Percutaneous shunt vessel embolisation with Amplatzer vascular plugs II and IV in the treatment of dogs with splenophrenic shunts: four cases (2019-2022).

OBJECTIVES: To describe the treatment of four dogs with splenophrenic shunts using percutaneous shunting vessel embolisation with Amplatzer vascular plugs II and IV and provide information on their clinical outcomes. MATERIALS AND METHODS: Dogs with splenophrenic shunts treated at a veterinary hospital from January 2019 to December 2022 were identified through a medical record search. RESULTS: Six dogs with splenophrenic shunts were identified. Two dogs were excluded because they were treated with laparoscopic surgery. Four underwent percutaneous shunting vessel embolization with Amplatzer vascular plugs and were included in the case series. A sheath was placed in the left external jugular vein and a balloon catheter was advanced to the shunting vessel under fluoroscopy. Portal vein pressure was confirmed to be within an acceptable range during temporary balloon occlusion. Based on preoperative CT angiography and intraoperative contrast examination, Amplatzer vascular plugs II were selected for two dogs and IV were selected for two dogs. Under fluoroscopy, the plug was deployed into the shunting vessel, and angiography confirmed occlusion. In all cases, the increase in portal pressure after temporary occlusion was within the acceptable range, and complete occlusion of blood flow was possible with a single plug. There were no major procedure-related complications. No dogs developed post-ligation seizures or signs of portal hypertension. In addition, improvements in ammonia values were observed in all cases. CLINICAL SIGNIFICANCE: Percutaneous splenophrenic shunt embolisation using Amplatzer vascular plugs II and IV is technically feasible in dogs, and assessed by intra-procedure angiography, a single plug completely obstructed blood flow in all dogs. Based on the literature search, this is the first report describing Amplatzer vascular plugs for the treatment of splenophrenic shunts.

Aberrant expression of beta- and gamma-catenin is an independent prognostic marker in oral squamous cell carcinoma.

Alteration in expression of E-cadherin and catenins is associated with loss of differentiation, acquisition of an invasive phenotype and poor clinical outcome in many types of cancer. To identify molecular prognostic markers, membrane expression levels of E-cadherin, and alpha-, beta- and gamma-catenin in biopsy samples (n=135) of oral squamous cell carcinoma (OSCC) were evaluated immunohistochemically in relation to preoperative tumour-related features, clinical course and prognostic value, and were found to be significantly correlated with an endophytic growth pattern and pathologically proved lymph-node metastasis. Alteration of expression of E-cadherin, and alpha-, beta- and gamma-catenin was also significantly correlated with poor disease-specific 5-year survival (P=0.0096, 0.0434, 0.0005 and 0.0005, respectively). Multivariate Cox proportional hazard regression analysis showed that alteration of beta- and gamma-catenin expression was a significantly independent prognostic parameter for survival (P=0.0112 and 0.0088, respectively), as was the case with endophytic growth pattern and advanced N-category. These results indicate that patients with OSCC and absent or reduced membrane expression of beta- and gamma-catenin should be considered a high-risk group for regional lymph-node metastasis and poor prognosis.

Intraoperative radiation therapy (IORT) for head and neck cancer.

PURPOSE: To determine the efficacy of intraoperative radiation therapy (IORT) for patients with advanced or recurrent head and neck cancer. METHODS AND MATERIALS: Intraoperative radiation therapy was given at 30 sites in 25 patients using a 6-18 MeV electron beam with or without conventional external beam irradiation. A single dose of 10-30 Gy was delivered after surgical resection. Sites treated with IORT were classified into three types after surgical resection: gross residual disease (GR, n = 7), microscopic residual disease (MR, n = 12), and close margin (CM, n = 11). Local control rate, patterns of recurrence, survival rate, and complications were analyzed. RESULTS: The 2-year cumulative local control rate within the IORT port was 54.1% for all cases, 0% for GR, 54.5% for MR, and 81.8% for CM. There were significant differences between GR and MR (p < 0.05), and GR and CM (p < 0.01). The majority of the failures inside the IORT port were associated with recurrence outside the port. Distant metastases occurred in five patients. Four of these had GR. The 2-year cumulative survival rate was 45.1% for all, 0% for GR, 33.0% for MR, and 70.0% for CM. Five patients (22%) experienced late complications. The 2-year cumulative complication rate was 32.8%. Four sites developed osteoradionecrosis and three developed carotid artery blowout. Incidence of complications increased when patients received over 20 Gy with a single dose of IORT. CONCLUSIONS: Considering both therapeutic ratio and patterns of failure, it is not suitable to treat patients with gross residual disease with IORT. We could not firmly determine the therapeutic value of IORT for patients with microscopic residual disease and close margin. For this subset, further study of moderate dose (less than 20 Gy) IORT combined with adequate postoperative irradiation is needed.

Human papillomavirus DNA in adenosquamous carcinoma of the lung.

AIM: To investigate the presence of human papillomavirus (HPV) DNA in adenosquamous carcinoma of the lung--which is relatively common in Okinawa but not in mainland Japan--and examine its histological features. METHODS: Of 207 cases where primary lung cancers were surgically removed between January 1995 and June 1997 in Okinawa, 23 were adenosquamous carcinoma. HPV was detected by non-isotopic in situ hybridisation (NISH) and polymerase chain reaction (PCR) amplification with primers specific for E6 and E7 regions of the HPV genome. PCR products were analysed by Southern blotting. Immunohistochemical determination of high molecular weight cytokeratin (HMC) and involucrin was also carried out. RESULTS: 18 cases were positive for HPV DNA by PCR and NISH. HPV types 6, 11, 16, and 18 were found. Seven cases were dual positive for different types of HPV. Using NISH, HPV was also found in the squamous cell components and in neighbouring enlarged adenocarcinoma cells. The HMC and involucrin were demonstrated immunohistochemically in the same areas. CONCLUSIONS: HPV DNA was found in a high proportion (78.3%) of adenosquamous carcinomas in Okinawa, a region where HPV has previously been shown to be prevalent in squamous cell carcinoma of the lung. The adenocarcinoma cells adjacent to the squamous cell carcinoma component were enlarged and positive for HPV, HMC, and involucrin. This is thought to indicate the transition from adenocarcinoma to squamous cell carcinoma.

Differences in EBNA2 and LMP-1 carboxy terminal region sequences of Epstein-Barr virus type A between the tumors in a multiple cancer patient.

Using PCR, type A Epstein-Barr virus (EBV) infection was demonstrated in a squamous cell carcinoma of the maxilla (in a 52-year-old man) and the tongue of the same patient 18 years later (at the age of 70). Furthermore, at the age of 72, this patient developed an EBV-infected anaplastic large cell lymphoma. Analysis of the terminal regions of the EBV genome revealed a monoclonal proliferation of EBV-infected lymphoma cells. However, sequence analysis of the EBV revealed a slight difference in the EBNA2 regions between the virus-infected lymphoma and the squamous cell carcinomas. The mutations at 48991 (G-->T) and 48998 (C-->A) were demonstrated in the lymphoma. Although the squamous cell carcinoma of the tongue occurred after an interval of 18 years, the mutation site in the carcinomas was the same, 49137 (A-->G), as compared with B95-8 strain EBV EBNA2. The mutations at 48991 and at 49137 were associated with amino acid changes, Arg-->Met and Thr-->Ala, respectively, but the alteration at 48998 was a silent mutation. Thirty-bp deletion in the LMP-1 carboxy terminal region was demonstrated in the virus-infected lymphoma, but not in the squamous cell carcinomas. On the other hand, HTLV-1 proviral DNA (tax, gag and env) was not detected in the lymphoma, nor was HPV demonstrated in the squamous cell carcinomas, although Okinawa is known as an HTLV-1 and HPV prevalence region. The T-cell receptor beta gene rearrangement was demonstrated in the lymphoma, but the t(2;5) fusion transcript was not detected using PCR. Cytogenetic analysis of the lymphoma cells showed a complex hypertriploid karyotype with 76XY. The type A EBV infection might play a role in the carcinogenesis of the tumors of our patient. Interestingly, the infected virus genome sequences, the EBNA2 and LMP-1 regions, which were closely associated with carcinogenesis in the squamous cell carcinomas and the lymphoma, showed slight differences.

Dislocation propagation in GaN films formed by epitaxial lateral overgrowth

We have investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) the relationship between surface morphological evolution and dislocation propagation in GaN films formed by epitaxial lateral overgrowth (ELO) in hydride vapour phase epitaxy. The SEM observations revealed that step and terrace structures were formed on (0001) surfaces of the films both in the earlier and the later stages of growth, suggesting the occurrence of step-flow growth during ELO. Bending dislocations with laterally propagated segments were frequently observed in the ELO films and their morphology led to a reduction in threading dislocation density in the film surface regions. Systematic TEM observations were performed to reveal the detailed structure of the bending dislocations. Comparison between the SEM and the TEM results showed that the lateral propagation of the dislocation was closely related to the appearance of the [1101) facets. A mechanism for dislocation propagation is discussed that explains the observed dislocation structure and surface step morphology.

Incidence of cleft lip or palate in 303738 Japanese babies born between 1994 and 1995.

To investigate the incidence of cleft lip or palate or both (CLP) in Japan, 303738 babies born in 1532 institutions between 1994 and 1995 were examined and 437 (0.14%) were found to have abnormalities. Of these babies, 32.1% had cleft lip, 43.3% had cleft lip and palate, and 24.8% had cleft palate (Table 2). These results show that the incidence of cleft lip and palate has declined compared with the period from 1981 to 1982.

Clinical course of diffuse invasive carcinoma of the tongue excised after Bleomycin treatment.

According to the mode of invasion across the tumour-host boundary which was described and graded by Jacobsson et al. (1973), the clinical course of diffuse invasive squamous cell carcinoma of the tongue (grade 4) was investigated comparing it with the other grade groups (grades 1-3). Metastasis to regional lymph nodes and local recurrence after surgery were extremely common in grade 4. These local recurrences led to death in most grade 4 cases while a better clinical outcome was achieved in the other grades. Grade 4 was further subclassified into a cord-like type (grade 4 C) and a diffuse type (grade 4 D) from the histological features of the tumour-host interface, with the latter being more malignant than the former.

Mode of invasion, bleomycin sensitivity, and clinical course in squamous cell carcinoma of the oral cavity.

Forty patients with squamous cell carcinoma of the oral cavity were treated with bleomycin prior to undergoing surgery. The degree of the clinical effect of bleomycin and the postoperative clinical course of each case were estimated from the viewpoint of correlation with the mode of invasion. A strong correlation was found among the mode of invasion, bleomycin sensitivity, and clinical course. A slight effect of bleomycin and poor prognosis existed in the group with a diffuse invasion of mode of invasion, while the greatest effect of bleomycin and good clinical course were achieved in the group with a well-defined tumor-host borderline.

Multivariate analysis of occult lymph node metastasis as a prognostic indicator for patients with squamous cell carcinoma of the oral cavity.

BACKGROUND: The biologic aggressiveness of squamous cell carcinoma of the oral cavity is reflected in its ability to metastasize to regional cervical lymph nodes. Patients with clinically negative cervical lymph nodes are believed to have a good prognosis; however, the prognosis of patients with lymph node metastasis occurring after excision or radiotherapy of the primary tumor is poor. METHODS: Univariate and multivariate analyses for occult lymph node metastasis (ONM) in 172 patients with clinically negative cervical lymph nodes were performed by the authors to elucidate the clinical and histologic tumor risk factors to enhance their ability to predict ONM. A multivariate Cox proportional hazards model and Hayashi's quantification theory type II were used to analyze prognostic factors and to determine the probability of ONM. RESULTS: Using Cox's proportional regression model, the factors linked to cancer specific survival were selected: tumor differentiation (P = 0.0330), mode of carcinoma invasion (P = 0.0175), and ONM (P = 0.0433). Pathologically identified metastatic lymph nodes were found in 21.5% of the cases studied (37 of 172 cases). The 5-year cancer specific survival was 94.0% for patients without lymph node metastasis, and 51.0% for patients with ONM (P < 0.0001, log rank test). The most significant predictors for ONM of each of the clinical and histologic factors, in descending order, were: mode of carcinoma invasion, intensity of lymphocytic infiltration, degree of differentiation, number of mitotic figures, and type of growth by means of Hayashi's quantification theory type II. The presence or absence of ONM in 147 of 172 patients (85.5%) was correctly predicted by the score at the point of intersection of the two curves, which was -0.03. Further investigation revealed that 28 of 32 new cases were differentiated accurately by means of this diagnostic system. CONCLUSIONS: The results of the current study suggest that this method of analysis can establish a reliable predictor of ONM, thereby facilitating correct choices for surgical procedures to enhance the survival rates of patients with clinically negative cervical lymph nodes.

Acinic cell carcinoma of minor salivary gland origin.

We describe a case of acinic cell carcinoma of the right soft palate in a 65-year-old man. The primary symptom was a painless swelling of the palate, which was partially ulcerated with a granulomatous appearance. Ultrastructurally, the tumor cells were mainly composed of differentiated acinuslike cells containing numerous round secretory granules identical to those in normal serous salivary glands. The tumor cells frequently contained numerous long crystalloid structures in the cytoplasm. Furthermore, tumor cells demonstrating degrees of squamous differentiation were present. These cells contained intracytoplasmic keratin filaments and a few keratohyaline granules. They formed a glandular acinar space in direct contact with the typical acinic cells with secretory granules. These observations suggest that acinic tumor cells have a degree of multipotentiality.

Comparative study of oral squamous cell carcinoma in Okinawa, Southern Japan and Sapporo in Hokkaido, Northern Japan; with special reference to human papillomavirus and Epstein-Barr virus infection.

In Okinawa, a subtropical island in Southern Japan, the incidence of oral squamous cell carcinoma is 1.5 times higher than that in mainland Japan. Sixty cases of oral squamous cell carcinoma from 1993 to 1996 in Okinawa and 42 cases over the same period in Sapporo were examined histologically. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) were detected by polymerase chain reaction (PCR) amplification with primers specific for HPV and EBV. In situ hybridisations of the viruses were also carried out. In the case of Epstein-Barr virus, in situ PCR was also performed. Thirty-five (58.3%) Okinawan tumours were well-differentiated in type, but in Sapporo, 18 (42%) were of such type. In Okinawa, tumours of the mouth floor (10 cases, 16.7%) and oropharynx (12 cases, 20%) were frequently observed, whereas in Sapporo only five cases (12%) of each were found. HPV was demonstrated in 78% of Okinawan cases and 26.2% of Sapporon cases by PCR or non-isotopic in situ hybridisation (NISH). There were 76.6% (46 cases) of Okinawan and 38.1% (16 cases) of Sapporo cases positive for EBV by PCR. In only 12 Okinawan cases and 4 Sapporon cases, were positive signals demonstrated by in situ PCR on the cancer cells themselves. EBV was demonstrated in the large number of infiltrating lymphocytes, most of which were CD3+, and a few were CD19+. In Okinawa, HPV might be an important causative factor of oral squamous cell carcinoma and EBV a less important factor, whereas in Sapporo HPV and EBV might play only a small part in the aetiology of the tumour.

PKN associates and phosphorylates the head-rod domain of neurofilament protein.

PKN is a fatty acid-activated serine/threonine kinase that has a catalytic domain highly homologous to that of protein kinase C in the carboxyl terminus and a unique regulatory region in the amino terminus. Recently, we reported that the small GTP-binding protein Rho binds to the amino-terminal region of PKN and activates PKN in a GTP-dependent manner, and we suggested that PKN is located on the downstream of Rho in the signal transduction pathway (Amano, M., Mukai, H., Ono, Y., Chihara, K., Matsui, T., Hamajima, Y., Okawa, K., Iwamatsu, A., and Kaibuchi, K. (1996) Science 271, 648-650; Watanabe, G., Saito, Y., Madaule, P., Ishizaki, T., Fujisawa, K., Morii, N., Mukai, H., Ono, Y. Kakizuka, A., and Narumiya, S. (1996) Science 271, 645-648). To identify other components of the PKN pathway such as substrates and regulatory proteins of PKN, the yeast two-hybrid strategy was employed. By this screening, a clone encoding the neurofilament L protein, a subunit of neuron-specific intermediate filament, was isolated. The amino-terminal regulatory region of PKN was shown to associate with the head-rod domains of other subunits of neurofilament (neurofilament proteins M and H) as well as neurofilament L protein in yeast cells. The direct binding between PKN and each subunit of neurofilament was confirmed by using the in vitro translated amino-terminal region of PKN and glutathione S-transferase fusion protein containing the head-rod domain of each subunit of neurofilament. PKN purified from rat testis phosphorylated each subunit of the native neurofilament purified from bovine spinal cord and the bacterially synthesized head-rod domain of each subunit of neurofilament. Polymerization of neurofilament L protein in vitro was inhibited by phosphorylation of neurofilament L protein by PKN. The identification and characterization of the novel interaction with PKN may contribute toward the elucidation of mechanisms regulating the function of neurofilament.

Translocation of PKN from the cytosol to the nucleus induced by stresses.

Effects of environmental stresses on the subcellular localization of PKN were investigated in NIH 3T3, BALB/c 3T3, and Rat-1 cells. The immunofluorescence of PKN resided prominently in the cytoplasmic region in nonstressed cells. When these cells were treated at 42 degrees C, there was a time-dependent decrease of the immunofluorescence of PKN in the cytoplasmic region that correlated with an increase within the nucleus as observed by confocal microscope. After incubation at 37 degrees C following beat shock, the immunofluorescence of PKN returned to the perinuclear and cytoplasmic regions from the nucleus. The nuclear translocation of PKN by heat shock was supported by the biochemical subcellular fractionation and immunoblotting. The nuclear localization of PKN was also observed when the cells were exposed to other stresses such as sodium arsenite and serum starvation. These results raise the possibility that there is a pathway mediating stress signals from the cytosol to the nucleus through PKN.