Search

Case Presentation A 33-year-old woman of Latin American origin was referred to our department by her primary care physician for a left lower lobe mass, which was incidentally found on a CT scan of her abdomen. The patient had complaints of abdominal pain for which she underwent imaging of her abdomen. Review of systems was negative for any respiratory complaints, and she denied any history of cigarette smoking or recreational drug use.

L-selectin (CD62L) is normally highly expressed in naive T cells. The expression levels of CD62L have been reported to be decreased on T cells during the inflammatory state. It is currently unknown whether the frequency of CD62L+ T cell subsets in the peripheral blood can be used as a marker to indicate is disease severity during inflammation. Our study evaluated whether circulating CD62L+ T cell subsets correlate with the severity of disease by testing an autoimmune condition of scurfy (sf) mouse associated with multi-organ inflammation due to regulatory T cell deficiency. We observed that scurfy mice spontaneously developed an inflammatory phenotype with a significant decrease in the percentage of CD62L-expressing CD4+ T and CD8+ T cells in the peripheral blood. The percentage of CD62L+CD4+ T and CD62L+CD8+ T cells negatively correlated with disease severity, as determined by the weight of spleen and liver, as well as the mean area of lymphocyte infiltrates in lung and liver. The percentage of CD8+ T cells also correlated directly with these markers of disease severity. To conclude, our results support the concept that circulating CD62L-expressing T cells may be used as markers of disease severity in sf mice which is equivalent to a syndrome characterized by immune dysregulation with polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX syndrome) in humans, or in other autoimmune or inflammatory conditions.

Purpose: RB94, a truncated form of RB110, has enhanced tumor suppressor potency and activity against all tumor types tested to date including bladder carcinoma. However, efficient, systemic delivery of the gene encoding RB94 specifically to tumors, is an obstacle to clinical application as an anticancer therapeutic. We have developed a systemically given, nanosized liposome DNA delivery system that specifically targets primary and metastatic disease. The ability of RB94, delivered via this nanocomplex, to sensitize bladder carcinoma to chemotherapy in vitro and in vivo was assessed.Experimental Design: The nanocomplex is an RB94 plasmid encapsulated by a cationic liposome, the surface of which is decorated with a tumor-targeting moiety, either transferrin (Tf/Lip/RB94) or an antitransferrin receptor single-chain antibody fragment (TfRScFv/Lip/RB94). The ability of the complex to sensitize human bladder carcinoma HTB-9 cells to chemotherapeutics was assessed in vitro by XTT assay. In vivo tumor specificity and efficacy were tested in mice carrying HTB-9 tumors by PCR and tumor growth inhibition, respectively.Results: Transfection with Tf/Lip/RB94 significantly sensitized HTB-9 cells to chemotherapeutic agents in vitro. Tumor specificity of the complex was shown in an orthotopic bladder tumor model by immunohistochemistry and PCR. Moreover, in mice bearing subcutaneous HTB-9 tumors, the combination of systemically given Tf/Lip/RB94 or TfRScFv/Lip/RB94 plus gemcitabine resulted in significant (P < 0.0005) tumor growth inhibition/regression and induction of apoptosis.Conclusions: Use of our tumor-targeting nanocomplex to specifically deliver the potent tumor suppressor RB94 efficiently to tumors has potential as a more effective treatment modality for genitourinary and other cancers.

29 Background: Uterine clear cell carcinoma (UCCC) is a high-grade endometrial carcinoma. The current treatment is hysterectomy with post-operative chemotherapy and/or radiation. The 5-year disease free survival remains dismal for UCCC with 65% for early-stage and 54% for advanced stage disease. In addition, UCCC may be more resistant to chemotherapy or radiation therapy than the endometrioid subtype. The aim of the current study is to investigate the HER2 gene amplification status in UCCC and its role for targeted therapy in UCCC. Methods: Twenty-nine cases of UCCC were retrieved from surgical pathology archives of Mayo Clinic at Rochester between 2011 and 2015. All cases except one case were hysterectomy specimens. The blocks contain the most characteristic morphology of UCCC were selected and corresponding paraffin sections were subjected to fluorescent in situ hybridization for amplification of HER2 gene (Hercept, Abbott Molecular) and parallel immunohistochemical (IHC) study. Results: A total of 9 (of 29; 31%) UCCCs showed HER2 amplification and 4 (of 29; 14%) were considered equivocal for HER2 amplification by FISH. A total of 3 (10%) tumors showed 3+ HER2 overexpression while 11 (38%) UCCCs showed 2+ HER2 overexpression, 9 (31%) showed 1+ expression with the remaining cases showing no expression of HER2. Importantly, we observed significant intratumoral heterogeneity with regard to HER2 expression. Comparing the results of IHC with HER2 gene status as determined by FISH, 2 (66%) of the 3 cases that showed 3+ HER2 expression also showed amplification for HER2 by FISH, while 1 (33%) was equivocal for HER2 amplification. Of the 11 tumors that showed 2+ HER2 expression, 6 (55%) were amplified by FISH and 1 (9%) was equivocal. Conclusions: This is the largest number of UCCC cases that has been studied on the HER2 amplification and corresponding protein overexpression. Our results indicate that the HER2 overexpression is common in UCCCs and is frequently associated with HER2 amplification. These results also suggest that targeted adjuvant therapy with trastuzumab-based immunotherapy should be evaluated in patients with UCCC showing HER2 protein overexpression or HER2 gene amplification.

Background. Papillary serous carcinoma of the peritoneum (PSCP) is a primary peritoneal tumor in women that histologically resembles papillary serous carcinoma of the ovary (PSCO). Recognition of PSCP as an entity is controversial, as is the histogenesis, histopathologic differential diagnosis, and treatment. Methods. Ten cases of PSCP retrieved from the pathology files of 4 hospitals in Kyoto and Nara, Japan, were studied clinicopathologically and immunohistochemically. Results. Patient ages at presentation ranged from 40 to 74 years (median, 56 years). All patients were Asian (Japanese). None of the patients had a history of asbestos exposure. Most of the patients had abdominal swelling, ascites with positive cytology, and elevated serum CA125. At surgery, omental tumors with dissemination to the abdominal and pelvic peritoneum were found in all patients. The histology was similar to that of Grade 2 to 3 PSCO. Immunohistochemical studies using a panel of monoclonal antibodies against carbohydrates showed that Lewis Y is a good marker, in addition to S-100, placental alkaline phosphatase, CA125, and CD15 for separating PSCP from malignant mesothelioma (MM). With cytoreductive surgery and cisplatin-based combination chemotherapy and in some cases adoptive immunotherapy and radiation, a median survival of 27 months and a 5-year survival rate of 27% were attained. One patient with Grade 3 tumor has survived for more than 6 years after surgery. Conclusions. (1) Papillary serous carcinoma of the peritoneum is a definite clinicopathologic entity; (2) immunohistochemistry is a useful tool for distinguishing PSCP from MM; (3) cytoreductive surgery and cisplatinbased combination chemotherapy with other adjunct therapies such as immunotherapy and radiation may improve patient survival in PSCP. Cancer 1995;76:429–36.

In this paper, we first propose an embedded wavelet image coding algorithm based on zero-blocks and array structures - called EZBA. Then, we discuss the hardware realization of the algorithm. In comparison with other methods, the EZBA is simpler to be realized and has higher compression efficiency. For hardware realization, we implement two main parts. One is the discrete wavelet transform (DWT); the other is the architecture of retrieving and coding algorithm (the EZBA itself). Experimental results show that the proposed EZBA outperforms other wavelet-based image coding schemes.

To understand better the pathophysiology of random skin flaps, randomized skin flaps of human (3 cases) and guinea pig (53 cases) were investigated. Proximal (normal), proximomedial (viable), mediodistal (between viable and necrotic parts), and distal (necrosis) locations of the skin flaps wete biopsied. Lipid peroxidase, hydrolytic enzymes of cytosol (Ca 2+ -dependent cysteine protease : calpain), and lysosome (acid phosphatase) of skin were used as markers. Measurements were taken of the flap blood flow ; the numbers of capillaries, postcapillary venules, pericapillary arterioles, leukocytes, and mast cells per unit square of dermis. Apoptotic cells were identified by specific staining. Flaps were sampled at postoperative weeks 1 and 3 (human) and hours 1 and 6, and days 1 to 7 (guinea pig). The values for normal skin were regarded as the control. Obstruction (by leukocytes) of venous microvessels, rather than arterial microvessels, was the major cause of temporary hypoxia in the proximomedial location, constant hypoxia (venous stasis) in the mediodistal location, and ischemia in the distal location. Increases in the numbers of mast cells (mastocytosis) and microvessels (angiogenesis) were significant only in the viable parts of the flaps. This phenomenon and the rate of blood flow increased with time in viable locations (guinea pig). Epidermal necrosis, dermal fibrosis, and apoptosis were evident mostly in the mediodistal location. Elevated levels of leukocytes, lipid peroxidase, acid phosphatase, and calpain, combined with necrotic changes, were seen mostly in the distal skin location. There is a strong possibility that the following factors are involved : lipid peroxidation and hydrolysis in necrosis of the distal flap location after ischemia; constant hypoxia in fibrosis and apoptosis in the mediodistal location ; and initial or temporary hypoxia in mastocytosis-induced angiogenesis in the viable location. The results presented here indicate that guidelines for further investigations include combined suppression of leukotaxis, lipid peroxidase, and hydrolysis, or the application of mast cell growth factors in an effort to salvage the flap maximally.

A unique case of bilateral luteinized thecomas of the ovary associated with sclerosing peritonitis is reported and the clinical and pathological features of this and previously reported cases are reviewed. The patient, 52 years of age, presented with abdominal distension and diarrhea. Pelvic imaging studies revealed bilateral ovarian tumors with ascites. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adhesiotomy of the small bowel were performed. Histologically, the ovarian tumor was composed of closely packed spindle to round-shaped cells, and within the spindle cell population, lutein-like cells were scattered singly or in clusters. Mitotic counts of spindle cells revealed 12 mitotic figures (MF) per 10 high-power fields (HPF) in one part of the left ovarian tumor, but other areas of the tumor showed less than 3 MF/10 HPF on average. The lesion from the resected small bowel showed prominent fibrosis, confined to the serosa with no evidence of metastasis from the ovarian tumor. The patient has undergone adhesiotomy with partial resection of the small bowel seven times since the first laparotomy because of the recurrent small bowel obstruction. The patient has survived with complications due to short bowel syndrome for 7 years after the initial surgery and so far no recurrence or metastasis of the ovarian tumor has been identified. The case reported here also supports the idea that luteinized thecoma of the ovary associated with sclerosing peritonitis may be a distinct clinicopathologic entity, in terms of the unique association and of the unique features of thecoma; that is, bilateral, hormonally inactive and apparently benign in spite of its highly mitotic activity. Additional attention should be paid to the patient's quality of life, which is often degraded by peritoneal fibrosis and small bowel obstruction.