Real-World Data on Subsequent Therapy for First-Line Osimertinib-Induced Pneumonitis: Safety of EGFR-TKI Rechallenge (Osi-risk Study TORG-TG2101).

BACKGROUND: Although osimertinib is a promising therapeutic agent for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the incidence of pneumonitis is particularly high among Japanese patients receiving the drug. Furthermore, the safety and efficacy of subsequent anticancer treatments, including EGFR-tyrosine kinase inhibitor (TKI) rechallenge, which are to be administered after pneumonitis recovery, remain unclear. OBJECTIVE: This study investigated the safety of EGFR-TKI rechallenge in patients who experienced first-line osimertinib-induced pneumonitis, with a primary focus on recurrent pneumonitis. PATIENTS AND METHODS: We retrospectively reviewed the data of patients with EGFR mutation-positive lung cancer who developed initial pneumonitis following first-line osimertinib treatment across 34 institutions in Japan between August 2018 and September 2020. RESULTS: Among the 124 patients included, 68 (54.8%) patients underwent EGFR-TKI rechallenge. The recurrence rate of pneumonitis following EGFR-TKI rechallenge was 27% (95% confidence interval [CI] 17-39) at 12 months. The cumulative incidence of recurrent pneumonitis was significantly higher in the osimertinib group than in the first- and second-generation EGFR-TKI (conventional EGFR-TKI) groups (hazard ratio [HR] 3.1; 95% CI 1.3-7.5; p = 0.013). Multivariate analysis revealed a significant association between EGFR-TKI type (osimertinib or conventional EGFR-TKI) and pneumonitis recurrence, regardless of severity or status of initial pneumonitis (HR 3.29; 95% CI 1.12-9.68; p = 0.03). CONCLUSIONS: Osimertinib rechallenge after initial pneumonitis was associated with significantly higher recurrence rates than conventional EGFR-TKI rechallenge.

A Phase â ¡ Study of Ubenimex Combined With Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non-Small-Cell Lung Cancer: TORG2241 (UBE-Q).

BACKGROUND: According to the results of the KEYNOTE-407 trial, pembrolizumab plus platinum-based chemotherapy is the standard of care for patients with previously untreated advanced squamous non-small-cell lung cancer (NSCLC). Ubenimex, a potent aminopeptidase inhibitor, is an oral drug with immunostimulatory and antitumor activities. We aim to assess the safety and efficacy of ubenimex in combination with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. PATIENTS AND METHODS: This prospective, single-arm, multicenter, phase II clinical trial is conducted to confirm the tolerability and efficacy of the tested drugs. Patients with previously untreated advanced squamous NSCLC will receive a predetermined daily dose of ubenimex orally plus 4 cycles of pembrolizumab, nab-paclitaxel, and carboplatin, followed by continuous administration of ubenimex and pembrolizumab for a maximum of 2 years. To confirm tolerability, the daily dose of ubenimex will begin at level 1 (30 mg), which will be increased to levels 2 (60 mg) and 3 (120 mg) according to the escalation criteria, with a standard 3 + 3 design for achieving the target dose-limiting toxicity rate of 33%. The efficacy, safety, and tolerability of ubenimex at the determined dose level will be analyzed. The primary endpoint of the efficacy evaluation will be the objective response rate assessed by an independent review committee. CONCLUSIONS: This is the first study to evaluate the efficacy and safety of ubenimex combined with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. The results will help devise future treatment strategies.

Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring EGFR mutation: an observational clinical study.

Background: The exosome-focused translational research for afatinib (EXTRA) study is the first trial to identify novel predictive biomarkers for longer treatment efficacy of afatinib in patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC) via a comprehensive association study using genomic, proteomic, epigenomic, and metabolomic analyses. Objectives: We report details of the clinical portion prior to omics analyses. Design: A prospective, single-arm, observational study was conducted using afatinib 40 mg/day as an initial dose in untreated patients with EGFR mutation-positive NSCLC. Dose reduction to 20 mg every other day was allowed. Methods: Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. Results: A total of 103 patients (median age 70 years, range 42-88 years) were enrolled from 21 institutions in Japan between February 2017 and March 2018. After a median follow-up of 35.0 months, 21% remained on afatinib treatment, whereas 9% had discontinued treatment because of AEs. The median PFS was 18.4 months, with a 3-year PFS rate of 23.3%. The median afatinib treatment duration in patients with final doses of 40 (n = 27), 30 (n = 23), and 20 mg/day (n = 35), and 20 mg every other day (n = 18) were 13.4, 15.4, 18.8, and 18.3 months, respectively. The median OS was not reached, with a 3-year OS rate of 58.5%. The median OS in patients who did (n = 25) and did not (n = 78) receive osimertinib during the entire course of treatment were 42.4 months and not reached, respectively (p = 0.654). Conclusions: As the largest prospective study in Japan, this study confirmed favorable OS following first-line afatinib in patients with EGFR mutation-positive NSCLC in a real-world setting. Further analysis of the EXTRA study is expected to identify novel predictive biomarkers for afatinib. Trial registration: UMIN-CTR identifier (UMIN000024935, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000028688.

Predictors of central line-associated bloodstream infections in cancer patients undergoing chemotherapy through implanted venous access ports: a retrospective, observational study.

Background: Central venous catheters (CVCs) are sometimes superior to peripheral vascular access for chemotherapy. Central line-associated bloodstream infections (CLABSIs) are an important complication of CVCs in chemotherapy. Methods: A retrospective, observational study was conducted to investigate patients with implanted venous access ports (PORTs) from July 2010 to June 2021 in a teaching hospital. General conditions of the PORTs, backgrounds, and characteristics of patients were compared between CLABSI cases and uninfected cases to identify predictors of CLABSI. Results: A total of 566 patients with PORTs who underwent chemotherapy were enrolled in this study, with CLABSI identified in 41 patients, for a total of 436,597 catheter-days. The median duration of PORT use was 26 vs. 494 days (P<0.001) in the CLABSI and uninfected groups, respectively. There were no significant differences in tumor classification, staging, white blood cell (WBC) count, neutrophil proportion, lymphocyte proportion, albumin, C-reactive protein (CRP), and performance status between the CLABSI and uninfected groups. Multivariable analysis showed that antibiotic usage within the previous week, total protein (TP), and immediate PORT use were independently associated with CLABSI, and their odds ratios (ORs) were 4.89 [95% confidence interval (CI): 1.67, 14.35], 1.95 (95% CI: 1.14, 3.53), and 3.13 (95% CI: 1.18, 8.30), respectively. The area under the curve (AUC) of the receiver-operating characteristic curve for TP was 0.63, and the cutoff value was 5.9 g/dL. Conclusions: PORT implantation should be avoided in patients who had antibiotic treatment episodes within 1 week, especially for those with low serum TP levels.

Effect of Adjuvant and Palliative Chemotherapy in Large Cell Neuroendocrine Carcinoma of the Lung: A Systematic Review and Meta-Analysis.

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subset of lung carcinoma with poor overall survival. METHODS: A systematic review following a meta-analysis of studies was performed to identify the effect of different selections of chemotherapy in LCNEC. Articles providing overall survival data for adjuvant chemotherapy or palliative chemotherapy for LCNEC were eligible. The odds ratio (OR) of mortality at one or two years after chemotherapy was evaluated. RESULTS: A total of 16 reports were finally included in the quantitative synthesis, involving a total of 5916 LCNEC patients. Adjuvant chemotherapy was administered to 1303 patients, and palliative chemotherapy was administered to 313 patients using either a small cell lung cancer (SCLC) or a non-small cell lung cancer (NSCLC) regimen. The OR for adjuvant chemotherapy was 0.73 (95% confidence interval (CI): 0.59 to 0.89, p = 0.002). The SCLC regimen showed an OR of 0.52 (95% CI: 0.11 to 2.38, p = 0.40) after one year, and 0.32 (95% CI: 0.11 to 0.89, p = 0.03) after two years, compared with the NSCLC regimen. CONCLUSIONS: Adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinoma improved the outcome after surgery. The SCLC regimen showed better survival than the NSCLC regimen as palliative chemotherapy.

Effectiveness of Cell-Free and Concentrated Ascites Reinfusion Therapy in the Treatment of Malignancy-Related Ascites: A Systematic Review and Meta-Analysis.

BACKGROUND: Malignancy-related ascites (MRA) is one of the symptoms causing discomfort in advanced cancer patients. Cell-free and concentrated ascites reinfusion therapy (CART) is one of the palliative treatments widely conducted in Japan only. METHODS: A systematic review following a meta-analysis of CART was performed. The efficiency and adverse events were evaluated. RESULTS: A total of 2567 patients and 6013 procedures of CART were identified in this study. The mean volume of MRA collected was 4.29 (95% confidence interval (CI) 3.47-5.11) L, and the volume reinfused after concentrating was 0.49 (95% CI 0.39-0.60) L. A total of 86.1 (95% CI 77.1-95.2) g protein and 42.9 (95% CI 36.0-50.0) g albumin was reinfused. The mean time to the next paracentesis was 20.7 (95% CI 15.6-25.8) days. The body weight was reduced by 3.38 (95% CI 1.90-4.86; p < 0.01) kg, and abdominal circumference was reduced by 7.86 (95% CI 6.58-9.14; p < 0.001) cm. Serum albumin increased an average of 0.14 (95% CI -0.01-0.28; p = 0.07) mg/dL the day after CART. Abdominal distension, dyspnea, and fatigue were alleviated by 6.0 (95% CI 5.59-6.51), 2.66 (95% CI 2.05-3.28), and 2.64 (95% CI 1.86-3.42) points using a numerical rating scale system ranging from 0 to 10. Overall, 17% (95% CI 0.03-0.31%) of patients had improved performance status after CART. Significant body temperature elevation was observed, at an average of 0.4 °C (95% CI 0.18-0.62 °C). CONCLUSIONS: CART might be a safe and effective palliative therapy in MRA and further clinical trials are necessary.

Pretreatment neutrophil-to-lymphocyte ratio predicts treatment efficacy and prognosis of cytotoxic anticancer drugs, molecular targeted drugs, and immune checkpoint inhibitors in patients with advanced non-small cell lung cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has recently attracted attention as a prognostic predictor in patients with non-small cell lung cancer (NSCLC) who receive immune checkpoint inhibitors (ICIs). However, the utility of NLR in relation to cytotoxic anticancer drugs or molecular targeted drugs remains unclear. We determined if NLR could predict the treatment efficacy and prognosis in NSCLC patients who receive cytotoxic anticancer drugs or molecular targeted drugs, as well as ICIs, in a cross-sectional manner. METHODS: Of 658 patients with advanced NSCLC who received first-line systemic treatment in our hospital between 2008 and 2019, 312 who met the analytical criteria were included in the study. We retrospectively analyzed the ability of NLR with a cut-off value of 5 to predict time to treatment failure (TTF) and overall survival (OS) in patients who received the following treatments: first-line treatment with molecular targeted drugs (mt group, n=100); first-line treatment with cytotoxic anticancer drugs (wt group, n=212); and first-line treatment with cytotoxic anticancer drugs followed by ICIs (ICI group, n=58). RESULTS: In the high- and low-NLR mt subgroups, median TTFs were 6.7 and 14.9 months (P<0.01), respectively, and median survival times (MSTs) were 17.8 and 39.1 months (P<0.01), respectively. In the high- and low-NLR wt subgroups, median TTFs were 1.5 and 5.8 months (P<0.01), and MSTs were 6.3 and 20.7 months (P<0.01), respectively. In the high- and low-NLR ICI subgroups, median TTFs were 1.3 and 6.8 months (P<0.01), and MSTs were 9.2 and 25.8 months (P<0.01), respectively. Multivariate analysis identified NLR as a significant independent predictor of TTF [hazard ratio (HR) 1.89, P=0.01; HR 2.51, P<0.01; and HR 5.06, P<0.01 in the mt, wt, and ICI groups, respectively) and OS (HR 3.81, P<0.01; HR 2.59, P<0.01; and HR 2.48, P<0.01, respectively). CONCLUSIONS: This study showed that NLR might be a predictor of treatment efficacy and prognosis in advanced NSCLC patients who receive various systemic treatments. This finding of consistent applicability of NLR to a wide variety of systemic treatments is of great significance.

Phase I/II study of carboplatin plus weekly nab-paclitaxel in patients aged ≥75 years with squamous-cell lung cancer: TORG1322.

OBJECTIVES: This phase I/II study assessed the efficacy and safety of combination therapy with carboplatin (CBDCA) and nab-paclitaxel (nab-PTX) in advanced elderly patients (aged ≥75 years) with advanced squamous cell lung cancer (SqCLC). MATERIALS AND METHODS: In this phase I study, the doses of carboplatin at an area under the curve (AUC) of 5 or 6 mg/mL/min on day 1 (levels 1 and 2, respectively) were administered along with weekly nab-PTX (100 mg/m2) on days 1, 8, and 15 every 4 weeks for up to 6 cycles using a modified 3 + 3 design. The primary endpoint for the phase II study was the 6-month progression-free survival (6 m PFS) rate. RESULTS: A total of 46 patients were enrolled in this study. Ten patients were enrolled in the phase I part. At dose level 1, 2/7 patients showed dose-limiting toxicities (DLTs) of grade 3 diarrhea and febrile neutropenia; at dose level 2, 1/3 patient exhibited grade 3 anorexia as a DLT. The recommended dose was determined to be level 2. Efficacy was then evaluated in 39 patients enrolled in a phase II study. The median number of cycles was 4 (range, 1-6), and the median follow-up time was 17.5 months (range, 5.6-28.9 months). The 6 m PFS rate was 59.4% (90% confidence interval [CI], 44.8%-71.4%), and the primary endpoint was met. The median overall survival time was 23.5 months (95% CI, 11.6-35.4), and the median PFS was 6.8 months (95% CI, 5.4-9.1). The response rate was 54%, and the disease control rate was 92%. Sixteen patients (41%) received immune checkpoint inhibitors post-study. Common grade 3 or 4 toxicities were neutropenia (61.5%), anemia (46.2%), thrombocytopenia (17.9%), and febrile neutropenia (15.4%). CONCLUSION: Combination chemotherapy consisting of CBDCA with weekly nab-PTX had a promising efficacy and acceptable toxicities in elderly patients (aged ≥75 years) with advanced SqCLC.

Real-world data of the association between quality of life using the EuroQol 5 Dimension 5 Level utility value and adverse events for outpatient cancer chemotherapy.

BACKGROUND: Outpatient cancer chemotherapy may lead to improved quality of life (QOL) by allowing treatment to continue without impairing the social lives of patients compared with hospitalization. However, the occurrence of serious adverse events may cause a decline in QOL. We investigated the relationship between outpatient chemotherapy-induced adverse events and QOL. METHODS: A single-center retrospective descriptive study was conducted in patients who received outpatient chemotherapy at Gifu University Hospital (Gifu, Japan) between September 2017 and December 2018. The utility values of QOL, type and severity of adverse events, type of cancer, chemotherapy regimen, and other patient demographics were analyzed. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. QOL was evaluated using the Japanese version of the EuroQol 5 Dimension 5 Level (EQ-5D-5L). Associations between the EQ-5D-5L utility value and serious adverse events were assessed using adjusted (age and sex) odds ratios obtained with a proportional odds logistic regression model. RESULTS: Data from 1008 patients who received 4695 chemotherapy cycles were analyzed. According to proportional odds logistic regression, the adverse events that significantly correlated with a decreased EQ-5D-5L utility value were malaise, edema of the limbs, peripheral neuropathy, pruritus, and dry skin. Based on the proportional odds logistic analysis, neither cancer type nor anticancer drugs were significantly correlated with the EQ-5D-5L utility value in patients who received chemotherapy. Pharmaceutical care for peripheral neuropathy significantly improved patients' EQ-5D-5L utility value from 0.747 to 0.776 (P < 0.01). CONCLUSIONS: Adverse events (i.e., peripheral neuropathy, malaise, and edema of the limbs) are significantly correlated with a decrease in QOL, regardless of the type of cancer or anticancer drugs used. Pharmaceutical care provided by pharmacists in collaboration with physicians may improve QOL.

Importance and Difficulty of Differentiating BMA-induced AFF Prodromal Symptoms from Hormonal Therapy-related Femoral Pain.

We herein report a case of breast cancer in a 74-year-old woman treated with exemestane as fourth-line hormonal therapy and bone-modifying agents for long time. She suddenly developed a right femoral shaft fracture during treatment. Her femoral fracture had a beaking sign on radiogram. Given this finding, her fracture was ultimately diagnosed as atypical femoral fracture (AFF). In this case, it was difficult to recognize the difference between groin pain as a prodromal symptom of AFF and that due to an adverse reaction to hormonal therapy. Therefore, clinicians should recognize the difficulty of this differentiation and consider the situation with caution.

Successful Treatment with Taxane-Based Chemotherapy in Advanced Sebaceous Carcinoma: A Case Report and Literature Review.

For sebaceous carcinoma (SC), a rare malignant tumor, no standard chemotherapy regimen for patients with distant metastasis has been studied. We experienced a case of eyelid SC with multiple lung metastases that responded to combination chemotherapy with carboplatin and paclitaxel with 11-month progression-free survival (PFS). This patient also responded to second-line treatment with docetaxel, another taxane, with 7-month PFS, resulting in at least 18 months of survival at the time of reporting. This report shows that taxane-based chemotherapy may be effective for advanced SC, for which no standard therapy has been established.

Significance of Earlier Initiation of Chemotherapy for Lung Cancer Complicated with Primary or Secondary Nephrotic Syndrome following Its Appropriate Differential Diagnosis.

We encountered a case of primary lung cancer complicated with membranous nephropathy as primary nephrotic syndrome. Because treatment approaches vary greatly for primary and secondary nephrotic syndrome, a renal biopsy was performed for diagnosis. Much time was required to make a definitive diagnosis of primary nephrotic syndrome, as opposed to paraneoplastic nephrotic syndrome. Consequently, the subsequent chemotherapy was ineffective and caused significant toxicity due to reduced performance status (PS) and progression of hypoalbuminemia. Therefore, it is imperative that a diagnosis be made and treatment be initiated without delay before PS declines and hypoalbuminemia progresses.

Need for Flexible Adjustment of the Treatment Schedule for Aprepitant Administration against Erlotinib-Induced Refractory Pruritus and Skin Rush.

Common dermatological side-effects associated with erlotinib, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), include pruritus and skin rash, which are mediated by substance P, leading to the occasional discontinuation of cancer treatment. Aprepitant is an antagonist of neurokinin-1 receptor, through which substance P activates the pruritogens. Thus, aprepitant is expected to offer a promising option for the treatment of erlotinib-induced pruritus. However, the appropriate treatment schedule for aprepitant administration is under consideration. Here, we discuss the need for flexible adjustment of the treatment schedule for aprepitant administration against erlotinib-induced refractory pruritus and skin rush. A 71-year-old female smoker presented with stage IV EGFR-mutated lung adenocarcinoma. She was started on erlotinib at 150 mg/day. However, by 28 days, severe pruritus and acneiform skin rush resistant to standard therapies occurred, resulting in the interruption of erlotinib therapy. After recovery, she was restarted on erlotinib at 100 mg/day. However, severe pruritus and skin rush developed again within 2 weeks. Then, we started the first 3-day dose of aprepitant (125 mg on day 1, 80 mg on day 3, and 80 mg on day 5) based on the results of the previous prospective study, which showed the success rate of 100% with at least the second dose of aprepitant. However, the pruritus and skin rush exacerbated again within 4 weeks. Therefore, we started the second 3-day dose of aprepitant, but in vain. At this point, as the patient-centered medicine, bi-weekly schedule of the 3-day dose of aprepitant was considered and, then, adopted. As the results, the pruritus and skin rush remained well-controlled throughout the subsequent treatment with erlotinib.

Promising Combination Therapy with Bevacizumab and Erlotinib in an EGFR-Mutated NSCLC Patient with MET Amplification Who Showed Intrinsic Resistance to Initial EGFR-TKI Therapy.

In lung cancer, several potential mechanisms of intrinsic and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been explored, including mesenchymal-epithelial transition factor (MET) signaling pathway activation. On the other hand, vascular endothelial growth factor (VEGF) production of EGFR-mutated lung cancer cells is stimulated by predominantly activated MET signaling pathway. Therefore, the inhibition of VEGF axis as the downstream target of MET signaling pathway seems promising. Here, for the first time, we report the potential efficacy of combination therapy with bevacizumab and erlotinib in an EGFR-mutated NSCLC patient with MET amplification who showed intrinsic resistance to initial EGFR-TKI therapy. The patient was a 60-year-old male smoker, showing performance status (PS) 2, who presented with stage IV lung adenocarcinoma (cT4N2M1a) harboring the EGFR exon 19 deletion mutation. He was started on gefitinib at 250 mg/day. However, by 28 days, his symptoms further deteriorated along with the increased tumor size, resulting in PS 3. Then, repeat biopsy was performed, showing the positive MET amplification and the preserved EGFR exon 19 deletion mutation. Therefore, on the basis of the potential efficacy for activated MET signaling pathway as well as the confirmed safety by the known phase II trial for EGFR-mutated patients, the patient was started on combination therapy with bevacizumab at 15 mg/kg every 3 weeks plus erlotinib at 150 mg/day. By 21 days, his symptoms gradually improved along with the decreased tumor size, resulting in better PS with no severe toxicities.

Improvement of Dysgeusia by Polaprezinc, a Zinc-L-carnosine, in Outpatients Receiving Cancer Chemotherapy.

BACKGROUND/AIM: Dysgeusia is one of the adverse events frequently affecting patients undergoing cancer chemotherapy. Dysgeusia-induced anorexia could decrease patient's quality of life. The present study was designed to determine whether the zinc-containing compound polaprezinc improves chemotherapy-induced dysgeusia. PATIENTS AND METHODS: The incidence of grade 2 dysgeusia was assessed in 634 patients receiving cancer chemotherapy in outpatient settings during January 2013 and June 2017. Polaprezinc was administered to patients showing grade 2 dysgeusia and the effect was compared with that in patients subjected to follow-up observation. RESULTS: Grade 2 dysgeusia appeared in 80 patients (12.6%), in whom pancreatic cancer and treatment with fluoropyrimidines were significant risks for dysgeusia. Polaprezinc, when administered to patients with grade 2 dysgeusia, significantly shortened the duration of dysgeusia compared with that in the follow-up observation group. Subgroup analysis indicated that polaprezinc was less effective in patients with pancreatic cancer, those receiving gemcitabine, or those whose age was 65 year-old and over. CONCLUSION: Chemotherapy-induced dysgeusia occurred with high frequency in patients with pancreatic cancer or in those receiving fluoropyrimidines. Polaprezinc was highly effective in improving the symptom of dysgeusia, except for patients with pancreatic cancer, those receiving gemcitabine and the elderly.

Prophylactic Effect of Polaprezinc, a Zinc-L-carnosine, Against Chemotherapy-induced Oral Mucositis in Pediatric Patients Undergoing Autologous Stem Cell Transplantation.

BACKGROUND/AIM: Polaprezinc suspension in sodium alginate (PZ-AG) reduces the incidence and severity of oral mucositis in adult patients receiving radiotherapy or high-dose chemotherapy. In the present study, the prophylactic effect of PZ-AG against oral mucositis was assessed in pediatric patients with hematological malignancies receiving high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: Data of 16 children who underwent HSCT during a period between January 2010 and December 2017 were obtained from medical records and they were retrospectively analyzed. Oral mucositis was evaluated by the WHO scale. RESULTS: Six (37.5%) of 16 children refused to take PZ-AG in a preliminary assessment and they were pretreated with azulene gargle. The remaining 10 (62.5%) patients were pretreated with PZ-AG for prevention of oral mucositis. Grade≥ 3 oral mucositis occurred in 5 (83.3%) of 6 patients receiving azulene gargle, but in 2 (20%) patients who took PZ-AG (p=0.035). The prevalence for the use of opioid analgesics was also significantly lower (30% vs. 100%, p=0.011), while the average duration of total parenteral nutrition use was significantly shorter (11.1 days vs. 24.3 days, p=0.016), in PZ-AG group than in azulene group. On the other hand, PZ-AG had no significant influence on the incidence of other adverse events, mean time to engraftment, or overall survival. CONCLUSION: PZ-AG was found to be highly effective in preventing oral mucositis in pediatric patients with hematological malignancies receiving high-dose chemotherapy followed by HSCT, as in adult patients.

Discrimination between Normal and Cancerous Cells from Dynamic Viscoelastic Properties with a Laser-induced Surface Deformation Microscope.

We have clarified the differences in the power-law between normal and corresponding cancerous cells from dynamic viscoelastic measurements in a frequency range of 102 to 105 Hz with a laser-induced surface deformation (LISD) microscope. From the differences in the power spectra at higher frequencies, it has been clarified that a normal cell obeys the power-law with a single exponent, while a cancer cell with two exponents, indicating that the plasma membrane in the cancerous cell has at least two layers with different viscoelastic properties. In LISD measurements, the extension of the upper limit of the applied frequency up to 105 Hz allows us to clarify the existence of the two power-law exponents in the cancerous cell. Understanding the differences between normal and cancerous cells from the power-law in addition to conventional elasticity would be useful for the identification of cancerous cells and for the construction of a mechanical model for their invasion.

A Patient with Advanced Gastric Cancer Who Achieved a Long-Term Prognosis by Early Diagnosis of Sister Mary Joseph's Nodule.

The patient was a 66-year-old woman. An induration of approximately 15 mm in size that accompanied redness was palpable in the umbilical fossa. She did not respond to 1-month antibiotic treatment provided by the previous physician. For this reason, a biopsy of the site was performed with the possibility of neoplastic disease in mind, resulting in the detection of adenocarcinoma. Subsequent detailed whole-body examination revealed advanced gastric cancer and peritoneal dissemination, and the induration in the umbilical fossa was diagnosed as a direct infiltration from the peritoneal dissemination. Metastasis or infiltration of malignant tumor to the umbilicus is called Sister Mary Joseph's nodule (SMJN), and considered as a sign of poor prognosis. However, this case was successfully treated and achieved a long-term prognosis by the early diagnosis of SMJN. In routine clinical practice, it is considered necessary to examine patients carefully, as not to overlook SMJN.

Paraneoplastic IgA Vasculitis in an Adult with Lung Adenocarcinoma.

A 50-year-old man with lung adenocarcinoma (c-T1aN2M1b) experienced reddish purpura mainly on the lower legs after receiving 12 cycles of second-line chemotherapy with docetaxel. There was tumor enlargement on computed tomography performed to assess the therapeutic response, so paraneoplastic IgA vasculitis was considered. IgA vasculitis was diagnosed based on a biopsy of the skin lesion and histology of an upper gastrointestinal hemorrhagic mucosal erosion. As IgA vasculitis can lead to serious gastrointestinal or systemic complications, IgA vasculitis should be considered as a differential diagnosis for rashes in patients with malignancy.