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Purpose: The COVID-19 pandemic has influenced various aspects of colorectal cancer (CRC) patient care, including diagnosis, treatment, and outcomes. This study assesses the pandemic's impact on CRC patients. Methods: We performed a retrospective analysis of medical records for CRC patients who underwent surgery at five hospitals affiliated with Hallym University from January 2017 to December 2022. Patients were divided into two groups: the pre-COVID group (2017– 2019) and the COVID group (2020– 2022). Results: Among 2038 patients, 987 (48.4%) were in the pre-COVID group, and 1051 (51.6%) were in the COVID group. The COVID group had more patients with two or more comorbidities (P < 0.001) and a higher incidence of rectal cancer (P = 0.010). While the rates of laparoscopic surgeries were similar, the COVID group had increased emergency surgeries (P = 0.005) and diversion procedures (P = 0.002). Additionally, the COVID group faced more overall complications (P < 0.001) and severe complications (Grade III–V, P = 0.004). There was a rise in lymphovascular invasion (P < 0.001) and T4 stage tumors (P < 0.001) within the COVID group. Despite these differences, both groups had similar 2-year overall survival rates (P = 0.409). Conclusion: Although patients treated during the COVID period experienced more frequent stoma formation, complications, and adverse prognostic factors, there were no differences in short-term oncologic outcomes, which was likely due to the follow-up period being insufficient to detect differences in OS. [ABSTRACT FROM AUTHOR]

Background/Aim: In vivo imaging with luciferaseluciferin has been limited by the inability to visualize the low emitted light, with the signal quantified only by photon counting using a cumbersome highly-cooled CCD camera in a dark room. In the present study, we demonstrate direct visualization of the luciferase-luciferin signal from an orthotopic lung cancer in a nude-mouse xenograft model with a sensitive low-light camera and optics. Materials and Methods: Mouse Lewis-lung carcinoma cells expressing luciferase (LL/2-Luc2) were injected transcutaneously into the lung of a nude mouse. One week later after cell injection, luciferase imaging for emission at 560 nm was performed using the UVP Biospectrum Advanced system after i.v. injection of D-luciferin potassium salt. The intensity of the visualized light was measured and quantified with the instrument. Results: A week following the implantation of LL/2- Luc2 cells in nude mice, the luciferase-luciferin signal from LL/2-Luc2 tumors in the lung was sufficiently visible through the skin to produce true images. At fifteen minutes, the intensity peaked and then progressively dropped due to clearance of luciferin from the tumor. Conclusion: Using the UVP Biospectrum Advanced system we demonstrated non-invasive visualization of true images from luciferase-luciferin signals from an orthotopic lung-cancer mouse model. The luciferase-luciferin emitted light was directly visible through the skin which is a major improvement over previous photon counting to detect the luciferase-luciferin signal. [ABSTRACT FROM AUTHOR]

Background. The objective of this study was to compare the long-term prognosis of patients with T1 and T2 colorectal cancer (CRC) according to lymph node metastasis (LNM) and to identify risk factors for LNM. Methods. We retrospectively reviewed patients who underwent curative resection for T1 or T2 CRC at five University-affiliated hospitals between January 2012 and December 2021. The patients were divided into several groups depending on the presence of LNM or the number of risk factors. Results. Of the total 765 patients, 87 (11.3%) patients had LNM. These patients had poorer recurrence-free survival (RFS) than patients without LNM (72.6% vs. 88.6%). The multivariable analysis showed that high-grade tumors (p = 0.003), lymphovascular invasion (p < 0.001), and rectal location (p = 0.049) were independent predictors of LNM. When divided into groups according to the number of the three risk factors, the risk of LNM increased from 5.4% (ultralow-risk group; no risk factor) to 60.0% (high-risk group; all three risk factors) and the 5-year RFS rate decreased from 96.3% in the ultralow-risk group to 60% in the high-risk group (p < 0.001). Conclusion. Radical surgery should be considered for T1 and T2 CRC patients with these risk factors. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic pancreaticoduodenectomy (LPD) is one of the most technically challenging operations of minimally invasive surgery. We aimed to analyze the learning curve of a single surgeon who conducted 115 LPDs at a single center. Materials and Methods: From August 2015 to August 2020, 115 patients underwent LPD. Patient characteristics and perioperative variables were retrospectively collected and analyzed. Cumulative summation (CUSUM) and risk-adjusted cumulative summation (RA-CUSUM) analyses were used to evaluate the LPD learning curve. All variables were compared after dividing the learning curve phases. Results: After 74 cases, operative time improved based on the CUSUM analysis of the operation time. From the RA-CUSUM analysis, three distinct phases of the learning curve were identified (phase I: 1-42 cases, phase II: 43-73 cases, and phase III: 74-115 cases). The mean operative time was significantly lower in phase III compared with that in phases I and II (348.5 minutes versus 444.6 minutes and 439.9 minutes, P < .001 and P < .001, respectively). The rate of estimated blood loss >500 mL was significantly decreased among the three phases (P = .017). The conversion rate significantly decreased from 11.9% in phase I to 6.5% in phase II to 0% in phase III (P = .023). The rates of overall complication (Clavien-Dindo >IIIA), postoperative pancreatic fistula, and postpancreatectomy hemorrhage were significantly decreased as phases progressed. Postoperative hospital stay, 30-day mortality, and 30-day readmission did not significantly differ among phases. Conclusions: According to learning curve analyses, the LPD failure rate plateaued after 42 cases and stabilized after 73 cases. [ABSTRACT FROM AUTHOR]

Background: Hybrid appendectomy (HA) has the technical advantages of the excellent visual field provided by laparoscopic surgery and is fast and easy similar to open surgery. We aimed to compare the safety and effectiveness of HA with single- and multiport laparoscopic appendectomy (SPLA and MPLA) in pediatric patients with acute appendicitis. Materials and Methods: This retrospective study compared the short-term operative outcomes between HA, SPLA, and MPLA groups. From January, 2010 to December, 2019, 239 patients aged <12 years who underwent laparoscopic appendectomy for acute appendicitis were included. The primary outcome was the 30-day postoperative complication rate, stratified according to the modified Clavien-Dindo classification. Results: In 239 patients, HA was more frequently performed in patients with a low body mass index (17.42 versus 18.97 kg/m2 in the SPLA group versus 18.44 kg/m2 in the MPLA group, P = .029) and tended to be more frequently adopted in uncomplicated appendicitis. In uncomplicated appendicitis, the HA group had a significantly shorter operation time than the MPLA group (31.77 versus 40.09 min, P < .001), but had a comparable operation duration with the SPLA group. The rate of 30-day postoperative complications was not significantly different between the groups (HA 7.6% versus SPLA 7.8% versus MPLA 5.4%, P = .841). The postoperative time to resume water intake was significantly longer in the SPLA group than in the HA and MPLA groups (P = .008). Conclusions: HA showed a short operation time, fast functional recovery, and acceptable postoperative complication rate in patients with uncomplicated appendicitis and can be safely and effectively performed in these patients. [ABSTRACT FROM AUTHOR]

Background: Single-port laparoscopic surgery (SPLS) was recently introduced as an innovative minimally invasive surgery method. Retrospective studies have revealed the safety and feasibility of SPLS for colon cancer treatment. However, no prospective randomized trials have been performed. The multicenter, randomized SIMPLE (single-port versus multiport laparoscopic surgery) trial aimed to investigate short-term perioperative outcomes of SPLS for colon cancer treatment, compared with multiport laparoscopic surgery (MPLS).Methods: Between August 2011 and April 2014, a total of 194 patients with colon cancer were recruited from seven hospitals in Korea. Patients were randomly allocated into the SPLS group (n = 99) or MPLS group (n = 95). The primary endpoint was postoperative complications. Operative, postoperative, and pathologic outcomes were analyzed after 50% of the patient study population had been recruited.Results: The patients' demographic characteristics, operative times, estimated blood volume losses, numbers of harvested lymph nodes, and lengths of both resection margins were not significantly different between groups. In the SPLS group, the rates of conversion to MPLS and open surgery were 12.9 and 2.2%, respectively. Postoperative complications occurred in 10.8% of the SPLS, and 12.5% of the MPLS patients (p = 0.714). Times to functional recovery, pain scores, and amounts of analgesia were similar between groups.Conclusion: The results of this interim analysis suggested that SPLS is technically safe and appropriate when used for radical resection of colon cancer. (ClinicalTrials.gov Identifier: NCT01480128). [ABSTRACT FROM AUTHOR]

Introduction: Single-port laparoscopic surgery (SPLS) has gained popularity due to its cosmetic benefit, and therefore, has been applied to several kinds of benign operations, such as appendectomy and cholecystectomy. The safety and suitability of SPLS for colon cancer has not been widely proved. We aimed at validating the safety, efficacy, and short-term quality of life (QOL) of SPLS compared with conventional laparoscopic surgery (CLS) in patients with colon cancer.Materials and Methods: Between June 2010 and April 2011, a total of 62 patients with pathology-proven colon cancer were randomly allocated to two groups: SPLS and CLS. Data were analyzed according to the intention-to-treat principle.Results: In total, there were 62 patients (35 men and 27 women) with a mean age of 63.0 years (range, 38-82). The baseline characteristics of the patients and tumor factors were well balanced between two groups. The operation time and estimated blood loss were similar, whereas intraoperative complications only occurred in three patients, all of whom were in the SPLS group. Conversion to CLS or open surgery occurred in 6 (19.4%) patients of the SPLS group. The number of harvested lymph nodes and length of proximal and distal resection margins were not statistically different between two groups. Postoperative complications and recovery of bowel function were similar in both groups, but fatal postoperative complication occurred in one case in the SPLS group. The QOL between two groups was identical in all domains until postoperative 12 months.Conclusions: SPLS for colon cancer is feasible and can be performed by following oncologic principles. However, surgeons should be aware of the potential for unexpected adjacent organ injury ( ClinicalTrial.gov identifier: NCT01203969). [ABSTRACT FROM AUTHOR]

Introduction: Single-port laparoscopic surgery (SPLS), one of the advanced techniques of laparoscopic surgery, is performed through a single multichannel port. Regarding colorectal surgery, several colorectal procedures, including right colectomy, sigmoidectomy, and total proctocelectomy with ileal pouch anal anastomosis, have been performed successfully. The aim of this study was to elucidate the feasibility and safety of SPLS for the treatment of the patient with colorectal cancer in Korea. Subjects and Methods: Data were collected retrospectively from six hospitals through a Web-based case reporting form, which requested baseline characteristics of the patient, intraoperative findings, postoperative course, pathologic results of the tumor, and postoperative surveillance. Results: From May 2009 to June 2012, 257 patients were included in this study. Anterior resection was performed in 117 patients, low anterior resection in 66 patients, and right colectomy in 53 patients. The primary entry incision site was umbilicus in all patients except for 2 cases; in these, stoma sites were used for the entry of the single port. The total mean incision length was 3.8±2.3 cm. Among 257 initially SPLS-attempted patients, 45 (17.5%) patients needed additional ports (one additional port in 44 patients), and 2 patients (0.78%) had to be converted to open laparotomy. Intraoperative complications were noted in 5 patients, including anastomotic failures in 3 patients and bleeding in 1 patient. Postoperative complications were noted in 34 patients (13.2%). Anastomotic leak developed in 11 patients, urinary retention in 5 patients, and wound complications in 4 patients. Re-admission was needed in 15 patients (5.8%). Conclusions: SPLS could be performed safely and appropriately in selected colorectal cancer cases by experts in laparoscopic colorectal surgery in Korea. Prospective randomized trials to demonstrate the benefit and effectiveness of SPLS in colorectal cancer surgery with long-term oncologic results are needed. [ABSTRACT FROM AUTHOR]

Background: We report a pure natural orifice translumenal endoscopic surgery (NOTES®; American Society for Gastrointestinal Endoscopy [Oak Brook, IL] and the Society of American Gastrointestinal and Endoscopic Surgeons [Los Angeles, CA]) rectosigmoidectomy in animal models using transgastric endoscopic inferior mesenteric artery (IMA) dissection and transanal rectal mobilization. Materials and Methods: Ten live animals (2 pigs weighing 35-40 kg each and 8 dogs weighing 25-30 kg each) were used. A gastrotomy was made using a needle-knife puncture and the balloon dilatation technique or following the creation of a submucosal tunnel. A circular stapler shaft was transanally inserted up to the sigmoid colon for spatial orientation and traction of the mesocolon. The IMA was endoscopically dissected using a Coagrasper™ (Olympus, Tokyo, Japan) and then clipped. Endoscopic division of the sigmoid mesocolon was conducted laterally toward the marginal artery. Transanal full-thickness circumferential rectal and mesorectal dissections were performed, and a colorectal anastomosis was performed using a circular stapler with a single stapling technique. During the transanal approach, the gastrotomy was closed using four endoscopic clips. Results: Endoscopic dissection of the IMA was successful in all cases, but minor bleedings occurred in 3 cases. The mean time from dissection and clipping to division of the IMA was 36.7 minutes (range, 25-45 minutes). The mean operation time was 180.5 minutes (range, 145-210 minutes). There were no intraoperative complications or hemodynamic instability. The mean length of the resected specimen was 11.2 cm (range, 9-17 cm). Conclusions: A pure NOTES approach to rectosigmoid resection using transgastric endoscopic IMA dissection is technically feasible in animal models. [ABSTRACT FROM AUTHOR]

Background: We attempted to assess the learning curve for laparoscopic resection for rectal cancer.Method: We included 381 patients who underwent laparoscopic resection for rectal cancer between December 2002 and December 2007. The operative experience was divided into four periods according to numbers of operations and significant changes in main surgical results.Results: Operative time decreased significantly after 90 operations. The overall anastomotic leakage rate was 3.7%; 14.6% for the first 50 patients and 5.4% for the following 40 patients. The overall conversion rate was 2.9%, 4-6% during the first and second periods, but decreasing thereafter. The number of harvested lymph nodes and distal resection margin was within an acceptable range during the entire period. For the patients with stage I-III tumors, the local recurrence rate was 4.4% and the overall recurrence rate was 22.9%. The local recurrence rate was 8.9% initially and decreasing to 1.4% after the second period. The cumulative incidence of local recurrence decreased to less than 7% after 120 patients and to less than 5% after 180 cases.Conclusion: The learning curve for laparoscopic surgery for rectal cancer changed over time. Moreover, the learning curve for oncological safety was longer than that for operative safety. [ABSTRACT FROM AUTHOR]

B Background: b Prospective data for the effects of FOLFOX chemotherapy on quality of life (QoL) has been limited. B Conclusions: b Patients with adjuvant FOLFOX chemotherapy had worse role and social functioning and had more fatigue, more nausea/vomiting, more appetite loss and more financial difficulties during chemotherapy period. [Extracted from the article]

Background/aim: Ivermectin is a widely-used anti-parasitic agent and has shown early promise as an anticancer agent. Recombinant methioninase (rMETase) is a methionine-depleting enzyme targeting the methionine addiction of cancer and has broad efficacy against all tested cancer types. However, the combination efficacy of ivermectin and rMETase on breast cancer cells remains unexplored. The present study aimed to determine the synergistic efficacy of ivermectin and rMETase on MCF-7 human breast cancer cells in vitro., Materials and Methods: The IC 10 of ivermectin and IC 50 of rMETase were determined on MCF-7 cells using the WST-8 reagent to measure cell viability in vitro. MCF-7 cells were treated with four groups: untreated control; ivermectin alone (4.89 μM, IC 10 ); rMETase alone (2.75 U/ml, IC 50 ); and a combination of ivermectin (4.89 μM) and rMETase (2.75 U/ml). Cell viability was assessed 72 hours after treatment with the WST-8 reagent., Results: Treatment with ivermectin (4.89 μM) did not significantly reduce the viability of MCF-7 cells. rMETase (2.75 U/ml) alone significantly reduced MCF-7 cell viability compared to the control group. The combination of ivermectin and rMETase resulted in a significantly greater reduction in cell viability than either agent alone, including a 9.9-fold greater efficacy than ivermectin alone, demonstrating synergistic efficacy (p<0.05)., Conclusion: The combination of ivermectin and rMETase had synergistic efficacy against MCF-7 breast cancer cells in vitro. The present findings suggest that the combination of ivermectin and rMETase is a promising strategy for breast cancer requiring further preclinical and clinical evaluation., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Chronic lymphocytic leukemia (CLL) is currently incurable. CLL is characterized by disordered DNA methylation. The aim of the present study was to target methylation with methionine restriction in a patient with progressive CLL., Case Report: Methionine restriction for the patient was achieved with a low-methionine vegan diet and oral recombinant methioninase (o-rMETase). The patient also received rituximab, once per week for four weeks, and acalabrutinib 100 mg, twice daily (bid) continuously. The patient's white blood cell count decreased by 95% from peak levels and extensive lymphadenopathy disappeared during combination treatment with o-rMETase, rituximab, and acalabrutinib., Conclusion: The combination of methionine restriction and first-line chemotherapy resulted in an apparent complete response (CR) in a CLL patient, a rare event. The duration of the CR will be monitored, and additional CLL patients will be treated similarly in the future., Competing Interests: The Authors declare no competing interests in relation to this study., (©2025 The Author(s). Published by the International Institute of Anticancer Research.)

Background/aim: Metastatic prostate cancer is a recalcitrant disease. Our laboratory has previously treated prostate-cancer patients with methionine restriction effected by a low methionine diet and oral recombinant methioninase (o-rMETase), both alone and in combination with other agents. The present case is a 66-year-old patient who had a radical prostatectomy in 2019 with a Gleason score 3+3 and 3+4. The patient subsequently was treated with immunotherapy in 2021 and salvage proton-beam therapy in 2022, and subsequently treated only with o-rMETase and a low-methionine diet. The aim of the present study was to determine the long-term efficacy of methionine restriction on the patient's prostate cancer., Case Report: Starting in September 2022, the patient started methionine restriction with a low methionine-diet and o-rMETase, twice a day, after meals, at 250 units/dose. Since the start of methionine restriction, the patients' prostate-specific antigen (PSA) has remained stable, under 2 ng/ml. Positron emission tomography/computed tomography (PET/CT) and prostate specific membrane antigen (PSMA)-PET imaging indicated in September 2023 a right pelvic-side-wall metastatic lymph node that was stable when the PSMA-PET scan was repeated in March 2024, with the standardized uptake value (SUV) decreasing from 19.39 to 14.98. A very small possible metastatic external-iliac lymph node was detected in March 2024. Thus, the lymph-node metastases were stable and did not increase., Conclusion: During the time the patient was on methionine restriction alone, effected by a low-methionine diet and o-rMETase, the metastatic prostate cancer did not progress. Further clinical studies of methionine restriction and metastatic prostate cancer are needed, including randomized clinical trials., Competing Interests: The Authors declare no competing interests., (©2025 The Author(s). Published by the International Institute of Anticancer Research.)

Background/aim: For second-line chemotherapy of soft-tissue sarcoma, gemcitabine is administered in combination with docetaxel. However, more effective treatments are required for advanced soft-tissue sarcoma, where the efficacy is limited. The purpose of the present study was to compare the efficacy of rMETase and gemcitabine against HT1080 human fibrosarcoma cells and Hs27 normal fibroblasts, as well as to identify and effectively treat HT1080 cells that are resistant to gemcitabine associated with elevated c-MYC., Patients and Methods: Cell viability was measured with the WST-8 reagent. Four groups of in vitro tests were conducted involving HT1080 and Hs27 cells: gemcitabine alone, rMETase alone, and a combination of gemcitabine plus rMETase. Gemcitabine resistant cells (GR-HT1080) were established by culturing HT-1080 cells in increasing concentrations of gemcitabine, ranging from 0.016 nM to 16 nM over five months. Western immunoblotting was performed to measure c-MYC levels in HT1080 and GR-HT1080 cells., Results: Gemcitabine had an IC 50 of 12.8 nM against HT1080 cells, 30.8 nM against GR-HT1080 cells, and 4.48 nM against Hs27 cells. The rMETase IC 50 value for HT1080 was 0.75 U/ml. The IC 50 value of rMETase for GR-HT1080 cells was 0.85 U/ml. The IC 50 value for rMETase on Hs27 cells was 0.93 U/ml. Gemcitabine and rMETase demonstrated synergy in killing fibrosarcoma cells, but no synergy was observed on normal fibroblasts. The c-MYC level that was more than 5.1 times higher in GR-HT1080 cells compared to HT-1080 cells. Both the parental HT1080 cells and the GR-HT1080 cells had a similar high sensitivity to rMETase alone., Conclusion: rMETase may be used as a future clinical strategy to overcome gemcitabine resistance in sarcoma., Competing Interests: The Authors declare no competing interests in relation to this study., (©2025 The Author(s). Published by the International Institute of Anticancer Research.)

Background/aim: Salmonella typhimurium A1-R (A1-R) targets and inhibits a wide range of cancer types without continuously infecting healthy tissue. Chloroquine, an antimalarial drug, induces apoptosis and inhibits autophagy in cancer cells. The aim of the present study was to determine the synergy of A1-R plus chloroquine on HT1080 human fibrosarcoma cells in vitro and in a nude-mouse model., Materials and Methods: HT1080 human fibrosarcoma cells were used for in vitro experiments. Four groups were analysed in vitro: No-treatment control; A1-R; chloroquine; A1-R plus chloroquine. The nude-mouse models of HT1080 human fibrosarcoma were randomly assigned into four groups: G1: untreated control; G2: Oral A1-R [5×10 7 colony forming units (CFU)/body, twice a week, 2 weeks]; G3: Chloroquine [100 mg/kg/body, intraperitoneal (IP) administration, twice a week, 2 weeks]; G4: Oral A1-R (5×10 7 CFU/body), twice a week, 2 weeks plus chloroquine (100 mg/kg/body, IP), twice a week, 2 weeks. Each cohort consisted of five mice. Tumor volume and body weight were assessed biweekly., Results: A1-R combined with chloroquine synergistically decreased the viability of HT1080 cells in vitro compared to other groups. Orally-administered A1-R at 5×10 7 CFU combined with IP-administered chloroquine eradicated HT1080 tumors in nude mice, without body-weight decrease., Conclusion: The combination treatment of A1-R plus chloroquine demonstrated synergy against HT1080 cancer cells in vitro and in vivo. A1-R was administered orally, suggesting its potential as a probiotic. The present results suggest the clinical potential of the combination of A1-R and chloroquine for soft-tissue sarcoma therapy, a recalcitrant disease., (Copyright © 2025, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Ivermectin was initially utilized as a veterinary medication, demonstrating efficacy against various parasites. Pancreatic cancer is currently one of the most recalcitrant diseases. The aim of the present study was to demonstrate the synergy of the combination of recombinant methioninase (rMETase) and ivermectin to eradicate human pancreatic cancer cells in vitro., Materials and Methods: MiaPaCa-2 human pancreatic cancer cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with the addition of 10% fetal bovine serum and 1 IU/ml penicillin/streptomycin. Reduction of cell viability by rMETase alone and ivermectin alone and their combination on MiaPaCa-2 cells was determined with the WST-reagent. Four experimental groups were examined in vitro: control group without treatment; ivermectin alone; rMETase alone; ivermectin combined with rMETase., Results: The IC 50 of ivermectin for MiaPaCa-2 cells was 5.9 μM. The IC 50 of rMETase on MiaPaCa-2 cells was 2.93 U/ml. Ivermectin (5.9 μM) plus rMETase (2.93 U/ml) synergistically greatly reduced the viability of MiaPaCa-2 cells, compared to ivermectin alone (80% reduction vs. 45% reduction, respectively p<0.05)., Conclusion: The combination of ivermectin and rMETase effectively eradicated MiaPaCa-2 pancreatic cancer cells. The present results indicate the future clinical potential of the combination of rMETase, currently administered orally to patients as a dietary supplement, and oral ivermectin on pancreatic cancer., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Methionine addiction, known as the Hoffman effect, makes cancer cells more sensitive to methionine restriction than normal cells. However, the long-term effects of methionine restriction on cancer and normal cells have not been thoroughly studied., Materials and Methods: HCT-116 human colorectal-cancer cells and Hs27 normal skin fibroblasts were treated with 0-8 U/ml of recombinant methioninase (rMETase) for 12 days. The cells were cultured in Dulbecco's modified Eagle's medium in 96-well tissue-culture plates., Results: HCT-116 cells were sensitive to all concentrations of rMETase from 0.125 U/ml to 8 U/ml. After day-8 of treatment, HCT-116 cells were acutely sensitive to rMETase, especially at rMETase concentrations of 0.5 U/ml or higher. Normal Hs27 fibroblasts were much less sensitive to rMETase: In the range of 0.125 U/ml to 0.5 U/ml, rMETase had no effect on Hs27 cells. rMETase concentrations up to 2 U/ml had a slight initial effect on Hs27 cells, whereas at concentrations ranging from 4 U/ml to 8 U/ml, rMETase reduced Hs27 viability over the 12-day test period, with acute loss of viability observed after eight days of exposure., Conclusion: Cancer cells were significantly more sensitive to rMETase than normal cells, with an acute loss of cell viability observed in cancer cells after eight days of treatment at concentrations of 0.5 U/ml or higher. These findings highlight the large difference in sensitivity between cancer and normal cells to rMETase and introduce the phenomenon of acute cell death in methionine restriction, which we term "methionine-depletion catastrophe"., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Ifosfamide is used clinically with doxorubicin as first-line chemotherapy for soft-tissue sarcoma. However, ifosfamide efficacy for soft-tissue sarcoma is limited due to frequent occurence of ifosfamide resistance and thus more effective therapy is needed. The present study aimed to determine the synergy of recombinant methioninase (rMETase) plus ifosfamide against HT1080 human fibrosarcoma cells in vitro. Additionally, the present study also investigated the efficacy of a methionine-restricted diet combined with ifosfamide in nude-mouse models of ifosfamide-resistant HT1080 (IR-HT1080)., Materials and Methods: Cell viability for HT1080 human fibrosarcoma cells was determined in four groups in vitro: No treatment control; ifosfamide alone; rMETase alone; and a combination of ifosfamide plus rMETase. HT1080 tumors were established in nude mice subcutaneously. The HT1080 tumor models were treated by administering ifosfamide by intraperitoneal injection twice a week, for a total of 11 doses. Surviving tumors were considered ifosfamide resistant (IR-HT1080). Four groups of IR-HT1080 nude-mouse models were subsequently established: Group 1 was a no-treatment control, Group 2 received ifosfamide, Group 3 was given a methionine-restricted diet (MR), and Group 4 received ifosfamide plus MR. Additionally, two groups of nude mice with parental HT1080 subcutaneous tumors were included: Group 5 was a no-treatment control, and Group 6 received ifosfamide for comparison., Results: The 50% inhibitory concentration (IC 50 ) for ifosfamide against HT1080 cells was 0.38 mM. The IC 50 for rMETase was 0.75 U/ml for HT1080 cells (data from [4]). The combination of rMETase (0.75 U/ml) plus ifosfamide (0.38 mM) was synergistic against HT1080 fibrosarcoma cells in vitro. The combination of ifosfamide plus MR eradicated the IR-HT1080 tumors in nude-mouse models, while each treatment alone achieved limited tumor inhibition., Conclusion: The present results suggest the combination of MR and ifosfamide has promising potential for overcoming ifosfamide resistance in future clinical applications., (Copyright © 2025, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The surgical environment can influence the clinical outcomes of procedures and patient conditions. This retrospective study aimed to evaluate how surgical timing affects short-term outcomes in emergency laparoscopic appendectomy for acute appendicitis. Methods: A total of 647 patients with acute appendicitis who underwent emergency laparoscopic appendectomy at Chuncheon Sacred Heart Hospital between January 2018 and June 2021 were included in this study. The study cohort was divided into the following two groups based on the timing of surgery: work hours and out-of-hours (weekends, holidays, or weekday nights). Clinical outcomes were then compared between the groups. Results: Work-hour and out-of-hours appendectomies were performed in 282 and 365 patients, respectively. Baseline characteristics and types of appendicitis were similar between the groups (complicated appendicitis: 26.6% in the work-hours group versus 30.4% in the out-of-hours group, P = .288). Operation times were comparable (35.10 minutes versus 34.33 minutes, P = .620), with no cases requiring conversion to open appendectomy in either group. The overall rate of 30-day postoperative complications did not differ significantly between the groups (7.8% versus 10.4%, P = .849). The severity of postoperative complications, categorized by the modified Clavien-Dindo classification, did not show significant differences between the groups ( P = .849). In addition, the time to functional recovery was similar in both groups. Conclusions: The clinical outcomes of out-of-hours laparoscopic appendectomy were similar to those of procedures performed during working hours. Therefore, scheduling emergency surgery can be determined based on the patient's condition and the hospital's capacity to manage acute appendicitis.

Background/aim: Docetaxel combined with gemcitabine is a second-line treatment for soft-tissue sarcoma; however, its effectiveness is limited because of docetaxel resistance. The objective of the present study was to determine the potential of recombinant methioninase (rMETase) to enhance the efficacy of docetaxel on high-docetaxel-resistant human fibrosarcoma cells in vitro., Materials and Methods: Docetaxel-resistant HT1080 (DTR-HT1080) human fibrosarcoma cells were established by culturing them in by progressively increasing concentrations of docetaxel from 0.02 to 9 nM in vitro. The IC 50 values for docetaxel and rMETase, as well as the efficacy of their combination, in inhibiting HT1080 human fibrosarcoma cells, DTR-HT1080 cells, and Hs27 normal human fibroblasts were determined. Four experimental groups were examined in vitro: control group without treatment; docetaxel alone; rMETase alone; docetaxel combined with rMETase., Results: The IC 50 of docetaxel for DTR-HT1080 cells was 7.57 nM, compared to the parental HT1080 cells with an IC 50 of 1.68 nM, a 4.5-fold increase. The IC 50 of docetaxel on Hs27 fibroblasts was 4.46 nM. The IC 50 of rMETase on HT1080 cells was 0.75 U/ml (data from [6]). The IC 50 of rMETase on DTR-HT1080 cells was 0.55 U/ml. The IC 50 of rMETase on Hs27 fibroblasts was 0.93 U/ml (data from [6]). Docetaxel (1.68 nM [IC 50 ]) plus rMETase (0.75 U/ml [IC 50 ]) synergistically reduced the viability of HT1080 cells (p<0.05). In contrast, docetaxel (4.46 nM) plus rMETase (0.93 U/ml) did not reduce the viability of Hs27 fibroblasts, compared to either agent alone. The combination of rMETase (0.55 U/ml [IC 50 ]) and docetaxel (1.68 nM [IC 50 of the parental cells]) overcame docetaxel resistance of DTR-HT1080 cells, resulting in an inhibition of 48.1% compared to docetaxel alone (6.8%) or rMETase alone (37.5%) (p<0.05). rMETase thus increased the efficacy of docetaxel 7-fold on docetaxel-resistant human fibrosarcoma cells., Conclusion: The combination of docetaxel and rMETase was synergistic on HT1080 fibrosarcoma cells, but not normal fibroblasts. rMETase plus docetaxel synergistically reduced the high docetaxel resistance of DTR-HT1080 cells. The present results indicate the clinical potential of rMETase to reduce docetaxel resistance in soft-tissue sarcoma patients in the future., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Salmonella typhimurium A1-R has been shown to target and inhibit many types of cancers in mouse models without continuous infection of normal tissue. The objective of the present study was to determine the effective dose of orally-administered Salmonella typhimurium A1-R, expressing-green fluorescent protein (GFP), on an HT1080 human-fibrosarcoma nude-mouse model., Materials and Methods: The HT1080-human- fibrosarcoma nude-mouse models were randomized into the following three groups: G1: untreated control; G2: Oral Salmonella typhimurium A1-R (5×10 7 colony forming units [CFU]/body, twice a week, 2 weeks); G3: Oral Salmonella typhimurium A1-R (3.3×10 8 CFU/body, twice a week, 2 weeks). Each group comprised five mice. Body weight and tumor volume were measured twice a week. The number of colonies of Salmonella typhimurium A1-R-GFP in excised tumors and excised livers in groups G2 and G3 were determined on day 3, day 7 and 14 by growth on agar plates. Tukey-Kramer analysis was used to examine the relationships between variables. Statistically-significant results are defined as those with p≤0.05., Results: Salmonella typhimurium A1-R was administered orally at a dose of 3.3×10 8 CFU, which successfully regressed the HT1080 tumor in nude mice. However, this effect was not observed at a lower dose of 5×10 7 CFU. After administering Salmonella typhimurium A1-R at 3.3×10 8 CFU, tumors and liver tissues were harvested, homogenized, and cultured on days 3, 7 and 14. Resulting GFP-expressing Salmonella typhimurium A1-R colonies were then counted. The number of GFP-bacterial colonies derived from excised tumors at intervals of 3, 7, and 14 days increased over time post-administration of oral GFP-Salmonella typhimurium. Conversely, the number of GFP-Salmonella typhimurium A1-R colonies that could be grown from excised livers decreased over time, following oral administration of GFP-Salmonella typhimurium. Additionally, the GFP-bacterial colonies grown from the excised tumors were significantly larger than those grown from the excised livers., Conclusion: The present study showed that an aggressive fibrosarcoma could be regressed by orally-administered Salmonella typhimurium A1-R which accurately targeted tumors without continuous growth in normal organs. The present results suggested the potential of orally-administered Salmonella typhimurium A1-R as a probiotic to treat aggressive soft-tissue sarcoma., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Methionine restriction selectively arrests cancer cells during the S-phase of the cell cycle. We hypothesized that DNA damage may occur in S-phase in cancer cells during methionine restriction. To determine if this occurs, we used MiaPaCa-2 Tet-On 53BP1-green fluorescent protein (GFP) pancreatic cancer cells, which report GFP fluorescence in real time after DNA-damage response (DDR) in these cells. We also determined whether a chemotherapy drug in combination with methionine restriction increases the rate of DNA damage., Materials and Methods: MiaPaCa-2 Tet-On 53BP1-GFP cells were used for in vitro experiments. The 25% and 50% inhibitory concentrations (IC 25 and IC 50 , respectively) of recombinant methioninase (rMETase) and paclitaxel on MiaPaCa-2 Tet-On 53BP1-GFP pancreatic cancer cells were determined. Cell viability and DDR with rMETase alone, paclitaxel alone, and their combination were measured in MiaPaCa-2 Tet-On 53BP1-GFP cells., Results: The IC 25 of rMETase on MiaPaCa-2 Tet-On 53BP1-GFP cells was 1.66 U/ml. The IC 25 for paclitaxel on MiaPaCa-2 Tet-On 53BP1-GFP cells was 3.31 nM. The combination of rMETase and paclitaxel synergistically reduced the viability of MiaPaCa-2 Tet-On 53BP1-GFP cells. The IC 50 of paclitacel on MiaPaCa-2 Tet-On 53BP1-GFP cells was 5.1 nM. The IC 50 of rMETase on MiaPaCa-2 Tet-On 53BP1-GFP cells was 2.3 U/ml. The combination of rMETase (IC 50 ) plus paclitaxel (IC 50 ) on MiaPaCa-2 Tet-On 53BP1-GFP cells also caused more DNA damage than either agent alone., Conclusion: The present study suggests the synergy of methionine restriction and chemotherapy is due, at least in part, to DNA damage of cancer cells., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)