[Efficacy of Cancer Treatment with Electronic Patient-Reported Outcome Monitoring and Future Expectations].

The Common Terminology Criteria for Adverse Events has been used to evaluate adverse events in oncology. However, it has been shown that medical practitioners who assess adverse events tend to underestimate symptoms more than the patients themselves who experience them, and monitoring of patient-reported outcomes(PROs)is considered essential to achieve patient-centered care. PRO is defined as"any report of a patient's health status obtained directly from the patient, without interpretation by a clinician or anyone else". PROs have been routinely collected in clinical practice using paper and pencil, but they can also be collected more easily and efficiently in the form of electronic PROs(ePROs)using tablets and smartphones. The ePRO system enables remote symptom monitoring and intervention, when necessary, as PROs entered by the patient are shared with the health care provider even when not in person, which not only improves the patient's quality of life but also has been reported to increase overall survival. In Japan, ePROs that can be used in routine medical care are already available, but they have not yet been widely adopted. This article outlines the necessity and usefulness of ePRO monitoring in the treatment of cancer patients, problems and solutions for its introduction and dissemination, and prospects in daily clinical practice.

Risk Evaluation of Proton Pump Inhibitors for Panitumumab-Related Hypomagnesemia in Patients with Metastatic Colorectal Cancer.

Hypomagnesemia commonly occurs as a side effect of panitumumab treatment. In severe cases, temporary discontinuation or dose reduction of panitumumab may be necessary. Proton pump inhibitors (PPIs) are reportedly potential risk factors for hypomagnesemia. We conducted a multicenter study to assess the impact of PPIs on the risk of grade 3-4 hypomagnesemia in patients with metastatic colorectal cancer (mCRC) receiving panitumumab. We adjusted for potential bias using a propensity score-matched analysis and retrospectively reviewed the medical records of patients. Hypomagnesemia severity was graded according to the Common Terminology Criteria for Adverse Events, version 5.0. A total of 165 patients were enrolled in this study. The incidence of grade 3-4 hypomagnesemia was significantly higher in the PPI group than in the non-PPI group, both before (20.0% [30/60] vs. 8.0% [8/105], p = 0.026) and after propensity score matching (16.2% [6/37] vs. 0% [0/37], p = 0.025). In the propensity score-matched cohort, the risk of grade 3-4 hypomagnesemia was significantly higher in the PPI group (odds ratio, 2.19; 95% confidence interval, 1.69-2.84; p = 0.025). These findings suggest that concomitant use of PPIs significantly increases the risk of grade 3-4 hypomagnesemia in patients with mCRC receiving panitumumab. Therefore, close monitoring of these patients is imperative.

Detailed exploration of pathophysiology involving inflammatory status and bleeding symptoms between lipopolysaccharide- and tissue factor-induced disseminated intravascular coagulation in rats.

Lipopolysaccharide (LPS) and tissue factor (TF) have frequently been used to induce disseminated intravascular coagulation (DIC) in experimental animal models. We have previously reported that the pathophysiology of DIC differs according to the inducing agents. However, inflammatory status and bleeding symptoms have not been fully compared between rat models of the two forms of DIC. We attempted to evaluate detailed characteristic features of LPS- and TF-induced DIC models, especially in regard to inflammatory status and bleeding symptoms, in addition to selected hemostatic parameters and pathologic findings in the kidneys. The degree of hemostatic activation in both types of experimental DIC was identical, based on the results of thrombin-antithrombin complex levels. Markedly elevated tumor necrosis factor, interleukin-6, and high-mobility group box-1 concentrations were observed with severe organ dysfunction and marked fibrin deposition in the kidney on administration of LPS, whereas markedly elevated D-dimer concentration and bleeding symptoms were observed with TF administration. Pathophysiology such as fibrinolytic activity, organ dysfunction, inflammation status, and bleeding symptom differed markedly between LPS- and TF-induced DIC models in rats. We, therefore, recommend that these disease models be assessed carefully as distinct entities to determine the implications of their experimental and clinical use.

Efficacy and Safety of Nivolumab in Patients with Advanced Non-small-cell Lung Cancer and Poor Performance Status.

Background: Nivolumab efficacy in patients with non-small-cell lung cancer (NSCLC) and performance status (PS) of 2-4 is unclear. We aimed to compare survival, treatment efficacy, and safety in patients with NSCLC with poor PS who received nivolumab plus best supportive care (BSC) with those in patients who received BSC alone in a palliative care unit (PCU). Patients and methods: This retrospective study included 99 consecutive patients with NSCLC who received nivolumab plus BSC or BSC alone between December 2015 and March 2018. Results: In total, 43 patients with PS of 0-1 (good PS group) and 20 patients with PS of 2-4 (poor PS group) received nivolumab plus BSC; the remaining 36 patients received BSC alone in the PCU (PC group). Median overall survival was 32 days [95% confidence interval (CI), 21-43] in the poor PS group and 31 days (95% CI, 25-37) in the PC group (hazard ratio, 0.653; 95% CI, 0.368-1.158; P = 0.137). Moreover, median overall survival in patients with PS of 3 or 4 among the poor PS group was not significantly longer than that in the PC group (HR, 1.235; 95% CI, 0.646-2.360; P = 0.516). The frequency of severe pneumonitis in the poor PS group was significantly higher than that in the good PS group (25% vs. 2%, P = 0.010). Conclusion: Survival benefit of nivolumab in patients with NSCLC with poor PS, especially 3 or 4, was not confirmed. Further studies with larger numbers of patients are required to confirm our results.

Risk factors for oxaliplatin-induced vascular pain in patients with colorectal cancer and comparison of the efficacy of preventive methods.

BACKGROUND: Vascular pain is a common adverse drug reaction in colorectal cancer patients receiving peripheral venous administration of oxaliplatin. The aim of this work was to identify risk factors for vascular pain, and to examine whether currently used treatments reduce its incidence. METHODS: We conducted a multicenter retrospective study in Japanese colorectal cancer patients receiving peripheral venous administration of oxaliplatin. The effects of various treatments (administration of analgesics, addition of dexamethasone to the infusion solution for pH adjustment, dilution of the infusion solution, or use of hot gel for warming the injection site) on the incidence of vascular pain were assessed. Risk factors for vascular pain were identified by multiple logistic regression analysis. RESULTS: One hundred and ninety patients who had received an oxaliplatin-containing regimen via a peripheral venous route were analyzed. None of the preventive methods examined significantly reduced the incidence of vascular pain. BMI (BMI < 22), clinical stage (I-III) and oxaliplatin dosage (130 mg/m2 versus dose reduction) were identified as independent risk factors for development of vascular pain. The incidence of oxaliplatin-induced vascular pain was significantly higher in patients who had two or more risk factors. CONCLUSIONS: BMI, clinical stage and oxaliplatin dosage were identified as independent predictive markers for oxaliplatin-induced vascular pain. Existing treatments for vascular pain are not effective in reducing its incidence.

Outcomes for patients with obstructing colorectal cancers treated with one-stage surgery using transanal drainage tubes.

BACKGROUND: Acute colorectal obstruction requires immediate surgical treatment. Although one-stage surgery with transanal drainage tubes (TDT) is reportedly safe and feasible, the long-term outcome of this procedure remains unclear. AIM: To assess the outcome of one-stage surgery using TDT in the acute left colon or rectal obstructions due to colorectal carcinomas. METHODS: Clinicopathological data were recorded from patients with colorectal cancer with acute obstructions between 2006 and 2013. RESULTS: A total of 43 patients were enrolled including 29 males and 14 females. Among 39 patients, TDT was successful in 33 (84 %) and was incomplete in 6. Thus, 33 patients received one-stage surgery with TDT decompression, and 9 patients, including 6 with incomplete decompression, received one-stage surgery with no decompression. No significant differences in clinicopathological factors were observed between decompression and non-decompression groups. Adjusted analyses revealed that decompression using TDT was significantly associated with OS (hazard ratio 0.24; 95 % confidence interval, 0.08-0.72; p = 0.01). Furthermore, OS in the TDT decompression group was significantly longer than that in the non-decompression group (p = 0.01). CONCLUSIONS: One-stage surgery with decompression using TDT may be effective to avoid stomas and to improve overall survival in patients with obstructing colorectal cancers.

Protecting cisplatin-induced nephrotoxicity with cimetidine does not affect antitumor activity.

The present study examined the influence of cimetidine on the nephrotoxicity and antitumor effects of cisplatin in vitro and in vivo. When the serum concentration of cimetidine was maintained over 20 µg/ml for 4 h by bolus and continuous intravenous infusion, cimetidine prevented nephrotoxicity of cisplatin without influencing antitumor activity. Cimetidine and the antioxidant N-acetylcysteine (NAC) significantly inhibited the in vitro growth inhibition of cisplatin in cells originating from the kidney, but not in SOSN2 osteosarcoma cells. Cimetidine (1 mM) also did not influence platinum concentration in the cells, regardless of whether the organic cation transporter 2 (OCT2) was expressed. Cisplatin did induce reactive oxygen species (ROS) in the KN41 kidney cell line and cimetidine and NAC significantly reduced ROS production. However, cisplatin did not produce ROS in osteosarcoma cells. From these results, cimetidine clearly inhibits nephrotoxicity induced by cisplatin without any influence on the antitumor activity of cisplatin on osteosarcoma in vitro and in vivo.

Intraductal papillary mucinous tumor of the pancreas associated with autosomal dominant polycystic kidney disease.

A 43-year-old male with a history of autosomal dominant polycystic kidney disease (ADPKD) was admitted to our center with severe abdominal pain and was diagnosed with acute pancreatitis. CT showed multiple cysts in the liver and both kidneys along with ADPKD and a cystic mass, 4 cm in diameter, in the pancreatic head. The main pancreatic duct was dilated to 1 cm in diameter. The patient was diagnosed with acute pancreatitis due to intraductal papillary mucinous tumor (IPMT), and pancreatoduodenectomy was performed. Histologic examination revealed a multiloculated cystic tumor filled with mucin in the head of the pancreas. Microscopically, the tumor was diagnosed as adenocarcinoma and was found to have invaded the main pancreatic duct. Although, in addition to our case, only seven cases with association between ADPKD and malignant neoplasms have been reported, five of these cases had neoplasms arising from the pancreas. Therefore, we suggest that some genetic interactions may exist between ADPKD and pancreatic carcinogenesis.