Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

Purpose  

An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival.     

Transurethral Foley catheter misplacement into the upper urinary tract in a patient with a history of lung cancer and chemotherapy: a case report and considerations to keep in mind

Indwelling urethral catheter placement is a common and comparatively safe procedure. Misplacement of a urethral catheter into the upper urinary tract is unusual, and only a few cases have been reported. We describe the case of a 43-year-old man who presented with oliguria and had a history of chemotherapy for known metastatic lung cancer. As he had no history of urological disease, urethral catheterization was expected to be uneventful. The catheter was unable to be pulled back to the bladder neck once the balloon was inflated, and the patient expressed discomfort. Subsequent computed tomography revealed that the tip of the catheter was placed in the middle of the right ureter. Unbeknownst to the physicians before urethral catheterization, the patient had severe lower urinary tract symptoms and urinary bladder dysfunction with hydronephrosis, likely due to chemotherapy. Based on the patient’s symptoms and imaging results, we judged the possibility of severe ureteral injury to be low. The malpositioned catheter was removed uneventfully after complete balloon deflation and then reinserted properly. He was admitted to the medical department but died as a result of an exacerbation of the underlying disease unrelated to the incident. If urethral catheter placement seems abnormal, physicians should aspirate and irrigate to confirm correct positioning before balloon inflation; then, they should carefully pull the inflated balloon near the neck of the bladder while monitoring the patient’s symptoms. Although urethral catheter placement is comparatively safe, physicians must keep in mind that patients who have undergone chemotherapy might be at a risk for this rare complication.     

The beneficial impacts of splanchnic vasoactive agents on hepatic functional recovery in massive hepatectomy porcine model

BackgroundExcessive portal pressure after massive hepatectomy can cause hepatic sinusoidal injury and have deleterious impacts on hepatic functional recovery, contributing to developing post-hepatectomy liver failure. This study aimed to assess the effects of splanchnic vasoactive agents on hepatic functional recovery and regeneration while clarifying the underlying mechanism, using a 70% hepatectomy porcine model.MethodsEighteen pigs undergoing 70% hepatectomy were involved in this study and divided into three groups: control (n=6), terlipressin (n=6), and octreotide (n=6). Terlipressin (0.5 mg) and octreotide (0.2 mg) were administered 3 times a day for each group with the first dose starting just before surgery until the 7th postoperative day, at which time the surviving pigs were sacrificed. During the period, portal pressure, liver weight, biochemical analysis, histological injury score, and molecular markers were evaluated and compared between groups.ResultsThe 7-day survival rates in the octreotide, terlipressin, and control groups were 100%, 83.3%, and 66.7%, respectively. The portal pressures decreased in both terlipressin and octreotide groups than the control group at 30 minutes, 1 hour and 6 hours after hepatectomy. The amount of regeneration measured by liver weight to body weight ratio at the time of sacrifice in the terlipressin group was smaller than that in the control group (117% vs. 129%, P=0.03). Serum aspartate aminotransferase (AST) and total bilirubin levels at 1 and 6 hours after hepatectomy and prothrombin time/international normalized ratio (PT/INR) at 6 hours after hepatectomy were significantly improved in the terlipressin and octreotide groups compared to the control group. Serum endothelin-1 (ET-1) was significantly lower in the terlipressin group than that in the control group 6 hours after hepatectomy (P<0.01). The histological injury score in the control group was significantly higher than that in the terlipressin group on the 7th postoperative day (P<0.01).ConclusionsSplanchnic vasoactive agents, such as terlipressin and octreotide, could effectively decrease portal pressure and attenuate liver injury after massive hepatectomy.     

Pseudoepitheliomatous hyperplasia in lichen sclerosus of the vulva.

Small tentacles or separated nests of squamous cells in the dermis are not uncommonly seen in long-standing vulvar lichen sclerosus (LS) associated with epidermal thickening. We recently encountered a case where separated nests of well-differentiated squamous cells in the dermis were difficult to distinguish from squamous cell carcinoma (SCC). Further biopsies showed similar nests originating from every hair follicle. We postulated a diagnosis of multifocal pseudoepitheliomatous hyperplasia (PEH) to explain this phenomenon. Because we could find no reference to PEH in the setting of LS, we reviewed the biopsies of 92 women with extragenital and vulvar LS with and without carcinoma to determine its frequency and histological appearance. The study population, which excluded the index case, comprised 10 women with extra-anogenital LS, 58 with vulvar LS without carcinoma, and 24 with vulvar LS with carcinoma. The presence of PEH, epidermal thickness, predominant dermal collagen change, degree of inflammation, and presence of fibrin and red blood cells were recorded. The presence or absence of lichen simplex chronicus (LSC), squamous cell hyperplasia (SCH), and differentiated vulvar intraepithelial neoplasia (VIN) were recorded. PEH was identified only in vulvar LS, where it was seen in 7/58 (12.1%) women without carcinoma, 1/24 (8.3%) with carcinoma, and 0/10 (0%) with extra-anogenital LS. Two forms of PEH were seen: predominantly epidermal 7/8 (87.5%) and predominantly follicular 1/8 (12.5%). PEH was associated with increased epidermal thickness, less dermal edema, more dermal inflammation, fresh fibrin, and red blood cell extravasation. In all cases, there was associated LSC, but there was no SCH or differentiated VIN. In conclusion, PEH may explain many of the cases of dermal tentacles and separated squamous nests in vulvar LS with LSC. The association with fresh fibrin and red blood cells suggests that PEH might be a reaction to tissue damage. PEH is distinguished from SCC by its lack of atypia, confinement to the abnormal collagen, and limited growth. The pathologist must be careful about making a diagnosis of PEH in LS with epidermal thickening, looking carefully for basal atypia and other features of differentiated VIN in the overlying epidermis or dermal proliferation. We do not know whether PEH occurs in differentiated VIN and, if it does, how it could be distinguished from SCC.     

The attitudes of cancer patients and their families toward the disclosure of terminal illness.

PURPOSE:To ascertain the attitude of cancer patients and their families toward disclosure of terminal illness to the patient. PATIENTS AND METHODS: We constructed a questionnaire that included demographic and clinical information and delivered it to 758 consecutive individuals (433 cancer patients and 325 families that have a relative with cancer) at seven university hospitals and one national cancer center in Korea. RESULTS: 380 cancer patients and one member from each of 281 families that have a relative with cancer completed the questionnaire. Cancer patients were more likely than family members to believe that patients should be informed of the terminal illness (96.1% v 76.9%; P <.001). Fifty percent of the family members and 78.3% of the patients thought that the doctor in charge should be the one who informs the patient. Additionally, 71.7% of the patients and 43.6% of the family members thought that patients should be informed immediately after the diagnosis. Stepwise multiple logistic regression indicated that the patient group was more likely than the family group to want the patient to be informed of the terminal illness (odds ratio [OR], 9.76; 95% CI, 4.31 to 22.14), by the doctor (OR, 4.00; 95% CI, 2.61 to 6.11), and immediately after the diagnosis (OR, 3.64; 95% CI, 2.45 to 5.41). CONCLUSION: Our findings indicated that most cancer patients want to be informed if their illness is terminal, and physicians should realize that the patient and the family unit may differ in their attitude toward such a disclosure. Our results also reflect the importance of how information is given to the patient.     

Comparison of the effects of dexmedetomidine and propofol on hypothermia in patients under spinal anesthesia: a prospective,randomized, and controlled trial

Background: Redistribution hypothermia caused by vasodilation during anesthesia is the primary cause of perioperative hypothermia. Propofol exerts a dose-dependent vasodilatory effect, whereas dexmedetomidine induces peripheral vasoconstriction at high plasma concentrations. This study compared the effects of dexmedetomidine and propofol on core temperature in patients undergoing surgery under spinal anesthesia.Methods: This prospective study included 40 patients (aged 19-70 years) with American Society of Anesthesiologists Physical Status class I-III who underwent elective orthopedic lower-limb surgery under spinal anesthesia. Patients were randomly allocated to a dexmedetomidine or propofol group (n = 20 per group). After induction of spinal anesthesia, patients received dexmedetomidine (loading dose: 1 μg/kg over 10 min; maintenance dose: 0.2-0.7 μg/kg/h) or propofol (loading dose: 75 μg/kg over 10 min; maintenance dose: 12.5-75 μg/kg/min). The doses of sedatives were titrated to maintain moderate sedation. During the perioperative period, tympanic temperatures, thermal comfort score, and shivering grade were recorded.Results: Core temperature at the end of surgery did not differ significantly between the groups (36.4 ± 0.4 and 36.1 ± 0.7°C in the dexmedetomidine and propofol groups, respectively; P = 0.118). The lowest perioperative temperature, incidence and severity of perioperative hypothermia, thermal comfort score, and shivering grade did not differ significantly between the groups (all P > 0.05).Conclusions: In patients undergoing spinal anesthesia with moderate sedation, the effect of dexmedetomidine on patients'' core temperature was similar to that of propofol.     

Induction of apoptotic cell death in human bladder cancer cells by ethanol extract of Zanthoxylum schinifolium leaf,through ROS-dependent inactivation of the PI3K/Akt signaling pathway

BACKGROUND/OBJECTIVESZanthoxylum schinifolium is traditionally used as a spice for cooking in East Asian countries. This study was undertaken to evaluate the anti-proliferative potential of ethanol extracts of Z. schinifolium leaves (EEZS) against human bladder cancer T24 cells.MATERIALS/METHODSSubsequent to measuring the cytotoxicity of EEZS, the anti-cancer activity was measured by assessing apoptosis induction, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). In addition, we determined the underlying mechanism of EEZS-induced apoptosis through various assays, including Western blot analysis.RESULTSEEZS treatment concentration-dependently inhibited T24 cell survival, which is associated with apoptosis induction. Exposure to EEZS induced the expression of Fas and Fas-ligand, activated caspases, and subsequently resulted to cleavage of poly (ADP-ribose) polymerase. EEZS also enhanced the expression of cytochrome c in the cytoplasm by suppressing MMP, following increase in the ratio of Bax:Bcl-2 expression and truncation of Bid. However, EEZS-mediated growth inhibition and apoptosis were significantly diminished by a pan-caspase inhibitor. Moreover, EEZS inhibited activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and the apoptosis-inducing potential of EEZS was promoted in the presence of PI3K/Akt inhibitor. In addition, EEZS enhanced the production of ROS, whereas N-acetyl cysteine (NAC), a ROS scavenger, markedly suppressed growth inhibition and inactivation of the PI3K/Akt signaling pathway induced by EEZS. Furthermore, NAC significantly attenuated the EEZS-induced apoptosis and reduction of cell viability.CONCLUSIONSTaken together, our results indicate that exposure to EEZS exhibits anti-cancer activity in T24 bladder cancer cells through ROS-dependent induction of apoptosis and inactivation of the PI3K/Akt signaling pathway.