Multiple input control strategies for robust and adaptive climate engineering in a low-order 3-box model.

A low-order 3-box energy balance model for the climate system is employed with a multivariable control scheme for the evaluation of new robust and adaptive climate engineering strategies using solar radiation management. The climate engineering measures are deployed in three boxes thus representing northern, southern and central bands. It is shown that, through heat transport between the boxes, it is possible to effect a degree of latitudinal control through the reduction of insolation. The approach employed consists of a closed-loop system with an adaptive controller, where the required control intervention is estimated under the RCP4.5 radiative scenario. Through the online estimation of the controller parameters, adaptive control can overcome key issues related to uncertainties of the climate model, the external radiative forcing and the dynamics of the actuator used. In fact, the use of adaptive control offers a robust means of dealing with unforeseeable abrupt perturbations, as well as the parametrization of the model considered, to counteract the RCP4.5 scenario, while still providing bounds on stability and control performance. Moreover, applying multivariable control theory also allows the formal controllability and observability of the system to be investigated in order to identify all feasible control strategies.

Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis.

Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta-analysis; they globally include 624 patients (163 ENE+ and 461 ENE-) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR = 2.51; 95% CI: 1.66-3.79, p < 0.0001, I(2) = 0%) and recurrence of disease (RR = 2.07, 95% CI: 1.38-3.10, p < 0.0001, I(2) = 0%). These findings recommend the consideration of ENE from the gross sampling to the histopathological evaluation, in perspectives to be validated and included in the oncologic staging.

Pathological complete response in a patient affected by multiple synchronous, breast and lung primary malignancies: a case report and review of the literature.

A pathological complete response in a patient affected by multiple synchronous, breast and lung primary malignancies is reported. A 63-year-old woman presented with an invasive ductal carcinoma of the breast and a lung adenocarcinoma. After multidisciplinary discussion, the patient underwent pulmonary left lower lobectomy followed by radio-chemotherapy with cisplatin and vinorelbine and started hormone therapy with letrozole. Ten months later, a left mastectomy with axillary lymph nodes dissection was performed. Histologically, a pathological complete response (pCR) was documented. With a review of the Literature, we discuss the issue of multiple primary malignancies, with its diagnostic and therapeutic implications. In cases of multiple synchronous malignancies it has been highlighted the importance of the choice of the best therapeutic approach for both the malignancies, reducing collateral individual effects.

Invasive procedure for intractable epistaxis in an old comorbid woman: a case report.

Epistaxis is a condition mainly self-limiting or easily treated conservatively, although in rare cases it could become life-threatening. We discuss the case of a 73 year comorbid old woman with severe and recurrent epistaxis treated with superselective catheterism and embolization of the internal maxillary artery. The possible underlying causes, including drug related issues, are discussed.

Cocaine and acute vascular diseases.

Cocaine is one of the most widely used drugs of abuse. Chest pain is the most common side effect requiring emergency visits after cocaine use. Vasoconstriction and platelet activation are the main effects of cocaine in the vasculature. In this brief review, we consider the most important clinical effects of cocaine abuse on the heart, brain and kidney. Symptoms related to cocaine toxicity such as myocardial infarction, congestive heart failure, arrhythmias, aortic dissection, stroke, renal failure, are similar to the clinical picture of atherosclerotic vascular damage, even if the age of cocaine abusers is usually in the second and third decades. Clinicians (especially emergency department physicians) should consider substance abuse among the differential diagnosis of chest pain in young people.

Multifocal, multicentric and contralateral breast cancers: breast MR imaging in the preoperative evaluation of patients with newly diagnosed breast cancer.

PURPOSE: This study was done to verify the usefulness of preoperative breast magnetic resonance (MR) imaging in patients with newly diagnosed breast cancer. MATERIALS AND METHODS: A retrospective analysis of 291 patients with invasive breast cancer newly diagnosed with conventional breast imaging (mammography and ultrasound) was performed. All patients underwent MR imaging prior to surgery. The MR imaging detection rate of additional malignant cancers occult to mammography and ultrasound was calculated. Data were analysed with Fisher's exact test (p<0.05) according to the following parameters: histopathological features of the index tumour (histological type and size) and mammographic density [according to the Breast Imaging Reporting and Data System (BI-RADS) classification from 1 fatty to 4 dense). The gold standard was the histological examination on the surgical specimen. RESULTS: MR imaging identified 40 mammographically and sonographically occult malignant lesions other than the index cancer in 27/291 patients (9%). These additional cancers were located in the same quadrant as the index cancer in 13 women (4%), in a different quadrant in 12 (4%) and in the contralateral breast in the remaining two (1%). The cancer detection rate in the subgroup of index cancers with lobular histological type was 25%, significantly higher (p=0.03) than the detection rate of 11% recorded in the subgroup of ductal cancers. The cancer detection rate in the subgroup of index cancers >2 cm was 27%, significantly higher (p=0.001) than the rate of 8% found in the subgroup of index cancers <2 cm. Mammographic density was not correlated (p=0.48) with MR detection of additional cancer, with 14% of additional malignancies being detected in both dense and fatty breasts. CONCLUSIONS: In patients with newly diagnosed invasive breast cancer, preoperative MR imaging is useful for detecting additional synchronous malignancies that are not detected on conventional breast imaging. The cancer detection rate is 9%. The use of preoperative MR imaging as an adjunct to conventional breast imaging in women with an infiltrating lobular index cancer and an index cancer >2 cm is especially beneficial.

MR-guided vacuum-assisted breast biopsy in the management of incidental enhancing lesions detected by breast MR imaging.

PURPOSE: The objective of this study was to determine the clinical value and accuracy of magnetic resonance (MR)-guided vacuum-assisted breast biopsy (VAB). MATERIALS AND METHODS: We retrospectively analysed 106 incidental breast lesions detected on MR imaging in 98 patients. Patients with nonpalpable suspicious lesions that were only MR visible were referred for MR-VAB performed with a 10-gauge needle. All patients with a VAB diagnosis of infiltrating carcinoma, carcinoma in situ or atypical epithelial hyperplasia were referred for surgery. Histopathology of the surgical specimen was considered the reference standard. RESULTS: MR-guided VAB was attempted in 29/106 lesions (27%); in 2/29 patients, the procedure could not be performed owing to failure to visualise the lesion. Lesions with clearly malignant features and borderline lesions (atypical ductal hyperplasias) were identified in 12 cases (44%) and benign entities in 15 (56%). Seven of 12 (58%) malignant lesions were <10 mm. Among the 27 successful MR-VAB procedures, VAB yielded one false-negative diagnosis (4%) and underestimation (4%). MR-guided VAB sensitivity and specificity were 92% and 100%, respectively, with a positive predictive value of 100% and a negative predictive value of 93%. CONCLUSIONS: The results of this study indicate that MR-guided VAB offers good accuracy in characterising nonpalpable breast lesions visible on MR imaging alone. Small lesion size (<1 cm) did not prove to be a limitation for the success of the procedure.

Inflammatory breast carcinoma and locally advanced breast carcinoma: characterisation with MR imaging.

PURPOSE: This study was done to identify the typical magnetic resonance (MR) imaging findings of inflammatory breast carcinoma (IBC) in comparison with noninflammatory locally advanced breast carcinoma (LABC). MATERIALS AND METHODS: MR images of 30 patients with IBC (T4d) were compared with those of a cohort of 30 patients with LABC (T3/T4a-c). The age distribution was approximately equal in the two groups. MR images were assessed for the following features: skin thickening (>4 mm), skin oedema, architectural distortion, enhancement pattern (mass-like/non-mass-like), time-signal intensity curve (continuous-persistent type/wash-out type), skin enhancement. Fisher's exact text was used to compare MR imaging appearances of IBC and LABC (significant p value <0.05). RESULTS: Skin involvement and enhancement pattern differed between groups: skin thickening was present in 16/30 IBC (53%) vs 8/30 LABC cases (27%, p=0.06), skin oedema was present in 26/30 IBC (87%) vs 8/30 LABC (27%, p < 0.0001), and skin enhancement in 10/30 IBC (33%) vs 2/30 LABC (7%, p=0.02); non-mass-like enhancement was present in 22/30 IBC (73%) vs 12/30 LABC (40%, p=0.02). CONCLUSIONS: IBC is a distinct clinical and pathological entity resulting in typical MR imaging features. Skin changes (thickening, oedema, enhancement) related to neoplastic involvement of the dermal lymphatics are suggestive of IBC and should prompt a skin biopsy to confirm or rule out the diagnosis.

Intra-operative frozen section technique for breast cancer: end of an era.

Data on 2436 primary breast carcinomas diagnosed between 1992 and 2006 were collected to evaluate the rate of frozen section procedures performed over time. Frozen section procedures performed to evaluate resection margins for conservative surgery or sentinel node status were excluded. Over time, there was a decrease in the use of frozen sections indistinctly extended to all pT cancer categories. The rate of cancers diagnosed with frozen sections was 51.2% in 1999, and 0% in 2005-2006. In the same period, the adoption of cytology and core biopsy for breast cancer diagnosis increased from 40% in 1992 to more than 90% since 1999. In an audited diagnostic activity on breast pathology, the routine use of frozen sections on primary lesions was considered inappropriate, particularly in assessment of clinically non-palpable lesions, and should be limited to cases with inadequate pre-surgical sampling.

B3 breast lesions determined by vacuum-assisted biopsy: how to reduce the frequency of benign excision biopsies.

PURPOSE: The aim of this study was to identify parameters allowing differentiation among the diverse group of B3 lesion at stereotactic vacuum-assisted biopsy (VAB) to identify patients with a low risk of cancer and who can therefore be referred for follow-up rather than surgery and thus reduce the number of unnecessary surgical procedures. MATERIALS AND METHODS: Among 608 VAB procedures performed for nonpalpable ultrasound (US)-occult mammographic abnormality, 102 cases of B3 were included in this study. Mammographic lesion type, lesion size, Breast Imaging Reporting and Data System (BIRADS) category, number of specimens per lesion and presence of atypia were retrospectively analysed. Results were compared with histological findings at surgery (53 cases) or mammographic findings during follow-up (49 cases). Statistical analysis was performed with univariate analysis (chi-square test), and statistical significance was set at p<0.05. RESULTS: The majority of cases were depicted as isolated microcalcifications (82.3%), were smaller than 10 mm (80.4%), had a low level of radiological suspicion (64.7%) and had 11 or more cores sampled (94.1%). Atypia at VAB was reported in 60 of 102 cases (58.8%). Carcinoma was found at excision in 5/60 (8%) B3 lesions with atypia and in no B3 lesions without atypia (p=0.146). Cancer at surgery was more frequent among cases of isolated microcalcifications (p=0.645), cases with high radiological suspicion (p=0.040) and those with a smaller number of cores sampled (borderline significant p=0.064). CONCLUSIONS: On the basis of our experience, the presence or absence of atypia in our series proved to be the reliable criterion to prompt or avoid surgery in cases with a VAB finding of B3 lesion. This criterion may therefore be adopted in practice to more accurately select patients for surgery.

Utility of second-look ultrasound in the management of incidental enhancing lesions detected by breast MR imaging.

PURPOSE: To assess the utility of second-look ultrasound (US) for identifying and characterising incidental enhancing lesions detected by breast magnetic resonance imaging (MRI). MATERIALS AND METHODS: From among 655 consecutive breast MRI studies, 62 lesions (MRI visible, nonpalpable, occult at first-look US and mammography) were recommended for second-look US. MRI enhancement of lesions was mass-like in 59 cases (95%) and non-mass-like in three (5%). Forty-two lesions (68%) were ≤10 mm; only three lesions (5%) were >20 mm. Of all lesions, the Breast Imaging Reporting and Data System (BI-RADS) MRI category was highly suggestive of malignancy in six cases (10%), suspicious abnormality in 33 (53%) and probably benign in 23 (37%). The correlation between MRI lesion appearance, lesion size, histopathology findings and detection rate at second-look US were analysed. The reference standard was histopathology and/or follow-up (range 18-24 months). Statistical analysis was performed with the Fisher exact test. RESULTS: Second-look US identified 44 out of 62 (71%) lesions depicted at MRI. The detection rate at second-look US was higher for mass-like MRI lesions (75%) than non-mass-like lesions (0%), for lesion size >10mm (90%) and for BI-RADS 4 lesions (88%). Second-look US-guided biopsy detected 12 out of 17 (71%) malignant lesions. There was no correlation between the likelihood of carcinoma and the presence of a sonographic correlate. CONCLUSIONS: Second-look US is a reliable problem-solving tool in identifying and characterising most incidental MRI findings. It contributes to accurately selecting the cases in which MRI-guided biopsy is required.

Fischer's score criteria correlating with histopathological prognostic factors in invasive breast cancer.

PURPOSE: This study aimed to evaluate whether the Fischer score criteria on contrast-enhanced magnetic resonance (CE-MR) imaging could correlate with histopathological prognostic factors in invasive breast cancer. MATERIALS AND METHODS: Seventy-two women with histologically proven invasive breast cancer underwent preoperative CE-MR imaging. Images were assessed for the following parameters, according to the scoring system described by Fischer in 1999: tumour shape, margins, internal enhancement, signal intensity increase, signal intensity course and overall Fischer score. Evaluated histopathological prognostic factors included histological type, associated extensive intraductal component, diameter, lymph node metastasis, tumour grade, and oestrogen receptor (ER), progesterone receptor (PgR), Ki67 proliferation, oncogene c-erbB-2 (HER2/neu) expression. Fisher's exact test was used to correlate the CE-MR imaging parameters and histopathological findings (with significance set a p < 0.05). RESULTS: Fischer's score was 0-4 in 14/72 (19%) cases, >4 in 58/72 (81%) and 3 in 5/72 (7%; false negative), with a sensitivity of 93%. A significant correlation (p=0.02) was found between stellate-dendritic shape and the presence of an associated extensive intraductal component (EIC), which was found in 78% of stellate tumours vs. 49% of round-oval tumours. A significant correlation (p=0.039) was found between Ki67 expression and signal intensity course (Ki67 overexpression was present in 81% of tumours with washout course vs. 21% with plateau course). CONCLUSIONS: The CE-MR imaging findings that correlate with prognostic factors are shape and signal intensity curve. Fischer's multifactorial analysis was helpful in the interpretation of CE-MR images, showing a sensitivity of 93% for invasive breast cancer.

Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas.

The microphthalmia transcription factor/transcription factor E (TFE)-family translocation renal cell carcinomas bear specific translocations that result in overexpression of TFE3 or TFEB. TFE3 fusion gene product overexpression occurs as consequence of different translocations involving chromosome Xp11.2, whereas TFEB overexpression is the result of the specific translocation t(6;11)(p21;q12), which fuses the Alpha gene to TFEB. Both TFE3 and TFEB are closely related members of the microphthalmia transcription factor/TFE-family, which also includes TFEC and microphthalmia transcription factor. These transcription factors have overlapping transcriptional targets. Overexpression of microphthalmia transcription factor has been shown to mediate the expression of cathepsin-K in osteoclasts. We hypothesize that the overexpression of the related TFE3 fusion proteins and TFEB in translocation renal cell carcinomas may have the same effect. We studied cathepsin-K in 17 cytogenetically confirmed microphthalmia transcription factor/TFE-family translocation renal cell carcinomas. Seven cases showed a t(6;11)(p21;q12), ten cases showed translocations involving Xp11.2; five cases t(X;1)(p11;q21) resulting in a PRCC-TFE3 gene fusion; three cases t(X;1)(p11;p34) resulting in a PSF-TFE3 gene fusion, one t(X;17)(p11;q25) resulting in an ASPL-TFE3 gene fusion, and one t(X;3)(p11;q23) with an unknown TFE3 gene fusion. As control we analyzed cathepsin-K in 210 clear cell, 40 papillary, 25 chromophobe renal cell carcinomas and 30 oncocytomas. All seven TFEB translocation renal cell carcinomas were labeled for cathepsin-K. Among the cytogenetically confirmed TFE3 translocation renal cell carcinomas, 6 out of 10 were positive. None of the other renal neoplasms expressed cathepsin-K. We conclude the following: (1) cathepsin-K is consistently and strongly expressed in TFEB translocation renal cell carcinomas and in 6 of 10 TFE3 translocation renal cell carcinomas. (2) Cathepsin-K immunolabeling in both TFE3 and TFEB translocation renal cell carcinomas distinguishes these neoplasms from the more common adult renal cell carcinomas, and may be a specific marker of these neoplasms. (3) These results further support the concept that the overexpression of TFE3 or TFEB in these neoplasms activates the expression of genes normally regulated by microphthalmia transcription factor in other cell types.

The role of cetuximab in pre-treated refractory patients with metastatic colorectal cancer: outcome study in clinical practice.

We carried out a multicentric retrospective study on cetuximab + chemotherapy in pre-treated refractory patients outside clinical protocols, by registering the main clinical and pathological parameters. We evaluated 144 pre-treated patients. Cetuximab was administered usually in combination with irinotecan (93.8%). A 45% disease control rate (complete plus partial responses plus stable disease) was obtained in 55 patients and was related to absence of weight loss (p<0.0001) and high grade (> or =2) skin toxicity (p<0.0001). Median time to progression (TTP) was 4 months (95%CI 2.7-5.3) and median overall survival (OS) was 11.8 months (95%CI 8.5-15.1). Performance status << or =1, no weight loss and high grade (>or =22) skin toxicity were related both to a longer TTP (p=0.035, p=0.035, p=0.0017) and OS (p<0.0001, p<0.0001, p=0.006). According to multivariate analysis, the absence of weight loss was related to longer TTP (HR 0.331, p=0.004) and OS (HR 0.176, p<0.0001), and EGFR over-expression (3+) to longer TTP (HR 0.402, p=0.020).

Rehabilitation of chronic graft versus host disease in children. A clinical series.

The study was aimed at evaluating clinical and functional assessment and results obtained following rehabilitative treatment in children affected by chronic graft versus host disease (cGVHD) after allogeneic transplantation of hemopoietic stem cells (HSCT). From 1999 to 2003 we evaluated 6 children with cGVHD after HSCT presenting severe complications and disabilities. Clinical and functional assessment was performed prior to rehabilitative treatment (T1), at follow-up at 6 (T6) and 12 (T12) months after treatment. Each child received a personalized rehabilitative treatment program based on the use of neuromotor re-education techniques, massotherapy, chest rehabilitation and occupational therapy. Six children presented sclerodermoid skin lesions, joint contractures, anchylosis, respiratory insufficiency, postural and walking alterations which led to reduction in motor performance and autonomy in daily living activity. After 1 year of rehabilitation treatment, 3 patients showed improvement in motor performance, 2 remained stable and 1 patient worsened. Rehabilitative treatment associated with pharmacological therapy has proven to be useful in patients affected by cGVHD. We believe that cGVHD is a pathology which must be seen by a physiatrist as early as possible at onset of first cutaneous signs of cGVHD to limit its invalidating evolution.

Real-time reading in mammography breast screening.

PURPOSE: This study was undertaken to assess the role of real-time reading in the mammography screening programme carried out at the Hospital of Marzana, Verona, Italy. MATERIALS AND METHODS: During the 5-year period 1999-2004, 54,472 women attended the screening programme (32,291 first calls: unadjusted uptake 41.4%, adjusted uptake 50.3%; 21,551 2- year routine recalls: unadjusted uptake 86.4%, adjusted uptake 89.9%). Further diagnostic investigations [(FDI), imaging and cytohistological] were performed immediately after real-time reading of the screening mammograms (FDI rate among first calls 10.9%; FDI rate among 2-year recalls 5.4%). Overall, cytohistological FDI were requested in 27% of imaging FDI, with a clear prevalence of cytological [fine-needle aspiration cytology (FNAC) 87%] over histological procedures [core needle biopsy (CNB) 11%; vacuum aspiration biopsy (VAB) 2%]. RESULTS: Imaging FDI proved to be conclusive in 73%. Cytohistological FDI led to the use of surgical biopsy (SB) in 39.5% (ratio between benign and malignant SB: 0.19/first calls, 0.14/2-year recalls). There were a total of 427 screen-detected breast cancers (BC), with a very good breast cancer detection rate (BCDR/first calls 9.7 per thousand; BCDR/2-year recalls 5.1 per thousand). In the 427 screen-detected BC, the incidence of pTis, pT1a,b cancers was 59.6% (diagnostic anticipation); the incidence of pN0 cancers was 61.2%; the incidence of conservative surgical procedures was 78.6%. In interval cancers, the false negative rate was 8.3% only, whereas the proportional incidence was very low indeed (14% first year; 38% second year). CONCLUSIONS: The high sensitivity exhibited by the Marzana mammography screening programme suggests that the value of real-time reading should be validated by other programmes adopting a similar approach.