Stereotactic ablative body radiotherapy with a central high dose using CyberKnife for metastatic lung tumors.

BACKGROUND: The CyberKnife system features a robotically-positioned linear accelerator to deliver real-time image-guided stereotactic ablative body radiotherapy (SABR). It achieves steep dose gradients using irradiation from hundreds of different directions and increases the central dose of the gross tumor volume (GTV) without increasing the marginal dose to the planning target volume. We evaluated the effectiveness and safety of SABR with a central high dose using CyberKnife for metastatic lung tumors. METHODS: A total of 73 patients with 112 metastatic lung tumors treated with CyberKnife were retrospectively analyzed. Local control, progression-free survival, and overall survival were calculated using the Kaplan-Meier method. The median age was 69.2 years. The most common primary sites were the uterus (n = 34), colorectum (n = 24), head and neck (n = 17), and esophagus (n = 16). For peripheral lung tumors, the median radiation dose was 52 Gy in 4 fractions, whereas for centrally located lung tumors, it was 60 Gy in 8-10 fractions. The dose prescription was defined as 99% of the solid tumor components of the GTV. The median maximum dose within the GTV was 61.0 Gy. The GTV and planning target volume were enclosed conformally by the 80% and 70% isodose lines of the maximum dose, respectively. The median follow-up period was extended to 24.7 months; it was 33.0 months for survivors. RESULTS: The 2-year local control, progression-free survival, and overall survival rates were 89.1%, 37.1%, and 71.3%, respectively. Toxicities of grade ≥ 2 were noted as grade 2 and 3 radiation pneumonitis in one patient each. The two patients with grade 2 or higher radiation pneumonitis had both received simultaneous irradiation at two or three metastatic lung tumor sites. No toxicity of grade ≥ 2 was observed in patients with metastasis in one lung only. CONCLUSIONS: SABR with a central high dose using CyberKnife for metastatic lung tumors is effective with acceptable toxicity. TRIAL REGISTRATION: Number: 20557, Name: Stereotactic ablative radiotherapy using CyberKnife for metastatic lung tumor, URL: http://www.radonc.med.osaka-u.ac.jp/pdf/SBRT.pdf , Date of registration: April 1, 2021 (retrospectively registered), Date of enrollment: May 1, 2014.

Triazolopyrimidine derivative NK026680 and donor-specific transfusion induces CD4+CD25+Foxp3+ T cells and ameliorates allograft rejection in an antigen-specific manner.

We have previously demonstrated the unique properties of a new triazolopyrimidine derivative, NK026680, which exerts immunosuppressive effects in rat heart transplant model and confers tolerogeneic properties on ex vivo-conditioned dendritic cells in mice. We herein demonstrate that NK026680 promotes the expansion of regulatory T cells (Tregs) with potent immunoregulatory effects when used in combination with donor-specific transfusion (DST). BALB/c (H-2d) heart graft were transplanted into C57BL/6 (H-2b) mice following intravenous injection of donor splenocytes (DST) and oral administration of NK026680. The NK026680 plus DST treatment markedly prolonged the survival time of the donor-graft, but not that of the 3rd party-graft (C3H; H-2k). Treg cells in the recipient spleen on day 0 expanded when stimulated with donor-antigens in vivo and in vitro. After heart transplantation, Treg cells accumulated into the graft and increased in the spleen. NK026680 plus DST also decreased activated CD8+ T cells in the spleen and inhibited infiltration of CD8+ T cells into the graft. Depletion of CD25+ cells inhibited the graft prolonging effect of the NK026680 plus DST treatment. NK026680 administration together with DST induces potent immunoregulatory effects in an antigen-specific manner, likely due to the in vivo generation of donor-specific Tregs.

[A Case of Giant Malignant Phyllodes Tumor Associated with Severe Anemia].

A 72-year-old woman noted a mass in the left breast about 5 years ago, but she did not consult a medical institution. She was taken in the ambulance and hospitalized to our department due to severe anemia and malnutrition. A computed tomography( CT)scan indicated an 18×12 cm tumor in her left breast. A fiborsarcoma protuberance was suspected based on needle core biopsy results. Simple mastectomy was performed to control hemorrhage and infection. The resected tumor weighed 2.6 kg. The pathological diagnosis was a malignant phyllodes tumor. We report a patient with giant malignant phyllodes tumor associated with severe anemia.

Efficacy of DHMEQ, a NF-κB inhibitor, in islet transplantation: II. Induction DHMEQ treatment ameliorates subsequent alloimmune responses and permits long-term islet allograft acceptance.

BACKGROUND: Long-term graft deterioration remains a major obstacle in the success of pancreatic islet transplantation (PITx). Antigen-independent inflammatory and innate immune responses strengthen subsequent antigen-dependent immunity; further, activation of nuclear factor (NF)-κB plays a key role during these responses. In this study, we tested our hypothesis that, by the inhibition of NF-κB activation, the suppression of these early responses after PITx could facilitate graft acceptance. METHODS: Full major histocompatibility complex (MHC)-mismatched BALB/c (H-2) mice islets were transplanted into streptozotocin-induced diabetic C57BL/6 (B6: H-2) mice. The NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) was administered for either 3 or 14 days after PITx. To some PITx recipients, tacrolimus was also administered. Islet allograft survival, alloimmune responses, and in vitro effects of DHMEQ on dendritic cells (DCs) were assessed. RESULTS: With a vehicle treatment, 600 islet allografts were promptly rejected after PITx. In contrast, 3-day treatment with DHMEQ, followed by 2-week treatment with tacrolimus, allowed permanent acceptance of islet allografts. The endogenous danger-signaling molecule high mobility group complex 1 (HMGB1) was elevated in sera shortly after PITx, whereas DHMEQ administration abolished this elevation. DHMEQ suppressed HMGB1-driven cellular activation and proinflammatory cytokine secretion in mouse bone marrow-derived DCs and significantly reduced the capacity of DCs to prime allogeneic T-cell proliferation in vitro. Finally, the DHMEQ plus tacrolimus regimen reverted the diabetic state with only 300 islet allografts. CONCLUSIONS: Inhibition of NF-κB activation by DHMEQ shortly after PITx suppresses HMGB1, which activates DCs and strengthens the magnitude of alloimmune responses; this permits long-term islet allograft acceptance, even in case of fewer islet allografts.

Increased tyrosine kinase activites may lead to the phenotypic differences of gastric cancer cells.

BACKGROUND: The aim of this study was to elucidate possible mechanisms responsible for the phenotypic difference in gastric cancer cells between the intestinal type and the diffuse type. MATERIALS AND METHODS: The gastric cancer cell lines MKN7 and KATO-III were used. Expression of adhesion molecules and protein tyrosine phosphorylation were examined by immunoblotting. Protein-protein interactions were determined by immunoblotting following immunoprecipitation. ERK activity was assessed by immunoblotting using anti-phospho-ERK antibody. RESULTS: E-cadherin expression in KATO-III was decreased compared to that in MKN7. The expression of alpha-, beta- and gamma-catenin was not significantly different; beta- and gamma-catenin were highly tyrosine phosphorylated in KATO-III but not in MKN7. In KATO-III, a number of tyrosine phosphorylated proteins, including extracellular signal-regulated protein kinases (ERKs) and epidermal growth factor receptor (EGFR), were observed irrespective of EGF stimulation and induction of ERK activity and EGFR tyrosine phosphorylation by EGF were less than that in MKN7. CONCLUSION: Increased tyrosine kinase activities may cause diminished expression of E-cadherin and tyrosine phosphorylation of catenins, resulting in the abrogated cell-cell adhesion in gastric cancer cells.

PCDDs, PCDFs, and coplanar PCBs in albatross from the North Pacific and Southern Oceans: levels, patterns, and toxicological implications.

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (coplanar PCBs) were determined in five albatross species collected from the North Pacific and Southern Oceans to assess the north-south differences in residue levels, accumulation patterns, and toxic potential. Black-footed and Laysan albatrosses from the North Pacific Ocean contained higher levels of PCDD/Fs and coplanar PCBs than albatrosses from the Southern Ocean, indicating that emission sources of these contaminants were predominant in the northern hemisphere. Residue levels in albatrosses from the remote North Pacific Ocean far from the point source of pollution were comparable to or higher than those in terrestrial and coastal birds from contaminated areas in developed nations, suggesting the specific exposure and accumulation of PCDD/Fs and coplanar PCBs in albatross. The long life span and ingestion of plastic resin pellets by albatrosses could be the plausible explanations for the elevated accumulation of persistent and lipophilic contaminants including PCDD/Fs and coplanar PCBs in these birds. Relative proportions of PCDFs and coplanar PCBs in albatross were higher than those observed in birds inhabiting terrestrial and coastal areas, suggesting that these toxic chemicals may have higher transportability by air and water than PCDDs. Congener patterns of PCDD/Fs in albatross showed less variability as compared to those in terrestrial species, indicating that contamination patterns of PCDD/Fs were similar within the open ocean environment. Contributions of PCDD/Fs to total TEQs in albatrosses from the open ocean were generally lower than those in terrestrial birds, suggesting different toxic potency of PCDD/Fs and coplanar PCBs on animals inhabiting open ocean and terrestrial environment. Whereas albatrosses from southern oceans retained lower TEQ concentrations, possible adverse effects of PCDD/Fs and coplanar PCBs to black-footed and Laysan albatrosses of the North Pacific Ocean may be suspected from TEQ levels.

Duodenum-preserving resection of the pancreatic head with the ultrasonic coagulating shears.

Duodenum-preserving resection of the pancreatic head is a risk factor for pancreatic fistula because of the wide surface of the transected pancreas. We report on a 72-year-old woman undergoing this procedure for cystadenoma in the pancreatic head using the ultrasonic coagulating shears. The soft pancreatic parenchyma was extensively transected around the cyst with the coagulating shears. Suture of the cut stump was not necessary due to absence of bleeding. The distal pancreatic duct was well preserved for pancreatojejunostomy. We oversewed the possible opening of the main pancreatic duct on the remaining pancreas attached to the duodenum after confirming the location by intrabiliary dye injection. The postoperative course was uneventful. The draining fluid amylase level was low and there were no viscous materials from the drains. We compared histologic changes of a porcine pancreas transected with the coagulating shears or electrocautery to evaluate the sealing effect of the transected surface. The cut stump was covered by a continuing layer of thick protein coagulum in cases of coagulating shears, but by a disrupted layer of coagulating necrosis with charring in cases of electrocautery. The coagulating shears are useful for pancreatic transection in duodenum-preserving resection of the pancreatic head to prevent bleeding and pancreatic fistula from the cut surface.

Peppermint oil reduces gastric spasm during upper endoscopy: a randomized, double-blind, double-dummy controlled trial.

BACKGROUND: GI endoscopy without general anesthesia causes a hyperperistaltic state in the stomach, which frequently necessitates the use of antispasmodic agents, such as hyoscine-N-butylbromide, but these drugs have side effects. Peppermint oil is harmless and acts locally to inhibit GI smooth muscle contraction. METHODS: A randomized double-blind, double-dummy, controlled trial was conducted in 100 patients to compare the antispasmodic effects of hyoscine-N-butylbromide administered intramuscularly and a placebo solution administered intraluminally by means of the endoscope, and also the effects of a placebo solution administered intramuscularly with those of a peppermint oil solution administered intraluminally. The percent change in diameter of the pyloric ring before and after the administrations was defined as the opening ratio, and the percent change in diameter between the maximally and minimally opened pyloric ring states was defined as the contraction ratio. Time until disappearance of the contraction ring(s) in the gastric antrum and side effects of the drugs were also determined. RESULTS: The opening ratio was significantly higher in the peppermint oil administration group than in the hyoscine-N-butylbromide injection group. The contraction ratio after peppermint oil administration was significantly lower than that after hyoscine-N-butylbromide injection. The time required for disappearance of the antral contraction ring(s) was shorter in the peppermint oil group (97.1 +/- 11.4) than in the hyoscine-N-butylbromide group (185.9 +/- 10.1 s; p < 0.0001). No significant side effects were associated with peppermint oil, whereas hyoscine-N-butylbromide injection produced side effects such as dry mouth, blurred vision, and urinary retention. CONCLUSIONS: Peppermint oil solution administered intraluminally can be used as an antispasmodic agent with superior efficacy and fewer side effects than hyoscine-N-butylbromide administered by intramuscular injection during upper endoscopy.

[Complete response in a case of recurrent gastric cancer treated with TS-1].

We report the case of 72-year-old man with recurrent gastric cancer who was successfully treated with TS-1. We performed only non-curative operation because the tumor had infiltrated the pancreas head and aspiration pneumonia complications developed under the anesthetic. Abdominal CT revealed local recurrence and metastasis of the paraaortic lymph node after 3 months, so we started TS-1 chemotherapy. One course consisted of daily oral administration of 100 mg TS-1 for 4 weeks and withdrawal for 2 weeks. The recurrent lesions disappeared completely after 1 course. Furthermore, this therapy was continued for 3 courses without any side effects.