch syndrome with a heterozygous germline mutation in MLH1. Nine years after the right hemicolectomy, the patient presented with an asymptomatic lump in the abdominal wall. CT imaging showed a 3 cm mass in the aponeurosis of the right external oblique muscle. The patient underwent successful resection of the parietal tumor. Pathological examination revealed an MPNST. No additional treatment was warranted, and the patient exhibited no signs of relapse during the six months following the surgery., Discussion: MPNSTs of the anterior abdominal wall are extremely rare and challenging. Some studies have investigated the presence of mismatch repair (MMR) deficiency in patients with sarcomas. Our case consolidates the hypothesis of an association between sarcomas and Lynch syndrome, which raises the question of the efficacy of immune checkpoint inhibitor therapy in these cases where treatment options remain limited., Conclusion: It is essential to have a deep understanding of the growth patterns of MPNSTs in the context of syndromes that predispose individuals to tumors, like Lynch syndrome. This knowledge is crucial for accurately predicting patient outcomes and developing appropriate plans for monitoring and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The case report describes a 73-year-old woman, with a history of diabetes, who presented with left hypochondrium pain. Interrogation revealed a long-term history of living with Echinococcus granulosus endemic area, associated to close contact with sheep and dogs. Upon physical examination, a painless mass of the left hypochondrium, fixed to the deep plane. Abdominal ultrasonography (USG) showed a 9 cm encapsulated mass in contact with the tail of the pancreas. Further investigation was carried out by performing an abdominal computed tomography (CT) scan showing: large cystic mass with a partially calcified thickened wall, containing multiple vesicles, measuring 11.5 cm, located at the tail of the pancreas. The patient was put under Albendazole for a week and then operated on. During laparotomy, a hydatid cyst was located in the tail of the pancreas. Conservative treatment was done sparing the healthy pancreatic parenchyma and avoiding major surgery for a diabetic patient., Competing Interests: The authors declare no competing interests., (Copyright: Anis Hasnaoui et al.)

Objective: The objective of this study was to identify the main determinants of heart rate variability (HRV) in male athletes aged 14 to 21 years who practice competitive contact sports and to integrate these determinants with the aim of defining normative values of short-term HRV in the time and frequency domains., Methods: Participants ( n  = 369) were aged 14 to 21 years and included 221 football players and 148 ice hockey players. HRV was measured for 5 min at rest, and standard HRV parameters in the time and frequency domains were calculated. Heart rate (HR), age, body mass index (BMI), number of sports weekly practices (WSP) and concussion history (mTBI) were considered determinants potentially able to influence HRV., Results: Multiple regression analysis revealed that HR was the primary determinant of standard HRV parameters. The models accounted for 13% to 55% of the total variance of HRV and the contribution of HR to this model was the strongest ( β ranged from -0.34 to -0.75). HR was the only determinant that significantly contributes to all HRV parameters. To counteract this dependence, we calculated HRV corrected by the mean RR interval (RRm). Such corrections do not remove any physiological differences in HRV; they simply remove the mathematical bias. HRV parameters were therefore normalized, and their normative limits were developed relative to the mean heart rate. After correction, the correlation coefficients between HR and all corrected HRV parameters were not statistically significant and ranged from -0.001 to 0.045 ( p  > 0.40 for all). The automatically corrected HRV calculator, which recalculates standard HRV parameters and converts them into corrected parameters in addition to determining whether a given value is within normal limits, facilitates clinical interpretation., Conclusion: This study provides for the first time corrected normative values of short-term and resting state HRV parameters in competitive contact sport athletes aged 14 to 21 years. These values were developed independently of the major determinants of HRV. The baseline values for HRV parameters given here could be used in clinical practice when assessing and monitoring cerebral concussions. They may assist in decision making for a safe return to play., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ziadia, Sassi, Trudeau and Fait.)

Axillary surgery in breast cancer (BC) is no longer a therapeutic procedure but has become a purely staging procedure. The progressive improvement in imaging techniques has paved the way to the hypothesis that prognostic information on nodal status deriving from surgery could be obtained with an accurate diagnostic exam. Positron emission tomography/magnetic resonance imaging (PET/MRI) is a relatively new imaging tool and its role in breast cancer patients is still under investigation. We reviewed the available literature on PET/MRI in BC patients. This overview showed that PET/MRI yields a high diagnostic performance for the primary tumor and distant lesions of liver, brain and bone. In particular, the results of PET/MRI in staging the axilla are promising. This provided the rationale for two prospective comparative trials between axillary surgery and PET/MRI that could lead to a further de-escalation of surgical treatment of BC. • SNB vs. PET/MRI 1 trial compares PET/MRI and axillary surgery in staging the axilla of BC patients undergoing primary systemic therapy (PST). • SNB vs. PET/MRI 2 trial compares PET/MRI and sentinel node biopsy (SNB) in staging the axilla of early BC patients who are candidates for upfront surgery. Finally, these ongoing studies will help clarify the role of PET/MRI in BC and establish whether it represents a useful diagnostic tool that could guide, or ideally replace, axillary surgery in the future.

Ewing's sarcoma/primitive neuroectodermal tumor is rare and aggressive with a poor prognosis. Intraabdominal metastases are an uncommon condition. Metastasis in the lesser sac is an exceptional occurrence. To the best of our knowledge, this location has not been described previously. We report a case of a 15-year-old patient treated for Ewing's sarcoma of the left arm 6 years back. She had developed a suspicious mass in the lesser sac 6 years following her primary tumor. The histopathologic exam revealed a tumor with "small round cells" that were positive for CD99, confirming the relapse of Ewing's sarcoma. The relapse was successfully managed with chemotherapy and surgery. Intraabdominal, extraintestinal masses in patients treated previously for Ewing's sarcoma should be considered as Ewing's sarcoma relapse in the differential diagnosis. We fully describe the management of this atypical relapse, with different components of clinical, radiological, and histological findings., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Northern Italy has been one of the European regions reporting the highest number of COVID-19 cases and deaths. The pandemic spread has challenged the National Health System, requiring reallocation of most of the available health care resources to treat COVID-19-positive patients, generating a competition with other health care needs, including cancer. Patients with cancer are at higher risk of developing critical illness after COVID-19 infection. Thus, mitigation strategies should be adopted to reduce the likelihood of infection in all patients with cancer. At the same time, suboptimal care and treatments may result in worse cancer-related outcome. In this article, we attempt to estimate the individual risk-benefit balance to define personalized strategies for optimal breast cancer management, avoiding as much as possible a general untailored approach. We discuss and report the strategies our Breast Unit adopted from the beginning of the COVID-19 outbreak to ensure the continuum of the best possible cancer care for our patients while mitigating the risk of infection, despite limited health care resources. IMPLICATIONS FOR PRACTICE: Managing patients with breast cancer during the COVID-19 outbreak is challenging. The present work highlights the need to estimate the individual patient risk of infection, which depends on both epidemiological considerations and individual clinical characteristics. The management of patients with breast cancer should be adapted and personalized according to the balance between COVID-19-related risk and the expected benefit of treatments. This work also provides useful suggestions on the modality of patient triage, the conduct of clinical trials, the management of an oncologic team, and the approach to patients' and health workers' psychological distress., (© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Cutaneous metastases are rare and represent a sign of poor prognosis. They are a sign of widespread disease. Breast cancer is the most common neoplasm leading to their appearance. Palliative care is the treatment of choice., Competing Interests: None declared., (© 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: The management of axilla after Primary Systemic Therapy (PST) for breast cancer is a highly debated field. Despite the proven axillary downstaging occurring after PST, there is still some degree of reluctance in applying sentinel node biopsy (SNB) in the neoadjuvant setting., Patients and Methods: We performed a retrospective analysis on 181 PST patients with axillary positive nodes at presentation treated between 2005 and 2017 at San Raffaele Hospital in Milan. The aim was to observe the application time trend of SNB, to determine the imaging staging power and the axillary downstaging according to molecular subtypes., Results: Median follow-up after surgery was 32.5(IQR: 12-59) months. After PST, 119 (65.7%) patients had no clinically palpable nodes, 72 (39.7%) converted to N0 on final imaging and 34 (18.8%) underwent SNB with an increasing application trend. Axillary-US showed the highest accuracy (69.3%) in re-staging axilla after PST. Staging power of preoperative testing varied with tumour biology: Positive Predictive Value was higher in Luminal A (80% for clinical examination and 100% for axillary-US) and Luminal B (72% and 70.5%) tumours, whilst Negative Predictive Value was higher in HER2 positive (100% and 93.3%), and triple negative (71.4% and 93.3%) tumours. Ninety five (52.5%) patients experienced axillary downstaging after PST, by molecular subtype 15% (3/20) in Luminal A, 46.4% (45/97) in Luminal B, 90.9% (20/22) in HER2+ and 70.3% (26/37) in triple negative breast tumours., Conclusion: SNB application after PST for breast cancer in node positive patients at presentation is increasing. Pre-operative axillary imaging and tumour biology help identify patients who might be candidates for SNB as a single staging procedure., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Dermatofibrosarcoma protuberans (DFSP) is a low-to-intermediate grade sarcoma of dermal origin that rarely presents in the vulva, typically occurring on the trunk of young to middle-aged adults. Even though it has a low potential for distant metastases, it often recurs locally. Therefore, surgical excision is the treatment of choice. We report a case of DFSP with fibrosarcoma transformation involving the vulva treated by large excision with tumor free margins followed by plastic reconstruction. Our aim is to highlight this rare disease and through literature evaluate the safety and efficacy of surgical treatment. Early recognition of this rare entity whose localization and the aggressive nature of the fibrosarcomatous component will be an issue in the surgical management., Competing Interests: The authors declare no competing interests.

Correct and consistent results in estrogen and progesterone receptors, HER2 and Ki67 proliferation rate testing are a basic prerequisite for selecting therapy and individualizing prognosis in patients with breast carcinoma. Preanalytic factors, including time from excision to fixation and time and type of fixation, are critical to obtain reproducible and reliable results in these immunohistochemical assays and their relevance has long been stressed. The ASCO-CAP guidelines on HER2 testing indicated that histologic material including both biopsies and surgical specimens must be fixed for at least 6 h in order to obtain reliable results; however, there is a very limited scientific support regarding the setting at 6 h the minimum fixation time. We demonstrate that with a short fixation time (30') and rapid processing with MW technology (69'), it is possible to achieve an adequate and reproducible assessment of HER2 status. We obtained similar results in HER2 evaluation in breast carcinoma biopsies treated with this short protocol and in the corresponding surgical specimens processed routinely with a 24 h formalin fixation time-i.e., within the guidelines interval time.

Aim: The aim of this paper was to assess the prognostic role of pretherapy partial volume corrected (PVC) 18F-fluorodeoxyglucose mean standardized uptake value (SUV) in breast cancer (BC)., Methods: Forty oncological patients, BC diagnosed by biopsy, with breast tumor mass diameter >1 cm measured to the mammography, designed for surgical intervention, underwent a pretherapy semi-quantitative 18F-FDG positron emission tomography/computed tomography (18F-FDG PET/CT) whole-body study for tumor staging. Mean Body-Weight Standardized Uptake Value with Correction for Partial Volume effect (PVC- SUVBW-mean) was calculated in all mammary detected lesions. Excised tissues from primitive BC were sectioned and classified according to the WHO guidelines, evaluating biological features. Univariate (Mann-Withney/Kruskal-Wallis) and multivariate (linear regression, hierarchical clustering) statistical tests were performed between PVC-SUVBW-mean and biological indexes. ROC analysis was performed. PVC-SUVBW-mean thresholds were derived allowing to distinguish groups of BC patients with different biological characteristics. Specificity and Sensitivity were also calculated., Results: Statistical and multiple correlations between pretherapy 18F-FDG PET PVC-SUVBW-mean and histological type, grade, ER/PgR hormone receptors and Mib-1 cellular proliferation index were found. In our samples, PVC-SUVBW-mean <≈4 g/cc was found correlated to BC patients with Invasive Lobular Carcinoma (ILC) or well differentiated Invasive Ductal Carcinoma (IDC), a positive expression of ER and PgR and a negative expression of MiB-1, while PVC-SUVBW-mean >≈7.00 is associated to BC patients with moderately and poorly differentiated IDC, negative expression of ER and PgR and a positive expression of MiB-1., Conclusion: Pretherapy PVC 18F-FDG PET PVC-SUVBW-mean measurement correlates with prognostic factors in BC and could be used to stratify patients before intervention.

Purpose: This study investigated the clinical application of a magnetic-resonance (MR)-guided breast biopsy (MRBB) system consisting of a nonmagnetic coaxial needle and a ferromagnetic core biopsy needle., Materials and Methods: MRBB was performed on 70 breast lesions. The biopsy device consisted of a nonmagnetic 14- to 16-gauge coaxial needle and a ferromagnetic 16- to 18-gauge biopsy needle., Results: Of the 70 lesions, 29 were malignant and 41 nonmalignant. All 29 malignant lesions underwent surgery and were confirmed as malignant at final histology. Of the 41 nonmalignant lesions, 35 underwent follow-up breast MR imaging (mean, 26 ± 19 months), which demonstrated no lesions changes; six lesions underwent surgery because of poor radiological-pathological correlation; of these 6 lesions, 3 were nonmalignant, one was borderline (lobular carcinoma in situ) and two were malignant (well-differentiated tubular carcinoma and infiltrating ductal carcinoma). Sensitivity, specificity, positive and negative predictive values and diagnostic accuracy were, respectively, 93.5%, 100%, 100%, 95.1% and 97.1% if the lobular carcinoma in situ was considered a nonmalignant histological result, and 90.6%, 100%, 100%, 92.7% and 95.7% if the lobular carcinoma in situ was considered malignant., Conclusions: MRBB with a ferromagnetic-nonmagnetic coaxial system represented an easy way to perform a biopsy procedure and was easily applicable in the routine clinical setting.

The CDC25A-CDK2 pathway has been proposed as critical for the oncogenic action of human epidermal growth factor receptor 2 (HER2) in mammary epithelial cells. In particular, transgenic expression of CDC25A cooperates with HER2 in promoting mammary tumors, whereas CDC25A hemizygous loss attenuates the HER2-induced tumorigenesis penetrance. On the basis of this evidence of a synergism between HER2 and the cell cycle regulator CDC25A in a mouse model of mammary tumorigenesis, we investigated the role of CDC25A in human HER2-positive breast cancer and its possible implications in therapeutic response. HER2 status and CDC25A expression were assessed in 313 breast cancer patients and we found statistically significant correlation between HER2 and CDC25A (P = .007). Moreover, an HER2-positive breast cancer subgroup with high levels of CDC25A and very aggressive phenotype was identified (P = .005). Importantly, our in vitro studies on breast cancer cell lines showed that the HER2 inhibitor efficacy on cell growth and viability relied also on CDC25A expression and that such inhibition induces CDC25A down-regulation through phosphatidylinositol 3-kinase/protein kinase B pathway and DNA damage response activation. In line with this observation, we found a statistical significant association between CDC25A overexpression and trastuzumab-combined therapy response rate in two different HER2-positive cohorts of trastuzumab-treated patients in either metastatic or neoadjuvant setting (P = .018 for the metastatic cohort and P = .021 for the neoadjuvant cohort). Our findings highlight a link between HER2 and CDC25A that positively modulates HER2-targeted therapy response, suggesting that, in HER2-positive breast cancer patients, CDC25A overexpression affects trastuzumab sensitivity.

Exact solutions for reflection and emission are compared to different approximations, the surface impedance boundary condition (SIBC) and the geometric optics approximation (GOA). The effects of the incidence angle, the material surfaces, the nature of polarization, and random roughness on the behavior of emissivity and reflectivity have been quantified. The contribution of the effects on the reflection and emission is used to investigate the domains of validity of approximation models.

Genetic abnormalities of pulmonary surfactant were identified by DNA sequence analysis in 14 (12 full-term, 2 preterm) of 17 newborn infants with fatal respiratory distress of unknown etiology. Deficiency of adenosine triphosphate-binding cassette protein, member A3 (n = 12) was a more frequent cause of this phenotype than deficiency of surfactant protein B (n = 2).

The effects of incidence angle, geometrical shape, and optical properties of dielectric rough surfaces on reflectivity and transmissivity are discussed. Radiative properties for various surface geometries are calculated. Since the integral method is computationally expensive, a geometric optics approximation is developed. The regions of validity of the approximation compared with the integral method are quantified. Curves are presented that show these radiative properties versus the correlation length at incidence angle for a fixed rms deviation of the surface. The surface geometry, incidence angle, multiple scattering, shadowing effects, and dielectric permittivity contributions to the domains of validity of the approximation method are discussed for both TE and TM polarizations.

Mutations in the gene encoding surfactant protein C (SP-C) SFTPC have been found to be associated with chronic interstitial lung disease. A 5-year-old girl oxygen dependent from birth and affected by interstitial lung disease (ILD) is heterozygous for a T to C change in exon 3 resulting in the substitution of threonine for isoleucine at codon 73 (173T), already described in association with ILD. We studied 25 members of her family where the 173T mutation in the SP-C gene is associated to chronic pulmonary diseases. Five members in the mother's family showed respiratory diseases with great diversity in clinical features: her mother was affected by restrictive pneumopathy and emphysema, her grand-mother by asthma and recurrent pneumonia, 2 uncles underwent lung transplantation in the adult age, an aunt was clinically diagnosed having pulmonary fibrosis. All the family members affected by pulmonary diseases and one with no clinical symptoms showed the presence of the mutation 173T. Among the other family members the mutation was found in six subjects for whom no clinical data were available, yet. Our results confirm that heterozygosity for the mutation 173T may cause chronic inflammation of the lung or progressive pulmonary fibrosis. In addition, the possibility to study a large pedigree allowed us to perform a genotype-phenotype correlation indicating a marked phenotypic variability. The diversity in symptoms, age at onset, clinical course, duration of lung disease in the relatives sharing this mutation indicates an incomplete penetrance of the mutation. This might be due to the influence of other genetic factors thus indicating that the phenotype may be complicated by additional components.

The feasibility and toxicity of allogeneic stem cell transplantation after nonmyeloablative conditioning including thiotepa, fludarabine, and cyclophosphamide have been investigated in 6 patients with breast cancer and 7 patients with renal cell cancer. The program included the use of escalating doses of donor lymphocyte infusions (DLI) and/or interferon alpha (IFNalpha) for patients showing no tumor response and no graft-versus-host disease (GVHD). Patients were at high risk of transplant-related mortality (TRM) because of age, advanced stage, and previous treatments. We observed a partial remission in 4 renal cancer and in 2 breast cancer patients (one at the molecular level in the bone marrow), occurring after cyclosporine withdrawal or after DLI and/or IFNalpha. All the responses were accompanied by the occurrence of acute GVHD. We conclude that reduced-intensity allogeneic stem cell transplantation is a feasible procedure in renal and breast cancer, and that the exploitation of graft-versus-tumor effect after DLI is a promising finding.

Objectives: To verify the importance of DNA ploidy on clinical outcome in endometrial carcinoma and to investigate whether the prognostic information obtained by this variable is independent from other clinical-pathologic features., Materials and Methods: Univariate and multivariate analysis of clinical and pathologic prognostic factors obtained from 203 consecutive cases of endometrial cancer, that had been surgically treated in our hospital, were performed., Results: Significant prognostic factors according to the Kaplan-Meier method were age at the time of diagnosis, grade of differentiation, peritoneal cytology, node involvement, vascular invasion, myometrial infiltration and ploidy. At multivariate analysis only DNA ploidy resulted to be an independent variable., Conclusions: In our analysis DNA content is the only parameter which preserved prognostic significance in multivariate analysis.

Atypically proliferating serous tumors (APST) account for 15% of all ovarian serous epithelial neoplasms. The differences between benign, borderline and malignant ovarian tumors is principally due to their cellular proliferative potential. By means of MIB1 expression we could recognize differences in proliferation among serous ovarian tumors, overcoming interobserver variability. Thirty-three patients with serous ovarian tumors, treated at S. Raffaele Hospital, University of Milan between November 1, 1992 and July 31, 1994 were used as study the population: 9 patients had serous cystoadenocarcinoma, 14 patients had APST and 10 patients had serous cystoadenoma. Pathological slides of all the cases were reviewed and immunohistochemical analysis was performed on formalin fixed, paraffin was embedded tissue. Pearson's Chi-square test and Fisher's exact test were performed for statistical evaluation. The percentage of MIB1 positive neoplastic cells ranged from, 0% to 2.1% (median 0.45%; mean 0.69%) in cystoadenomas, 1.3% to 7% (median 2.9%; mean 3.98%) in APSTs and 4.7% to 20.3% (median 6.95%; mean 9.51%) in cystoadenocarcinomas (p < 0.0001; F = 47.7). A High percentage expression of MIB1 in a serous tumor, initially diagnosed as APST, promoted a wider sampling of the surgical specimen confirming the presence of a carcinomatous component. MIB1 index is reported as representative of cellular proliferative potential. The analysis of MIB1 index provided valuable information in addition to that gained by conventional microscopic study in all cases where diagnostic difficulties arose in assessing APST.

Background: Recent studies have demonstrated that the use of radiolabeled monoclonal antibodies (MoAbs) directed against tumor-associated antigens could help in the recognition of primary tumors, their extent, and their metastases by external scintigraphy (used preoperatively) or by hand-held gamma-detecting probe (GDP) (used intraoperatively)., Methods: The authors evaluated carcinoembryonic antigen (CEA), c-erb B-2 protein, and TAG-72 expression in 100 cases of breast carcinoma using F023C5 (anti-CEA), B72.3, and anti-c-erb B-2 protein MoAbs that were previously investigated for their usefulness in radioimmunoguided surgery and external scintigraphy. The goal of this study was to examine the biodistribution of each antibody in primary, multifocal, and metastatic lesions to evaluate the suitability of their simultaneous use in GDP and external scintigraphy., Results: Results showed immunoreactivity for c-erb B-2 protein in 39 of 99 cases, for B72.3 in 41 of 100 cases, and for CEA in 15 of 100 cases. Multifocal lesions demonstrated positivity for c-erb B-2 protein in 37.4% of cases (6 of 16), for B72.3 in 68.8% of cases (11 of 16), and for CEA in 6.2% of cases (1 of 16). In lymph node metastases, immunoreactivity was found for c-erb B-2 protein in 36.4% of cases (12 of 33), for B72.3 in 63.7% of cases (21 of 33), and for CEA in 24.3% of cases (8 of 33). When the authors considered the immunoreactivity of all three MoAbs, the percentage of positive cases they observed was 60% in primary tumors (60 cases), 78% in lymph node metastases, and 81.2% in multifocal lesions., Conclusions: These results suggest that in vivo tumor radioimmunodetection could be improved by the use of more antibodies directed against different tumor-associated antigens.

c-myc oncoprotein expression was evaluated in 36 non-small-cell lung carcinomas using immunohistochemical and flow cytometric analysis. Formalin fixed and paraffin embedded material was used. The same monoclonal antibody (mouse anti-human c-myc) was employed both for immunohistochemistry and flow cytometry. For the immunohistochemical evaluation we calculated the percentage of stained cells on 200 neoplastic cells. c-myc oncoprotein was measured using flow cytometry by linking the monoclonal with a secondary FITC-conjugated antibody; for each sample 20,000 events were analysed and the percentage of cells positive for green fluorescence was calculated. DNA content was obtained by propidium iodide staining. Results showed a high correlation between immunohistochemical and cytometric data, suggesting that flow cytometry could be used as an alternative to immunohistochemistry in evaluating nuclear antigens. Moreover, using flow cytometry information on DNA content can be obtained simultaneously.

Seventy-three patients with endometrial carcinoma have been retrospectively evaluated in this paper. Stage, grade, depth of myometrial invasion, flow cytometric DNA ploidy and ERB-B2 oncogene expression by immunohistochemical method have been analyzed on paraffin embedded tissue. Results showed the existence of a significant correlation between stage and grade of neoplasia and between DNA ploidy and course of disease; it has been observed that patients with aneuploid tumor tend to have a shorter time before relapse of disease. No significant correlation between depth of myometrial invasion and survival was found. Besides, it has been shown that tumours with ERB-B2 oncogene hyperexpression seem to have a more aggressive evolution.

Purpose: Radiolabeled monoclonal antibodies (MAbs) have been reported to allow tumor intraoperative detection by means of a gamma-detecting probe. The technology is called the Radioimmunoguided Surgery (RIGS) system. The main inconveniences of the method are 1) the long interval needed for clearance of unattached MAbs from the patient's body, between the injection of the MAb and surgery, and 2) the low sensitivity of current MAbs used in detecting small tumors. We describe a new method to overcome these inconveniences using biotinylated MAbs and avidin in order to obtain a rapid blood clearance of the radiolabeled MAbs both anticarcinoembryonic antigen and antitumor-associated glycoprotein-72 MAbs., Methods: Twenty patients with primary and recurrent colorectal cancer have been enrolled in the study; 125I-biotinylated MAbs FO23C5 (anticarcinoembryonic antigen) and B72.3 (antitumor-associated glycoprotein-72) followed by cold avidin were injected in 13 patients and 7 patients, respectively., Results: A decrease of 94 +/- 3 percent of circulating radioactivity was achieved in 3 to 5 days. Patients underwent surgery approximately seven days after MAb injections rather than after four weeks. Tumors were localized in 14/20 (70 percent) patients (true positive), 2 (10 percent) were false negative, and 4 (20 percent) were true negative. The overall sensitivity level in early-stage primary cancers was 37 percent when related to the presence of disease and 75 percent when related to antigenic expression. The sensitivity for more advanced cancer and for recurrences was 100 percent. Moreover, the in vivo tumor targeting of biotinylated MAb was demonstrated in frozen tumor section by direct streptoavidin-peroxidase staining., Conclusions: The avidin-biotin system may enhance applicability and effectiveness of radioimmunoguided surgery (RIGS).

Correlation between human papillomavirus infection and DNA ploidy in the prognosis of uterine cervical intraepithelial neoplasia. Due to the increasing frequency of human papillomavirus (HPV) infection of cervical epithelium in patients with cervical intraepithelial neoplasia (CIN) of different grades, methods are needed to identify progressive lesions. HPV typing as well as quantitative DNA analysis are possible tools to identify high-risk lesions. The aim of our study was to compare the results of "in situ" hybridization and of DNA content analysis with behavior of CIN I and CIN II lesions in 14 patients with HPV infection. Three of the 4 cases with regression of the cervical lesions were diploid, with HPV 16/18 detected in 2 of the 3. The 5 cases with progression were aneuploid, and 4 of them were HPV positive. In the 3 cases with no changes a near-diploid DNA content was observed. DNA analysis was not available in 2 cases. These preliminary results suggest that progressive CIN cases are aneuploid, and that DNA ploidy could be an objective prognostic marker.

The recognition and treatment of neoplastic lesions in early phases are among the most important aims of research using monoclonal antibodies (MoAb). Recent studies have demonstrated that the use of radiolabelled MoAb directed against tumor associated antigens and hand-held gamma detecting probe (GDP) could help in the recognition of primary tumors and metastases. The goal of this study was to investigate the in vivo antibody reaction as shown by histologic preparations after injection of 125I biotinylated MoAb (B72.3 or F023C5) before surgery and to compare the immunohistochemical results with those obtained with GDP in colorectal cancer. We studied 15 cases of patients with primary or recurrent colorectal cancer. The biotinylated, radiolabelled antibody administered in vivo could be seen in frozen sections with streptoavidin peroxidase complex. In 14 cases there was agreement between GDP observations and detection of the in vivo injected biotinylated MoAb with direct staining using streptoavidin peroxidase conjugate. The use of MoAbs thus provides a means of correlating the intraoperative signal with the presence of the injected antibodies on the tumor.

Cytofluorometric analysis of FCM-DNA ploidy also seems to have prognostic value in prostatic carcinoma. Determination of the DNA index preoperatively from needle biopsy samples would be advantageous since it would enable the type of intervention to be established in advance. The finding of intratumoural variability in the DNA index in different solid tumours prompted us to compare the data obtained from needle biopsy and surgical specimens of prostatic cancer. Although the results obtained confirmed the heterogeneity of DNA content in prostatic carcinoma, they nonetheless indicate that preoperative DNA analysis is useful, in particular when aneuploidy is observed, since it provides the clinician with additional information on which to base treatment decisions.

To discriminate benign from malignant parathyroid glands lesions is often difficult, because the morphologic features lack absolute diagnostic value. The differential diagnosis between chief cell hyperplasia and parathyroid adenoma is frequently based on physical features such as increased gland weight and number of enlarged glands. A carcinoma is identified by the evidence of local invasion, metastases or recurrence. Nevertheless the lesions classified as benign for lack of histologic features of aggressiveness can show nuclear atypia, increased mitotic figures and broad fibrous bands. Since DNA aneuploidy is present in a great number of human neoplasms and DNA aneuploidy has been suggest to be a marker of malignancy, flow cytometric assessment of ploidy appeared a possible method for rapid and objective distinction between benign and malignant lesions. Flow cytometric DNA content was evaluated on 113 parathyroid glands: the parathyroids were resected from 26 patients with hyperparathyroidism and from 17 patients with adenoma. The analysis was performed on paraffin-embedded specimens according to Hedley with minor modifications. Interpretable histograms were obtained for 103 parathyroids gland (mean CV = 5.3). Aneuploidy was detected in 22.5% of glands; in 12 instances of parathyroid hyperplasia the glands of the same patient showed different DNA Indexes. Cytometric results and morphological features do not correlate as far as aneuploidy and cellular atypia are involved. Although our results fail to show any correlation between morphology of parathyroid cells and DNA content, and abnormal DNA content suggests a careful follow up of these patients.

To differentiate histologically partial hydatidiform moles (PM) and complete hydatidiform moles (CM) may be difficult. Cytogenetic studies have shown that PMs often had a triploid karyotype while CMs were always diploid. We assessed the DNA content of 31 paraffin-embedded cases of trophoblastic disease with flow cytometry. Twenty-four cases were histologically diagnosed as PM, 3 cases as CM; the others as hydropic abortion (2 cases), choriocarcinoma (1 case), and persistent trophoblastic disease (1 case). Four normal term placentas were used as diploidy controls. In 9 cases the results of the cytogenetic analysis were available. All placental specimens included also maternal tissue as an internal control. Eight of the 24 histologically diagnosed PMs were triploid; there was agreement in 8 cases out of 9 (90%) between the flow cytometric analysis and the karyotypic determination of ploidy. All normal controls as well as the hydropic abortion, the CM and the persistent trophoblastic disease were diploid. Abnormal content of DNA (DI = 1.3) was observed in the choriocarcinoma. Our results show that flow cytometric analysis of DNA content is a reliable and fast method of diagnosing PM on paraffin-embedded material.