Diagnostik und endoskopische Therapie beim zentralen Gallengangskarzinom

Klatskin-Tumore sind cholangiozellul?re Karzinome, die sich im Bereich der Hepatikusgabel manifestieren [20]. Ihre funktionelle Bedeutung für den Galleabstrom resultiert aus ihrer Lokalisation und ihrer Wachstumsform. Ihre Resektabilit?t h?ngt von der Tumormasse und der zentrifugalen Ausbreitung in die Hepatikusg?nge ab [3, 5, 19, 24]. Der diagnostische Goldstandard für die exakte Ausbreitungsdiagnostik ist nach wie vor die endoskopische retrograde Cholangio-Pankreatikographie (ERCP) [7, 13, 14]. Zum Diagnosezeitpunkt sind die meisten Klatskin-Tumore nicht mehr kurativ resektabel [5, 18]. Wird die Cholestase nicht behandelt, kommt es zu einem progredienten Leberversagen. Ziel endoskopischer Therapieverfahren ist die gezielte Galleableitung mit dem Erhalt von ausreichend funktionstüchtigem Parenchym [11, 21]. Für die Therapieplanung ist eine umfassende pr?interventionelle Bildgebung des gesamten Gallenwegssystems erforderlich. Hierbei spielt die Magnetresonanz-Cholangio-Pankreatikographie (MRCP) eine zunehmend wichtigere Rolle [14]. Sehr hoffnungsvoll sind multimodale pr?operative Therapieans?tze, die zuvor inoperable Klatskin-Tumore wieder in eine kurativ resektable Situation überführen [1, 12, 30]. Neue Ans?tze ergeben sich unter anderem durch die intrakavit?re photodynamische Therapie [4, 25].     

急性胰腺炎——早期选择性内镜治疗

胆石症是除了酗酒以外急性胰腺炎最常见的病因。胆石性急性胰腺炎的发病机制目前还不明了，除了胰管的梗阻外，胆汁致胰腺发生细菌性感染也是重要的原因。     

Analysis of Tie2-expressing monocytes (TEM) in patients with colorectal cancer

Tie2-expressing monocytes (TEM) promote tumor angiogenesis and growth in experimental cancer models. The role of TEM in cancer patients is unknown. We studied TEM in healthy volunteers and colorectal cancer (CRC) patients. Although TEM were detectable in the blood and tumor lesions of CRC patients, their frequency and functional phenotype showed no correlation with levels of angiopoietin-2 or vascular endothelial growth factor, microvessel density, tumor markers, tumor stage, or outcome of antiangiogenic therapy. These unexpected findings are at odds with murine tumor models and question the diagnostic or therapeutic value of TEM in human cancer.     

TEM8 interacts with the cleaved C5 domain of collagen alpha 3(VI)

Tumor endothelial marker (TEM)8 was uncovered as a gene expressed predominantly in tumor endothelium, and its protein product was recently identified as the receptor for anthrax toxin. Here, we demonstrate that TEM8 protein is preferentially expressed in endothelial cells of neoplastic tissue. We used the extracellular domain of TEM8 to search for ligands and identified the alpha 3 subunit of collagen VI as an interacting partner. The TEM8-interacting region on collagen alpha 3(VI) was mapped to its COOH-terminal C5 domain. Remarkably, collagen alpha 3(VI) is also preferentially expressed in tumor endothelium in a pattern concordant with that of TEM8. These results suggest that the TEM8/C5 interaction may play an important biological role in tumor angiogenesis.     

Loosely coupled coaxial TEM applicators for deep-heating

The development of a coaxial TEM (transverse electromagnetic) deep-heating, non-contacting applicator employing two axially spaced concentric sleeves is described which has electrostatic characteristics and has been named the ESA. Thermal data obtained with the FDA/CDRH elliptic-shaped human torso phantom (with fat overlay) showed nearly uniform heating (+/- 10%) throughout the inner cross-section. Saline tank measurements on a torso cross-section confirmed similar SAR uniformity. Animal experiments with a pig, both with and without blood flow, verified deep-heating and suggested that some preferential central heating occurred. The absence of excessive surface heating indicated that the major portion of the E-field excitation is axially aligned. The non-contacting applicator does not require a water bolus, and experiments showed that moderate patient movement had minor effect on performance.     

Further evidence for preoperative chemoradiotherapy and transanal endoscopic surgery (TEM) in T2-3s,N0,M0 rectal cancer

Purpose

Preoperative chemoradiotherapy and local excision via transanal endoscopic surgery (TEM) in T2–3s,N0,M0 rectal cancer achieve promising results in selected patients. We describe our long-term follow-up experience with this combination, and evaluate complete clinical and pathological responses, local recurrence and overall survival.

Methods

The prospective observational follow-up study carried out since 2007. Out of 476 consecutive patients treated with TEM, we selected those with adenocarcinoma of low or moderate grade of differentiation, clinical stages T2-superficial T3,N0,M0, who refused radical surgery. Preoperative chemoradiotherapy comprised 5-fluorouracil or capecitabine combined with radiotherapy at a dose of 50.4 Gy. TEM was performed after 8 weeks. Complications were recorded and long-term follow-up was conducted.

Results

Fifteen patients undergoing preoperative chemoradiotherapy and TEM (median age 76 years, 95 % CI 70.3–80.4, and median follow-up 38 months, 95 % CI 20–44) were studied. No local recurrence was observed, and only one patient (6.7 %) presented systemic relapse. The overall survival was 76 %. Complete clinical response was achieved in seven patients (46.7 %) and complete pathological response in four (26.7 %). With regard to toxicity associated with neoadjuvant treatment, four patients (26.7 %) developed grade 3 adverse effects; no grade 4 or 5 adverse effects were observed. There was no postoperative mortality.

Conclusions

The results of our study, with a response rate of 26.7 % and without local relapse, support the treatment of T2–3s,N0,M0 of rectal cancer with preoperative chemoradiotherapy and local excision (TEM).

     

Long-Term Complete Clinical and Hematological Response With Bortezomib: The Report of a Case With TEM(P)I Syndrome and a Review of the Literature

TEMPI syndrome was first defined in 2011 and classified as a plasma cell neoplasm with associated paraneoplastic syndrome in 2016. The pathogenesis of the syndrome is not well understood. Recognition of a combination of telangiectasia, erythrocytosis with a high erythropoietin level, monoclonal gammopathy, perinephric fluid collection, and intrapulmonary shunt is the first step in managing the disease. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other dermatological, renal, and pulmonary disorders. Without early diagnosis significant disability results from the pulmonary damage. The article we present here describes a clinical case of TEMPI-syndrome in a 58-year-old woman, which illustrates the difficulties associated with the timely recognition of this unusual disease. Here, we also review the clinical features of TEMPI syndrome, differential diagnosis and available treatment options, based on current literature. Although limited in number, with the addition of new patients to the literature, TEMPI syndrome is evolving into a well characterized multisystem syndrome. This rare disorder should not be missed, especially if the patient has a putative diagnosis of essential telangiectasia with a monoclonal gammopathy and polistemia. Increasing the awareness of clinicians about the disease and adding new patient data to the literature may contribute to a better understanding of the pathophysiology of the disease and standardization of treatment.     

Direct binding of the human homologue of the Drosophila disc large tumor suppressor gene to seven-pass transmembrane proteins, tumor endothelial marker 5 (TEM5), and a novel TEM5-like protein

The human homologue of the Drosophila discs large tumor suppressor gene (hDlg) is a member of the membrane-associated guanylate kinase family with three PSD-95/Dlg/ZO-1 (PDZ) domains. hDlg has been shown to bind tumor suppressor proteins, adenomatous polyposis coli (APC) and protein tyrosine phosphatase and tensin homologue (PTEN), and several viral oncoproteins, and has been implicated in the negative regulation of cell proliferation. hDlg has furthermore been shown to localize at the plasma membrane of synapses and to scaffold cell surface receptors and channels. In epithelial cells, hDlg localizes at the basolateral plasma membrane, but its localization mechanism is unknown. We searched here for a transmembrane protein that directly bound to hDlg. hDlg bound tumor endothelial marker 5 (TEM5), a seven-pass transmembrane protein that is homologous to the family B of G-protein-coupled receptors (GPCRs). TEM5 has previously been reported to display elevated expression during tumor angiogenesis and neoangiogenesis. The PDZ domains of hDlg bound the C-terminal PDZ-binding motif of TEM5. The expression of TEM5 was detected in endothelial cells of embryonic liver, where hDlg colocalized with TEM5. hDlg furthermore bound a novel seven-pass transmembrane protein, which was homologous to TEM5, and was named here a TEM5-like protein (TEM5-like). These results suggest that hDlg localizes at the plasma membrane through TEM5 and TEM5-like and furthermore scaffolds these GPCRs in endothelial cells during tumor angiogenesis and neoangiogenesis.     

TEM7 (PLXDC1), a key prognostic predictor for resectable gastric cancer,promotes cancer cell migration and invasion

Tumor endothelial marker 7 (TEM7) is a new candidate of molecular target for antiangiogenic therapy. This study aims to evaluate its expression in gastric cancer (GC) and to explore the correlation between its expression and the clinical outcome of patients. Expression of TEM7 was analyzed in both tumor tissues and cell lines of GC by real-time quantitative RT-PCR (qRT-PCR) and Western blot. RNA interference (RNAi) approaches were used to investigate the biological functions of TEM7. The effects of TEM7 on cell migration and invasion were evaluated by Transwell assays. In vitro experiments revealed that TEM7 was significantly overexpressed in GC cell lines (N87, AGS and SGC-7901) by 2-fold to 4-fold, and knockdown of TEM7 could significantly inhibit cancer cell migration and invasion. For GC patients, TEM7 gene expression was elevated in tumors in most cases (25/31), and its expression was closely correlated with tumor differentiation, depth of cancer invasion, lymphatic metastasis and TNM stage. The overall survival of TEM7 (-) group was significantly higher than that of TEM7 (+) group (P = 0.048) and TEM7 (++) group (P = 0.003). TEM7 is highly expressed in GC and is likely correlated with tumor invasion and migration, and thus its expression is closely related to the clinical outcome of patients.     

人脑星形细胞瘤的CT和TEM联合研究

人脑星形细胞瘤的ＣＴ和ＴＥＭ联合研究图１星形细胞瘤（Ⅱ－Ⅲ级）。平扫显示左额额颞呈混杂密度病灶，形态不规则，病灶边缘不清楚、占位效应明显（↑）。图２与图１同一肿瘤的增强扫描，肿瘤呈现不规则，不均匀的增强。占位效应明显（↑）。图３星形细胞瘤（Ⅱ－Ⅲ级）...     

A three-dimensional model for the ’coaxial TEM’ deep-body hyperthermia applicator

A rigorous three-dimensional electromagnetic model predicting the complete field distribution in the space interior to the ’coaxial TEM’ applicator is presented. The applicator consists of a radiating ring aperture, with a given electric-field distribution in the wall of a hollow circular cylinder. The method of calculation employs the spatial Fourier transform of all field quantities with respect to the axial co-ordinate, after which the field equations are solved in the spectral domain. Subsequently, an inverse Fourier transform is carried out to compute the quantities that are of interest to the optimum clinical deep-body hyperthermia system. Numerical results for a number of representative applicator configurations are given. The present results are compared with the ones that are obtained by a model based on the far-field approximation of a distribution of dipole sources located in the ring aperture.     

Toxicology and pharmacokinetics of (1,1-bis(aminomethyl)cyclohexane)oxalatoplatinum(II) (TNO-38)

Preclinical studies on toxicology and pharmacokinetics were performed for (1,1-bis(aminomethyl)cyclohexane)oxalatoplatinum(II) (TNO-38) in rats and a dog after ld₁₀ and ld₅₀ assessment in mice. In drug-treated rats, ura and creatinine concentrations were 1,4-1.9 times those in control rats. Histopathology showed necrosis of tubular epithelium of the kidneys, which was comparable to damage observed after treatment with cisplatin (CDDP), and extensive necrosis of crypt epithelium, especially in the ileum.Similar to CDDP, TNO-38 was emetic in the dog. Non-specific subacute inflammatory changes were observed in the ileum. Renal damage was much less pronounced.Half-lives of distribution and elimination were 6.2 min and 5.2 days, respectively. The cumulative excretion of Pt in urine over 1 and 7 days after drug treatment was 38.3 and 49.3% of the dose, respectively. Twelve weeks after drug administration, Pt concentrations were highest in kidneys and liver.TNO-38 is adequately water soluble. Its reported antitumour activity is consistently lower than that of CDDP. The drug's toxicity was, in general, comparable to that of CDDP. Its pharmacokinetic profile was very similar to that of CDDP. It is concluded that TNO-38 should probably not be further evaluated in clinical studies.     

Antitumor effects of three platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)-platinum (II) monohydrate (DWA2114R), cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP), in mice.

(-)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R), cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP) were compared for their antitumor effects and nephrotoxicity-inducing activities at the same dosage (1/8, 1/4, 1/3, 1/2, 2/3 or 3/4 of the LD10 or LD10) on the basis of their intravenous lethal doses in mice. DWA2114R was effective against murine tumor lines, Colon 26 and Colon 38 carcinomas, M5076 ovarian sarcoma and P388 L1210 leukemias, implanted subcutaneously (s.c.). Triple injection every other day of DWA2114R was more effective than a single injection at each sublethal dose. The antitumor effects of DWA2114R against these tumors were more effective than or were similar to those of CBDCA and CDDP. The antitumor effect against CDDP-resistant L1210 leukemia implanted s.c. was only observed in the treatment of DWA2114R, but not in CBDCA and CDDP. No excellent antitumor effects of three platinum complexes were observed against Lewis lung carcinoma and B16 melanoma implanted s.c. even at triple injection every other day, and no effect was obtained against Meth-A fibrosarcoma under similar conditions. While the treatment of CDDP showed marked increases in levels of blood urea nitrogen and of urinary protein and sugar at effective doses in the antitumor evaluations, the treatment of DWA2114R as well as CBDCA showed no increase in these parameters. These results indicate that DWA2114R represents a desirable second generation antitumor platinum complex.     

Maximizing rectal cancer results: TEM and TATA techniques to expand sphincter preservation

Rectal cancer management benefits from a multidisciplinary approach involving medical and radiation oncology as well as surgery. Presented are the current dominant issues in rectal cancer management with an emphasis on our treatment algorithm at the Lankenau Medical Center. By basing surgical decisions on the downstaged rectal cancer we explore how sphincter preservation can be extended even for cancers of the distal 3 cm of the rectum. TATA and TEM techniques can be used to effectively treat cancer from an oncologic standpoint while maintaining a high quality of life through sphincter preservation and avoidance of a permanent colostomy. We review the results of our efforts, including the use of advanced laparoscopy in the surgical management of low rectal cancers.     

Isolation and characterization of a scFv antibody specific for tumor endothelial marker 1 (TEM1), a new reagent for targeted tumor therapy

Tumor endothelial marker 1 (TEM1) is a protein predominantly expressed on the cell surface of endothelial cells in newly developing blood vessels and on tumor cells. It is therefore ideally suited as a target for anti-angiogenic tumor therapy. Using phage display technology a single chain antibody fragment (scFv-CM6) was isolated that specifically binds to the extracellular part of TEM1. Antibody specificity was determined in ELISA, by Western analysis, fluorescence microscopy and flow cytometry performed with TEM1-expressing cells. ScFv-CM6 was further functionalized and coupled to liposomes. Such immunoliposomes loaded with the cytotoxic drug N4-octadecyl-1-beta-D-arabinofuranosylcytosine-(5'-5')-3'-C-ethinylcytidine showed increased binding affinity and up to 80% higher cytotoxic activity towards TEM1-expressing IMR-32 tumor cells compared with control liposomes.