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Background: The efficacy of adjuvant chemotherapy in elderly patients aged ≥ 80 years with stage III colorectal cancer remains unclear. In parallel with a multicenter prospective phase II trial evaluating the efficacy of uracil-tegafur and leucovorin as adjuvant chemotherapy (HiSCO-03), we conducted a prospective observational study of these patients to assess survival outcomes, including those ineligible for chemotherapy. Methods: This multi-institutional prospective cohort study included 17 institutions in Hiroshima, Japan. Patients aged ≥ 80 years with stage III colorectal cancer who underwent curative resection were enrolled. The primary endpoint was 3-year disease-free survival, and the secondary endpoints were 3-year overall and relapse-free survival. Propensity score matching was used to assess the effects of adjuvant chemotherapy on survival outcomes. Results: A total of 214 patients were analyzed between 2013 and 2018, including 99 males and 115 females with a median age of 84 years (range 80–101 years). Recurrence occurred in 58 patients and secondary cancers were observed in 17. The 3-year disease-free, overall, and relapse-free survival rates were 63.3%, 76.9%, and 62.9%, respectively. Adjuvant chemotherapy was administered to 65 patients with a completion rate of 52%. In a study of 80 patients that adjusted for background factors using propensity score matching, patients who completed the planned treatment showed improved disease-free survival (3-year disease-free survival: completed, 80.0%; not received, 65.5%; and discontinued, 56.3%; p = 0.029). Conclusions: Completion of adjuvant chemotherapy may improve the prognosis of patients with colorectal cancer aged ≥ 80 years, although the number of patients who would benefit from it is limited. [ABSTRACT FROM AUTHOR]

Celiac axis compression syndrome (CACS) blocks adequate hepatic arterial flow and is a risk factor for hepatic artery thrombosis after liver transplantation. We report a case of living donor liver transplantation in a 65-year-old Brazilian male with liver cirrhosis of Child-Pugh class C and hepatocellular carcinoma caused by hepatitis C virus infection. The patient underwent living donor liver transplantation using the graft of his 34-year-old daughter. Stenosis of the celiac artery was detected on preoperative computed tomography (CT), and CACS was suspected. Maintaining blood supply through the hepatic artery to prevent potential graft loss is essential in liver transplantation. A decrease in common hepatic artery (CHA) flow due to CACS could disturb graft blood supply or lead to hepatic artery thrombosis. In this case, we confirmed CACS through dynamic CT and used intraoperative Doppler ultrasonography (US) to plan the surgical procedure. Three types of hepatic artery reconstruction have been described in liver transplantation for CACS, namely the release of the median arcuate ligament (MAL), aorto-hepatic graft reconstructions, and reconstruction preserving the gastroduodenal artery (GDA) without MAL release. We found that clamping the GDA completely abolished hepatic inflow, but clamping the CHA did not change the hepatic inflow. Therefore, we performed arterial reconstruction without division of the GDA. The patient's postoperative course was good, with excellent hepatic artery flow, as assessed by Doppler US. Preoperative dynamic CT evaluation, adequate preparation of surgical procedures, and intraoperative evaluation by Doppler US is recommended in liver transplantation patients with CACS. • CACS increases the risk for complications in liver transplantation patients. • Monitoring hepatic blood flow with intraoperative Doppler US improves outcomes. • A flowchart was created for surgical planning for optimal revascularization. [ABSTRACT FROM AUTHOR]

Highlights: [•] We developed a new method for evaluating properties of IP3R ligands using fluorescent biosensors. [•] This method revealed a diversity in subtype selectivity of adenophostin A and its analogs. [•] We also found a compound showing a partial agonistic effect on IP3R1. [Copyright &y& Elsevier]

Abstract: Indole derivatives 3a and 3b of adenophostin A (2) in which the adenine of 2 was replaced with indole or 4-fluoroindole was designed as potential inositol trisphosphate receptor ligands. These target compounds were successfully synthesized from the key disaccharide unit 6. Biological evaluation showed that 3b selectively activates IP3R1, a subtype of IP3 receptors. [Copyright &y& Elsevier]

• Anti-donor T-cell responses are not necessarily attenuated during cytomegalovirus infection. • Anti-third-party T-cell responses are attenuated before cytomegalovirus infection. • Caution is exercised in reducing the dose of immunosuppressants in cytomegalovirus infection. Cytomegalovirus (CMV), the most common opportunistic infection of kidney transplantation (KT), is preventable by prophylactic and preemptive antiviral drugs in CMV-immunoglobulin (Ig)G–positive donors. Our preemptive therapy optimized immunosuppressive doses based on mixed lymphocyte response (MLR) results, regardless of preoperative CMV-IgG serostatus pairing. This study used the MLR to compare the anti-donor T-cell responses between CMV antigenemia-positive and -negative cases. One hundred patients underwent KT using a cyclosporine (CsA)-based immunosuppressive regimen at Hiroshima University Hospital. CMV antigenemia-positive cells were defined as 4/50,000 CMVpp65-positive cells. T-cell responses to allo-antigens were measured using MLR assays to evaluate patients' anti-donor immune reactivity. After analyzing the proliferation of CD4+ and CD8+ T-cell subsets, the stimulation indices of CD4+ or CD8+ T cells were quantified. The study used no prisoners, and the participants were neither coerced nor paid. The manuscript was created in compliance with the Helsinki Congress and the Declaration of Istanbul. Forty-three patients tested positive for CMV antigenemia within 3 months after KT. No significant differences were found between the CMV antigenemia-positive and -negative groups in the stimulation indices for CD4+ and CD8+ T-cell responses to anti-donor stimulation. However, T-cell responses to third-party stimuli during the postoperative month 1 were significantly less in the CMV antigenemia-positive than -negative group. Anti-donor T-cell responses are not necessarily attenuated during CMV infection in KT recipients. In CMV-infected KT recipients, caution should be exercised against inadvertent dose reduction of immunosuppressants. [ABSTRACT FROM AUTHOR]

The regimen of oxaliplatin with 5-fluorouracil plus l-leucovorin (FOLFOX) has become one of the most commonly used first-line chemotherapy for patients with advanced colorectal cancer and it provides an increase in disease-free survival as well as an overall survival benefit. Although FOLFOX chemotherapy has helped to improve the clinical outcomes in these patients, the regimen is associated with some therapeutic issues or uncontrolled side effects. Gastrointestinal, neurosensory, and hematological toxicities have frequently been observed in patients treated with FOLFOX, and consequently, some palliative treatment has been established to combat such complications. However, pulmonary toxicities including drug-induced interstitial pneumonia (DI-IP) is rarely observed in these patients and a curative treatment is yet to be established. DI-IP due to chemotherapy is most commonly observed in patients treated with mitomycin, paclitaxel, docetaxel, or gemcitabine. Steroid therapy is mostly used to treat DI-IP, although the efficacy of such treatments is not supported with adequate evidence. FOLFOX-induced interstitial pneumonia (FIIP) is rarely observed, and several case reports of FIIP treated with steroids have been published previously that showed the mortality is extremely high. Here, we present a 74-year-old woman who received modified FOLFOX6 as adjuvant chemotherapy after rectal cancer surgery. The patient experienced FIIP, which improved after application of steroid pulse (high-dose methylprednisolone at 1,000 mg/day for 3 days) and tapering (starting with prednisolone at 40 mg/day) therapy. Our data suggest that such a steroid therapy could represent an effective treatment option for FIIP. [ABSTRACT FROM AUTHOR]

• Efforts to minimize rewarming during vascular anastomosis improve graft outcomes. • A thermal barrier bag keeps the graft cooler even with prolonged anastomosis. • In long anastomosis time, the thermal barrier bag is preferred. In kidney transplantation (KT), efforts to minimize rewarming and optimize anastomosis time during vascular anastomosis improve graft outcomes. We recently reported the safety and efficacy of a pouch-type thermal barrier bag (TBB) made of elastomer gel to reduce second-warm ischemic injury during vascular anastomosis. We aimed to examine the usefulness of the TBB in prolonged vascular anastomosis in KT performed by young transplant fellows. Young transplant fellows performed KT under the supervision of certified transplant surgeons. The kidney graft was placed inside the TBB with an outlet for vessels and preserved during vascular anastomosis. A non-contact infrared thermometer measured the graft surface temperature before and after vascular anastomosis. After completion of the anastomosis, the TBB was manually slid out of the transplanted kidney and removed before graft reperfusion. Clinical data, including patient characteristics and perioperative variables, were collected. The primary endpoint was the median graft surface temperature at the end of the anastomosis. Ten living-donor kidney transplant recipients with a median age of 56.5 years (range, 40–69 years) underwent KT procedures performed by young transplant fellows. The median anastomosis time was 53 (43–67) min. At the end of anastomosis, the median graft surface temperature was 17.7°C (16.3–18.3°C); no serious adverse events or delayed graft function were observed. The TBB can keep transplanted kidneys at a low temperature even with prolonged vascular anastomosis time, thus contributing to the functional preservation of transplanted kidneys and stable transplant outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Abdominal aortic calcification (AAC) is a well-known risk marker for cardiovascular disease. However, its clinical effect on patients who underwent radical surgery for colorectal cancer (CRC) stages II–III is unclear. This study aimed to analyze the associations between AAC and prognosis of patients with stage II–III CRC. Methods: To evaluate the effect of AAC on clinical outcomes, prognosis, and metastatic patterns of CRC, we analyzed 362 patients who underwent radical surgery for stage II–III CRC between 2010 and 2018. Results: The high AAC group had significantly worse overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) after propensity score matching to adjust for differences in baseline characteristics of patients and tumors. In the multivariate Cox regression analyses, a high AAC was an independent risk factor for poor OS (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.23–4.59; p = 0.01), poor CSS (HR, 5.22; 95% CI, 1.74–15.6; p < 0.01), and poor RFS (HR, 1.83; 95% CI, 1.19–2.83; p < 0.01). A high AAC was not associated with a risk of lung metastasis or local or peritoneal recurrence, but a risk for liver metastasis of CRC. Conclusion: A high AAC showed a strong relationship with poor OS, CSS, and RFS after curative resection for stage II–III CRC. A high AAC was also associated with a risk for liver metastasis, which may worsen the prognosis in stage II–III CRC. AAC could be a new clinical tool for predicting the prognosis for patients in stage II–III CRC. [ABSTRACT FROM AUTHOR]