Reassessment of the clinical significance of portal-superior mesenteric vein invasion in borderline resectable pancreatic cancer.

OBJECTIVE: The principal objective of this study is to clarify the prognostic significance of borderline resectable pancreatic cancer (BRPC). The second objective is to evaluate the prognostic impact of the depth of pathological venous invasion. METHODS: The study included 122 pancreatic cancer patients who underwent curative surgery. All computed tomography scans of the patients were retrospectively interpreted and classified according to the NCCN guidelines, version 1.2016, as resectable (-) or borderline resectable (+) in each arterial (BR-A) and venous (BR-PV) involvement. RESULTS: The overall survival (OS) rate was significantly higher in BR-A(-) patients (n = 94) than in BR-A(+) patients (n = 28) (P = 0.001), whereas there was no difference between BR-PV(-) (n = 101) and BR-PV(+) patients (n = 21) (P = 0.257). In a multivariate analysis, the independent predictors of OS included BR-A(+) (P = 0.002), lymph node metastasis (P = 0.008), pathological venous invasion (P = 0.003), and adjuvant chemotherapy (P = 0.001). Of 39 patients who underwent venous resection, no significant difference was observed between BR-PV(-) (n = 20) and BR-PV(+) patients (n = 19) in resection rate, lymph node metastasis, the presence of extrapancreatic nerve invasion, recurrence rate, frequency of initial recurrence at a liver or local site, and OS. Pathological venous invasion was significantly deeper in BR-PV(+) patients. However, the depth of invasion was not associated with OS. CONCLUSION: The definition of venous involvement in the current guidelines predicted the depth of pathological venous invasion but not OS in BRPC patients. Further prospective, randomized studies are needed to establish treatment strategies for BRPC patients with isolated venous involvement.

Biodegradable gelatin/beta-tricalcium phosphate sponges incorporating recombinant human fibroblast growth factor-2 for treatment of recession-type defects: A split-mouth study in dogs.

BACKGROUND AND OBJECTIVE: Tissue engineering by using recombinant human (rh) growth factor technology may offer a promising therapeutic approach for treatment of gingival recession. Fibroblast growth factor-2 (FGF-2) has shown the ability to promote periodontal regeneration. Gelatin/beta-tricalcium phosphate (gelatin/ß-TCP) sponges have been developed to control the release of growth factors. The present study evaluated the periodontal regenerative efficacy of rhFGF-2 by comparing gelatin/ß-TCP sponges incorporated with rhFGF-2 to the scaffolds alone in artificially created recession-type defects in dogs. MATERIAL AND METHODS: Critically sized buccal gingival recession defects were surgically created on maxillary canine teeth of five dogs. In each animal, defects were randomized to receive either a gelatin/ß-TCP sponge soaked with rhFGF-2 (gelatin/ß-TCP/rhFGF-2) or phosphate-buffered saline (gelatin/ß-TCP). Eight weeks after surgery, biopsy specimens were obtained and subjected to microcomputed tomography and histological analyses. RESULTS: Complete root coverage was achieved in both groups. Microcomputed tomography revealed significantly greater new bone volume in the gelatin/ß-TCP/rhFGF-2 group. Histologically, both groups achieved periodontal regeneration; however, gelatin/ß-TCP/rhFGF-2 sites exhibited more tissue regeneration, characterized by significantly larger amounts of new cementum and new bone. Gelatin/ß-TCP sites featured increased long junctional epithelium and connective tissue attachment. In the gelatin/ß-TCP/rhFGF-2 sites, new bone exhibited many haversian canals and circumferential lamellae as well as remarkably thick periosteum with blood vascularization and hypercellularity. CONCLUSION: Within the limitations of this study, rhFGF-2 in gelatin/ß-TCP sponges exhibits an increased potential to support periodontal wound healing/regeneration in canine recession-type defects.

Risk factors for aerobic bacterial conjunctival flora in preoperative cataract patients.

PurposeTo investigate the relationship between the background of preoperative cataract patients and bacterial conjunctival flora.MethodsA total of 990 cataract patients who had completed preoperative examinations in 2007 and 2008 were included. Patients using topical antibiotics at the preoperative examination or having a history of intraocular surgery were excluded. Conjunctival cultures had been preoperatively obtained. Patient characteristics were investigated via medical records. Risk factors for conjunctival flora of seven typical bacteria were analyzed by univariate and multivariate analyses.ResultsThe detection rate of alpha-hemolytic streptococci and Enterococcus faecalis increased with age (P=0.044 and P=0.002, respectively). The detection rate of Gram-negative bacilli was higher among patients with oral steroid use or lacrimal duct obstruction (P=0.038 and P=0.002, respectively). The detection rate of Corynebacterium species was higher among older patients and men, and lower among patients with glaucoma eye drop use (P<0.001, P=0.012 and P=0.001, respectively). The detection rate of methicillin-susceptible coagulase-negative Staphylococci was higher among men and lower among patients with a surgical history in other departments (P=0.003 and P=0.046, respectively). The detection rate of methicillin-resistant coagulase-negative Staphylococci (MR-CNS) was higher among patients with oral steroid use, a visit history to ophthalmic facilities, or a surgical history in other departments (P=0.002, P=0.037 and P<0.001, respectively).ConclusionsElderly patients, men, patients with lacrimal duct obstruction or immunosuppressed patients are more likely to be colonized by pathogens that cause postoperative endophthalmitis. Moreover, MR-CNS colonization was associated with healthcare-associated infection.

Ridge augmentation using recombinant human fibroblast growth factor-2 with biodegradable gelatin sponges incorporating ß-tricalcium phosphate: a preclinical study in dogs.

BACKGROUND AND OBJECTIVE: Fibroblast growth factor-2 (FGF-2) regulates the proliferation and differentiation of osteogenic cells, resulting in the promotion of bone formation. Biodegradable gelatin sponges incorporating ß-tricalcium phosphate (ß-TCP) have been reported as a scaffold, which has the ability to control growth factor release, offering sufficient mechanical strength and efficient migration of mesenchymal cells. In this study, we evaluated the effects of the combined use of recombinant human FGF-2 (rhFGF-2) and gelatin/ß-TCP sponge on ridge augmentation in dogs. MATERIAL AND METHODS: Six male beagle dogs were used in this study. Twelve wk after tooth extraction, bilateral 10 × 5 mm (width × depth) saddle-type defects were created 3 mm apart from the mesial side of the maxillary canine. At the experimental sites, the defects were filled with gelatin/ß-TCP sponge infiltrated with 0.3% rhFGF-2, whereas gelatin/ß-TCP sponge infiltrated with saline was applied to the control sites. Eight wk after surgery, qualitative and quantitative analyses were performed. RESULTS: There were no signs of clinical inflammation at 8 wk after surgery. Histometric measurements revealed that new bone height at the experimental sites (2.98 ± 0.65 mm) was significantly greater than that at the control sites (1.56 ± 0.66 mm; p = 0.004). The total tissue height was greater at the experimental sites (6.62 ± 0.66 mm) than that at the control sites (5.95 ± 0.74 mm), although there was no statistical significant difference (p = 0.051). Cast model measurements revealed that the residual defect height at the experimental sites (2.31 ± 0.50 mm) was significantly smaller than that at the control sites (3.51 ± 0.78 mm; p = 0.012). CONCLUSION: The combined use of rhFGF-2 and gelatin/ß-TCP sponge promotes ridge augmentation in canine saddle-type bone defects.

Effect of a tunnel-structured ß-tricalcium phosphate graft material on periodontal regeneration: a pilot study in a canine one-wall intrabony defect model.

BACKGROUND AND OBJECTIVE: Tissue regeneration is affected by the porosity, chemical properties and geometric structure of graft materials. Regeneration of severe periodontal defects, such as one-wall intrabony defects, is difficult because of reduced tissue support, and bone grafts are commonly used in such cases. In the present study, a tunnel-structured ß-tricalcium phosphate (tunnel ß-TCP) graft material designed to stimulate bone formation was fabricated. The objective of this pilot study was to evaluate the effect of this graft material on periodontal regeneration in one-wall intrabony defects in dogs. MATERIAL AND METHODS: Six male beagle dogs were used in this study. First, the mandibular second and third incisors were extracted. Experimental surgery was performed 12 wk after tooth extraction. Bilateral 4 × 8 mm (width × depth) one-wall intrabony defects were created in the mesial side of the mandibular canines. At the experimental sites, the defects were filled with tunnel ß-TCP, whereas the control defects were left empty. Twelve weeks after surgery, qualitative and quantitative histological analyses were performed. RESULTS: There were no signs of clinical inflammation 12 wk after surgery. Coronal extension indicative of new bone formation was higher at the experimental sites than at the control sites, although the differences between both the sites in the newly formed cementum and connective tissue attachment were not significant. Newly formed periodontal ligament and cementum-like tissue were evident along the root surface at the experimental sites. The inner surface of the tunnels was partially resorbed and replaced with new bone. New blood vessels were observed inside the lumens of tunnel ß-TCP. CONCLUSION: Tunnel ß-TCP serves as a scaffold for new bone formation in one-wall intrabony defects.

Economic evaluation of chemoprevention of breast cancer with tamoxifen and raloxifene among high-risk women in Japan.

Raloxifene was approved for chemoprevention against breast cancer among high-risk women in addition to tamoxifen by the US Food and Drug Administration. This study aims to evaluate cost-effectiveness of these agents under Japan's health system. A cost-effectiveness analysis with Markov model consisting of eight health states such as healthy, invasive breast cancer, and endometrial cancer is carried out. The model incorporated the findings of National Surgical Adjuvant Breast and Bowel Project P-1 and P-2 trial, and key costs obtained from health insurance claim reviews. Favourable results, that is cost saving or cost-effective, are found by both tamoxifen and raloxifene for the introduction of chemoprevention among extremely high-risk women such as having a history of atypical hyperplasia, a history of lobular carcinoma in situ or a 5-year predicted breast cancer risk of > or =5.01% starting at younger age, whereas unfavourable results, that is 'cost more and gain less' or cost-ineffective, are found for women with a 5-year predicted breast cancer risk of < or =5.00%. Therapeutic policy switch from tamoxifen to raloxifene among postmenopausal women are implied cost-effective. Findings suggest that introduction of chemoprevention targeting extremely high-risk women in Japan can be justifiable as an efficient use of finite health-care resources, possibly contributing to cost containment.

Gaps in the information shared on consumer healthcare products.

We conducted a questionnaire survey of visitors to the Japan Drugstore Show 2006 and an additional questionnaire survey of pharmacists in 2008 to ascertain the current information gaps between consumers and manufacturers of consumer healthcare products (CHPs). Three main gaps were apparent: first was a gap between information that consumers wanted to receive and information that was widely disclosed by manufacturers of CHPs, second was a gap between the advisors whom consumers regarded as appropriate and the advisors who consumers had actually consulted, and a gap between what consumers expect pharmacists to know and pharmacists' actual knowledge. Manufacturers' efforts alone will not be able to close these gaps because of the number of regulations. Thus, a new social system should be constructed to supply adequate information on CHPs and consumers should enjoy free access to this information.

Docetaxel plus prednisolone for the treatment of metastatic hormone-refractory prostate cancer: a multicenter Phase II trial in Japan.

BACKGROUND: Docetaxel-based chemotherapy has been shown to be effective and well tolerated by Western patients with metastatic hormone-refractory prostate cancer (HRPC). This study was undertaken to assess the feasibility of docetaxel in combination with prednisolone in Japanese patients with HRPC. METHODS: Patients aged 50-74 years with measurable metastatic HRPC were included in this non-comparative Phase II study. Treatment consisted of docetaxel 70 mg/m(2) once every 3 weeks plus prednisolone 5 mg twice daily, for a maximum of 10 cycles. The primary endpoint was overall tumor response rate, assessed by Response Evaluation Criteria in Solid Tumors; secondary endpoints included prostate-specific antigen (PSA) response and toxicity. RESULTS: A total of 43 patients were evaluable for efficacy and toxicity. The response rate was 44.2% (90% CI, 31.2-57.8%), with partial responses in 19/43 patients. The median duration of response was 19.3 weeks. PSA responses were recorded in 44.4% of patients (95% CI, 27.9-61.9%). The most common non-hematological adverse events (of any grade) possibly related to treatment were alopecia (88.4%), anorexia (65.1%) and fatigue (53.5%). Grade 3/4 leukopenia and neutropenia occurred in 81.4 and 93.0% of patients, respectively; however, the grade 3/4 rates of febrile neutropenia (16.3%) and infection without fever (14.0%) were lower. CONCLUSION: The combination of docetaxel and prednisolone was feasible and active in Japanese patients with HRPC, with a manageable adverse-event profile similar to that observed in Western patients.

Questionnaire on the awareness of generic drugs among outpatients and medical staff.

Generic drugs are not as widely used in Japan as they are in the West. The objective of this study was to survey the awareness of generic drugs among outpatients and medical staff and propose methods of promoting the use of generic drugs. Our survey showed that 86.7% of respondents were aware of generic drugs. This is a higher awareness rate than that in a survey of other groups conducted last year. One reason to explain this higher awareness is the recent increase in generic drug advertisements both in newspapers and on television. However, a point of note is that generic drug usage has not increased. Our survey also showed that generic drug awareness was differed widely among age groups, as younger respondents were much more aware of generic drugs than older respondents. Still, about 40% of respondents who were aware of generic drugs did not realize that they were less expensive than name-brand drugs ? including 30% of medical staff. In addition to continuing advertisement of generic drugs in the media, medical doctors and pharmacists should also be encouraged to endorse the use of generic drugs. Furthermore a new system allowing for substitution prescriptions started in April 2008 and consequently pharmacists can now play an important role in promoting the use of generic drugs.

Glycolipid composition in bladder tumor: a crucial role of GM3 ganglioside in tumor invasion.

Glycolipids were extracted from primary bladder tumors of 14 patients and 2 normal counterparts. Their expression pattern was assessed by thin-layer chromatography (TLC). The most remarkable change was massive accumulation of GM3 in superficial bladder tumors compared with invasive tumors. This change was also confirmed by immunohistochemistry using anti-GM3 monoclonal antibody. The activities of glycosyltransferases responsible for GM3 synthesis (GM3 synthase, Gb3 synthase and GD3 synthase) were consistent with upregulated expression of GM3 in superficial tumors. It was suggested that the marked GM3 accumulation in superficial tumors was caused not only by upregulated GM3 synthase but also by downregulated activities of Gb3 and GD3 synthase. Histopathologic examination revealed an inverse correlation of the amount of GM3 expressed with invasive potential. Exogenously supplemented GM3 suppressed invasion potential in human bladder tumor cell lines (T-24, KK-47). These results indicate that the amount of GM3 expressed may serve as an indicator of the invasion potential of bladder tumor. Furthermore, new antiinvasion therapeutics may be possible by administration of GM3.

Enhanced GM3 expression, associated with decreased invasiveness, is induced by brefeldin A in bladder cancer cells.

We reported previously that non-invasive bladder cancer expresses high level of GM3 ganglioside, whereas invasive tumors have low levels. Since glycosphingolipid synthesis in Golgi is modified greatly by a macrocyclic lactone isolated from fungi, brefeldin A (BFA), we studied effects of BFA on expression of glycosphingolipids and on invasiveness of bladder cancer cell lines. Only GM3 synthesis in invasive tumors was greatly enhanced upon treatment with BFA; synthesis of other glycosphingolipids with lacto-series type 2 or globo-series structure in both invasive and non-invasive tumors was not changed. Invasiveness of bladder cancer cells was greatly decreased in association with the great increase of GM3 synthesis induced by BFA treatment. Level of sialyl-Lex expressed in invasive cell line YTS1, which provides the adhesive property of the cells to E-selectin, was unchanged upon BFA treatment. All the bladder cancer cell lines, regardless of invasiveness, highly express tetraspanin CD9. GM3 has been implicated as a co-factor of CD9 in control of tumor cell motility. Down-regulation of CD9 is associated with metastatic properties of tumor cells and survival of patients with colonic cancer. Therefore, enhanced synthesis of GM3 induced by BFA, causing decrease of invasiveness in bladder cancer, is ascribable to the capability of GM3 to interconnect integrin with CD9, in analogy to colonic cancer and perhaps many other types of cancer.

Recurrence pattern of metastatic testicular cancers after chemotherapy.

Recurrence pattern of metastatic testicular cancer after the initial treatment was investigated. Seventy-seven patients with metastatic testicular cancer were treated by cisplatin-based chemotherapy. Patients with residual masses after chemotherapy and whose tumor markers were normalized underwent surgical resections. Of the 77 patients, 61 achieved cancer free status and 4 who did not need the study criteria excluded. Recurrences were detected in 12 (21.1%) patients, 2 (7.1%) patients among 28 stage II patients; 10 (34.5%) patients among 29 stage III patients; none (0%) patients among 14 seminoma patients and 12 (27.9%) patients among 43 non-seminoma patients. All recurrences were detected within 17 months (median, 3) after the initial treatment. Of the 12 patients experiencing recurrence, 4 died of cancer. The recurrence rate of the patients in stage III was significantly higher than that in stage II. No recurrence was detected in patients with seminoma. Follow-up studies after treatment should include serum tumor markers and computed tomographic scanning of lung, abdomen and pelvis at defined intervals. Intensive follow-up will be needed especially for the patients in stage III and with non-seminoma. Follow-up within the first two years is especially important in detecting recurrence after chemotherapy.

PTHrP and PTH/PTHrP receptor expressions in human endometrium.

We investigated menstrual cycle-dependent changes in the expression of PTHrP and PTH/PTHrP receptor in the human endometrium by immunohistochemistry, and competitive reverse transcription and polymerase chain reaction (RT-PCR). Human endometrial tissues were obtained from patients who underwent gynecological surgery due to cervical cancer (carcinoma in situ) or ovarian cancer. The mean age of the 20 patients was 36.5 (range 31-44) years. For analysis of mRNA expression, specimens from proliferative (mid, n=5; late, n=5) and secretory (early, n=4; mid, n=4) phases were used. Immunohistochemical expression of PTHrP and PTH/PTHrP receptor was observed in the cytoplasm of both epithelial and stromal cells. Stronger staining of PTHrP was found in glandular epithelial cells than in stromal cells. The staining during the proliferative phase was stronger than that in the secretory phase and the difference was particularly remarkable when comparing samples from the same patient. PTH/PTHrP receptor was also present in both epithelial and stromal cells of the endometrium. However, no difference was observed in receptor expression between the proliferative and secretory phases. Competitive RT-PCR revealed that the expression of PTHrP mRNA was higher during the proliferative phase than in the secretory phase, although no difference was observed in PTH/PTHrP receptor mRNA expression. The data suggest that endometrial proliferation may be mediated by a local PTHrP autocrine and/or paracrine mechanism.

Adenocarcinoma arising from the prostatic duct mimicking transitional cell carcinoma.

A 71-year-old man was first diagnosed with primary transitional cell carcinoma of the prostate with a skip lesion on the distal urethra. The patient received three courses of intra-arterial chemotherapy of cisplatin (CDDP) and pirarubicin (THP-ADM) followed by a radical prostatectomy. Histopathologic examination of the prostatectomy specimen revealed adenocarcinoma invasion along the prostatic duct extending to the peripheral acini, which was diagnosed as ductal adenocarcinoma. The clinical and histopathologic features of this case are entirely different from usual adenocarcinomas of the prostate. This rare histopathologic feature should be recognized as 'ductal carcinoma of the prostate', to distinguish it from papillary adenocarcinoma or adenocarcinoma with endometrioid features. The patient has had no sign of recurrence 14 months after the operation. CDDP-based chemotherapy followed by radical prostatectomy may be one of the promising therapeutic modalities for this rare entity.

Trans-urethral whole layer core biopsy for detection of residual tumor after neoadjuvant therapy in invasive bladder cancer.

The most essential information necessary for the treatment of bladder cancer is to know its exact staging. We have developed a percutaneous whole layer core biopsy (PC-WLCB) of the bladder tumor and applied it successfully since April 1985 for the staging and evaluation of neoadjuvant therapy in locally invasive bladder cancer. We report here a modified method, the trans-urethral WLCB (TU-WLCB) and present its clinical results. Methods: A 20 F. rigid nephroscope was introduced trans-urethrally and an 18 gauge, 350mm-long biopsy needle or newly developed 450mm-long biopsy needle was advanced to the tumor through the nephroscope. Biopsy was performed under trans-abdominal ultrasound guidance. Results: Specimens of all 20 TU-WLCB cases included the muscle layer and adipose tissue, and demonstrated small focus of residual cancers after neoadjuvant therapy. Serious complications were not observed so far. Conclusion: TU-WLCB may prove to be a reliable method to stage and evaluate neoadjuvant therapy for invasive bladder cancer.

Two patients with N3 bladder cancer successfully treated by internal iliac arterial infusion chemotherapy and irradiation: case reports.

The prognosis of patients with bladder cancer with pelvic lymph node metastasis is poor, and only 30% of them have been reported to achieve 5- and 10-year survival rates. Prognosis of the patients with pelvic lymph node metastasis larger than 5 cm (N3) is especially poor. and no patient has been reported to have survived more than 3 years. The authors report the successful treatment of two patients with pelvic N3 bladder cancer by internal iliac arterial infusion chemotherapy combined with whole-pelvis irradiation.

Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive and -negative diffuse large B cell lymphoma.

We analyzed nucleotide sequence and intraclonal diversity of the rearranged immunoglobulin heavy chain gene variable region (VH gene) of CD5+ and CD5- diffuse large B cell lymphoma (DLBCL) to clarify the cell origin of de novo CD5+ DLBCL. Ten cases of CD5+ DLBCL and 29 cases of CD5- DLBCL were analyzed. The frequencies of somatic mutation were 0.7 to 12.9% (average, 6.2%) in CD5+ DLBCL and 2.0 to 25.9% (average, 11.1%) in CD5- DLBCL. The ongoing mutation rate was estimated from the number of further single base-substitutions, expressed as a percentage of the total number of nucleotides in 10 cloned PCR products for each case (%). The averages of the ongoing mutation rate of CD5+ DLBCL (four cases) and CD5 DLBCL (seven cases) were 0.051% and 0.197%, respectively. The rate of CD5+ DLBCL was significantly lower than that of CD5- DLBCL (t-test, P = 0.024). These data may indicate that the cell origin of CD5+ DLBCL is different from that of CD5- DLBCL. CD5 is not an activated antigen in DLBCL, but a specific marker of the B1 subset of the B cells, and de novo CD5+ DLBCL may therefore be derived from this unique subset.