Non-surgical ablative therapies for inoperable benign insulinoma.

PURPOSE: Benign insulinoma is the most common functioning neuroendocrine tumor of the pancreas. The gold-standard therapeutic approach for insulinoma is surgery, which allows for tumor removal, histology and immunochemical analyses. If surgery is not feasible, minimally invasive ablative procedures performed by interventional radiology can lead to partial or complete remission of hormone hypersecretion and tumor control in insulinoma patients. METHODS: We performed a review of existing literature on non-chemotherapeutic/radioactive ablative techniques employed for the treatment of benign, otherwise inoperable, pancreatic insulinoma. For this purpose, feasibility, effectiveness and safety of ablative treatments for pancreatic insulinoma were reviewed from literature data published from 1982 to date. RESULTS: A total of 44 insulinoma cases treated with non-surgical ablative techniques were desumed, and divided as follows: 7 cases of tumor embolization, 26 ethanol ablations, 7 radiofrequency ablations, 2 high intensity focused ultrasound ablation, 1 irreversible electroporation and 1 percutaneous microwave ablation. Most cases involved single insulinoma, predominantly located in the pancreas head and body. In the majority of patients, ablation was chosen instead of surgery due to severe comorbidities. After an average follow-up of 16 months, the overall success rate of non-surgical ablative treatments of insulinoma was 84%, the recurrence/persistence rate was 16%, and transient adverse events were noted in 23% of cases. Adverse events were usually self-limiting and medically manageable. CONCLUSIONS: Non-surgical ablation is a feasible, safe and repeatable procedure in patients with pancreatic insulinoma, who are not candidate to surgery or refuse it. Partial or complete control of symptoms and tumor growth is experienced by the majority of patients.

Placement of port-a-cath through the right internal jugular vein under ultrasound guidance.

PURPOSE: This study was undertaken to demonstrate the effectiveness of ultrasound (US)-guided placement of porta-cath (PC) through the right internal jugular vein (RIJV) by evaluating the onset of early and late complications. MATERIALS AND METHODS: From 30 June 2008 to 30 June 2011, we placed 695 port-a-caths in 694 patients with a mean age of 58 years. Exclusion criteria were active infection, bleeding disorders and life expectancy <6 months. The procedures were performed in the angiography suite under local anaesthesia. After US-guided puncture of the RIJV, the subcutaneous pocket was prepared, followed by tunnelling of the vein and closure of the surgical wound. In order to evaluate pneumothorax (PNX), all patients underwent chest X-ray a few hours after the end of the procedure unless there were clinical indications. We evaluated the technical success of the procedure and the rate of complications. RESULTS: Technical success was achieved in all cases. The device was kept in place for an average of 168 days. There was one case of PNX (0.14%) as shown on chest X-ray and five cases of late complications (0.70%): one case of intracatheter thrombosis (0.14%), two cases of disconnection between the reservoir and catheter (0.28%) and two cases of PC infection (0.28%). CONCLUSIONS: This procedure incurs very small number of complications compared with other positioning techniques using accesses such as the subclavian vein. Complications recorded in our study are comparable, in type and incidence, to those found by other authors, with the most frequent being device infection.

[Analysis of bone marrow angiogenesis in multiple myeloma]. / Analýza angiogeneze v kostní dreni u plazmocytárního myelomu.

The authors studied angiogenesis in trephine biopsy samples taken from the hip bone from a total of 51 patients with an as yet untreated plasma cell myeloma / multiple myeloma (MM). Microvessel density calculated to 1 mm2 was represented by monoclonal antibodies against CD34 and nestin. It was discovered that proliferating vessels labeled with anti-nestin antibody nearly never occur in the interstitial type of infiltration. The amount of proliferating vessels in nodular infiltrates is significantly lower compared to the capillary network labeled with antibodies against CD34. The density of proliferating vessels in nodular infiltrates significantly correlates with the proliferation index Ki67 of myeloma cells, not, however, with the degree of MM differentiation.

Randomized study of interferon beta-1a, low-dose azathioprine, and low-dose corticosteroids in multiple sclerosis.

BACKGROUND: Studies evaluating interferon beta (IFNbeta) for multiple sclerosis (MS) showed only partial efficacy. In many patients, IFNbeta does not halt relapses or disability progression. One strategy to potentially enhance efficacy is to combine IFNbeta with classical immunosuppressive agents, such as azathioprine (AZA) or corticosteroids, commonly used for other autoimmune disorders. OBJECTIVE: The Avonex-Steroids-Azathioprine study was placebo-controlled trial and evaluated efficacy of IFNbeta-1a alone and combined with low-dose AZA alone or low-dose AZA and low-dose corticosteroids as initial therapy. METHODS: A total of 181 patients with relapsing-remitting MS (RRMS) were randomized to receive IFNbeta-1a 30 microg intramuscularly (IM) once weekly, IFNbeta-1a 30 microg IM once weekly plus AZA 50 mg orally once daily, or IFNbeta-1a 30 microg IM once weekly plus AZA 50 mg orally once daily plus prednisone 10 mg orally every other day. The primary end point was annualized relapse rate (ARR) at 2 years. Patients were eligible for enrollment in a 3-year extension. RESULTS: At 2 years, adjusted ARR was 1.05 for IFNbeta-1a, 0.91 for IFNbeta-1a plus AZA, and 0.73 for combination. The cumulative probability of sustained disability progression was 16.8% for IFNbeta-1a, 20.7% for IFNbeta-1a plus AZA, and 17.5% for combination. There were no statistically significant differences among groups for either measure at 2 and 5 years. Percent T2 lesion volume change at 2 years was significantly lower for combination (+14.5%) versus IFNbeta-1a alone (+30.3%, P < 0.05). Groups had similar safety profiles. CONCLUSION: In IFNbeta-naïve patients with early active RRMS, combination treatment did not show superiority over IFNbeta-1a monotherapy.

[Bone marrow angiogenesis in patients with multiple myeloma as a marker of biological behaviour]. / Angiogeneze v kostní dreni pacientu s plazmocytárním myelomem jako ukazatel biologického chování.

Angiogenesis, the creation of new blood vessels from preexisting vascular nets, plays a major role in the development, progression and dissemination of solid malignant tumors. Research over the last few years has shown a correlation of angiogenesis and the biological behaviour of haematologic malignancies. This study focused on the relation of vasoformation, stage of differentiation of tumour plasmocytes and type of bone marrow infiltration in patients with multiple myeloma (MM) prior to treatment. We evaluated trephine biopsy samples from 55 patients for microvessel density in 1 mm2 field by monoclonal antibody anti CD34. Angiogenesis correlated with the type of infiltration and with stage of morphological differentiation. It was highest in the nodular type of infiltration with a low level of differentiation, and lowest in grade 1 differentiation with an interstitial type of infiltration.

[Diagnosis of lymphoproliferative diseases from bone marrow biopsies]. / Zkusenosti s diagnostikou lymfoproliferativních onemocnení v biopsii kostní drene.

The cytological, histological and immunophenotypical markers of lymphoproliferative diseases are evaluated in the collection of 950 trepanobiopsies, and correlated with types of extramedullary malignant lymphoma. The diagnostic significance of tumor infiltrates topography and basic rules of the differential diagnoses of malignant lymphomas in the bone marrow biopsies are discussed.

Intraarterial chemotherapy with polyoxyethylated castor oil free paclitaxel, incorporated in albumin nanoparticles (ABI-007): Phase I study of patients with squamous cell carcinoma of the head and neck and anal canal: preliminary evidence of clinical activity.

BACKGROUND: This study was designed to determine the feasibility, maximum tolerated dose, and toxicities of intraarterial administration of paclitaxel-albumin nanoparticles in patients with advanced head and neck and recurrent anal canal squamous cell carcinoma. Antitumor activity also was assessed. METHODS: Forty-three patients (31 with advanced head and neck and 12 with recurrent anal canal squamous cell carcinoma) were treated intraarterially with ABI-007 every 4 weeks for 3 cycles. In total, 120 treatment cycles were completed, 86 in patients with head and neck carcinoma (median, 3 cycles; range, 1-4) and 34 in patients with anal canal carcinoma (median, 3 cycles; range, 1-4). ABI-007 was compared preliminarily with Taxol for in vitro cytostatic activity. Increasing dose levels from 120 to 300 mg/m2 were studied in 18 patients. Pharmacokinetic profiles after intraarterial administration were obtained in a restricted number of patients. RESULTS: The dose-limiting toxicity of ABI-007 was myelosuppression consisting of Grade 4 neutropenia in 3 patients. Nonhematologic toxicities included total alopecia (30 patients), gastrointestinal toxicity (3 patients, Grade 2), skin toxicity (5 patients, Grade 2), neurologic toxicity (4 patients, Grade 2) ocular toxicity (1 patient, Grade 2), flu-like syndrome (7 patients, Grade 2; 1 patient, Grade 3). In total, 120 transfemoral, percutaneous catheterization procedure-related complications occurred only during catheterization of the neck vessels in 3 patients (2 TIA, 1 hemiparesis) and resolved spontaneously. CONCLUSIONS: Intraarterial administration of ABI-007 by percutaneous catheterization does not require premedication, is easy and reproducible, and has acceptable toxicity. The maximum tolerated dose in a single administration was 270 mg/m2. Most dose levels showed considerable antitumor activity (42 assessable patients with 80.9% complete response and partial response). The recommended Phase II dose is 230 mg/m2 every 3 weeks.

[Percutaneous implant of Denver peritoneovenous shunt: a new opportunity for the interventional radiologist]. / L'impianto percutaneo dello shunt peritoneo-venoso di Denver: Una nuova opportunità per il radiologo interventista.

PURPOSE: The study is aimed at presenting our experience in the implant of Denver peritoneovenous shunts. Medical treatment-resistant ascites, either neoplastic or related to hepatic failure, is highly symptomatic and its treatment is indicated in order to improve patients' quality of life. One of the most efficient methods of treatment consists in implanting a peritoneovenous shunt. The availability of this device and its percutaneous implantation provide Interventional Radiologists with the possibility of expanding their repertoire. MATERIAL AND METHODS: Thirteen shunts were implanted in 12 patients, 10 with neoplastic ascites and 2 with hepatic failure-related ascites. In 1 patient a second device had to be implanted. All the procedures were performed in the Interventional Radiology Department, under local anesthesia and mild sedation. The central venous access was by the subclavian vein in 7 cases and the internal jugular vein in 6 cases. The puncture kit is consists of 2 needles, 1 for venous puncture and 1 for peritoneal puncture, 2 angiographic J-guide wires, 2 peel-away introducers, and a chamber containing the double valve-pump connected with both the venous and the peritoneal catheters. The whole device is placed subcutaneously thus allowing fluids to flow from the peritoneum to the vein either spontaneously, if intra-abdominal pressure exceeds 3cm of water, or by manual compression exerted on the pump itself. RESULTS: All implants were successfully performed. One transient complication occurred consisting in a mild inflammatory reaction along the subcutaneous catheter route, which promptly solved by antibiotic therapy. So far a total of 1773 catheter/days have been accumulated. 7/10 of the neoplastic patients died from progressive disease after 915 catheter/days (median 120, range 30-180). In a cirrhotic patient the first shunt occluded after 430 days due to hemoperitoneum caused by hepatic biopsy: it was removed and a new one implanted. Five shunts are in now use, with a follow-up of 30, 48, 70, 120 and 160 days each. DISCUSSION: The implanting technique was well tolerated by all patients and it could be performed under local anesthesia. The central vein puncture was easy for both accesses but the introducer diameter (12F) and the possibility of clavicle pinch-off induced us to use the internal jugular approach in the last six cases, which provided a reduced risk of pneumothorax and a better catheter track. In the patients with neoplastic ascites we observed neither disease dissemination nor changes in the patients' changed related to the shunt. Our results show that the implant of Denver venous-peritoneal shunts is a relatively easy procedure, which can be performed by Interventional Radiologists on a regular basis.

Expression of Bcl-2 in dysplastic and neoplastic cervical lesions in relation to cell proliferation and HPV infection.

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death in a variety of tumors. The bcl-2 proto-oncogene is involved in the development of human follicular lymphomas and also in a number of solid tumors such as carcinomas of prostate, breast, lung and GIT. The present study was designed to analyze the role of Bcl-2 expression in cervical intraepithelial squamous neoplasias (CIN) and cervical invasive carcinomas. Special attention was given to the association of Bcl-2 expression with the grade of the lesion, proliferative activity (expression of nuclear antigen of proliferative cells - PCNA) and human papillomavirus (HPV) DNA positivity. We examined tissue samples obtained from 86 women with varying degrees of cervical disease. Bcl-2 and PCNA were investigated using immunohistochemical staining and detection of HPV DNA was performed by hybridization in situ. Increased Bcl-2 expression was observed in advanced degrees of dysplasia and in carcinomas. We found a strong association between the presence of Bcl-2 in pathological epithelium with both the degree of dysplasia and the proliferative activity. We also observed a significant correlation between the amount of Bcl-2 positive lymphocytes infiltrating the lesions and the degree of disease. We, therefore, suggest that Bcl-2 expression in these lymphocytes may influence the antiviral or antitumor immune response. On the other hand we did not detect any significant correlation between the Bcl-2 oncoprotein and the presence of HPV. These results indicate that Bcl-2 may play an important role in the development of cervical cancer.

Stereotactic breast biopsy: en bloc excision of microcalcifications with a large-bore cannula device.

OBJECTIVE: Breast calcifications pose a significant diagnostic and procedural dilemma. We evaluated en bloc stereotactic excision of indeterminate and suggestive microcalcifications for histologic diagnosis using a large-bore cannula biopsy device. MATERIALS AND METHODS: We retrospectively reviewed 61 groups of microcalcifications removed with a large-bore cannula biopsy device from 59 patients (age range, 35-72 years old). The cannula diameter was 20 mm in 47 cases, 15 mm in nine cases, and 10 mm in five cases. The median lesion diameter was 6.6 mm (range, 4-17 mm). The procedure was performed by radiologists in an outpatient setting, with patients undergoing local anesthesia. All patients with a diagnosis of malignancy underwent surgery. RESULTS: In all instances, microcalcifications were removed in a single pass, in a single intact tissue specimen, through a maximum skin incision of 2 cm (0.8 inch). Twenty-five malignancies, 34 benign lesions, and two cases of lobular carcinoma in situ were identified. Sixteen malignancies were noninvasive and nine were invasive. No residual tumor was found at surgery in six of the 18 cases with involved margins and in five of the seven cases with uninvolved margins. One case of lobular carcinoma in situ with involvement of the margins additionally showed ductal carcinoma in situ at surgery. CONCLUSION: Mammographically identified microcalcifications are excised en bloc with the large-bore cannula biopsy device, providing a stereotactically localized tissue sample that is comparable with that obtained with open surgical biopsy and allows evaluation of the margins. This surgical radiologic procedure may represent a valid alternative, in selected patients, to conventional surgical biopsy after radiologic localization.

First clinical experience with a high-capacity implantable infusion pump for continuous intravenous chemotherapy.

PURPOSE: To evaluate the efficiency of a new high-capacity pump for systemic venous chemotherapy and to verify the quality of implantation by interventional radiology staff. METHODS: A total of 47 infusion pumps with a 60-ml reservoir and variable flow rates (2, 6, 8, or 12 ml/24 hr) were implanted by radiologists in 46 patients with solid tumor metastases requiring treatment with a single, continuously infused cytostatic agent. The reservoir was refilled transcutaneously, usually once weekly. The flow accuracy of the pump was assessed from actual drug delivery recorded on 34 patients over a minimum observation period of 180 days. RESULTS: No early complications occurred in any of the 47 implants in 46 patients. A total of 12 (25.53%) complications occurred between 3 and 24 months after implantation. Seven (14.90%) of these were due to the external design of the pump, while five (10.63%) were related to the central venous catheter. In the 34 patients available for pump evaluation (follow-up of at least 180 days), the system was used for a total of 14,191 days (range 180-911 days, mean 417.38 days), giving an overall complication rate of 0.84 per 1000 days of operation. The mean flow rate accuracy was 90.26%. CONCLUSION: The new implantable pump showed good flow rate accuracy and reliable operation. The pump-related complications were related to its external design and have now been corrected by appropriate modifications. From a radiologic and surgical viewpoint, the venous implantation procedure is identical to that of conventional vascular access devices and can be performed by radiologists familiar with these techniques. The current limitations lie in the high cost of the pump and, for certain drugs, the short time between refills.

[Inflammatory stromal reaction in epithelial neoplasia of the uterine cervix in correlation with HPV infection]. / Zánetlivá stromální reakce v epiteliálních neoplaziích delozního hrdla v korelaci s infekcí HPV.

260 cases of women with epithelial neoplasias of the uterine cervix were studied: HPV infection was detected by DNA in situ hybridization and serology, simultaneously structure and intensity of stromal inflammatory reaction (SR) were evaluated (semiquantitatively) as well as standard clinical immunological parametres investigated by serology. Results proved the same character of SR in intraepithelial lesions and invasive carcinomas and the intensity of SR increasing in relation to the gravity of epithelial dysplasia. There was not found any significant difference in SR between cases with detected HPV infection and cases lacking it. Summarized immunological parametres were in limits of normal reference range.

Stereotactic excisional breast biopsy performed by interventional radiologists using the advanced breast biopsy instrumentation system.

The Advanced Breast Biopsy Instrumentation (ABBI) system, which uses surgical cannulas up to 20 mm in diameter, is an alternative to conventional surgical biopsy for the diagnosis of non-palpable breast lesions. Since the need for radiological skill outweighs the surgical content of the technique, we evaluated the feasibility of complete management of the procedure by interventional radiologists. 35 of the 111 patients originally scheduled for the procedure were excluded, three because the lesion could not be visualized and 32 because of insufficient thickness of the compressed breast. The procedure had to be abandoned in one case due to a technical failure. 77 stereotactic excisional breast biopsy procedures were performed using the ABBI system in 75 patients with suspicious non-palpable mammographic lesions. The procedure was carried out under local anaesthesia in the radiology department, using a dedicated Lorad (R) radiographic system. 31 (40%) masses without calcifications, 11 (14%) masses with calcifications and 35 (46%) clusters of microcalcifications without tumour mass were sampled. 43 (56%) benign lesions and 34 (44%) malignant lesions were diagnosed. The overall mean diameter of the lesions was 8.7 mm (range 3-22 mm). All 34 patients with malignancies and lobular carcinoma in situ subsequently underwent surgery, the results of which are reported. Three (4%) haematomas were detected and aspirated percutaneously. Two technical problems occurred: an ABBI cannula malfunction, and a computer failure of the digital imaging system during the procedure. The average procedure time was 80 min and the cost of each procedure was 2,800,000 Italian lire (1555 US$). It is concluded that tissue sampling with the ABBI system can be performed entirely by radiologists without significant problems. The procedure was well tolerated by all patients. The quality of the biopsy specimen was identical to that of a surgical specimen but with the advantages of stereotactic precision for localization of the lesion.

[Detection and typing of HPV DNA in situ--improvement in diagnosis of lesions of the uterine cervix]. / Prukaz a typizace HPV DNA in situ--príspevek ke zlepsení diagnostiky lézí delozního cípku.

We examined the cervical samples from 63 female patients with various grades of cervical intraepithelial neoplasia (CIN), invasive squamous cell carcinoma (INCA) or inflammation. All the women with the diagnosis of CIN were selected on the basis of cytological prediction of HPV infection (koilocytosis, dyskeratosis). The analysis of human papillomavirus (HPV) genome by DNA hybridization in situ was done in all cases. Simultaneously, the immunohistochemical expression of papillomavirus common antigen (PVCA) and proliferating cell nuclear antigen PCNA/cykline was determined. The results confirm the correlation between high risk HPV types 16, 18, 33 and higher grade of dysplasia (CIN) as well as higher proliferative activity. On the other hand, the detection of HPV DNA does not correlate with PVCA expression or with cytological/histological diagnosis of koilocytosis. This finding shows that common cytological or histological examinations may be unreliable and in particular the significance of koilocytosis must be reevaluated.

[Malignant B-monocytoid mantle zone lymphoma]. / Maligní lymfom plást'ové zóny, B-monocytoidní typ.

Three cases of B-monocytoid malignant lymphoma were studied by histology, immunohistology and electron microscopy. Two of them were primarily extranodal (in parotid gland and palatine tonsil), the third was in lymph nodes. All tumours were characterized by patients' long survival without signs of generalization.

[Myocyte transformation in autologous transplantation of colonic smooth muscle in domestic pigs]. / Transformance myocytu autologního transplantátu hladké svaloviny tracníku u vepre domácího.

Autologous gut smooth muscle graft of two piglets was used for creating a ring in sigmoidostomy. The graft was investigated several times by histology and electron microscopy. A sort of myofibroblasts were observed the 7th day in the smooth muscle. Three months later the smooth muscle was completely transformed into a cellular connective tissue comprising myofibroblasts and fibroblasts. The experiment points to possible relation of smooth muscle cell, myofibroblast and fibroblast.

[Expression of the blood group antigens A and B in carcinoma of the urinary bladder]. / Exprese krevních skupinových antigenu A a B v karcinomu mocového mechýre.

In 21 patients with transitional cell carcinoma of the urinary bladder expression of A and B blood group antigens was studied by means of monoclonal antibodies on using indirect immunoperoxide reaction. Expression of the investigated antigens was found to be dependent on the degree of histological differentiation of the tumor tissue. In well-defined carcinomas mostly pronounced expression of A and B blood group antigens was observed. Middle and low-differentiated carcinomas were characterized by reduction or even total deletion of expression. The expected favorable prognosis in transitional cell carcinomas expressing A and B blood group antigens failed to be confirmed. The expression of incompatible A-like antigens in 0 and B blood group patients with carcinoma is discussed. (Tab. 3, Fig. 3, Ref. 22.).

Selective monocellular necrosis of Hodgkin's/Reed-Sternberg cells and their immunoreactivity to human serum antinuclear antibodies in NS- and MC-types of malignant lymphogranuloma.

The selective (apoptotic) necrosis of Hodgkin's cells in malignant lymphogranuloma appears to be etiologically quite different from focal one due to ischemic-vascular causes. The morphology and supposed etiopathogenesis of this cellular lesion, as well as the karyoclastic process-presumably apoptotic in nature-are briefly described and considered as a mechanism leading to cellular regression with subsequent destructuralization and release of DNA-reactive nucleoprotein material in form of free hematoxylin bodies. An original observation of the immunoreactivity of Hodgkin's cells with antinuclear antibodies of human serum in a case of collagenosis is also described.

[Expression of A,B and H blood group antigens in urothelial carcinoma of the urinary bladder]. / Exprese krevních skupinových antigenu A, B a H v uroteliálním karcinomu mocového mechýre.

Expression of blood group antigens A, B, and H was studied in transitional carcinoma of the urinary bladder. Positive result was obtained in 16 cases of a group of 21 tumours by indirect immunoperoxidase reaction with monoclonal antibodies. A relation of quantitative expression to histological grading of tumour differentiation was noticed. Well differentiated transitional carcinomas mostly had more conspicuous expression of A, B, and H antigens. However, expected more favourable prognosis in cases of transitional carcinoma with expression of A, B, and H blood group antigens failed to be proved.

Histochemistry of mucosubstances in the diffuse and intestinal types of gastric cancer.

Histochemical properties of the mucus were studied in 48 diffuse types and 46 intestinal types of gastric carcinoma. Diffuse type was characterized by the prevalence of intracellular secretion of mucopolysaccharides with a significant involvement of sulfated ones. In the intestinal type, extracellular secretion predominated with the occurrence of pure acid mucopolysaccharides and a smaller portion of sulfated ones. The secretion of pure neutral mucopolysaccharides was minimal in both types of gastric cancer. In the intestinal type carcinomas, incomplete intestinal type IIb metaplasia was frequently found in marginal areas of the tumor.