Usefulness of pre- and post-treatment volumetric PET/CT parameters in predicting prognosis and evaluating recurrence for chemoradiotherapy-treated hypopharyngeal cancer.

OBJECTIVE: To investigate the usefulness of pre- and post-treatment metabolic tumor volume (MTV) obtained from positron emission tomography (PET) in predicting prognosis and evaluating recurrence in patients with hypopharyngeal cancer (HPC). MATERIALS AND METHODS: Forty-three consecutive HPC patients treated with chemoradiotherapy were retrospectively analyzed. Maximum standard uptake value (SUVmax) and MTV of tumor (T) and lymph node (N) were analyzed. RESULTS: On multivariate analysis using pre-treatment parameters, MTV-T (p = 0.049) and MTV-TN (p = 0.043) were significantly associated with local control (LC), and MTV-N (p = 0.049) was significantly associated with disease-specific survival (DSS). Post-treatment MTV-TN was also significantly associated with prognosis (p < 0.001 in LC; p = 0.002 in DSS) and recurrence (area under curve 0.95). Neither pre- nor post-treatment SUVmax was significantly associated with prognosis. CONCLUSION: Pre- and post-treatment MTV appears useful for predicting prognosis and evaluating recurrence.

A Case of Localized Malignant Peritoneal Mesothelioma With Lung Cancer Detected by 18F-FDG PET/CT.

A 62-year-old woman was referred for cough and lower abdominal pain. F-FDG PET/CT showed strong uptake not only in the left lung mass and hilar and mediastinal lymph nodes, but also a huge lower abdominal mass. All lesions were initially thought to be multiple metastases because bronchial biopsy of the lung mass showed poorly differentiated adenocarcinoma. However, the abdominal mass was found to be malignant peritoneal mesothelioma after surgical resection. It was difficult to diagnose this case correctly before resection because localized malignant peritoneal mesothelioma is rare.

Comparison of MR imaging features of uterine neuroendocrine carcinoma and uterine malignant lymphoma.

PURPOSE: We retrospectively investigated the characteristic magnetic resonance (MR) imaging findings of uterine neuroendocrine carcinoma (UNEC) compared to those of uterine malignant lymphoma (UML). METHODS: Nine consecutive female patients with UNEC and 5 female patients with UML participated in this study. MR imaging features were evaluated retrospectively. RESULTS: On MR imaging, seven of 9 UNEC lesions and no UML lesions showed an exophytic growth pattern. All 9 UNEC lesions and no UML lesions showed a growth pattern along the surface of the endocervix or endometrium. Only 1 UNEC lesion and all 5 UML lesions showed diffuse enlargement of the uterus. No UNEC lesions and all 5 UML lesions showed a multinodular shape. These findings showed significant differences between lesions. Findings for margin, endophytic growth pattern, signal intensity, and homogeneity on T2-weighted and T1-weighted imaging did not differ significantly between lesion types. Apparent diffusion coefficient was significantly lower for UML lesions than for UNEC lesions, but was quite low for both types. Local invasion to surrounding tissues was more frequent in UML lesions than in UNEC lesions. There was no significant difference in the frequency of lymphadenopathy between two entities. CONCLUSIONS: UNEC lesions tended to show an exophytic growth pattern and growth along the surface of the endocervix or endometrium, even when diffuse enlargement of the uterus was present, while all UML lesions showed a multinodular shape and diffuse enlargement of the uterus without thickening of the cervical epithelium and endometrium.

MR imaging and MR cholangiopancreatography of cholangiocarcinoma developing in printing company workers.

PURPOSE: To retrospectively investigate magnetic resonance (MR) imaging findings of occupational cholangiocarcinoma (oCC) occurring among workers in printing companies in Japan, compared to those of non-occupational cholangiocarcinoma (nCC), primary sclerosing cholangitis (PSC), and age-matched normal controls (NORs). MATERIALS AND METHODS: Participants comprised 27 consecutive patients (oCC, n = 5; nCC, n = 8; PSC, n = 6; NOR, n = 8) who underwent MR imaging between May 2009 and October 2012. MR imaging was evaluated with respect to tumor characteristics, abnormal MR cholangiographic findings (PSC-like findings), bile duct stricture, and signal changes of the hepatic parenchyma. RESULTS: Tumors were detected in all nCCs and four oCCs. Tumors displayed a mass-forming type in all nCCs and two oCCs, and an intraductal growth type in two oCCs. Abnormal cholangiographic findings were detected in all oCCs and PSCs, but not in any nCCs or NORs. All oCCs and seven nCCs showed biliary strictures longer than 1 cm; five PSCs showed biliary strictures shorter than 1 cm. Both intra- and extrahepatic biliary strictures were detected in three PSCs and two oCCs. Peripheral hepatic hyperintensity on T2-weighted imaging was detected in two nCCs, two PSCs, and two oCCs. CONCLUSION: These results indicated that MR imaging of oCC showed findings of both PSC and nCC.

Bacteria-induced hatching of Trichuris muris eggs occurs without direct contact between eggs and bacteria.

Using three isolates of the murine parasitic nematode Trichuris muris, E, E/J (the E isolate maintained in Japan), and S, I have previously demonstrated that when the embryonated eggs of the E/J and E isolates are incubated with the intestinal bacteria Escherichia coli and Staphylococcus aureus, they are induced to hatch in vitro. However, the eggs of the S isolate are unresponsive to these bacteria. In the present study, I investigated whether direct contact between the embryonated eggs of the E/J and E isolates and bacteria is required to induce their hatching. To do so, a new co-culture system for eggs and bacteria (E. coli or S. aureus) was developed to block any direct contact between the eggs and the bacteria. In the hatching experiment using the new system, when direct contact between the eggs and bacteria was completely prevented, the eggs still hatched. However, the peak levels of hatching without direct contact were about 20 % lower than those with direct contact, and peak hatching occurred later without direct contact. This evidence suggests that hatching occurs without direct contact between the eggs and bacteria, and that unidentified material derived from active bacteria induces the hatching of embryonated eggs of the E/J and E isolates of T. muris in vitro.

Whole-body imaging of tumor cells by azaelectrocyclization: visualization of metastasis dependence on glycan structure.

Noninvasive imaging of cancer metastasis through the efficient cell labeling constitutes a major technological breakthrough for cancer research and patient monitoring post-surgery. In the current work, we expanded our cell surface labeling technique on the whole-body fluorescence imaging of tumor metastasis in BALB/c nude mice. Four kinds of human cancer cells (two cancer cell lines, MKN45 and HCT116, and their transfected versions expressing surface glycan-related genes, MKN45-GnT-V and HCT116-GMDS) were labeled by azaelectrocyclization with Hilyte Fluor 750 for 10 min and without affecting cell viability. Fluorescence-labeled cancer cells were injected into the abdominal cavities of BALB/c mice and whole-body scans were performed with an eXplore Optix device. In accordance with previous findings, the fluorescence imaging clearly showed that tumor metastasis was dependent upon the cell surface glycans: A larger polylactosamine structure or the loss of fucosylation on the cancer cell surfaces, respectively, enhanced the metastatic potential of the tumor cells. Our noninvasive technique provides the landmark opportunity for sensitively monitoring the dynamics of the cancer cells depending on their surface structures and/or the host environments, thus impacts on the cancer prognosis and the therapeutic applications.

Characteristics and incidence of large eggs in Trichuris muris.

The production of small numbers of large eggs among the standard-sized eggs of Trichuris trichiura is well known. Large eggs have also been observed in Trichuris muris, but they have not been studied previously. This paper compares the characteristics of the large eggs (LEs, ≥74.5 µm long) and standard-sized eggs (SEs, <74.5 µm long) in cultures of T. muris. Among 112,554 cultured eggs, LEs occurred at very low frequency (0.03 %, i.e., about three large eggs per 10(4) cultured eggs). Embryonated eggs represented 93.72 % of SEs, but only 25.00 % of LEs were embryonated. Embryonated LEs and SEs contained fully matured larvae. An atypical category of unembryonated egg, which contained an incompletely developed larva, an abnormal larva, or granular components, was common among the LEs. However, similar atypical unembryonated SEs were rarely observed. These observations suggest that the LEs that occur very infrequently in T. muris result from an abnormality of embryonation (larval development).

Evidence for bacteria-independent hatching of Trichuris muris eggs.

Hatching of infective larvae from embryonated eggs in the intestine is an essential first step in Trichuris infections. There are three isolates of the murine parasitic nematode Trichuris muris: E, E-J (the E isolate maintained in Japan), and S. Incubation of T. muris embryonated eggs with the intestinal bacteria Escherichia coli and Staphylococcus aureus induced in vitro hatching of the eggs, but Enterococcus faecalis failed to induce hatching. Bacteria-induced in vitro hatching of embryonated eggs occurred in the E and E-J isolates, whereas the S isolate was unresponsive to bacteria. T. muris worms recovered from infected mice showed no significant difference between the E-J and S isolates in their infectivity to susceptible B10.BR mice (P>0.05). In vivo hatching of embryonated eggs occurred at 30 min post-infection in the upper and lower halves of the small intestine of ddY mice infected with the E-J or S isolates, and on average, 65% of embryonated eggs recovered from the upper half of the small intestine were hatched in both the E-J and S isolates. In comparison with Enterococcus, the bacteria E. coli and S. aureus represent relatively minor components of the flora of the upper half of the small intestine of mice. These observations point to the possibility that bacteria-independent hatching might also occur in vivo, at least for the S isolate, and imply the existence of a very different system of induction of hatching in vivo.

Cell surface biotinylation by azaelectrocyclization: easy-handling and versatile approach for living cell labeling.

Versatile method for living cell labeling has been established. Cell surfaces are initially biotinylated by azaelectrocyclization, and then treated with the fluorescence-labeled avidin or the anti-biotin antibody.

Monitoring of chemotherapy response in malignant pleural mesothelioma using fluorodeoxyglucose positron emission tomography.

We report a 56-year-old man who underwent monitoring of the response to chemotherapy of malignant pleural mesothelioma (MPM). (8)F-fluoro-2-deoxy-(D)-glucose positron emission tomography (FDG-PET) and computed tomography (CT) were performed prior to chemotherapy and after the first and second courses of chemotherapy. The tumor lesion exhibited shrinkage on CT and a decrease in the standardized uptake value (SUV) max after the first course of chemotherapy, but exhibited size enlargement and an increase in SUV max after the second course of chemotherapy. These findings suggest that results of quantification of metabolic response by FDG-PET are related to the objective response as determined by CT in patients with MPM.

Dendritic cells have a crucial role in the production of cytokines in mesenteric lymph nodes of B10.BR mice infected with Trichuris muris.

Dendritic cells bridge innate and adaptive immunity and establish protective immunity to pathogens. Protection against the murine nematode parasite Trichuris muris depends on the T helper 2 (Th2) response and requires the Th2 cytokines interleukin 4 (IL-4), IL-10, or IL-13. To examine if the Th2 response to T. muris infection is regulated by CD11c(+)B220(-) dendritic cells in mesenteric lymph nodes, dendritic cell-enriched and dendritic cell-depleted fractions were obtained from mesenteric lymph node cells of T. muris-infected mice, and production of cytokines in cultures of these fractions was measured. At day 14 postinfection, no worm expulsion was observed, and high levels of interferon gamma production occurred in dendritic cell-enriched fractions. Expulsion of worms occurred on days 20 and 25 postinfection, and IL-10 production was induced in dendritic cell-enriched fractions on these 2 days. No cytokine production was observed in mesenteric lymph node cells and dendritic cell-depleted fractions during T. muris infection. The occurrence of worm expulsion was consistent with IL-10 production in dendritic cell-enriched fractions. IL-10 inhibits Th1 cells and promotes the Th2 response, and results from this study suggest that CD11c(+)B220(-) dendritic cells in the mesenteric lymph nodes are required for IL-10 production and the IL-10-dependent protective Th2 response.

Usefulness of F-18 FDG-PET in a long-term hemodialysis patient with renal cell carcinoma and pheochromocytoma.

A patient who had been on long-term hemodialysis (HD) was diagnosed as having renal cell carcinoma (RCC) and pheochromocytoma. Abdominal computed tomography scanning demonstrated a right renal mass and a right adrenal mass, whereas positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) revealed increased accumulation in both the renal and adrenal masses. FDG-PET is useful for detecting RCC in HD patients because FDG is not excreted in the urine, but it is difficult to distinguish pheochromocytoma from an adrenal metastasis by this imaging method.

Comparison of dynamic FDG-microPET study in a rabbit turpentine-induced inflammatory model and in a rabbit VX2 tumor model.

PURPOSE: We investigated the optimum time for the differentiation tumor from inflammation using dynamic FDG-microPET scans obtained by a MicroPET P4 scanner in animal models. MATERIALS AND METHODS: Forty-six rabbits with 92 inflammatory lesions that were induced 2, 5, 7, 14, 30 and 60 days after 0.2 ml (Group 1) or 1.0 ml (Group 2) of turpentine oil injection were used as inflammatory models. Five rabbits with 10 VX2 tumors were used as the tumor model. Helical CT scans were performed before the PET studies. In the PET study, after 4 hours fasting, and following transmission scans and dynamic emission data acquisitions were performed until 2 hours after intravenous FDG injection. Images were reconstructed every 10 minutes using a filtered-back projection method. PET images were analyzed visually referring to CT images. For quantitative analysis, the inflammation-to-muscle (I/M) ratio and tumor-to-muscle (T/M) ratio were calculated after regions of interest were set in tumors and muscles referring to CT images and the time-I/M ratio and time-T/M ratio curves (TRCs) were prepared to show the change over time in these ratios. The histological appearance of both inflammatory lesions and tumor lesions were examined and compared with the CT and FDG-microPET images. RESULTS: In visual and quantitative analysis, All the I/M ratios and the T/M ratios increased over time except that Day 60 of Group 1 showed an almost flat curve. The TRC of the T/M ratio showed a linear increasing curve over time, while that of the I/M ratios showed a parabolic increasing over time at the most. FDG uptake in the inflammatory lesions reflected the histological findings. For differentiating tumors from inflammatory lesions with the early image acquired at 40 min for dual-time imaging, the delayed image must be acquired 30 min after the early image, while imaging at 90 min or later after intravenous FDG injection was necessary in single-time-point imaging. CONCLUSION: Our results suggest the possibility of shortening the overall testing time in clinical practice by adopting dual-time-point imaging rather than single-time-point imaging.

Large-scale synthesis of immunoactivating natural product, pristane, by continuous microfluidic dehydration as the key step.

An efficient protocol of dehydration was developed under microfluidic conditions. The method was applied to a multikilogram synthesis of pristane, a biologically important natural product, which is now widely used as an adjuvant for monoclonal antibody production. [reaction: see text].

Highly sensitive detection of HPV-DNA in paraffin sections of human oral carcinomas.

BACKGROUND: Although human papillomavirus (HPV) infection has been shown to be a significant carcinogen in cervical squamous cell carcinoma (SCC), its significance in oral SCC remains unclear. METHODS: We developed highly sensitive detection methods for HPV to elucidate the prevalence and localization of HPV in paraffin sections from human oral SCC using modified in situ polymerase chain reaction (PCR) and in situ hybridization AT tailing (ISH-AT). Analyses revealed a high prevalence of several HPV types (HPV-16, -18, -22, -38 and -70) under optimal conditions. The ISH-AT method can be used as an alternative to in situ PCR. RESULTS: Various staining patterns were observed in the 20 cases examined, and HPV-positive cells were localized within the surface epithelium as well as in neoplastic cells. We demonstrated that HPV-DNA could be detected in paraffin sections using either the method of in situ PCR or ISH, providing an appropriate primer and probe are used. CONCLUSION: These results suggest that HPV infection could be one of several risk factors being involved in oral SCC.