Context Transanastomotic internal pancreatic duct stent placement during reconstruction following pancreaticoduodenectomy is thought to be one of the strategies for preventing postoperative pancreatic fistula and widely performed. However complications related to internal stent migration have very rarely been reported. Here we report a rare case of internal pancreatic stent retrograde migration into the left biliary tree through afferent limb of a Roux-en-Y reconstruction after pancreaticogastrostomy following pancreaticoduodenectomy. Case report A seventy-four-year-old woman underwent subtotal stomach preserving pancreaticoduodenectomy with right hemicolectomy for intraductal papillary mucinous neoplasm of the pancreas head and adenocarcinoma of the cecum. Pancreaticogastrostomy was undertaken during subtotal stomach preserving pancreaticoduodenectomy with internal pancreatic stent placement. Post operative course was uneventful and she was discharged on the fifteenth postoperative day. She remained almost asymptomatic after discharge except for slight vague abdominal pain. Twenty-seven days after the operation, an internal pancreatic stent was detected at right upper quadrant in routine abdominal X-ray at the time of outpatient visit. An abdominal computed tomography scan revealed that a stent was migrated into the left hepatic duct trough hepaticojejunostomy. Enteroscopic retrieval of the stent was then successfully undertaken. Conclusions In the present case, an internal pancreatic stent unexpectedly migrated into the hepatic duct against the peristaltic direction of the afferent limb. Although complications related to surgically placed internal pancreatic stent migration have rarely been reported so far, surgeons should be aware of the possibility of internal stent migration and any postoperative imaging studies should be considered focusing on the position of the devices placed intraoperatively.

Purpose: Identifying prospective predictors of a poor treatment outcome in acute to subacute sciatica would be of great importance for clinical practice. This study aimed to determine what baseline factors are associated with short- to medium-term outcomes on acute to subacute sciatica caused by lumbar disk herniation (LDH) after epidural injections. Methods: Variables including demographic data, neurological and radiological examination, the visual analog scale (VAS), the Roland-Morris Disability Questionnaire (RMDQ), and the Spielberger State-Trait Anxiety Inventory from 48 LDH patients (25 males and 23 females between 20 and 60 years old) with acute to subacute sciatica before and 1, 3, and 6 months following epidural injections were measured. A poor outcome was defined as a VAS reduction of less than 50% or a RMDQ reduction of less than an important change. Results: In multiple logistic regression analysis, the presence of a high trait anxiety (OR=0.133, 95% CI;0.027-0.651) and motor disturbances (OR=3.517, 95% CI;1.098-11.267) were significantly associated with an increasing risk of poor outcome at the 1-month assessment. At the 3-month assessment, the presence of a high trait anxiety (OR=0.115, 95% CI;0.022-0.611) was the only prognostic factor. At the 6-month assessment, the presence of a high trait anxiety (OR=0.065, 95% CI;0.007-0.570) was the only significant prognostic factor.

Lycoperine A was synthesized through a highly convergent route in which a double alkylation of 2,6-dicyano-N-benzylpiperidine with the octahydroquinoline moiety gave the lycoperine skeleton. The octahydroquinoline was prepared by a desymmetrization reaction of 5-methylcyclohexane-1,3-dione. Hydrolysis, reductive amination, and cyclization gave lycoperine A in 13 steps and 3% overall yield. The absolute configuration of lycoperine A was assigned as 6R,6'R,8R,8'R,13S,17R.

Authors' A Prevention Univers i t Pharmacol Tanta, Egy Note: Supp Research O Correspon Targeting C Prefectural Kyoto 602E-mail: tsak

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Abstract The histone deacetylase inhibitors (HDIs) valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat) are used clinically for the treatment of epilepsy and cutaneous T-cell lymphoma, respectively. HDIs have been shown to be more effectively utilized in combination with other agents despite the promising anti-tumor effect of HDIs alone. Therefore, additional mechanism-based therapeutic strategies for use of HDIs in combination with other agents should be investigated to overcome resistance to HDIs or to increase the efficacy of HDIs. The natural endogenous ligand of peroxisome proliferator-activated receptor γ (PPARγ) 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a member of cyclopentenone prostaglandins and known to be a potent anti-neoplastic agent. Thus, we examined whether VPA or SAHA in combination with 15d-PGJ2 could show synergistic anti-tumor activitiy in colon cancer DLD-1 cells. Cell viability was determined using a Cell Counting Kit-8 assay. Apoptosis and reactive oxygen species (ROS) generation were determined using flow cytometry analysis. Western blotting and real-time RT-PCR analysis were carried out to investigate the expressions of apoptosis-related molecules. Small interfering RNA or transient transfection with plasmids was used for gene silencing, gene overexpression or luciferase assays. Mice bearing DLD-1 xenograft were divided into 4 groups (n=5) and injected everyday (i.p.) with diluent, VPA (100 mg/kg), 15d-PGJ2 (5 mg/kg) or a combination for 25 days. Cotreatment with VPA or SAHA at clinically achievable concentrations and 15d-PGJ2 synergistically induced cell death and drastically caused caspase-dependent apoptosis in DLD-1 cells. The apoptosis induced by VPA/15d-PGJ2 cotreatment was due to alterations of apoptosis-related genes such as an antiapoptotic Bcl-2 family member Bcl-XL, X-chromosome-linked inhibitor of apoptosis (XIAP), C/EBP homologous protein (CHOP) and death receptor 5 (DR5) via ROS generation, subsequent endoplasmic reticulum stress and/or histone deacetylase inhibition. Moreover, VPA/15d-PGJ2 cotreatment induced ROS-dependent apoptosis in other malignant tumor cells and was more effective than a VPA or 15d-PGJ2 monotherapy in vivo. These results suggest that cotreatment with the clinically relevant HDIs and 15d-PGJ2 may warrant clinical investigation as a rational combination therapy against a broad spectrum of malignant tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5415.

AbstractPurpose: The clinically relevant histone deacetylase inhibitors (HDI) valproic acid (VPA) and suberoylanilide hydroxamic acid exert variable antitumor activities but increase therapeutic efficacy when combined with other agents. The natural endogenous ligand of peroxisome proliferator–activated receptor γ 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a potent antineoplastic agent. Therefore, we investigated whether these HDIs in combination with 15d-PGJ2 could show synergistic antitumor activity in colon cancer DLD-1 cells.Experimental Design: Cell viability was determined using a Cell Counting Kit-8 assay. Apoptosis and reactive oxygen species (ROS) generation were determined using flow cytometry analysis. Western blotting and real-time reverse transcription-PCR analysis were carried out to investigate the expression of apoptosis-related molecules. Mice bearing DLD-1 xenograft were divided into four groups (n = 5) and injected everyday (i.p.) with diluent, VPA (100 mg/kg), 15d-PGJ2 (5 mg/kg), or a combination for 25 days.Results: HDI/15d-PGJ2 cotreatments synergistically induced cell death through caspase-dependent apoptosis in DLD-1 cells. Moreover, HDIs/15d-PGJ2 caused histone deacetylase inhibition, leading to subsequent ROS generation and endoplasmic reticulum stress to decrease the expression of antiapoptotic molecules Bcl-XL and XIAP and to increase that of proapoptotic molecules CAAT/enhancer binding protein homologous protein and death receptor 5. Additionally, VPA/15d-PGJ2 cotreatment induced ROS-dependent apoptosis in other malignant tumor cells and was more effective than a VPA or 15d-PGJ2 monotherapy in vivo.Conclusions: Cotreatments with the clinically relevant HDIs and the endogenous peroxisome proliferator–activated receptor γ ligand 15d-PGJ2 are promising for the treatment of a broad spectrum of malignant tumors. Clin Cancer Res; 16(8); 2320–32. ©2010 AACR.

Cucurbitacin B (cucB) is a triterpenoid constituent of Cucurbitaceae vegetables and a promising phytochemical for cancer prevention. However, the mechanism of anti-tumor activity of cucB remains unknown, especially in colon cancers. Here, we demonstrate for the first time that cucB inhibited growth of human colon cancer SW480 cells through a reactive oxygen species (ROS)-dependent mechanism. CucB induced G(2) phase arrest and apoptosis in a dose-dependent manner. At the molecular level, cucB reduced the expression of cyclin B1 and cdc25C proteins and activated caspases in SW480 cells. On the other hand, the state of phosphorylation of signaling transducer and activator of transcription 3 (STAT3) was unchanged. We found that cucB increased intracellular ROS levels, and N-acetylcysteine, a well-known antioxidant, reduced the changes in expression of the molecules, and suppressed both G(2) arrest and apoptosis. These results suggested that cucB induced G(2) arrest and apoptosis through a STAT3-independent but ROS-dependent mechanism in SW480 cells.

There have been reports that nerve block treatments, in addition to the WHO―recommended drug therapy, are useful for pain relief and QOL improvement. In order to gain insight into the general perception of the usefulness among doctors involved in palliative care medicine as well as to obtain constructive feedback, a survey was conducted targeting those doctors who are considered influential in the field of palliative care. Among the doctors, thirty percent responded that they would consider nerve block treatments after providing drug therapies. They also have high regard for subarachnoid or epidural continuous infusion and expressed expectations regarding anesthesiologists, role in the practice. Overall, it was suggested anesthesiologists should actively educate doctors in other medical fields on various aspects of the nerve block treatment including situations where such treatment may be indicated.

BACKGROUND:The chemopreventive effects of dietary phytochemicals on malignant tumors have been studied extensively because of a relative lack of toxicity. To achieve desirable effects, however, treatment with a single agent mostly requires high doses. Therefore, studies on effective combinations of phytochemicals at relatively low concentrations might contribute to chemopreventive strategies.RESULTS:Here we found for the first time that co-treatment with I3C and genistein, derived from cruciferous vegetables and soy, respectively, synergistically suppressed the viability of human colon cancer HT-29 cells at concentrations at which each agent alone was ineffective. The suppression of cell viability was due to the induction of a caspase-dependent apoptosis. Moreover, the combination effectively inhibited phosphorylation of Akt followed by dephosphorylation of caspase-9 or down-regulation of XIAP and survivin, which contribute to the induction of apoptosis. In addition, the co-treatment also enhanced the induction of autophagy mediated by the dephosphorylation of mTOR, one of the downstream targets of Akt, whereas the maturation of autophagosomes was inhibited. These results give rise to the possibility that co-treatment with I3C and genistein induces apoptosis through the simultaneous inhibition of Akt activity and progression of the autophagic process. This possibility was examined using inhibitors of Akt combined with inhibitors of autophagy. The combination effectively induced apoptosis, whereas the Akt inhibitor alone did not.CONCLUSION:Although in vivo study is further required to evaluate physiological efficacies and toxicity of the combination treatment, our findings might provide a new insight into the development of novel combination therapies/chemoprevention against malignant tumors using dietary phytochemicals.

Excellent outcomes were achieved with spinal cord stimulation (SCS) for 7 to 10 days on 2 patients who developed postherpetic neuralgia. Both patients were within 2 to 3 months of the onset of the condition, and nerve blocks provided only temporary pain relief and drug therapies had poor efficacy. The authors believe that limited-duration SCS for subacute postherpetic neuralgia is a useful treatment approach that may prevent the pain from progressing to chronic postherpetic neuralgia.

Synthesis and structure-activity relationship studies of a series of 4-aminoquinazoline derivatives led to the identification of (1R,2S)-17, N-[(1R,2S)-2-({2-[(4-chlorophenyl)carbonyl]amino-6-methylquinazolin-4-yl}amino)cyclohexyl]guanidine dihydrochloride, as a highly potent ORL1 antagonist with up to 3000-fold selectivity over the mu, delta, and kappa opioid receptors. Molecular modeling clarified the structural factors contributing to the high affinity and selectivity of (1R,2S)-17.

帯状疱疹後神経痛 (PHN) は, 多面的治療, すなわち種々の治療法を組み合わせた治療がなされているが, 依然, 難治性である. 当科において発症から3ヵ月以降に初診となった帯状疱疹後痛58症例を検討した. 発症3～5ヵ月 (帯状疱疹後痛) は12症例, 発症6ヵ月以降 (PHN) は46症例であった. 治療により帯状疱疹後痛は7症例 (58.3%) , PHNでは14症例 (30.4%) で疼痛の軽減を認め, 前者では5症例 (41.7%) , 後者では6症例 (13.0%) で治療を終了できた. 多くの症例で神経ブロックを主体とした治療を施行していた. 一方, 受診までに多面的治療を受けてきた症例, 来院しなくなる症例や侵襲的な治療を望まない症例も多く, 多面的治療を施行するうえでの限界も示唆された. またPHNに対する種々の治療法から, 薬物療法以外の主に神経ブロック治療, 高周波熱凝固療法と硬膜外脊髄電気刺激療法の治療効果について考察した. 高周波熱凝固療法や硬膜外脊髄電気刺激療法では, 効果が得られる症例もあるが, 長期予後も含めてさらなる検討が必要である. 現在, 施行されている治療法のなかで格段に進歩しているものは見当たらない. 単一の治療法ではなく, 薬物療法を主体とした効果が得られると思われる種々の治療法を組み合わせた多面的な治療が施行されているのが現状であり, 症例のADLやQOLの維持・向上を目指した治療法を選択していくことが重要となっている. PHNの病態がさらに解明され, 個々の治療法についてもさらなる検討がなされていくことが望まれる.

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We have developed highly enantioselelctive reactions of silicon enolates with N-acyl-alpha-iminophosphonates leading to optically active alpha-amino phophonates. A copper (II)-diamine complex was shown to be effective in this reaction, and high levels of yield and selectivity were achieved. It is noteworthy that this reaction opens a way to various biologically important, optically active alpha-amino phosphonate derivatives.

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