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.

Highly efficient terahertz radiation from a thin foil irradiated by a high-contrast laser pulse.

Radially polarized intense terahertz (THz) radiation behind a thin foil irradiated by ultrahigh-contrast ultrashort relativistic laser pulse is recorded by a single-shot THz time-domain spectroscopy system. As the thickness of the target is reduced from 30 to 2 µm, the duration of the THz emission increases from 5 to over 20 ps and the radiation energy increases dramatically, reaching ∼10.5mJ per pulse, corresponding to a laser-to-THz radiation energy conversion efficiency of 1.7%. The efficient THz emission can be attributed to reflection (deceleration and acceleration) of the laser-driven hot electrons by the target-rear sheath electric field. The experimental results are consistent with that of a simple model as well as particle-in-cell simulation.

Comparative study of treatment efficacy and the incidence of post-inflammatory hyperpigmentation with different degrees of irradiation using two different quality-switched lasers for removing solar lentigines on Asian skin.

BACKGROUND: Quality-switched (QS) lasers are well-known effective treatment for removing solar lentigines. However, the high incidence of post-inflammatory hyperpigmentation (PIH) raises concern in darker skin types. This is the first study comparing efficacies and incidences of PIH in Asian skin with different degrees of irradiation between two QS lasers. METHOD: In total, 355 solar lentigines in 193 cases, skin types III-V, were randomly divided into four groups. All cases received single laser treatment. Clinical results were evaluated after 4 weeks. Groups 1 and 3 were treated 'aggressively' with endpoints of very obvious immediate whitening (IW) of the lesion. Groups 2 and 4 were treated 'mildly' with endpoints of slight IW of the lesion. Groups 1 and 2 were irradiated with the QS ruby, and groups 3 and 4 with the QS frequency doubled Nd:YAG laser. RESULTS: There were no statistically significant differences in degrees of clearance among the four groups. However, PIH incidences were very different: 33.33%, 7.47%, 23.18% and 8.47% in groups 1, 2, 3 and 4 respectively. The difference between aggressively and mildly irradiated groups (1 and 3 vs. 2 and 4) was statistically significant (P < 0.001). However, there was no statistical difference between the two aggressively or the two mildly irradiated groups. There were no significant differences between skin types. CONCLUSION: Aggressive irradiation using QS lasers resulted in a high PIH incidence, while having no advantage in efficacy. For darker skin types, mild irradiation reduces the PIH risk with no disadvantage in efficacy.

Amplification of plant genomic DNA by Phi29 DNA polymerase for use in physical mapping of the hypermethylated genomic region.

Plant genomes contain a heavily methylated region in which cytosines are methylated in both the symmetrical and asymmetrical sequences. The physical mapping of such a hypermethylated region is difficult because many restriction enzymes are sensitive to methylated cytosine residues in their recognition sites. The Phi29 DNA polymerase provides an efficient and representative amplification of the genomic DNA that is methylation-free. Using this amplified genomic DNA, we were able to show that a heavily methylated genomic DNA region becomes amenable to physical mapping with any restriction enzymes. This protocol will be especially useful for analysis of the heavily methylated region of plant genomes.

Mandibular reconstructive surgery in a patient with median cleft of the lower lip and mandible.

A patient 15 years and 11 months of age with median cleft of the lower lip and mandible underwent mandibular reconstructive surgery using autogenous iliac bone and a titanium mesh tray. Functional and morphological results are satisfactory 4 years after surgery.

Photorejuvenation for Asian skin by intense pulsed light.

BACKGROUND: Dermabrasion and deep chemical peeling are used in the treatment of photoaged skin. These ablative procedures are effective enough to produce a certain improvement but have often caused postinflammatory hyperpigmentation among Asian patients. To avoid such adverse effects, a new, nonablative procedure has been sought. OBJECTIVE: To determine the effectiveness of photorejuvenation for Asian skin using intense pulsed light (IPL). The specific parameters used, improvement ratios, side-effects, and downtime required are also discussed. METHODS: Ninety-seven patients were treated for photoaging using IPL. The cutoff filters of 550 nm and 570 nm were utilized for three to six treatments at intervals of 2 to 3 weeks. RESULTS: Treatment results were evaluated and rated by both patients and physicians at the end of the third treatment based on improvement in pigmentation, telangiectasia, and skin texture. A combined rating of "good" or "excellent" was given to more than 90% of the patients for pigmentation, more than 83% for telangiectasia, and more than 65% for skin texture. There were some minor complications in four cases: one had erythema that continued to the next day and three had minor blisters leaving no marks. CONCLUSION: Photorejuvenation using IPL is a completely safe and effective procedure even for Asian skin. It will be increasingly used for skin rejuvenation in the future.

Production of functionally deficient dendritic cells from HTLV-I-infected monocytes: implications for the dendritic cell defect in adult T cell leukemia.

Adult T cell leukemia (ATL) is induced by an infection with human T lymphotropic virus type I (HTLV-I) and is accompanied by immunodeficiency. Monocyte-derived immature dendritic cells (DCs) donated by 11 ATL patients were suppressed in the ability to take up fluorescein isothiocyanate (FITC)-dextran and were down-regulated in the expression of CD1a and CD86 antigens (Ags). Monocytes from the patients showed impaired expression of CD14 and HLA-DR Ags. These results suggest intrinsic abnormalities of monocytes and a defect of DC maturation in ATL patients. Therefore, we examined the influence of HTLV-I infection of monocytes on their differentiation to DCs. Monocytes obtained from healthy donors were susceptible to HTLV-I infection in vitro. HTLV-I-infected monocytes were down-regulated in the expression of CD14 Ags, and immature DCs obtained from them expressed CD1a poorly and were impaired in the ability to take up FITC-dextran. Mature DCs differentiated from these cells could not stimulate autologous CD4(+) T cell or CD8(+) T cell proliferation, even after being secondarily pulsed with HTLV-I at an immature DC stage. These results suggest that HTLV-I-infected monocytes cannot properly differentiate to DCs and that this might be one of the important mechanisms producing dysfunctional DCs in ATL patients.

Sclerosant therapy for delayed cardiac tampo-nade after coronary artery bypass grafting.

A 56-year-old Japanese male with delayed cardiac tamponade which occurred 13 months after coronary artery bypass grafting (CABG) is presented. The patient was admitted to our hospital suffering from dypnea due to cardiac tamponade. Pericardiocentesis yielded a viscous bloody fluid. The patient recovered after continuous drainage followed by an intra-pericardial administration of minocycline hydrochloride. Sclerosant therapy is considered to be a treatment of choice for delayed cardiac tamponade following CABG.

Monocyte-driven activation-induced apoptotic cell death of human T-lymphotropic virus type I-infected T cells.

We attempted apoptotic cell death induction of T cells infected with human T lymphotropic virus type I (HTLV-I) which induces HTLV-I-associated myelopathy/tropical spastic paraparesis and adult T cell leukemia. T cells acutely infected and expressing HTLV-Igag Ags were killed by cross-linking their TCR with anti-CD3 mAb. Cells in apoptotic process were found by staining with annexin V. The apoptosis was not affected by costimulation through CD28 molecules and was resistant to ligation of Fas molecules. Whereas the virus-infected T cells expressed higher levels of HLA-DR, CD25, CD80, and CD86 Ags than apoptosis-resistant PHA-blasts, the T cell apoptosis was enhanced by addition of exogenous IL-2. Furthermore, in this apoptosis, monocytes played an important role because T cells infected in the absence of monocytes were resistant to the death signals. The apoptosis-sensitive T cells responded to TCR signaling more strongly by proliferating than those apoptosis-resistant cells. Monocytes weakly affected the expression levels of viral Ags on T cells. However, HTLV-I-infected monocytes primed T cells to die by subsequent TCR signaling. T cells primed with the monocytes, subsequently infected in the absence of monocytes, were killed by TCR signaling. These observations suggest that primed and infected T cells could be killed by activation-induced cell death.

NF-kappaB involvement in the activation of primary adult T-cell leukemia cells and its clinical implications.

The HTLV-I provirus-encoded Tax protein induces NF-kappaB in Tax-transfected Jurkat T cells or HTLVL-I- infected T cells in vitro. Tax induction of NF-kappaB is presumed to be involved in proliferation and activation of primary leukemia cells in vivo. Recent studies have demonstrated that NF-kappaB activities in human T cells are mediated by at least four c-Rel-related DNA binding proteins - p50, p55, p75 and p85. We examined the significance of NF-kappaB induction in primary adult T cell leukemia cells and the induction kinetics of each of the four NF-kappaB species. Marked NF-kappaB activity was detected using an electrophoretic mobility shift assay (EMSA) in the primary cells of patients with acute disease, but little activity was noted in the cells of chronic patients. NF-kappaB activity was enhanced in a time-dependent manner in acute type cells cultured with mitogen-free medium; there was no induction of activity in chronic type cells. UV crosslinking demonstrated all four species of NFkappaB complex - high levels of p50 and lower levels of p55 and p75, in acute type cells; chronic type cells showed only the p50. As a control, normal resting T cells similarly showed only p50; control cells showed little change in activity when cultured without mitogenic stimulation, analogous to chronic type ATL. Northern blotting revealed enhancement of c-rel (encoding p85) and KBFI (encoding p50 and p55) expression in acute type cells during culture, while there was no significant enhancement of mRNAs in chronic type ATL cells or unstimulated normal T cells. Northern blotting also revealed that Tax is upregulated at the mRNA level in acute- but not chronic-type cells during culture. Expression of c-rel and KBF1 mRNAs in acute type cells appeared to be related to Tax mRNA expression. These results suggest that Tax is capable of inducing nuclear expression of all four NF-kappaB species in primary ATL cells of acute type patients, with marked effects on p55, p75, and p85. Tax induction of NF-kappaB species is regulated, at least in part, at a pretranslational level involving increases in c-rel and KBF1 mRNA.

Marked suppression of T cells by a benzothiophene derivative in patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.

In a search for new anti-autoimmune agents that selectively suppress activation of autoreactive T cells, one such agent, 5-methyl-3-(1-methylethoxy)benzo[b]thiophene-2-carboxamide (CI-959-A), was found to be effective. This compound, which is known to suppress tumor necrosis factor alpha (TNF-alpha)-induced CD54 expression, inhibited the primary proliferative response of the T cell to antigen (Ag)-presenting cells (APCs) including allogenic dendritic cells (DCs), autologous Epstein-Barr virus-infected B cells, and human T lymphotropic virus type I (HTLV-I)-infected T cells. Autoreactive T cells from patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) spontaneously proliferate in vitro, and their activation is reported to be associated with CD54 expression. The spontaneous proliferation of T cells from patients with HAM/TSP was entirely blocked by CI-959-A. However, in this study, the T-cell proliferation in 15 patients with HAM/TSP was found to depend more extensively on major histocompatibility complex (MHC) class II and CD86 than on CD54 Ags. Since most important APCs for the development of HAM/TSP are DCs and HTLV-I-infected T cells, the effect of CI-959-A on DC generation and on the expression of surface molecules on activated T cells is examined. CI-959-A suppressed recombinant granulocyte-macrophage colony stimulating factor (GM-CSF)- and recombinant interleukin-4-dependent differentiation of DCs from monocytes and inhibited the expression of CD54 and, more extensively, MHC class II and CD86 Ags. CI-959-A showed little toxicity toward lymphoma or HTLV-I-infected T-cell lines or toward monocytes and cultured DCs. These results suggest that CI-959-A might be a potent anti-HAM/TSP agent.

[Crescentic glomerulonephritis in a patient with rheumatoid arthritis].

A 56-year-old female with rheumatoid arthritis was admitted because of bilateral hip pain. In a few months of her hospitalization, a relatively abrupt renal dysfunction was emerged besides complement breakdown, and renal biopsy revealed crescentic glomerulonephritis. Immunofluorescence study showed peripheral granular deposits of IgG, IgM, and C3 in the glomeruli. Cresents were predominantly composed of macrophages and glomerular epithelial cells. Amyloid nephropathy, renal vasuculitis, and association of other collagen vascular diseases were negligible for the causative factor. It was suggested that immune complexes were formed in the glomeruli, in which both humoral and cellular immune responses were to be induced, that brought cescents formation in the lesions. Crescentic glomerulonephritis in patients with rheumatoid arthritis is rare and a possible pathogenetic mechanisms involved in the development of renal dysfunction are discussed with the special reference to immune complex-induced inflammation.

[Application of a new compact and cell dense continuous culture system for LAK cells generated from cryo-preserved lymphocytes].

Recently, the adoptive immunotherapy using lymphokine activated killer (LAK) cells has been applied for various cancer patients. It is quite useful to generate LAK cells from cryo-preserved lymphocytes in order to make a rational treatment schedule. We made basic studies on the induction of LAK cells from frozen lymphocytes using our high yield continuous cell culture system. It was demonstrated that our culture bag can be used to proliferate frozen lymphocytes cultured in interleukin-2 (IL-2) to thirty four-fold the initial cell number in 14 days with comparable cytotoxicity to that of fresh lymphocytes cultured in the same system.

[An undifferentiated carcinoma of the stomach--a report of 2 cases].

Two cases of an undifferentiated carcinoma of the stomach have been investigated by conventional histologic, immunohistochemical, and ultrastructural methods. The patients were a 73-year-old man and 65-year-old man. A postoperative histological examination of the resected stomach of each patient disclosed large areas of an undifferentiated carcinoma which were relatively well demarcated from areas of the adenocarcinoma. In the undifferentiated carcinomatous areas, the reticulin fiber stain was epithelial in pattern, and mucin staining proved negative. Similarly both Grimelius and Fontana-Masson staining also negative. In like manner immunostains using cytokeratin , vimentin , IgG, IgA, s-100 protein, and NSE were all negative, and an electron microscopic study showed no neurosecretory granules or mucin secretory granules. Based on these findings, the diagnosis of either a malignant lymphoma or small cell anaplastic carcinoma could be excluded, and thus an undifferentiated carcinoma was the determination.

A new surgical method for repair of funnel chest.

We have devised a new surgical procedure for the repair of funnel chest deformity, which we have used in 148 of our 154 patients. The procedure involves resection of the deformed thoracic wall, including ribs and sternum, rib-sternal turnover, and anastomosis of the internal thoracic artery and veins. Several preoperative and postoperative examinations, such as bone biopsy, sternal puncture and indium chloride test, revealed definite signs of living tissue. This procedure results in minimal secondary deformity postoperatively and is indicated for adults as well as children.