Characterization of an uncooled mid-infrared Schottky photodetector based on a 2D Au/PtSi/p-Si nanohole array at a higher light modulation frequency.

In this study, an uncooled 2D nanohole array PtSi/p-Si Schottky mid-infrared (MIR) photodetector, which is essential for on-chip Si-based low-barrier MIR detectors, is presented. Room temperature operation introduces susceptibility to thermal noise and can impact stability. Through modulation frequency and reverse bias optimization, the stability improved by 7 times at 170 Hz and -3.5V, respectively. The effective light detection and stability were confirmed through ON/OFF response measurements over a longer time. The wavelength-dependent responsivity, measured with a tunable MIR laser, confirmed the responsiveness of the device in the MIR region of 2.5 µm to 4.0 µm, with a maximum specific detectivity (D*) of 2.0×103 c m H z 1/2 W -1 at 3.0 µm; this result shows its potential applicability for noninvasive human lipid monitoring. Overall, this study focuses on the crucial role of signal analysis optimization in enhancing the performance of MIR photodetectors at room temperature.

Three Patients of the Early Onset Epileptic Spasms without Hypsarrhythmia.

Epileptic spasms without hypsarrhythmia occur when patients do not display hypsarrhythmia on electroencephalogram (EEG) at the onset and throughout the clinical course. We report three patients of epileptic spasms in patients with early onset, all of whom experienced other types of seizures.We detail three patients (two boys and one girl) of epileptic spasms without hypsarrhythmia, occurring between 1 and 3 months of age, with no abnormalities detected on neurometabolic analysis and brain magnetic resonance imaging. Long-term video-EEG monitoring revealed epileptic spasms with focal onset seizures in two patients, and epileptic spasms followed by generalized tonic-clonic seizures in one patient. Hypsarrhythmia was never observed in repeated EEG examinations. Two patients achieved seizure freedom and improved development through treatment with topiramate alone or in combination with valproate, without requiring hormonal therapies or vigabatrin. The remaining patient achieved seizure freedom following administration of antiseizure medications, including topiramate, after a trial of adrenocorticotropic hormone therapy.We report the cases of three patients with early onset epileptic spasms without hypsarrhythmia. All patients achieved seizure freedom after topiramate treatment. Topiramate may be considered as a relatively effective antiseizure medication for early onset epileptic spasms without hypsarrhythmia.

Oncologic investigation of the interval from stent placement to surgery in patients with obstructive colorectal cancer.

PURPOSE: Self-expandable metallic stent (SEMS) placement is widely used as a bridge to surgery (BTS) procedure for obstructive colorectal cancer. However, evidence regarding the optimal interval between SEMS placement and elective surgery is lacking. METHODS: We retrospectively collected data from patients with BTS between January 2013 and October 2021. Inverse probability treatment-weighted propensity score analyses were used to compare short- and long-term outcomes between the short-interval (SI) and long-interval (LI) groups, using a cutoff of 20 days. RESULTS: In total, 138 patients were enrolled in this study (SI group, n = 63; LI group, n = 75). In the matched cohort, the patients' backgrounds were well balanced. The incidence of Clavien-Dindo grade ≥ II postoperative complications was not significantly different between the SI and LI groups (19.0% vs. 14.0%, P = 0.47). There were no significant differences between the SI and LI groups in the 3-year recurrence-free survival (68.0% vs. 76.4%, P = 0.73) or 3-year overall survival rates (86.0% vs. 90.6%, P = 0.72). CONCLUSIONS: A longer interval did not deteriorate the oncological outcomes. Individual perioperative management with an appropriate interval to improve the patient's condition is required to ensure safe surgery.

Pks-positive Escherichia coli in tumor tissue and surrounding normal mucosal tissue of colorectal cancer patients.

A significant association exists between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Escherichia coli (E. coli) containing polyketide synthetase (pks) island contribute to colorectal carcinogenesis by producing colibactin, a polyketide-peptide genotoxin. However, the functions of pks+ E. coli in initiation, proliferation, and metastasis of colorectal cancer (CRC) remain unclear. We investigated the clinical significance of pks+ E. coli to clarify its functions in CRC. This study included 413 patients with CRC. Pks+ E. coli of tumor tissue and normal mucosal tissue were quantified using droplet digital PCR. Pks+ E. coli was more abundant in Stages 0-I tumor tissue than in normal mucosal tissue or in Stages II-IV tumor tissue. High abundance of pks+ E. coli in tumor tissue was significantly associated with shallower tumor depth (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 2.3-11.3, p < 0.001) and absence of lymph node metastasis (HR = 3.0, 95% CI = 1.8-5.1, p < 0.001) in multivariable logistic analyses. Pks+ E. coli-low and -negative groups were significantly associated with shorter CRC-specific survival (HR = 6.4, 95% CI = 1.7-25.6, p = 0.005) and shorter relapse-free survival (HR = 3.1, 95% CI = 1.3-7.3, p = 0.01) compared to the pks+ E. coli-high group. Pks+ E. coli was abundant in Stages 0-I CRC and associated with CRC prognosis. These results suggest that pks+ E. coli might contribute to carcinogenesis of CRC but might not be associated with tumor progression.

Intradiscal Condoliase Injection Therapy for Recurrent Lumbar Disc Herniation: Case Series and Literature Review.

Background and objectives: Although chemonucleolysis with condoliase for lumbar disc herniation (LDH) has become common, few reports have described its application in the treatment of recurrent LDH. Therefore, this study aimed to evaluate the safety and efficacy of condoliase treatment in six patients with recurrent LDH and review the available literature on condoliase treatment for LDH. Materials and Methods: Six patients (four men and two women; mean age, 64.7 years) with recurrent LDH who were treated with condoliase at our hospital between 2019 and 2022 were included. The clinical records and images of the patients were retrospectively evaluated. In addition, the available English literature on condoliase treatment for LDH was retrieved and reviewed. Results: Among the six patients included in the study, three showed >50% improvement in leg pain after treatment, which is a lower efficacy rate than that in previous reports. In addition, two patients required surgery after treatment, which is a higher rate than that in previous reports. The mean intervertebral disc height significantly decreased from 8.4 mm before treatment to 6.9 mm after treatment, consistent with the results of previous studies. None of the cases showed Modic type I changes on magnetic resonance imaging. Conclusions: Although the efficacy of condoliase treatment for recurrent LDH may be lower than that for primary LDH, this treatment was found to be safe and applicable for recurrent LDH.

Segmental or right hemi-colectomy? The optimal surgical procedure for transverse colon cancer: a propensity score-matched, multicenter, retrospective study.

PURPOSE: Extended colectomy is sometimes chosen for treatment of transverse colon cancer (TCC) because of concerns about short- and long-term outcomes. However, there is still a lack of evidence regarding the optimal surgical procedure. METHODS: We retrospectively collected and analyzed data of patients who underwent surgical treatment of pathological stage II/III TCC at four hospitals from January 2011 to June 2019. We excluded the patients with TCC located at distal transverse colon, and just evaluated and analyzed proximal and middle third TCC. Inverse probability treatment-weighted propensity score analyses was used to compare short- and long-term outcomes between patients who underwent segmental transverse colectomy (STC) and those who underwent right hemicolectomy (RHC). RESULTS: In total, 106 patients were enrolled in this study (STC group, n = 45; RHC group, n = 61). The patients' backgrounds were well balanced after matching. The incidence of major postoperative complications (Clavien-Dindo grade ≥ III) was not significantly different between the STC and RHC groups (4.5% vs. 5.6%, respectively; P = 0.53). The 3-year recurrence-free survival and overall survival rates were not significantly different between the STC and RHC groups (88.2% vs. 81.8%, P = 0.86 and 90.3% vs. 91.9%, P = 0.79, respectively). CONCLUSION: RHC has no significant benefits over STC with respect to either short- or long-term outcomes. STC with necessary lymphadenectomy could be an optimal procedure for proximal and middle TCC.

Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial.

INTRODUCTION: Regorafenib is a multi-kinase inhibitor approved for patients with metastatic colorectal cancer (mCRC) who were previously treated with standard therapies. A few reports showed the impact of KRAS mutation on therapeutic efficacy of regorafenib. Only one study reported poor prognoses for patients treated with regorafenib who had large amounts of circulating cell-free DNA (cfDNA). In the present study, we evaluated the impact of KRAS mutations in tissue or plasma and amounts of cfDNA on prognoses of mCRC patients treated with regorafenib. METHOD: This is a biomarker investigation of the RECC study, which evaluated efficacy of regorafenib dose-escalation therapy. Plasma samples were obtained just before initiation of treatment with regorafenib. KRAS mutations were evaluated using tissue and plasma samples. cfDNA was extracted from plasma samples and quantified. RESULTS: Forty-five patients were enrolled in this biomarker study. Median progression-free survival (PFS) and overall survival (OS) of patients without KRAS mutations in tissues were 1.9 months (95% confidence interval [CI] 1.7-2.0) and 8.9 months (95% CI: 6.5-11.2), and those of patients with KRAS mutations were 1.4 months (95% CI: 1.3-1.5) and 6.8 months (95% CI: 5.0-8.5). Median PFS and OS of patients with plasma KRAS mutations were 1.9 months (95% CI: 1.8-1.9) and 7.0 months (95% CI: 5.3-8.7), respectively. Median PFS and OS of patients without plasma KRAS mutations were 1.7 months (95% CI: 1.1-2.3) and 8.9 months (95% CI: 6.7-11.2), respectively. Prior to administration of regorafenib, KRAS mutations were detected in 6 of 16 (37.5%) patients who had no tissue KRAS mutations. Median OS of patients with high cfDNA concentration (>median) was significantly poorer than that of patients with low cfDNA. CONCLUSION: KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer prognoses for patients receiving late-line regorafenib chemotherapy.

Postoperative infectious complications have a negative oncological impact in patients after stent placement with malignant large bowel obstruction.

PURPOSE: In this study, we aimed to investigate the oncological impact of postoperative infection in patients with malignant large bowel obstruction managed by self-expandable metallic stent placement as a bridge to surgery. METHODS: The cohort of this multicenter retrospective study comprised 129 patients with pathological stage II/III malignant large bowel obstruction who had undergone bridge to surgery. Patients were allocated to no-postoperative infection (n = 116) and postoperative infection groups (n = 13). RESULTS: The postoperative infection group had a significantly greater proportion of men, fewer harvested lymph nodes, and longer postoperative hospital stays than did the no-postoperative infection group. Self-expandable metallic stent-related variables, including clinical failure, were not associated with postoperative infection. Male sex and low body mass index were identified as risk factors for postoperative infection by multivariate logistic regression. Three-year relapse-free survival rates were 75.5% and 30.8% in the no-postoperative infection and postoperative infection groups, respectively; this difference is statistically significant. Male sex, postoperative infection, and T4 were identified as independent prognostic factors by multivariate Cox proportional hazard analysis. The postoperative infection group had a significantly higher total recurrence rate and shorter interval to recurrence than did the no-postoperative infection group. CONCLUSION: To the best of our knowledge, this is the first study to show that postoperative infection in bridge to surgery patients has a negative oncological impact. This finding indicates that further improvement in perioperative management of bridge to surgery patients is required to minimize postoperative infection and that patient-risk stratification and additional therapy would contribute to improving oncological outcomes.

The T-CEA score: a useful prognostic indicator based on postoperative CEA and pathological T4 levels for patients with stage II-III colorectal cancer.

PURPOSE: To investigate a prognostic score for stage II-III colorectal cancer (CRC) based on post-CEA and pT4 levels. METHODS: Two cohorts of stage II-III CRC patients who underwent curative surgery between 2011 and 2017 were included. The prognostic score (T-CEA score) was calculated as follows: T-CEA-0, post-CEA ≤ 5 ng/mL and pT1-3; T-CEA-1, post-CEA > 5 ng/mL or pT4; T-CEA-2, post-CEA > 5 ng/mL and pT4. RESULTS: The T-CEA scores of the 587 patients were as follows: T-CEA-0 (n = 436; 74%), T-CEA-1 (n = 129; 22%), and T-CEA-2 (n = 10; 2%). The 5-year recurrence-free survival (RFS) rates of the T-CEA-0, 1, and 2 groups were 80.3%, 54.8%, and 0%, respectively (P < 0.01), and the 5-year overall survival (OS) rates were 90.9%, 74.2%, and 0%, respectively (T-CEA-0 vs T-CEA-1: P < 0.01, T-CEA-1 vs T-CEA-2: P = 0.04). Multivariate analysis revealed that an elevated T-CEA score of 1 or 2 was a significant risk factor for poor RFS (HR: 2.89, P < 0.01) and OS (HR: 2.85, P < 0.01). CONCLUSION: The T-CEA score is a reliable and convenient prognostic score for stage II-III CRC.

Bidirectional effects of voluntary exercise on the expression of Bdnf isoforms in the hippocampus of Hatano rat strains displaying different activity levels.

Brain-derived neurotrophic factor has functional mRNA isoforms, whose expression is assumed to mediate the beneficial effects of exercise in neuropsychiatric disorders. This study aims to reveal the mechanism of intensity-dependent effects of voluntary exercise, focusing on the expression of Bdnf mRNA isoforms in Hatano rats. Animals with different voluntary activity were housed in cages with a locked or unlocked wheel for 5 weeks. The expression levels of Bdnf isoforms and the corresponding coding sequences (CDS) were measured in the hippocampus using real-time polymerase chain reaction (PCR). We found that exercise increased the expression of Bdnf isoform containing exon 1 in the high-intensity-running strain and decreased the expressions of Bdnf exon 1, 3, 6, 7, 8, and 9a in mild-intensity-running animal. The expression of Bdnf CDS was increased by exercise in both strains. These results suggest that expressions of Bdnf isoforms depend on the intensities of voluntary exercise, but the involvement of subjects' genetic background could not be excluded. Our finding also implies that the bidirectional effects of exercise may not be mediated via the final product of Bdnf.

Useful Preoperative Simulation of Laparoscopic Surgery for Rectal Cancer in Patients with Kyphosis.

Kyphosis complicates abdominal surgery. Here, we report a case of rectal cancer in a patient with kyphosis who underwent successful laparoscopic surgery after a preoperative simulation. An 81-year-old woman with rectal cancer was admitted to our department, and laparoscopic surgery was planned. Physical examination revealed severe kyphosis. To ensure successful laparoscopic surgery, we conducted a detailed preoperative simulation, including three-dimensional CT simulations of port arrangement and anatomy, simulation of body position, selection of surgical instruments, and preoperative discussion with the anesthesiologist. We planned to insert the first port in the umbilical region for pneumoperitoneum and the camera port in the ventral region under pneumoperitoneum. We planned to insert the ports on the right side of the patient's body from the caudal regions, after considering the location of the inferior mesenteric artery and the limitations in degrees and space attributable to the costal arch and promontorium. Beach chair position was planned. We used a fan-shaped retractor and sponge retractor to remove the small intestine from the surgical view. In preoperative discussions with the anesthesiologist, we decided to maintain pneumoperitoneum pressure at less than 8 mm Hg during the operation, to safeguard respiratory function. Lower anterior resection with D2 lymph node dissection was performed, without intraoperative complications. At 2 years postoperatively, the patient was healthy with no signs of recurrence. Laparoscopic surgery appears to be a suitable choice for patients with kyphosis. We believe that preoperative simulation will result in successful outcomes.

A Case of a Fixed Giant Peritoneal Loose Body outside the Peritoneum and near the Rectovesical Excavation.

A peritoneal loose body (PLB) is tissue completely separated from other intraperitoneal organs. It is rare and usually found incidentally during laparotomy, examination, or autopsy. PLBs are usually located free in the peritoneal cavity and not in the extraperitoneal space. They are thought to originate when epiploic appendices are released into the abdominal cavity after ischemic necrosis. We report a case of a giant PLB outside the peritoneal cavity, adjacent to the rectovesical excavation, that was identified preoperatively inan asymptomatic 83-year-old man undergoing evaluation for cholecystolithiasis. Computed tomography revealed a mass with well-defined margins in the rectovesical excavation. The mass (diameter, 60 mm) consisted of a calcified core and peripheral soft tissue and did not appear to invade adjacent organs. Although there were no symptoms or tumor growth over time, we scheduled a laparoscopic extraction for definitive diagnosis. On laparoscopic exploration, a white ovoid mass was found in the rectovesical excavation; there was no invasion of adjacent organs. We diagnosed a giant PLB. Postoperative recovery was uneventful. Most PLBs are asymptomatic and do not require surgery, except when symptoms are present, when the PLB is large, or when malignancy is suspected. PLB is rarely extraperitoneal and is usually freely mobile; however, in our patient, it was fixed and outside the abdominal cavity, near the rectovesical fossa. Although it could not be diagnosed preoperatively as being extraperitoneal, imaging findings were typical of PLB; thus, it was possible to remove the mass laparoscopically without bowel resection.

Surgical Site Infections in Gastroenterological Surgery.

Surgical site infections (SSIs) remain one of the most common serious surgical complications and are the second most frequent healthcare-associated infection. Patients with SSIs have a significantly increased postoperative length of hospital stay, hospital expenses, and mortality risk compared with patients without SSIs. The prevention of SSI requires the integration of a range of perioperative measures, and approximately 50% of SSIs are preventable through the implementation of evidence-based preventative strategies. Several international guidelines for SSI prevention are currently available worldwide. However, there is an urgent need for SSI prevention guidelines specific to Japan because of the differences in the healthcare systems of Japan versus western countries. In 2018, the Japan Society for Surgical Infection published SSI prevention guidelines for gastroenterological surgery. Although evidence-based SSI prevention guidelines are now available, it is important to consider the appropriateness of these guidelines depending on the actual conditions in each facility. A systemic inflammatory host response is a hallmark of bacterial infection, including SSI. Therefore, blood inflammatory markers are potentially useful in SSI diagnosis, outcome prediction, and termination of therapeutic intervention. In this review, we describe the current guideline-based perioperative management strategies for SSI prevention, focusing on gastroenterological surgery and the supplemental utility of blood inflammatory markers.

Biomarkers for anti-vascular endothelial growth factor drugs.

Angiogenesis is regulated by interactions between vascular endothelial growth factors (VEGFs) and VEGF receptors. VEGF-A, VEGF-D, placental growth factor (PlGF) and plasminogen activator inhibitor-1 (PAI-1) have tumor angiogenic activity. VEGF-A and PAI-1 levels in the blood may impact the activity of bevacizumab, and VEGF-D levels may similarly diminish the efficacy of ramucirumab. However, the dynamics of these angiogenic biomarkers for anti-VEGF therapy have not been well established; therefore, they were evaluated in this retrospective study, which included two cohorts. Cohort 1 included patients who were treated with cytotoxic agents and bevacizumab as first-line chemotherapy, and Cohort 2 comprised patients who were treated with cytotoxic agents and anti-VEGF drugs (bevacizumab, ramucirumab or aflibercept) as second-line chemotherapy. VEGF-A, VEGF-D, PlGF and PAI-1 levels were measured before starting chemotherapy and were re-assessed every 1-2 months until disease progression. Bevacizumab had reduced benefit as a first-line chemotherapeutant in patients with very low or very high levels of VEGF-A. Bevacizumab increased VEGF-A and PlGF levels, but not VEGF-D or PAI-1. Anti-VEGF drugs offered the greatest benefit to patients with high PAI-1 before first- and second-line chemotherapy. PAI-1 levels were not affected by anti-VEGF drugs. Since ramucirumab increased VEGF-D, it offered less benefit to patients with high VEGF-D in second-line chemotherapy. Conversely, aflibercept offered greater benefits to patients with high VEGF-D, without increasing VEGF-D. These biomarkers may be useful for the prediction of drug efficacy and may predict resistance to anti-VEGF drugs.

Biweekly TAS-102 and bevacizumab as third-line chemotherapy for advanced or recurrent colorectal cancer: a phase II, multicenter, clinical trial (TAS-CC4 study).

BACKGROUND: TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects. METHODS: This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m2) was given twice daily on days 1-5 and days 15-19 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion for 30 min every 2 weeks. The primary end point was progression-free survival (PFS), and secondary end points were time-to-treatment failure (TTF), response rate (RR), OS, and safety. RESULTS: 44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%). CONCLUSIONS: Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects.

Room-temperature plasmonic mid-infrared photodetector based on PtSi/p-Si low Schottky-barrier junction.

In this study, a low Schottky-barrier photodetector with a plasmonic assist using a two-dimensional (2D) nanohole array was demonstrated, which receives mid-infrared (MIR) light at room temperature. In the structural design, it was confirmed that the 2D nanohole-array photodetector has high absorbance in the MIR region using rigorous coupled-wave analysis. The result showed that the nanoholes formed in p-type silicon (p-Si), platinum silicide (PtSi), to form Schottky barriers, and gold (Au), for photocurrent extraction, had high absorbance in the MIR region along with the Fabry-Perot resonance mode toward the depth of the nanohole. The 2D nanohole array, with Au/PtSi/p-Si layers, has high absorbance for illuminating MIR light near 3.46 µm from the backside. The current-voltage characteristics indicated a low Schottky barrier of 0.32 eV, confirming the photoresponsive potential in the MIR photodetection. The photocurrent response to the modulation signal was obtained at room temperature. In addition, signal processing through transimpedance and lock-in amplifiers enabled us to obtain characteristics with high linearity for light intensities in milliwatts. Light acquisition for 2.5-3.8-µm-long MIR wavelength became possible, and applications in gas sensing, including vibrational absorption bands of alkane groups, are expected.

Clinical impact of laparoscopic surgery and adhesion prevention material for prevention of small bowel obstruction.

Aim: Adhesive small bowel obstructions (SBO) are one of the most common complications following abdominal surgery, and they decrease patient quality of life. Since 2000, laparoscopic surgery has been employed with increasing frequency, as has adhesion prevention material (APM). In this study we tried to evaluate whether laparoscopic surgery and APM reduce the incidence of SBO. Methods: In Cohort 1, we included patients who developed SBO and received inpatient treatment between 2015 and 2018. We evaluated the elapsed time between precedent surgery and the onset of SBO, and what kind of surgery most often causes SBO. In Cohort 2, we included patients who underwent digestive surgery between 2012 and 2014 and evaluated SBO incidence within 5 y after the precedent surgery. Results: In all, 2058 patients were included in Cohort 1. Of these, 164 had experienced no precedent surgery. Among patients with a history of abdominal surgery, 29.7% experienced SBO within 1 y after the precedent surgery and 48.1% within 3 y. Altogether, 18798 patients were analyzed in Cohort 2. The incidence of SBO after laparoscopic colorectal surgery was lower than that of open colorectal surgery (P < .001), and laparoscopic gastroduodenal surgery was also lower (P = .02). However, there were no differences between laparoscopic and open surgery for other types of surgery. The use of APM had no effect on SBO incidence in any type of abdominal surgery. Conclusions: Laparoscopic surgery helps to reduce SBO incidence only in colorectal surgery, and possibly in gastroduodenal surgery. APM does not reduce SBO after abdominal surgery.

Efficacy and safety of regorafenib dose-escalation therapy for Japanese patients with refractory metastatic colorectal cancer (RECC study).

BACKGROUND: Regorafenib significantly improves overall survival in previously treated metastatic colorectal cancer patients. However, various toxicities, such as hand-foot skin reaction (HFSR), fatigue, and liver dysfunction have limited the use of regorafenib. These toxicities appear soon after treatment initiation. The ReDOS study demonstrated the effectiveness of a weekly dose-escalation therapy of regorafenib starting with a lower daily dose; however, its usefulness in Asian subjects is unknown. We conducted a phase II study to evaluate the safety and survival benefit of regorafenib dose-escalation therapy for Japanese patients. METHODS: Patients with sufficient organ function, who had previously received more than two lines of chemotherapy were included. Regorafenib was started at 80 mg/day and escalated to 120 mg/day in Week 2 and 160 mg/day in Week 3, if no severe drug-related toxicities were observed. The primary endpoint was cancer progression-free survival (PFS). Tumor response and progression were assessed radiologically every 8 weeks. This study was registered in the University Hospital Medical Information Network (UMIN#UMIN000028933). RESULTS: 57 patients were enrolled and all started regorafenib at 80 mg/day. 32 patients (56.1%) were subsequently escalated to 120 mg/day and 19 (33.3%) to 160 mg/day. Only 8 patients (14.0%) discontinued treatment because of adverse events. Median PFS was 1.9 months. Median overall survival was 8.9 months, the response rate was 0%, and the disease control rate was 31.6%. The most frequent adverse event greater than grade 3 was hypertension (19.3%), followed by HFSR (14.0%). CONCLUSIONS: Regorafenib dose-escalation therapy is well tolerated with PFS-like regorafenib standard therapy.

[Long-Term Response to UFT/UZEL/Bevacizumab Therapy for Lung Metastasis after Surgery for Early-Stage Colon Cancer in a Late-Stage Elderly Patient].

Late-stage elderly patients have low tolerance to chemotherapy, and they have difficulties when they are treated with standard chemotherapy. We report a case of a late-stage elderly patient who had a long-term response to UFT/UZEL/bevacizumab( Bev)therapy for lung metastasis after surgery for early-stage colon cancer. He was 82-years-old and underwent laparoscopy-assisted sigmoid colectomy for sigmoid colon cancer at another hospital. The pathological diagnosis was pT1b, ly1, v0, N0, M0, pStage Ⅰ. Six months after the surgery, a small nodule was noted in the middle lobe of the right lung. It grew five months later and was definitely diagnosed as lung metastasis. Considering his physical condition and tumor size, we opted to introduce less invasive chemotherapy instead of standard chemotherapy. UFT/UZEL/Bev was started 14 months after surgery. Although he required dose reduction due to anorexia, he safely continued the treatment with partial response (PR), which was maintained for 2 years and 6 months. While UFT/UZEL/Bev has no convincing evidence, it may be an option for vulnerable patients, especially those with non-life-threatening disease.

Toxicological effects of Tris (1,3-dichloro-2-propyl) phosphate exposure in adult male rats differ depending on the history of exposure in the neonatal period.

There is increasing concern about multiple high concentration exposure to toxins in disaster and emergency situations. However, conventional toxicology testing methods may not adequately address these situations. Thus, we assessed whether the toxic effects of exposure in the adulthood differ depending on the presence or absence of neonatal exposure to Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in male rats to investigate the effects of exposure history of chemicals. In the neonatal stage [postnatal days (PNDs) 1-7], animals were treated with either sesame oil (5 ml/kg/day) as a control or TDCIPP (250 mg/kg/day) dissolved in sesame oil. In adulthood (PND 101-107), animals were treated with either sesame oil (5 ml/kg/day) or TDCIPP (650 mg/kg/day). One day after the final administration, dissection was performed, and body and organ weight, hematology, blood biochemistry, and histopathology were examined. The results demonstrated that the toxic effects of TDCIPP exposure in adulthood on adrenal gland size, serum iron content, and unsaturated iron binding capacity were enhanced by TDCIPP exposure in the neonatal stage. From these findings, it was indicated that the toxic effects of TDCIPP exposure in the adult stage are affected by pediatric exposure. These results suggest that the toxic effects of high-dose and long-term unsteady exposure to chemicals in large-scale disasters may change based on the exposure history of chemicals.