Feasibility and usefulness of recommended screenings at long-term follow-up clinics for hematopoietic cell transplant survivors.

PURPOSE: Advances in allogeneic hematopoietic cell transplantation (allo-HCT) have resulted in a growing number of transplant survivors; however, long-term survivors are at risk of developing late complications, and published guidelines recommend screening of this population. We conducted a single-center prospective study to evaluate the adherence to and usefulness of recommended screenings at a long-term follow-up (LTFU) clinic. METHODS: We included consecutive patients who received allo-HCT at our center from 2014, as well as post-HCT patients visiting our outpatient clinic. Visits and screenings were planned at 3 months, 6 months, and 1 year after allo-HCT, and annually thereafter. Outcomes were reported by physicians including the incidence of findings at each screening that led to interventions. RESULTS: Among the 216 participants, 95% visited the LTFU clinic, and 94% completed planned screenings. However, the rate of secondary cancer screenings targeting high-risk subjects was lower (38% to 68%). The overall percentage of screening results leading to interventions was 4.5%, with higher percentages (> 10%) for bone density testing, ophthalmological examinations, dental assessment, upper gastrointestinal endoscopy, and colonoscopy, with two patients diagnosed with secondary cancers. CONCLUSIONS: Although the overall screening rate was high, it should be possible to improve the detection rate of late complications by decreasing screening failures, especially the screening for secondary cancers limited for high-risk survivors. A nationwide effort to educate HCT survivors and health practitioners using standardized nationwide LTFU tools may be effective, along with the development of institutional, local, and nationwide networks to maintain effective follow-up systems.

Prognostic Impact of Pretransplantation Quality of Life and Its Post-Transplantation Longitudinal Change after Allogeneic Hematopoietic Cell Transplantation: A Prospective Study That Administered the Short-Form Health Survey (SF-12) and EuroQol 5.

In allogeneic hematopoietic cell transplantation (allo-HCT), investigator-based clinical variables have been used for pretransplantation prognostic prediction, risk adjustment, and post-transplantation long-term screenings. Although several studies have investigated the prognostic significance of pretransplantation patient-reported outcomes (PROs) and longitudinal trends in PROs after allo-HCT, few have assessed these outcomes using the Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12) and EuroQol 5 Dimension (EQ-5D) index. The present study used 18 items from the SF-12 and EQ-5D index to evaluate the prognostic impact of pretransplantation quality of life (QOL) on allo-HCT outcomes and longitudinal changes in QOL in allo-HCT recipients. This single-center prospective study included consecutive patients who underwent allo-HCT at our center between October 2014 and September 2016. All participants were followed up until October 2017. The SF-12 and EQ-5D index were administered to assess patient-reported QOL before allo-HCT and at 3 months, 6 months, 1 year, and 2 years after allo-HCT when participants visited the long-term follow-up clinic. Longitudinal trends in the QOL-adjusted means were estimated using linear mixed-effects, adjusting for pretransplantation covariates and reasons for missing QOL data. Among 157 patients who underwent allo-HCT, 145 (92%) were registered in this study, and 143 with available QOL data were analyzed. The median pretransplantation scores were 45.3 for the SF-12 physical component score (PCS), 55.6 for the mental component score (MCS), 38.8 for the role/social component score (RCS), 70.0 for the visual analog scale (VAS), and 49.0 for the EQ-5D index. Overall survival (OS) was significantly improved in patients with higher pretransplantation scores on the PCS, RCS, and EQ-5D index, and multivariable analyses showed that the median pretransplantation RCS was significantly associated with OS after allo-HCT (hazard ratio, 3.66; P = .003). The longitudinal trends in the SF-12 score showed that the PCS was improved at 2 years after allo-HCT and was comparable to the normative score for the general population. The MCS remained comparable to or higher than the normative score after allo-HCT. The RCS improved significantly beginning at 6 months after allo-HCT but remained lower than the normative score at 2 years. The VAS and EQ-5D index values showed a drop at 3 months after allo-HCT. Patient-reported QOL assessed by 18 questions on the SF-12 and EQ-5D predicted prognosis, and may be used as a prognosticator to determine treatment strategies, including preparative regimens. Although we experienced a certain amount of patient attrition in the longitudinal follow-up of QOL data, we demonstrated characteristic trajectories of QOL in different domains after adjusting for background covariates and reasons for the lack of QOL data.

[Radiation-induced lumbosacral plexopathy with severe burning pain after 17 years of radiation therapy for cervical cancer: a case report].

A 73-year-old woman was admitted with severe burning pain, hyperesthesia, and weakness in the right lower extremity. The patient had undergone radio- and chemotherapy after surgery for cervical cancer 17 years earlier. We diagnosed radiation-induced lumbosacral plexopathy because of conduction block in the deep peroneal nerve and myokymic discharge in the tibialis anterior muscle. Pelvic computed tomography and magnetic resonance imaging ruled out recurrent tumor and nerve-compressing lesions. Although radiation-induced lumbosacral plexopathy is usually characterized by lower motor neuron syndrome, we report a rare case presenting with severe pain and hyperesthesia.

Response of meningeal carcinomatosis from breast cancer to capecitabine monotherapy: a case report.

A 62-year-old woman with breast cancer received neoadjuvant chemotherapy followed by breast-conserving surgery and sentinel node biopsy. During adjuvant endocrine therapy with aromatase inhibitor, she developed multiple bone metastases. Thereafter, she received tamoxifen and zoledronate therapy. In May 2011, she developed a tongue deviation and was diagnosed as having meningeal carcinomatosis. The tongue deviation disappeared 3 weeks after taking capecitabine (2,400 mg/day). Magnetic resonance imaging of the brain showed regression of meningeal carcinomatosis. Levels of tumor markers CEA and CA15-3 changed from 96.0 IU/ml and 3.5 ng/ml to 47.0 IU/ml and 1.5 ng/ml, respectively. Progression-free survival with capecitabine monotherapy was 5 months.

Preoperative serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen level predicts postoperative distant metastasis in patients with non-small-cell lung cancer.

OBJECTIVES: To examine the relationship between preoperative serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (I-CTP) levels and postoperative distant metastasis in patients with non-small-cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 143 patients in whom preoperative serum I-CTP level was measured from January 2006 to March 2011, including 91 males and 52 females with an average age of 70.1 ± 8.2 years. Histological subtypes included adenocarcinoma (n = 95), squamous cell carcinoma (n = 34) and other (n = 14). Preoperative serum carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA) levels were also measured. Patients with abnormal renal function or preoperative bone fractures were excluded. RESULTS: The mean preoperative serum I-CTP level was 4.1 ± 1.6 ng/ml, and the preoperative serum I-CTP level was elevated (>4.5 ng/ml) in 29 patients. Distant metastasis was detected in 21 patients during the 39 ± 18 (range 1-79) months of follow-up. The rate of distant metastasis was significantly higher in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (≤4.5 ng/ml) (P < 0.0001). The 5-year recurrence-free survival rate was lower in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (41.8 vs 92.9%; P < 0.0001). CONCLUSIONS: An elevated preoperative serum I-CTP level predicts postoperative distant metastasis in patients with NSCLC.

Paracrine IL-33 stimulation enhances lipopolysaccharide-mediated macrophage activation.

BACKGROUND: IL-33, a member of the IL-1 family of cytokines, provokes Th2-type inflammation accompanied by accumulation of eosinophils through IL-33R, which consists of ST2 and IL-1RAcP. We previously demonstrated that macrophages produce IL-33 in response to LPS. Some immune responses were shown to differ between ST2-deficient mice and soluble ST2-Fc fusion protein-treated mice. Even in anti-ST2 antibody (Ab)-treated mice, the phenotypes differed between distinct Ab clones, because the characterization of such Abs (i.e., depletion, agonistic or blocking Abs) was unclear in some cases. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the precise role of IL-33, we newly generated neutralizing monoclonal Abs for IL-33. Exogenous IL-33 potentiated LPS-mediated cytokine production by macrophages. That LPS-mediated cytokine production by macrophages was suppressed by inhibition of endogenous IL-33 by the anti-IL-33 neutralizing mAbs. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that LPS-mediated macrophage activation is accelerated by macrophage-derived paracrine IL-33 stimulation.