Argyrophilic grain disease in individuals younger than 75 years: clinical variability in an under-recognized limbic tauopathy.

BACKGROUND AND PURPOSE: Argyrophilic grain disease (AGD) is a limbic-predominant 4R-tauopathy. AGD is thought to be an age-related disorder and is frequently detected as a concomitant pathology with other neurodegenerative conditions. There is a paucity of data on the clinical phenotype of pure AGD. In elderly patients, however, AGD pathology frequently associates with cognitive decline, personality changes, urine incontinence and cachexia. In this study, clinicopathological findings were analysed in individuals younger than 75. METHODS: Patients were identified retrospectively based on neuropathological examinations during 2006-2017 and selected when AGD was the primary and dominant pathological finding. Clinical data were obtained retrospectively through medical records. RESULTS: In all, 55 patients (2% of all examinations performed during that period) with AGD were identified. In seven cases (13%) AGD was the primary neuropathological diagnosis without significant concomitant pathologies. Two patients were female, median age at the time of death was 64 years (range 51-74) and the median duration of disease was 3 months (range 0.5-36). The most frequent symptoms were progressive cognitive decline, urinary incontinence, seizures and psychiatric symptoms. Brain magnetic resonance imaging revealed mild temporal atrophy. CONCLUSIONS: Argyrophilic grain disease is a rarely recognized limbic tauopathy in younger individuals. Widening the clinicopathological spectrum of tauopathies may allow identification of further patients who could benefit from tau-based therapeutic strategies.

Intracellular zinc increase inhibits p53(-/-) pancreatic adenocarcinoma cell growth by ROS/AIF-mediated apoptosis.

We show that treatment with non-toxic doses of zinc in association to the ionophore compound pyrrolidine dithiocarbamate (PDTC) inhibits p53(-/-) pancreatic cancer cell growth much more efficiently than gemcitabine, the gold standard chemotherapeutic agent for pancreatic cancer. Both the metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine and the radical scavenger N-acetyl-l-cysteine are able to recover cell growth inhibition by Zn/PDTC, demonstrating that this effect depends on the increased levels of intracellular zinc and of reactive oxygen species (ROS). Zn/PDTC treatment induces a strong apoptotic cell death that is associated to ROS-dependent nuclear translocation of the mitochondrial factor AIF, but not to the regulation of apoptotic genes and caspase activation. Primary fibroblasts are more resistant than pancreatic cancer cells to Zn/PDTC treatment and exhibit a lower basal and Zn/PDTC-induced enhancement of intracellular zinc. We show that Zn/PDTC induces p53 proteasomal degradation and that the proteasome inhibitor MG132 further increases fibroblast growth inhibition by Zn/PDTC, suggesting that p53 degradation plays an important role in fibroblast resistance to Zn/PDTC.

Zinc depletion efficiently inhibits pancreatic cancer cell growth by increasing the ratio of antiproliferative/proliferative genes.

We investigated the ability of the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) to reduce pancreatic cancer cell viability. TPEN was much more efficient to inhibit pancreatic adenocarcinoma cell growth than a panel of anti-cancer drugs, including 5-fluorouracil, irinotecan, cisplatin, edelfosine, trichostatin A, mitomycin C, and gemcitabine, the gold standard chemotherapeutic agent for pancreatic cancer. Moreover, TPEN showed a dose- and time-dependent anti-proliferative effect significantly higher on pancreatic cancer cells than on normal primary fibroblasts. This effect may be explained by a significantly higher zinc depletion by TPEN in pancreatic cancer cells as compared to fibroblasts. Cell viability reduction by TPEN was associated to both G1-phase cell cycle arrest and apoptosis, and to the increased ratio of the expression level of cyclin-Cdk inhibitor versus cyclin genes and apoptotic versus anti-apoptotic genes. Finally, we show that apoptotic cell death induced by TPEN involved mitochondrial injury and caspase 3 and caspase 8 activation. In this study, we suggest that zinc depletion may be an efficient strategy in the treatment of pancreatic cancer because of its reduced antiproliferative effect on normal cells.

Intrathoracoscopic localization techniques. Review of literature.

BACKGROUND: Several techniques for localizing pulmonary nodules have been described, but the advantages and disadvantages of each method remain unclear. We reviewed ultrasound, endofinger, finger palpation and wait and watch, radioguided, vital dye, fluoroscopic, agar marking, and needle wire methods for localizing pulmonary nodules. METHODS: Original, peer-reviewed, and full-length articles in English were searched with PubMed and ISI Web of Sciences. Case reports and case series with less than 10 patients were excluded. RESULTS: All localization techniques showed good reliability, but some carry a high rate of major or minor complications and drawbacks. CONCLUSION: No ideal localization technique is available; thus, the choice still depends on surgeon's preference and local availability of both specialists and instruments.

Impact of laparoscopy and ultrasonography in gastrointestinal malignancies.

BACKGROUND/AIMS: An adequate preoperative disease staging is highly required before surgical treatment, even in gastrointestinal malignancies. Our study wants to give a contribution in order to define echolaparoscopy weight in gastrointestinal tumors and its impact in surgical therapy. METHODOLOGY: 33 patients were affected by pancreas, 22 by stomach, 16 by extrahepatic biliary tract and 18 by liver cancers; every patient was considered worthy of radical or palliative surgery according to preoperative staging (thorax-abdominal CT and percutaneous ultrasonography). Paired sample t-tests were used to analyze the results of each methodical and probability values of less than 0.05 were considered significant. RESULTS: Preoperative instrumental examinations gave correct evaluations only in 44 of 89 cases (49%) while echolaparoscopic gave correct evaluations in 82 on 89 cases (92%) (P<0.05). So after echolaparoscopic in only 7 cases we performed an explorative laparotomy. CONCLUSIONS: Laparoscopy and ultrasound impact on therapy is worthy of attention. It seems to be able to give advantages in staging gastrointestinal malignancies, except for pancreas cancers, in which some limits and negative aspects have been demonstrated, regarding the possibility of giving correct diagnosis of portal axis infiltration.

A new approach to the cure of the Ogilvie's syndrome.

The Authors describe a their own observation of 25 cases of acute colonic pseudo obstruction, better known as "Ogilvie Syndrome" with the objective to demonstrate that an early recognition and prompt appropriate therapy, better if conservative, can reduce the morbidity and the mortality of the Syndrome. The surgical therapy is reserved only to that cases in which the risk of perforation of the cecum represent an absolute indication to intervention.

Single pulmonary nodules: localization with intrathoracoscopic ultrasound -- a prospective study.

This prospective study, based on 13 patients with single pulmonary nodules of width between 10 and 30 mm, was performed to verify the utility of intrathoracoscopic ultrasound to localize the single pulmonary nodule. In all 13 cases the ultrasound examination was able to localize the position of nodules, but the homogeneous hypoechoic pattern of nodules observed in ten of 13 cases did not prove whether the lesion was benign or malign. In conclusion, we can confirm that intrathoracoscopic ultrasound examination is a safe, risk-free and less expensive method of localizing the single pulmonary nodules.

Significance of a single pulmonary nodule in patients with previous history of malignancy.

OBJECTIVES: To determine the diagnosis, treatment and follow-up in patients with a solitary lung nodule and a previous primary extrapulmonary neoplasm. METHODS: The authors evaluated the charts of 45 patients with an extrapulmonary malignant neoplasm and a solitary pulmonary nodule. The histologic characteristics of the nodule were correlated with those of the extrapulmonary neoplasm. RESULTS: The histology of the nodule was not known preoperatively in 43 cases (93.5%); in the remaining three cases cytologic examination had shown the presence of atypical cells. The majority of pulmonary lesions (73.9%) were found during the follow-up of the previous tumour, but a significant percentage of nodules (17.4%) were found incidentally. Pre- or intraoperative localisation of the nodule was done in 19 cases (41.3%), and was successful in nine cases (47.4%). Thoracoscopy was performed in 44 patients (95.6%). The coincidence between the pathology of the previous tumour and that of the nodule was 41.3% (19/46). The coincidence rate was 100% for the tumours of ovary, prostate, and sarcomas. CONCLUSIONS: The advent of minimally invasive surgical techniques has made a definitive diagnosis likely, providing also therapy with a less painful engagement for the patient and a less cost for the community.

Lymphatic mapping for the dissection of the sentinel node in the treatment of breast carcinoma.

The Authors present the preliminary results of a study aimed at verifying the effectiveness of lymphatic mapping for the dissection of the sentinel lymph node in the treatment of breast carcinoma. The lymphoscintigraphy method was used in the study performed on 24 patients to evidence the sentinel lymph node. The sentinel lymph node was identified in 23/24 patients (95,8%), with 100% accuracy, negative predictions were 100% (21/21). Consistently with the low number of cases treated, our results seem to guarantee the same prognostic accuracy obtained using radical lymphadenectomy extended to the third lymph node level.

Experimental study on protein transmission through the human muscle fascia: preliminary results and application theory in lymphedema.

The presence of proteins (albumin and globulins) in lymphedematous tissue not only gives rise to colloidosmotic pressure but also produces an electrostatic charge endowing the proteins with individual features and different migration rates. The working hypothesis of the experimental study is to transfer lymph proteins from the upper fascia accumulation area to a subfascial drainage area by subjecting them to an adequate difference in potential. A double chamber, variable volume system with separation wall able to contain a 1 cm square of muscle fascia, was designed and built; the aim of the apparatus was to reproduce the subcutaneus zone separated by the fascia interposition, from the muscle-vascular zone. At the system was applied a variable electric field in six different experiments: 4 using porous synthetic membranes and 2 using human muscle fascia.

Prognostic and therapeutic impact of sentinel node micrometastasis in patients with invasive breast cancer.

AIMS AND BACKGROUND: Locoregional lymph node status is one of the most important prognostic factors determining the need for adjuvant chemotherapy in patients with breast cancer. Many authors have reported that micrometastases were not detected by routine sectioning of lymph nodes but were identified by multiple sectioning and additional staining. Among lymph node-negative patients 15-20% had an unfavorable outcome at five years from primary surgery. Sentinel lymph node (SLN) biopsy is an accurate technique for identifying axillary metastases because the pathologist utilizes hematoxylin-eosin (H-E) staining together with immunohistochemistry (IH) to examine all lymph node sections. Sentinel node micrometastasis has therefore become an important tumor-related prognostic factor. METHODS AND STUDY DESIGN: From November 1997 to October 2001 we examined in 210 patients the pathological features of primary breast lesions and SLN metastases and we correlated these with the tumor status of non-SLNs in the same axillary basin. We applied IH examination to both SLNs and non-SLNs of patients who were negative for metastasis by standard H-E examination. RESULTS: In this study lymph node staging was based on SLN findings, primary tumor size and the presence of peritumoral lymphovascular invasion (LVI). We found 18 SLN micrometastases (9%) in 210 patients and one of these (5.5%) of patients with SLN micrometastasis) also had one non-SLN metastasis: this patient had LVI and a larger primary tumor than patients with SLN micrometastasis without non-SLN metastasis. We also found 24 SLN macrometastases (11.5%) in 210 patients and 13 of these (54.2% of patients with SLN macrometastases) had one or more non-SLN metastases. CONCLUSIONS: According to the results reported in the literature, tumor cells are unlikely to be found in non SLNs when the primary lesion is small and SLN involvement micrometastatic (5.5% in our experience, 7% in Giuliano's). Our findings suggest that axillary lymph node dissection may not be necessary in patients with SLN micrometastasis from T1 lesions.

Sentinel node biopsy in the evaluation of the internal mammary node chain in patients with breast cancer.

AIMS AND BACKGROUND: In patients with breast cancer the presence of internal mammary chain (IMC) metastases changes tumor staging, and the occurrence of IMC drainage is quite common in breast cancer. Nevertheless, IMC dissection is not a routine procedure in modern surgical approaches towards breast cancer. We therefore need minimally invasive techniques for accurate assessment of the IMC nodal basin. The aim of this study was to investigate whether sentinel node biopsy (SLNB) could offer a solution. METHODS AND STUDY DESIGN: From November 1997 to June 2001 143 female patients who were eligible for breast cancer surgery were included in the study. All patients had T1 breast cancer and clinically negative axillae. Patients were submitted to preoperative lymphoscintigraphy with subsequent SLNB. We used a 99m-technitium nanocolloid tracer (Nanocoll) that was injected peritumorally so as to have about 10 MBq of radioactivity at the time of surgery. Scintigraphy was performed about 17 hours after tracer administration. During surgery, lymphoscintigraphic imaging and a gamma ray detection probe were used to locate the sentinel node. Histological examination after embedding in paraffin was usually requested and multilevel sectioning of the sentinel node (SLN) was performed, with hematoxylin and eosin staining and immunohistochemistry. RESULTS: Preoperative lymphoscintigraphy localized SLNs in the IMC basin in 27 of 143 patients (18.9%). Harvesting of IMC-SLNs based on lymphoscintigraphy results was successful in 20 of 27 patients (74.1%). Histological examination revealed micrometastases in four of the 20 harvested nodes. One of these patients showed no axillary drainage and no axillary lymph node dissection was therefore performed. In the remaining three patients also axillary SLNs were harvested, which turned out to be free from metastatic involvement. CONCLUSIONS: In our experience lymphoscintigraphy with SLNB was an accurate method to detect IMC metastases in patients with breast cancer. We recommend peritumoral tracer injection and a reasonable interval between injection and scintigraphy. IMC-SLN biopsy did not result in any serious additional complications or morbidity. In our study this approach led to improved cancer staging: four of 20 harvested IMC-SLNs proved to be micrometastatic. None of these four patients had metastatic axillary SLNs. Exclusive drainage to the IMC is present in only a small number of breast cancer patients, and our results suggest that it is possible to avoid unnecessary axillary node dissection in such cases.

Reliability and accuracy of sentinel node biopsy in cutaneous malignant melanoma.

AIMS AND BACKGROUND: The aims of this study were 1) to investigate whether sentinel lymph node (SLN) biopsy could become the method of choice for the early detection of metastatic disease in patients with malignant melanoma and 2) to identify those patients with lymph node metastases who could benefit from regional lymphadenectomy. METHODS AND STUDY DESIGN: Our study started in March 1998 and involved 110 patients with primary cutaneous malignant melanoma stage I or II (AJCC) in whom the primary lesion had been surgically removed no more than 90 days previously. On the day of lymph node dissection patients were given an intradermal injection of colloid particles of human serum albumin labeled with technetium-99m and an injection of isosulfan blue. The surgical procedure was usually performed with local anesthesia but in some cases locoregional or general anesthesia was preferred. Contralateral and ipsilateral lymphatic areas were scanned with a hand-held gamma camera (Scintiprobe MR 100) to measure the background and identify the hot point indicating the location of the sentinel node to direct the incision. RESULTS: The combined use of lymphoscintigraphy, isosulfan blue and gamma probe allowed us to identify sentinel nodes in 108 of 110 patients (98.18%) while the SLN was blue in only 90 cases (81.81%). The SLN was positive for metastases in 13 of the 108 patients (12.03%) and regional and distal lymphadenectomy was performed in all of them. The distribution of positive SLNs by primary lesion thickness was as follows: 0.76-1.5 mm: one positive SLN/44 patients (2.27%); 1.51-4 mm: six positive SLNs/51 patients (11.7%); > 4 mm: six positive SLNs/15 patients (40%). Only four of 12 patients with ulcerated cutaneous melanoma had positive SLNs. The patients in our study underwent follow-up visits every four months. The median follow-up was 481 days (range, 97-1271 days). CONCLUSIONS: In patients with primary cutaneous melanoma the histological status of the SLN accurately reflects the presence or absence of metastatic disease in the relevant regional lymph node basin. Complete lymph node dissection should only be performed in patients with positive SLNs. Patients with lesions > 4 mm are likely to develop recurrences and to die of systemic disease, so in these patients the usefulness of SLN biopsy is questionable. In conclusion, sentinel node mapping is a rational approach for the selection of patients who might benefit from early lymph node dissection of the affected basin.

[Therapy and follow-up of breast cancer. Experiences in 11 years of observation]. / Terapia e follow-up del carcinoma mammario. Esperienze di 11 anni di osservazioni.

Out of 1260 biopsies performed on neoplasias of the breast in 11 years' surgical practice, 463 (36,7%) malignant tumours were encountered. The surgical strategy in the latter cases was based on two basic parameters: a) the histological report on the intraoperative biopsy; b) the clinical stage (TNM). After surgery oncological treatment followed the now universal standard practice: --T1, T2, T3, N+, M0 and T4 independent of N or M: multiple chemotherapy for 6-12 months then periodic check ups as in N- cases. --M1: multiple chemotherapy, hormone and radiation treatment combined in various ways. The results obtained in terms of trouble free periods and survival are in line with reports in the literature including those describing a larger number of cases.

Seldom found acute abdomen: perforated diverticulum in the transverse colon.

The authors report a recently examined rare case of isolated perforated diverticulum of the transverse colon. At surgery, a perforated omentum-sealed diverticulum was found in the third distal wall of the transverse colon. A diverticulectomy was performed. The postoperative course was excellent.

Primary lung epithelioid hemangio-endothelioma with multiple bilateral metachronous localizations: case report and review.

The authors report a case of primary epithelioid (EH) in a 73-year-old female.

["Simulated walking" in the duplex evaluation of the venous system. The clinical and instrumental correlations]. / La "deambulazione simulata" nella valutazione del sistema venoso con duplex. Correlazioni clinico-strumentali.

The goals of non-invasive duplex vascular diagnosis of the venous system of the lower limbs are: 1) To make evaluation of the venous system during deambulation feasible under physiological, pathological and post-surgical or elastocompressive conditions. Moreover, any such evaluation must be achieved using a standardized, easy, highly reproducibly method which is inexpensive and utilizes the diagnostic instruments available. 2) To achieve detailed, selective localization of the valvular and parietal dysfunctions at the basis of any reflux pathology. 3) To identify and quantify venous flux and reflux during deambulation. The present work gives the results achieved over the period of one year after a new method simulating deambulation (Walk System 1 patented) was set up for several utilizations, principally correlated to the use of conventional duplex scanning in studying the venous system. The main purpose of the Walk System 1 is step simulation to uncover the location and extent of venous disease. This application test of: a pneumatic pump which compresses the calf to 100-120 mmHg in 0.3 sec thus simulating muscolar pumping during deambulation; standard 40 mmHg compression of the foot in order to rule out any hemodynamic involvement of the foot pump venous system. We can use this pump in the hemodynamic component, a part, during the step simulation, with synchronism with calf pump in TVP prophylaxis or in vascular therapy; an easy-to-use application software able to quickly pulsed Doppler data of flux and reflux by means of the flux and reflux orthodynamic indices or with measures in ml/sec. The study was performed on 80 lower limbs in normal subjects in order to define the normality range and in 380 lower pathologic limbs. The study has yielded a clinical-instrumental correlation between the hemodynamic data observed during inflation-deflation of the calf cuff, positioning the pulsed Doppler sample volume in the saphenous vein in the saphenous-femoral ostium zone and the underlying venous morphology. The results have made it possible to determine physiological S-F reflux and to establish 4 pathological classes of orthodynamic S-F reflux, each class corresponding to a specific range in the orthodynamic reflux index (class 0 = 0 < RI < 0.25; class 1 = 0.25 < RI < 2; class 2 = 2 < RI < 3.5; class 3 = 3.5 < RI < 6; class 4 = RI > 5) and to a particular morphological conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of therapy with aminaftone on chronic venous and lymphatic stasis]. / Effetti della terapia con aminaftone sulla stasi venosa e linfatica cronica.

Following a short introduction on the physiopathology of the phlebo-lymphatic system, the results of a study carried out on 114 patients suffering from chronic venous insufficiency (CVI) treated at the Department of General Clinical Surgery and Surgical Therapy of the University of Ferrara are reported. These patients were subdivided into two random groups and treated with common phlebotonic drugs and aminaftone, respectively. Both groups were also subjected to those physical and medical measures that are usually adopted for the treatment of such patients. The therapeutic effects were assessed by comparing symptomatology before and after 90 days of treatment, both subjectively (patient's assessment of the symptoms by means of a scoring system) and with objective methods (measurements and echo-Doppler examinations). The differences between the two groups were statistically very significant in favour of patients who had taken aminaftone. Excellent results were obtained in the treatment of CVI as well as in lymphatic-related pathology (lymphedema).

[Benzogammapirone in the treatment of digestive hemorrhages]. / Il "benzogammapirone" nel trattamento di emorragie digestive

Given the difficulties of treating digestive haemorhages with normal coagulant methods, and considering that most haemorrhages are due to vascular factors, a vasoprotective substance was associated with common coagulant therapies. Benzogammapirone was used orally and by selective arterial infusion. The series is presented and the results discussed.

[Peripheral lymphatico-venous anastomosis. New surgical technic]. / Anastomosi linfatico-venose periferiche. Nuova tecnica chirurgica.

A new surgical technique for peripheral lymphatic-venous anastomosis is presented. It is designed especially for cases of node block, e.g. lymphoedema after mastectomy. The distal ends of the collectors are sectioned downstream from the block and passed through a patch, which also serves to close a phlebotomy on an adjacent vein. An experimental study and preliminary clinical results are discussed.