Clinical role of post-angioplasty hyperemic microvascular resistances in chronic ischemic left ventricular dysfunction.

AIMS: To investigate the impact of hyperemic microvascular resistances (HMRs) on myocardial perfusion and contractility after percutaneous coronary intervention (PCI) in chronic ischemic left ventricular dysfunction (CILVD). METHODS: The current retrospective study included 48 patients with CILVD of the left anterior descending territory undergoing HMRs assessment before and after PCI with a dual-sensor intracoronary pressure-flow wire. The severity of resting myocardial underperfusion and contractile dysfunction of the left anterior descending territory was scored as summed rest score (SRS-T) by single photon emission tomography, wall motion score index (WMSI-T) and left ventricular ejection fraction (LVEF) by transthoracic echocardiography before PCI and after 3 months. Patients were divided into two groups according to the mean post-PCI HMRs. RESULTS: Mean post-PCI HMRs were 2.05 ±â€Š0.43 mmHg/cm/s; increased HMRs (i.e. >2 mmHg/cm/s) were found in 17 patients (35.4%, group B) (3.29 ±â€Š0.77 mmHg/cm/s), whereas 31 patients (64.6%, group A) showed lower values (1.35 ±â€Š0.34 mmHg/cm/s; P < 0.001). Pre-PCI HMRs, WMSI-T and SRS-T were similar among groups.After PCI, a significant improvement of LVEF, WMSI-T and SRS-T was observed only in group A (6.6 ±â€Š7.4%, 0.44 ±â€Š0.42 and 3.9 ±â€Š2.9, respectively) compared with group B (1.3 ±â€Š1.9%, 0.02 ±â€Š0.07 and 1.1 ±â€Š1.9; P = 0.011, P < 0.001 and P = 0.028, respectively).Post-PCI HMRs predicted the absence of improvement of LVEF and WMSI-T at a cutoff value of 1.95 mmHg/cm/s (area under the curve 0.69 and 0.73; P = 0.038 and 0.017, respectively), with a positive predictive value of 96 and 100%, respectively. CONCLUSION: Increased post-PCI HMRs may predict the lack of functional improvement of the revascularized myocardium in CILVD.

Comparative analysis of iterative reconstruction algorithms with resolution recovery for cardiac SPECT studies. A multi-center phantom study.

BACKGROUND: This investigation used image data generated by a physical phantom over a wide range of count statistics to evaluate the effectiveness of several of the newer commercially available SPECT reconstruction iterative algorithms (IRR) in improving perfusion defect contrast and spatial resolution, while controlling image noise. METHODS: A cardiac phantom was imaged using four different gamma cameras over a wide range of counts statistics (from 6 to 0.8 Mcounts). Images were reconstructed with FBP, OSEM, and the IRR available on site. IRR were applied without corrections (IRR NC), with attenuation correction (IRR AC), scatter correction (IRR SC), and attenuation + scatter corrections (IRR SCAC). Four image performance indices related to spatial resolution, contrast, and image noise were analyzed. RESULTS: IRR NC always determined significant improvements in all indices in comparison to FBP or OSEM. Improvements were emphasized with IRR SC and IRR SCAC. Count reduction from 6 to 1.5 Mcounts did not impair the performances of any of the considered indices. CONCLUSIONS: This is the first study comparing the relative performance of different, commercially available, IRR software, over a wide range of count statistics; the additional effect of scatter and attenuation corrections, alone or in combination, was also evaluated. Our results confirm that IRR algorithms produce substantial benefits with respect to conventional FBP or OSEM reconstruction methods, as assessed through different figures of merit, in particular when SC and/or SCAC are also included.

Ghrelin-producing well-differentiated neuroendocrine tumor (carcinoid) of tailgut cyst. Morphological, immunohistochemical, ultrastructural, and RT-PCR study of a case and review of the literature.

Well-differentiated neuroendocrine tumors (carcinoids) arising in the presacral space are rare neoplasms that can arise in association with either sacrococcygeal teratomas or tailgut cysts. Although tumors arising in tailgut cysts are more frequent than those associated with teratomas, they are still very rare, and only 13 cases have been reported in the literature. We describe the first case of a carcinoid composed of ghrelin-producing cells arising in a tailgut cyst. Ghrelin production was demonstrated using immunohistochemistry, electron microscopy, and reverse transcription-polymerase chain reaction methods. A 73-year-old woman with back and pelvic pain was found to have a presacral mass histologically diagnosed, on needle biopsy, as a well-differentiated neuroendocrine tumor. Workup did not show another primary tumor or metastatic disease. The patient underwent laparoscopic resection of the mass, and the pathological diagnosis of the surgical specimen was of a tailgut cyst-associated carcinoid composed of ghrelin-producing cells. In addition, we have accurately reviewed the literature on presacral carcinoids, associated or unassociated with tailgut cysts, to give the reader a comprehensive overview of these very rare tumor types.

Thyroid metastases from typical carcinoid of the lung differentiating between medullary thyroid carcinoma and neuroendocrine tumor metastasis to the thyroid.

BACKGROUND: Although very rare, carcinoid tumors of the lung may present as thyroid metastatic nodules, thus raising diagnostic difficulties for clinicians, surgeons, and pathologists. The most problematic differential diagnosis is with medullary thyroid carcinoma (MTC), a well-differentiated neuroendocrine tumor showing cytological and histological features similar to those of a lung carcinoid. SUMMARY: We report a case of thyroid metastases from a typical carcinoid of the lung. The thyroid tumors were diagnosed in a 37-year-old woman known to have a lung nodule radiologically identified 8 years earlier, for which neither cytological nor histological analyses were performed. Fine-needle aspiration cytology of the thyroid nodule suggested a neuroendocrine tumor, possibly a MTC. However, the lack of both elevated calcitonin (CT) blood level and CT immunoreactivity in cytological smears ruled out the diagnosis of MTC in favor of a metastatic neuroendocrine tumor. Octreoscan demonstrated the neuroendocrine nature of the known lung neoplasm and the patient underwent right lung lobectomy together with total thyroidectomy. Histology examination confirmed the diagnosis of thyroid metastases from typical carcinoid of the lung. The patient is alive and free of disease 7 years after surgery. CONCLUSION: The rarity of this case offered the opportunity to discuss the most important criteria for distinguishing metastatic from primary neuroendocrine tumors of the thyroid and the indolent behavior of metastatic typical carcinoids of the lung.

Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy.

Typing somatostatin receptor expression in neuroendocrine tumors is of relevance to target somatostatin analogue-based diagnostic approach and treatment. The expanding use of immunohistochemistry to detect somatostatin receptors is to date not paralleled by an accurate methodological setting and standardized interpretation of the results. A multicentric study was designed to compare somatostatin receptor immunohistochemical expression with in vivo scintigraphic data and verify its usefulness in the clinical management of neuroendocrine tumors. After methodological setting by testing different somatostatin receptor antibodies, 107 cases of neuroendocrine tumors with available somatostatin receptor scintigraphy data and pathological material were retrospectively analyzed for somatostatin receptor types 2A, 3 and 5 immunohistochemical expression, and compared with scintigraphic images and, whenever available, with the clinical response to somatostatin analogue treatment. Restricting 'positive cases' to the presence of a membrane pattern of staining, an overall somatostatin receptor type 2A immunohistochemistry/somatostatin receptor scintigraphy agreement of 77% (chi2 test P<0.0001) was reached. Lower concordance ratios were detected in preoperative and metastatic tumor samples, possibly as a consequence of somatostatin receptor expression heterogeneity. Pure somatostatin receptor type 2A cytoplasmic staining showed poor correlation with somatostatin receptor scintigraphy (54% concordance rate). The immunohistochemical detection of somatostatin receptor types 3 and 5, which showed almost exclusively a cytoplasmic pattern, did not improve the concordance with scintigraphic data. In a pilot series, somatostatin receptor type 2A immunohistochemistry correlated with clinical response in 75% of cases. In conclusion, we propose a scoring system for somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors correlated with in vivo data, based on the evidence that only membrane (rather that cytoplasmic) staining should be considered for a reliable, standardized and clinically relevant report.

Multifocality and multicentricity are not contraindications for sentinel lymph node biopsy in breast cancer surgery.

BACKGROUND: After the availability of the results of validation studies, the sentinel lymph node biopsy (SLNB) has replaced routine axillary dissection (AD) as the new standard of care in early unifocal breast cancers. Multifocal (MF) and multicentric (MC) tumors have been considered a contraindication for this technique due to the possible incidence of a higher false-negative rate. This prospective study evaluates the lymphatic drainage from different tumoral foci of the breast and assesses the accuracy of SLNB in MF-MC breast cancer. PATIENTS AND METHODS: Patients with preoperative diagnosis of MF or MC infiltrating and clinically node-negative (cN0) breast carcinoma were enrolled in this study. Two consecutive groups of patients underwent SLN mapping using a different site of injection of the radioisotope tracer: a) "2ID" Group received two intradermal (i.d.) injections over the site of the two dominant neoplastic nodules. A lymphoscintigraphic study was performed after each injection to evaluate the route of lymphatic spreading from different sites of the breast. b) "A" Group had periareolar (A) injection followed by a conventional lymphoscintigraphy. At surgery, both radioguided SLNB (with frozen section exam) and subsequent AD were planned, regardless the SLN status. RESULTS: A total 31 patients with MF (n = 12) or MC (n = 19) invasive, cN0 cancer of the breast fulfil the selection criteria. In 2 i.d. Group (n = 15) the lymphoscintigraphic study showed the lymphatic pathways from two different sites of the breast which converged into one major lymphatic trunk affering to the same SLN(s) in 14 (93.3%) cases. In one (6.7%) MC cancer two different pathways were found, each of them affering to a different SLN. In A Group (n = 16) lymphoscintigraphy showed one (93.7%) or two (6.3%) lymphatic channels, each connecting areola with one or more SLN(s). Identification rate of SLN was 100% in both Groups. Accuracy of frozen section exam on SLN was 96.8% (1 case of micrometastasis was missed). SLN was positive in 13 (41.9%) of 31 patients, including 4 cases (30.7%) of micrometastasis. In 7 of 13 (53.8%) patients the SLN was the only site of axillary metastasis. SLNB accuracy was 96.8% (30 of 31), sensitivity 92.8 (13 of 14), and false-negative rate 7.1% (1 of 14). Since the case of skip metastasis was identified by the surgeon intraoperatively, it would have been no impact in the clinical practice. CONCLUSION: Our lymphoscintigraphic study shows that axillary SLN represents the whole breast regardless of tumor location within the parenchyma. The high accuracy of SLNB in MF and MC breast cancer demonstrates, according with the results of other series published in the literature, that both MF and MC tumors do not represent a contraindication for SLNB anymore.

Serum cytokeratin fragment 21.1 (CYFRA 21.1) as tumour marker for breast cancer: comparison with carbohydrate antigen 15.3 (CA 15.3) and carcinoembryonic antigen (CEA).

Serum carbohydrate antigen 15.3 (CA 15.3) and carcinoembryonic antigen (CEA) are currently employed in clinical practice as markers for breast cancer, particularly in the follow-up and therapy monitoring. However, the American Society for Clinical Oncology (ASCO) stated in its clinical practice guidelines for the use of tumour markers in breast carcinoma that neither CA 15.3 nor CEA are recommended for routine use in screening, diagnosis and surveillance after primary treatment, or in monitoring response to treatment, because current literature data are insufficient. Cytokeratin fragment 21.1 (CYFRA 21.1) assay detects a serum fragment of cytokeratin 19 (CK19) and is employed in the diagnosis and management of lung cancer, particularly of squamous cell histotype. Breast carcinoma has been demonstrated to express CK19 fragments in the primary and metastatic lesions and CK19 mRNA is detectable in peripheral blood from patients affected by breast cancer. We measured serum markers CYFRA 21.1, CEA and CA 15.3 in the sera from 212 females affected by histologically proven breast carcinoma. Patients comprised 96 individuals with untreated primary disease (54 stage I-II, 18 stage III and 24 stage IV), 30 regional (chest-wall and/or lymph-nodes) relapsing disease and 68 metastatic (haematogenous metastases) relapsing disease. Forty-eight patients previously treated by surgery and without any evidence of disease were enrolled to evaluate the role of serum markers in the monitoring for recurrence of the disease. One hundred healthy age-matched females and 65 patients affected by benign mammary gland disease (including 38 patients with mastopathy and 27 with fibroadenoma) were enrolled as controls. Serum levels of all markers increased from controls to patients affected by breast cancer, from stage I-II to stage IV of the breast cancer and from local to advanced recurrence. The comparison of diagnostic accuracy in the detection of primary and relapsing breast cancer showed no significant differences between markers. Univariate and multivariate survival analysis showed a significant statistically prognostic value for CA 15.3 and CYFRA 21.1 but not for CEA. However, the factors N and M were confirmed to be very strong predictors of the patients' survival. Finally, CEA and CYFRA 21.1 detected less recurrences than CA 15.3. In conclusion, our data show no significant improvement in the diagnosis, prognostic evaluationand follow-up of breast cancer by CYFRA 21.1 and CEA assays compared to CA 15.3 assay. Considering the ASCO statement on tumour markers in breast cancer, the CYFRA 21.1 assay should not be employed in clinical practice.