Patient-Reported Quality of Life Before and After Chemoradiation for Intact Pancreas Cancer: A Prospective Registry Study

PurposeOur purpose was to determine the effect of chemoradiotherapy (CRT) on patient-reported quality of life (QOL) for patients with intact pancreas cancer.Methods and MaterialsWe reviewed a prospective QOL registry for patients with intact, clinically localized pancreatic ductal adenocarcinoma treated with CRT between June 2015 and November 2018. QOL was assessed pre-CRT (immediately before CRT, after neoadjuvant chemotherapy) and at the completion of CRT with the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) and its component parts: FACT-General (FACT-G) and hepatobiliary cancer subscore (HCS). A minimally important difference from pre-CRT was defined as ≥ 6, 5, and 8 points for FACT-G, HCS, and FACT-Hep, respectively.ResultsOf 157 patients who underwent CRT, 100 completed both pre- and post-CRT surveys and were included in the primary analysis. Median age at diagnosis was 65 years (range, 23-90). National Comprehensive Cancer Network resectability status was resectable (3%), borderline resectable (40%), or locally advanced (57%). Folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) (75%) or gemcitabine and nab-paclitaxel (42%) were given for a median of 6 cycles (range, 0-42) before CRT. Radiation therapy techniques included 3-dimensional conformal (22%), intensity modulated photon (55%), and intensity modulated proton (23%) radiation therapy to a median dose of 50 Gy (range, 36-62.5). Concurrent chemotherapy was most commonly capecitabine (82%). Sixty-three patients (63%) had surgery after CRT. The mean decline in FACT-G, HCS subscale, and FACT-Hep from pre- to post-CRT was 3.5 (standard deviation [SD], 13.7), 1.7 (SD 7.8), and 5.2 (SD 19.4), respectively. Each of these changes were statistically significant, but did not meet the minimally important difference threshold. Pancreatic head tumor location was associated with decline in FACT-Hep. Nausea was the toxicity with the greatest increase from pre- to post-CRT by both physician-assessment and patient-reported QOL.ConclusionsFor patients with intact pancreatic adenocarcinoma, modern CRT is well tolerated with minimal decline in QOL during treatment.     

Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Inhibition of phosphoribosylpyrophosphate synthetase by 4-methoxy-(MRPP) and 4-amino-8-(D-ribofuranosylamino) pyrimido[5,4-d]pyrimidine (ARPP)

The basis for the antitumor activities of the exocyclic amino nucleosides 4-amino-(ARPP) and 4-methoxy-8-(D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (MRPP) was investigated. The primary target of these nucleosides appeared to be 5-phospho-alpha-D-ribofuranose-1-pyrophosphate (PRPP) synthetase. MRPP-5'-monophosphate was a competitive inhibitor (Ki = 40 microM) of the activation of this enzyme by the cofactor inorganic phosphate (K alpha = 2.2 mM). Consequently, ARPP and MRPP treatment of WI-L2 cultures rapidly inhibited both de novo pyrimidine and purine synthesis as well as the nucleotide salvage reactions dependent on PRPP, ARPP or MRPP treatment completely prevented [14C]bicarbonate incorporation into acid-soluble pyrimidine and purine nucleotides. The rate of salvage of [8-14C]hypoxanthine to form IMP was decreased by 85%. Treatment of cells with these agents caused a 50% reduction in the steady-state level of PRPP. When the capacity of the treated cells for sustained synthesis of PRPP was examined by adenine incorporation, the rate of adenine uptake was inhibited by greater than 50%. In vivo treatment of BDF1 mice with a single dose of ARPP (173 mg/kg) or MRPP (62 mg/kg) extended the mean life span of the mice, which had been inoculated intraperitoneally 1 day earlier with 1 x 10(6) L1210 murine leukemia cells, by 62 and 82% respectively. These studies indicate that MRPP and ARPP inhibit PRPP synthetase, and that PRPP synthetase may be a viable target in the development of certain antitumor agents.     

Iotrol versus metrizamide in lumbar myelography: a double-blind study

In a prospective, randomized, double-blind study, 49 patients underwent lumbar myelography using iotrol (24 patients) or metrizamide (25 patients). The diagnostic imaging adequacy of iotrol was comparable with that of metrizamide. After iotrol myelography, adverse reactions were fewer, less severe, and of shorter duration than were those following metrizamide myelography. Thirteen of 24 patients (54%) receiving iotrol reported some adverse reactions compared with 24 of 25 patients (96%) receiving metrizamide. Five moderate and one severe adverse reaction occurred in the group receiving iotrol. Fourteen moderate and eight severe adverse reactions occurred in the group receiving metrizamide. Thirty-eight patients underwent electroencephalography both before and after myelography (19 iotrol and 19 metrizamide). None of the EEGs obtained after iotrol myelography changed from baseline, while seven of the EEGs obtained after metrizamide myelography showed changes from baseline. Iotrol was judged superior to metrizamide as a contrast medium in this patient population.     

臂丛神经根性损伤膈神经移位术对青壮年患者早期呼吸功能的影响

目的研究臂丛神经损伤膈神经移位术对青壮年患者早期呼吸功能的影响.方法对16例接受膈神经移位治疗的患者,在术前、术后（10 d）进行肺功能指标的比较,同时定期进行门诊随访,观察呼吸系统自觉症状程度.结果13例术后出现了不同程度的供氧不足症状,16例全部出现一侧膈肌抬高,术后第10天肺活量（VC）、肺活量预计值百分数（VC%）分别比术前减少37.98%和26.88%,两者差异有统计学意义（tvc=11.532、tvc%=0,P＜0.01）.其它项目如残气量（RV）较术前轻度下降,肺总量（TLC）下降值达到术前肺总量的36.49%,残气量/肺总量比值（RV/TLC%）较术前上升了4.75%,上述各指标的差值均有统计学意义.1 s用力呼气量/用力肺活量比值（FEV1/FVC）和术前比基本无改变,但其差值有统计学意义.膈神经移位右侧（10例）与左侧（6例）术前、术后肺活量比较差异有统计学意义.术后随访8个月～2年,所有患者均无明显呼吸困难和胸闷等症状.结论膈神经移位术后对青壮年患者肺容量有较大的丧失,肺通气功能减弱和小气道阻力增加,但其丧失程度在机体自身代偿耐受范围内,不会导致急剧发生的严重呼吸功能障碍.建议对右侧臂丛神经根性损伤的患者,术前进行严格的肺、心功能检查,避免发生较为严重的并发症.