Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06).

BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).

Less-Suture Vascular Anastomosis: Development of Alternative Protocols with Multifunctional Self-Wrapping, Transparent, Adhesive, and Elastic Biomaterials.

Blood vessel anastomosis by suture is a life-saving, yet time-consuming and labor-intensive operation. While suture-less alternatives utilizing clips or related devices are developed to address these shortcomings, suture anastomosis is still overwhelmingly used in most cases. In this study, practical "less-suture" strategies are proposed, rather than ideal "suture-less" methods, to reflect real-world clinical situations. In the case of rat artery (d = 0.64 mm) anastomosis, the less-suture anastomosis involves the application of thin, adhesive, transparent, and self-wrapping films to the site. This surprisingly reduces the number of stitches required from ten (without films) to four (with films), saving 27 min of operating time per vessel. Furthermore, the decreased number of stitches largely alleviates fibrosis-mediated wall-thickening. Thus, a less-suture strategy is particularly useful for anastomosis of multiple vessels in emergency conditions and small-diameter vessels.

Photometric determination of peracetic acid by reaction with potassium iodide solution.

Peracetic acid (PAA) is a strong oxidizing agent and is considered an ideal disinfectant because of its excellent disinfecting effect at low concentration, low corrosiveness, and relatively low cost. Commercially available PAA solution is a mixture of PAA, acetic acid, and hydrogen peroxide. However, PAA naturally decomposes faster than hydrogen peroxide. Therefore, accurately quantifying the concentration of PAA in the PAA peroxide mixture via a simple method is important. In the present study, a new method was developed, in which the spectral change of I- ion at 226 nm and the absorption value from the generated I2 at 460 nm were used to determine the concentration of PAA, following a chemical reaction with 0.1 mM potassium iodide (KI) solution without the use of any other chemicals. In this work, the measurable concentration of PAA was as low as 0.0001 wt% (13.1 µM) and as high as 0.0015 wt% (197.2 µM), which matches well with high linearity (99.95% at 226 nm and 99.91% at 460 nm). This work could also be the high selectivity method toward PAA in the PAA peroxide mixture.

A simple spectrophotometric determination of hydrogen peroxide solution via spectral delta from redox reaction with sodium hypochlorite.

Hydrogen peroxide (H2O2) is widely used in the synthesis of organic chemicals, bleaching of paper pulp, and the treatment of wastewater and as a food additive, important mediator of redox processes in natural water, and a disinfectant. However, H2O2 stock solution is unstable and slowly decomposes when exposed to, for example, light, elevated temperatures, or metal compounds. Therefore, the ability to measure the exact concentration of H2O2 stock solution is important for its proper use in diverse applications. This work proposes a simple method for the spectrophotometric determination of H2O2 solution via chemical reaction with sodium hypochlorite that is inexpensive and easy to acquire. The proposed method is based on the stoichiometric spectral change of hypochlorite ion at 292.5 nm following a redox reaction with a sample solution of H2O2. Due to high relationship between the spectral delta value and the applied H2O2 concentration (0.00188-0.03000%), H2O2 stock solution can be easily quantified.

A simple method for extracting phycocyanin from Arthrospira (Spirulina) platensis by autolysis.

Phycocyanin (PC) is a natural blue pigment that has great commercial value in food and pharmaceutical industry. Arthrospira (Spirulina) platensis is a photosynthetic spiral-shaped cyanobacterium containing a rich PC pigment. Autolysis is the enzymatic digestion of cells by the action of its own enzymes. To develop an effective and economical extraction process, an autolysis process was incorporated into the conventional freezing-thawing method. In the present study, 91% of maximal extraction yield of PC with 1.194 purity (A620/A280) was obtained via autolysis after 3 h of incubation at 37 °C without using an extraction salt solution or a successive freezing-thawing process. In addition to temperature, the initial concentration of bicarbonate in growth medium and the concentration of wet biomass are important parameters that influence the extraction yield of PC by autolysis.

Prognostic model in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitors after platinum failure.

Immune checkpoint inhibitors (ICIs) have become a standard treatment for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy. However, the prognostic factors for patients with mUC receiving ICIs are not well established. We retrospectively collected clinical and laboratory data and reviewed the survival outcomes of patients with mUC who were treated with ICIs after platinum-based chemotherapy. We used univariate and multivariable Cox proportional hazard models to identify independent prognostic factors, and the concordance index (C-index) to evaluate the performance of the new prognostic model. In addition, bootstrap analysis was employed for internal validation of the prognostic model. A total of 224 patients were included in the study. With a median follow-up of 10.5 months (interquartile range, 5.1-17.4 months), median overall survival (OS) was 13.6 months (95% confidence interval [CI], 9.7-17.3 months). In multivariable analysis, independent prognostic factors predicting adverse OS were the presence of liver metastasis (LM), hypoalbuminemia, and neutrophil-lymphocyte ratio (NLR) >5. When patients were categorized into 3 risk groups, median OS was not reached (NR) (95% CI, 17.3-NR), 9.5 months (6.8-NR), and 2.9 months (2.3-4.4) for patients with a score of 0, 1, and 2+, respectively. The C-index for the new model was 0.763 (95% CI, 0.739-0.787). A novel prognostic model, including LM, hypoalbuminemia, and NLR, was developed and validated to estimate OS in patients with platinum-refractory disease on second- or subsequent-line ICI therapy. Further investigations, including prospective validation, are needed.

A phase II study of chemotherapy in combination with telomerase peptide vaccine (GV1001) as second-line treatment in patients with metastatic colorectal cancer.

Background: GV1001 is a human telomerase peptide vaccine that induces a CD4/CD8 T-cell response against cancer cells, thereby affording an immunological anti-tumor effect. Here, we evaluated the efficacy and safety of GV1001 in combination with chemotherapy in patients with metastatic colorectal cancer who had failed first-line chemotherapy. Methods: This multicenter, non-randomized, single-arm phase II study recruited recurrent or metastatic colorectal cancer patients with measurable disease who had failed first-line chemotherapy. Patients received GV1001 and chemotherapy concomitantly based on a pre-established schedule. Cytotoxic chemotherapy and targeted agents (bevacizumab, cetuximab, or aflibercept) were allowed to be used at the discretion of the investigator. The primary endpoint was the disease control rate; secondary endpoints were the objective response rate, progression-free survival, overall survival, and safety outcomes. The baseline serum eotaxin level (a potential predictive biomarker of GV1001) was analyzed. To determine whether an adequate immune response had been induced, a delayed-type hypersensitivity test and a T-cell proliferation test were performed. Results: From May 13, 2015 to October 13, 2020, 56 patients with recurrent or metastatic colorectal cancer treated in seven hospitals of South Korea were enrolled. The median patient age was 64 years (range, 29-82 years); 67.9% were men. Of all patients, 66.1% had left-side colorectal cancer and the RAS mutation was present in 25%. The disease control rate and the objective response rates were 90.9% (95% confidence interval [CI]: 82.4-99.4%) and 34.1% (95% CI, 20.1-48.1%), respectively. The median progression-free survival was 7.1 months (95% CI, 5.2-9.1 months) and the median overall survival was 12.8 months (95% CI, 9.9-15.8 months). The most common all-grade adverse events were neutropenia (48.2%), nausea (26.8%), neuropathy (25.0%), stomatitis (21.4%), and diarrhea (21.4%). Immune response analysis showed that no patient had positive delayed-type hypersensitivity test results; antigen-specific T-cell proliferation was observed in only 28% of patients. The baseline eotaxin level was not associated with any efficacy outcome. Conclusion: Although no clear GV1001-specific immune response was observed, the addition of GV1001 vaccination to chemotherapy was tolerable and associated with modest efficacy outcomes.

Potential of Bacterial Strains Isolated from Coastal Water for Wastewater Treatment and as Aqua-Feed Additives.

Bacteria have various and sustained effects on humans in various fields: molecular biology, biomedical science, environmental/food industry, etc. This study was conducted to evaluate the wastewater treatment capacity and feed-additive fish-growth effect of four strains of bacteria: Pseudoalteromonas mariniglutinosa, Psychrobacter celer, Bacillus albus, and Bacillus safensis. In a wastewater degradation experiment, (i) nitrate-N and nitrite-N were removed within 1 h in all of the 4 bacterial strains; (ii) the removal rates of TAN and TN were higher in all of the strains relative to the B. subtilis. In a feed-additive experiment (5% Kg-1), (i) the growth of fish was higher in all of the 4 bacterial strains with the B. subtilis relative to the commercial feed; (ii) there was no significant growth difference for B. albus and B. safensis relative to the B. subtilis, but growth was higher in P. mariniglutinosa and P. celer. The results indicated that the 4 bacterial strains can be effectively utilized for biological wastewater treatment processes and as aqua-feed.

Transvenous injection of n-butyl 2-cyanoacrylate to obliterate the pathologic cavernous sinus as a salvage technique for incompletely obliterated complex cavernous sinus dural arteriovenous fistula after transvenous coil embolization.

A Barrow type D of complex cavernous sinus dural arteriovenous fistula (CS-dAVF) was completely obliterated by using coils, n-butyl 2-cyanoacrylate (NBCA) and Onyx via transvenous approach. Especially in this case, after transvenous coil embolization of the pathologic cavernous sinus (CS), transvenous injection of NBCA was done to obliterate residual shunts recruited into CS. The complex CS-dAVF was completely obliterated without periprocedural complications. Transvenous injection of NBCA could be considered as a feasible option for obliteration of pathologic CS in a case of incompletely obliterated complex CS-dAVF after transvenous coil embolization.

Treatment and Outcomes of Metastatic Pancreatic Cancer in Elderly Patients.

BACKGROUND AND AIMS: Although pancreatic cancers are common in older age-groups, the prognosis remains poor due to limited studies on treatment approaches and outcomes in a given population. We aimed to examine treatment patterns and their outcomes in older patients with metastatic pancreatic cancer in a real-world context. MATERIALS AND METHODS: We conducted a retrospective study including 167 patients with metastatic pancreatic cancer (aged ≥70 years and male/female: 78/89) between January 2010 and July 2015. Patients' retrieved data from medical records were analyzed according to treatment types, followed by a review of clinicopathologic variables and treatment outcomes. RESULTS: Of the 167 eligible patients for the study, only 21.6% (n = 36) received palliative chemotherapy. The median age of the chemotherapy group was 74.0 years and 78.6 years for the supportive care group. The median survival of the chemotherapy group was 9.2 months (range: 1.0-24.9 months), compared with that of the supportive care group, which was 2.3 months (range: 0.1-31.8 months). Among the patients in the chemotherapy group, 50% (n = 18) received gemcitabine-based double therapy, and 30% patients (n = 9) received second-line chemotherapy. CONCLUSIONS: Our results showed that older patients with metastatic pancreatic cancer were less likely to receive chemotherapy. However, the survival benefit from chemotherapy was comparable to that of younger patients' counterpart. Thus, further study involving identification of older patients who would benefit from cytotoxic chemotherapy is needed.

Lenalidomide for anemia correction in lower-risk del(5q) myelodysplastic syndrome patients of Asian ethnicity.

BACKGROUND: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. METHODS: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. RESULTS: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). CONCLUSION: Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

2020 Korean guidelines for the management of metastatic prostate cancer.

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.

Evaluation of floc-harvesting technologies in biofloc technology (BFT) system for aquaculture.

This study was conducted to examine floc-harvesting performance by three separation technologies, namely sedimentation, centrifugation, and membrane filtration, for biofloc generated from a BFT system in aquaculture. According to the experimental results, sedimentation demonstrated the poorest harvesting performance with the lowest energy consumption; centrifugation showed the highest harvesting performance with the highest energy burden; membrane filtration achieved better harvesting performance than sedimentation and better energy efficiency than centrifugation. In terms of large-scale floc recovery, a two-step harvesting process utilizing centrifugation with membrane filtration was found to be a reliable way to overcome the limitation of sedimentation and obtain moderate energy-efficiency. Overall, the energy-consuming aspects of the floc-recovery process on an industrial scale should be concerned, even though the use of biofloc as an aquaculture feed would be a positive in terms of an environment-friendly approach to recycling of aquaculture wastewater.

Biological wastewater treatment: Comparison of heterotrophs (BFT) with autotrophs (ABFT) in aquaculture systems.

The present study was conducted to compare wastewater purification capacities between heterotrophs (BFT) and autotrophs (ABFT) and to evaluate the effects on the growth of fish (Nile tilapia, Oreochromis niloticus) in aquaculture systems. The wastewater treatment capacity of heterotrophs is far superior to that of autotrophs, but the BFT system requires more energy for aquaculture than does the ABFT system. Regardless, both systems effected positive influences on fish growth performance, showing excellent water-purification capacities compared with the control group (CON). No significant differences were found between CON and ABFT or between ABFT and BFT, but there were significant differences between CON and BFT. Both systems BFT and ABFT were revealed to be cost effective in relation to CON, having reduced water replacement by 82%. Therefore, the BFT and ABFT systems could be economical aquaculture systems if due advantage is taken of what both have to offer.

Tuna byproducts as a fish-meal in tilapia aquaculture.

Potentiality of the use of tuna byproducts as a fish-meal replacement on Nile tilapia (Oreochromis niloticus) was examined for 84 weeks by tracking the concentrations of cadmium and mercury in the internal organs, muscles and fish whole body through generation including their immature eggs and their larvae. The results confirmed that the tuna byproducts can be used as a fish-meal substitute in tilapia aquaculture, because their acceptable ranges for cadmium and mercury consequently did not exceed the food safety values (both < 0.5 mg kg-1), despite their proportional increases in the fish body. The use of tuna byproducts as a protein source is expected to reduce the cost of feed with other fishmeal substitutes in tilapia aquaculture. However, fish (flounder) indiscriminately consuming tuna byproduct feed were prohibited and recalls of sales were issued by the government (July 2018, Republic of Korea), as the threshold for mercury in the fish bodies had been exceeded (0.6-0.8 mg kg-1). Further study of the use of tuna byproducts as fishmeal replacements for other species in aquaculture is needed, as concentration ratios can vary depending on the species.

Quantitative analysis of prompt gamma ray imaging during proton boron fusion therapy according to boron concentration.

The purpose of this study is to evaluate the prompt gamma ray imaging technique according to the clinical boron concentration range during proton boron fusion therapy (PBFT). To acquire a prompt gamma ray image from 32 projections, we simulated four head single photon emission computed tomography and a proton beam nozzle using a Monte Carlo simulation. We used modified ordered subset expectation maximization reconstruction algorithm with a graphic processing unit for fast image acquisition. Boron concentration was set as 20 to 100 µg at intervals of 20 µg. For quantitative analysis of the prompt gamma ray image, we acquired an image profile drawn through two boron uptake regions (BURs) and calculated the contrast value, signal-to-noise ratio (SNR), and difference between the physical target volume and volume of the prompt gamma ray image. The relative counts of prompt gamma rays were noticeably increased with increasing boron concentration. Although the intensities on the image profiles showed a similar tendency according to the boron concentration, the SNR and contrast value were improved with increasing boron concentration. This study suggests that a tumor monitoring technique using prompt gamma ray detection can be clinically applicable even if the boron concentration is relatively low.

Morphobiochemical diagnosis of acute trabecular microfractures using gamma correction Tc-99m HDP pinhole bone scan with histopathological verification.

We prospectively performed gamma correction pinhole bone scan (GCPBS) and histopathologic verification study to make simultaneous morphobiochemical diagnosis of trabecular microfractures (TMF) occurred in the femoral head as a part of femoral neck fracture.Materials consisted of surgical specimens of the femoral head in 6 consecutive patients. The specimens were imaged using Tc-99m hydroxymethylene diphosphonate (HDP) pinhole scan and processed by the gamma correction. After cleansing with 10% formalin solution, injured specimen surface was observed using a surgical microscope to record TMF. Morphological findings shown in the photograph, naive pinhole bone scan, GCPBS, and hematoxylin-eosin (H&E) stain of the specimen were reciprocally correlated for histological verification and the usefulness of suppression and enhancement of Tc-99m HDP uptake was biochemically investigated in TMF and edema and hemorrhage using gamma correction.On the one hand, GCPBS was able to depict the calcifying calluses in TMF with enhanced Tc-99m HDP uptake. They were pinpointed, speckled, round, ovoid, rod-like, geographic, and crushed in shape. The smallest callus measured was 0.23 mm in this series. On the other hand, GCPBS biochemically was able to discern the calluses with enhanced high Tc-99m HDP uptake from the normal and edema dipped and hemorrhage irritated trabeculae with washed out uptake.Morphobiochemically, GCPBS can clearly depict microfractures in the femoral head produced by femoral neck fracture. It discerns the microcalluses with enhanced Tc-99m HDP uptake from the intact and edema dipped and hemorrhage irritated trabeculae with suppressed washed out Tc-99m HDP uptake. Both conventional pinhole bone scan and gamma correction are useful imaging means to specifically diagnose the microcalluses naturally formed in TMF.

Dapsone therapy for refractory immune thrombocytopenia patients: a case series.

BACKGROUND: Dapsone has been recommended as a second-line immunosuppressive agent for patients with immune thrombocytopenia (ITP). METHODS: We retrospectively analyzed the efficacy and safety of dapsone therapy in patients with ITP. RESULTS: Nine ITP patients were treated with dapsone at a dose of 50-100 mg/day between May 2013 and March 2016. All patients were refractory to multiple previous treatments, with a median of 7 agents (range, 4-8), and 3 patients had undergone a previous splenectomy. The median pre-treatment platelet count was 4×109/L (range, 3-27×109/L). Only 1 patient (11.1%) responded to dapsone therapy. No severe adverse events were observed, except for 1 case of dapsone hypersensitivity syndrome. CONCLUSION: Although dapsone is still useful for some patients, it may be ineffective in heavily pretreated patients with profound thrombocytopenia.

Comparison between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT): a monte carlo study.

The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams. The peak value of the maximum dose level when the boron particle was accurately labeled at the region was 192.4% among the energies. In all, we confirmed that prompt gamma rays of 478 keV and 719 keV were generated by the nuclear reactions in PBFT and BNCT, respectively. We validated the dramatic effectiveness of the alpha particle, especially in PBFT. The utility of PBFT was verified using the simulation and it has a potential for application in radiotherapy.

Dynamic filtration with a perforated disk for dewatering of Tetraselmis suecica.

Dynamic filtration equipped with a perforated disk was adopted for the first time to dewater and concentrate Tetraselmis suecica, from a typical solution of 2-100 g/L of dense biomass suited for the downstream process. An ultrafiltration membrane, polyethersulfone 150 kDa, was found to best perform in terms of high biomass retention and filtration rate. At 1600 rpm, the highest rotation speed of the disk we tested, plateau permeate flux increased up to 20.2 times higher than those with no rotation; this improvement was attributed to fouling reduction (up to 98%) via distinctively high-shear stress on the membrane surface. Even at a high biomass concentration (100 g/L) where fouling formation was very serious, the heightened shear stress caused high flux to be maintained and fouling resistance to be reduced in an effective way. When trans-membrane pressure was increased in a stepwise manner, flux continuously rose at high rotation speed; at low speed, on the other hand, the limiting flux was observed. The dynamic filtration with the perforated disk, which was an effective high-shear stress generator, was proven to be a promising dewatering means of T. suecica, and especially so for the production of highly concentrated biomass.