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Annals of Surgical Treatment and... Nov 2023In recent years, the rise of minimally invasive surgery has driven the development of surgical devices. Indocyanine green (ICG) fluorescence imaging is receiving... (Review)
Review
In recent years, the rise of minimally invasive surgery has driven the development of surgical devices. Indocyanine green (ICG) fluorescence imaging is receiving increased attention in colorectal surgery for improved intraoperative visualization and decision-making. ICG, approved by the U.S. Food and Drug Administration in 1959, rapidly binds to plasma proteins and is primarily intravascular. ICG absorption of near-infrared light (750-800 nm) and emission as fluorescence (830 nm) when bound to tissue proteins enhances deep tissue visualization. Applications include assessing anastomotic perfusion, identifying sentinel lymph nodes, and detecting colorectal cancer metastasis. However, standardized protocols and research on clinical outcomes remain limited. This study explores ICG's role, advantages, disadvantages, and potential clinical impact in colorectal surgery.
PubMed: 38023438
DOI: 10.4174/astr.2023.105.5.252 -
BMC Cancer Nov 2023Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic... (Randomized Controlled Trial)
Randomized Controlled Trial
Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial).
BACKGROUND
Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT).
METHODS
A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness.
DISCUSSION
This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness.
TRIAL REGISTRATION
This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.
Topics: Humans; Neoadjuvant Therapy; Quality of Life; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Rectal Neoplasms; Chemoradiotherapy; Neoplasm Staging
PubMed: 37923987
DOI: 10.1186/s12885-023-11363-7 -
Cancer Reports (Hoboken, N.J.) Nov 2023There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer...
BACKGROUND AND AIM
There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer numerous beneficial effects on intestinal health. However, the effects of refined DFs on intestinal health remain unclear. Therefore, we elucidated the impact of the refined DF inulin on colonic inflammation and tumorigenesis.
METHODS
Four-week-old wild-type (WT) mice were fed diets containing insoluble DF cellulose (control) or refined DF inulin for 4 weeks. A subgroup of mice was then switched to drinking water containing dextran sulfate sodium (DSS, 1.4% wt/vol) for colitis induction. In another subgroup of mice, colitis-associated colorectal cancer (CRC) was initiated with three 7-day alternate cycles of DSS following an initial dose of mutagenic substance azoxymethane (AOM; 7.5 mg/kg body weight; i.p.). Post 7 weeks of AOM treatment, mice were euthanized and examined for CRC development.
RESULTS
Mice consuming inulin-containing diet exhibited severe colitis upon DSS administration, as evidenced by more body weight loss, rectal bleeding, and increased colonic inflammation than the DSS-treated control group. Correspondingly, histological analysis revealed extensive disruption of colon architecture and massive infiltration of immune cells in the inulin-fed group. We next examined the effect of inulin on CRC development. Surprisingly, significant mortality (~50%) was observed in the inulin-fed but not in the control group during the DSS cycle. Consequently, the remaining inulin-fed mice, which completed the study exhibited extensive colon tumorigenesis. Immunohistochemical characterization showed comparatively high expression of the cell proliferation marker Ki67 and activation of the Wnt signaling in tumor sections obtained from the inulin-fed group. Gut microbiota and metabolite analysis revealed expansion of succinate producers and elevated cecal succinate in inulin-fed mice. Human colorectal carcinoma cells (HCT116) proliferated more rapidly when supplemented with succinate in an inflamed environment, suggesting that elevated luminal succinate may contribute to tumorigenesis.
CONCLUSIONS
Our study uncovers that supplementation of diet with refined inulin induces abnormal succinate accumulation in the intestinal lumen, which in part contributes to promoting colon inflammation and tumorigenesis.
Topics: Humans; Animals; Mice; Inulin; Succinic Acid; Dextran Sulfate; Inflammation; Colitis; Colonic Neoplasms; Colorectal Neoplasms; Carcinogenesis; Cell Transformation, Neoplastic
PubMed: 37489647
DOI: 10.1002/cnr2.1863 -
The Oncologist Nov 2023In this phase Ib study MODURATE, we optimized the dosing schedule and tested the efficacy and safety of trifluridine/tipiracil, irinotecan, and bevacizumab in patients...
BACKGROUND
In this phase Ib study MODURATE, we optimized the dosing schedule and tested the efficacy and safety of trifluridine/tipiracil, irinotecan, and bevacizumab in patients with metastatic colorectal cancer with fluoropyrimidine and oxaliplatin treatment failure.
METHODS
We included a dose escalation (3 + 3 design) and an expansion cohort. Patients were administered trifluridine/tipiracil (25-35 mg/m2 twice daily, days 1-5), irinotecan (150-180 mg/m2, day 1), and bevacizumab (5 mg/kg, day 1) every 2 weeks. The recommended phase II dose (RP2D) in the dose escalation cohort was administered to at least 15 patients in both cohorts combined.
RESULTS
Twenty-eight patients were enrolled. Five dose-limiting toxicities were observed. RP2D was defined as trifluridine/tipiracil 35 mg/m2, irinotecan 150 mg/m2, and bevacizumab 5 mg/kg. Of 16 patients who received RP2D, 86% (14/16) experienced grade ≥3 neutropenia without febrile neutropenia. Dose reduction, delay, and discontinuation occurred in 94%, 94%, and 6% of patients, respectively. Three patients (19%) showed partial response and 5 had stable disease for >4 months, with a median progression-free and overall survival of 7.1 and 21.7 months, respectively.
CONCLUSION
Biweekly trifluridine/tipiracil, irinotecan, and bevacizumab administration may have moderate antitumor activity with high risk of severe myelotoxicity in previously treated patients with metastatic colorectal cancer [UMIN Clinical Trials Registry (UMIN000019828) and Japan Registry of Clinical Trials (jRCTs041180028)].
Topics: Humans; Bevacizumab; Irinotecan; Colorectal Neoplasms; Uracil; Trifluridine; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Rectal Neoplasms; Drug Combinations
PubMed: 37284901
DOI: 10.1093/oncolo/oyad143 -
Revista Espanola de Enfermedades... Nov 2023Kerosene has been described as an uncommon burn injury agent(1). We report a case of a 47-year-old male who presented to the Emergency Department with proctalgia after...
Kerosene has been described as an uncommon burn injury agent(1). We report a case of a 47-year-old male who presented to the Emergency Department with proctalgia after self-administration of an unknown enema in the context of cocaine intoxication. Physical examination revealed severe perianal inflammation (Figure 1.A) without suppuration and computerized tomography (CT) scan showed free air in mesorectum and retroperitoneum without intraperitoneal free air or fluid (Figure 1.B and 1.C). Rigid rectoscopy demostrated erythematous rectal mucosa without perforation. Subsequently, perineal drainage and debridement were performed. On the fifth postoperative day, the patient reported worsening proctalgia. Examination under anesthesia revealed the presence of new-onsetanal ulcers (Figure 1.D), rigid rectoscopy identified deep ulcers limited to the rectal mucosa and colonoscopy ruled out colon involvement. During reevaluation, the patient disclosed the use of sailboat engine lubrican as the enema, with kerosene being one of its components. These findings were consistent with rectal burn injuries resulting from exposure to kerosene. A laparoscopic end-loop colostomy was performed without any postoperative complications. Follow-up examinations with rigid rectoscopy showed improvement of rectal ulcers (Figure 1.E and 1.F). To our knowledge, this is the first case of rectal burn injuries after kerosene exposure(2,3). Aggressive washout, early colostomy and serial follow-up scopes are key components in the management of these rare injuries.
PubMed: 38031923
DOI: 10.17235/reed.2023.10098/2023 -
World Journal of Surgical Oncology Jul 2023To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N downstaging.
METHODS
PubMed, MEDLINE, Embase, and Cochrane Database of collected reviews were searched up to June 30, 2022. This study conducted systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sheet. Odds ratios (ORs) and confidence intervals (CIs) which calculated by random-effects models were displayed in forest plots. Newcastle-Ottawa scale was used to assess the risk of bias of the observational cohort studies.
RESULTS
This systematic review and meta-analysis comprised eight cohorts out of seven studies, with 2294 patients in total. We performed two-way comparison for metformin in diabetic patients vs (1) non-metformin drugs in diabetic patients and (2) nondiabetic patients. In diabetes patient studies, the metformin group had a significantly increased pathological response on TRG (OR: 3.28, CI: 2.01-5.35, I = 0%, p < 0.001) and T downstaging (OR: 2.14, CI: 1.24-3.67, I = 14%, p = 0.006) in comparison with a non-metformin group. When compared with nondiabetic patients, the pathological response on TRG (OR: 2.67, CI: 1.65-4.32, I = 43%, p < 0.001) and T downstaging (OR: 1.96, CI: 1.04-3.71, I = 66%, p = 0.04) were also higher in metformin group. The limitation was that no randomized controlled trials were available based on current literature review. Small sample sizes for diabetic metformin or non-metformin users in rectal cancer patients reduced the power of the study.
CONCLUSIONS
For patients with rectal cancer and treated with neoadjuvant chemoradiotherapy, metformin administration in diabetic patients increased the pathological response on tumor-regression grade and T downstaging. Further well-designed, high-quality randomized controlled trials are required to reveal the actual effect of metformin.
Topics: Humans; Metformin; Neoadjuvant Therapy; Chemoradiotherapy; Rectal Neoplasms; Diabetes Mellitus; Treatment Outcome
PubMed: 37491250
DOI: 10.1186/s12957-023-03087-6 -
Cancer Research Oct 2023Appendiceal adenocarcinomas (AA) are a rare and heterogeneous mix of tumors for which few preclinical models exist. The rarity of AA has made performing prospective...
UNLABELLED
Appendiceal adenocarcinomas (AA) are a rare and heterogeneous mix of tumors for which few preclinical models exist. The rarity of AA has made performing prospective clinical trials difficult, which has partly contributed to AA remaining an orphan disease with no chemotherapeutic agents approved by the FDA for its treatment. AA has a unique biology in which it frequently forms diffuse peritoneal metastases but almost never spreads via a hematogenous route and rarely spreads to lymphatics. Given the localization of AA to the peritoneal space, intraperitoneal delivery of chemotherapy could be an effective treatment strategy. Here, we tested the efficacy of paclitaxel given by intraperitoneal administration using three orthotopic patient-derived xenograft (PDX) models of AA established in immunodeficient NSG mice. Weekly intraperitoneal paclitaxel treatment dramatically reduced AA tumor growth in all three PDX models. Comparing the safety and efficacy of intravenous with intraperitoneal administration, intraperitoneal delivery of paclitaxel was more effective, with reduced systemic side effects in mice. Given the established safety record of intraperitoneal paclitaxel in gastric and ovarian cancers, and lack of effective chemotherapeutics for AA, these data showing the activity of intraperitoneal paclitaxel in orthotopic PDX models of mucinous AA support the evaluation of intraperitoneal paclitaxel in a prospective clinical trial.
SIGNIFICANCE
The activity and safety of intraperitoneal paclitaxel in orthotopic PDX models of mucinous appendiceal adenocarcinoma supports the evaluation of intraperitoneal paclitaxel in a prospective clinical trial of this rare tumor type.
Topics: Female; Humans; Animals; Mice; Paclitaxel; Prospective Studies; Adenocarcinoma, Mucinous; Adenocarcinoma; Ovarian Neoplasms
PubMed: 37433032
DOI: 10.1158/0008-5472.CAN-23-0013 -
MSystems Mar 2024High-fat diet (HFD) is well known to impact various aspects of gut health and has been associated with many diseases and inflammation. However, the impact of HFD feeding...
High-fat diet (HFD) is well known to impact various aspects of gut health and has been associated with many diseases and inflammation. However, the impact of HFD feeding on HIV-1 rectal transmission has not yet been well addressed. With an increasing threat of HIV-1 infection in men who have sex with men (MSM), where the rectal route is the primary mode of infection, it is imperative to understand the impact of HFD on gut microbiota and inflammation and consequently, its effect on HIV-1 rectal transmission. Here, we utilized our double humanized bone marrow, liver, thymus (dHu-BLT) mouse model to assess the impact of HFD feeding on the host's susceptibility to HIV-1 rectal transmission. We found that feeding an HFD successfully altered the gut microbial composition within 3 weeks in the dHu-BLT mouse model. In addition, levels of inflammatory mediators, specifically IL-12p70, IP-10, ICAM-1, and fecal calprotectin, were significantly higher in HFD-fed mice compared to control mice on a regular chow diet. We also observed that significantly different inflammatory markers (IL-12p70 and ICAM-1) were negatively correlated with the number of observed ASVs, Shannon diversity, and Faith's diversity in the HFD-fed group. Notably, when repeatedly challenged with a low dose of HIV-1 a rectal route, mice receiving an HFD were significantly more susceptible to HIV-1 rectal infection than control mice. Together, these results underscore the impact of HFD feeding on the gut microbiota and inflammation and suggest the significance of diet-induced gut microbial dysbiosis and inflammation in promoting viral infection.IMPORTANCEHFD induces gut microbial dysbiosis and inflammation and has been associated with many infections and disease progression; however, its impact on HIV-1 rectal transmission is largely unknown. Given the increasing threat of HIV-1 incidence in men who have sex with men (MSM), it has become crucial to comprehend the impact of factors associated with gut health, like HFD consumption, on host susceptibility to HIV-1 rectal transmission. This is particularly important since anal intercourse remains the primary mode of HIV transmission within the MSM group. In this study, utilizing our unique mouse model, featuring both the human immune system and gut microbiota, we showed that HFD feeding led to gut microbial dysbiosis, induced inflammation, and increased HIV-1 rectal transmission. Collectively, our study highlights the significant impact of HFD on gut microbiota and inflammation and suggests an HFD consumption as a potential risk factor for promoting HIV-1 rectal susceptibility.
Topics: Male; Humans; Mice; Animals; Diet, High-Fat; HIV-1; Homosexuality, Male; Intercellular Adhesion Molecule-1; Dysbiosis; Sexual and Gender Minorities; Inflammation; HIV Seropositivity
PubMed: 38303112
DOI: 10.1128/msystems.01322-23 -
EBioMedicine Feb 2024Limited therapeutic options are available for metastatic colorectal cancer (mCRC) patients after failure of first- and second-line therapies, representing an unmet...
Efficacy, safety and genomic analysis of SCT200, an anti-EGFR monoclonal antibody, in patients with fluorouracil, irinotecan and oxaliplatin refractory RAS and BRAF wild-type metastatic colorectal cancer: a phase Ⅱ study.
BACKGROUND
Limited therapeutic options are available for metastatic colorectal cancer (mCRC) patients after failure of first- and second-line therapies, representing an unmet medical need for novel therapies.
METHODS
This is an open-label, single arm, multicenter, phase Ⅱ study aiming to perform the efficacy, safety and genomic analysis of SCT200, a noval fully humanized IgG1 anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in patients with fluorouracil, irinotecan and oxaliplatin refractory RAS and BRAF wild-type mCRC. SCT200 (6 mg/kg) was given weekly for the first six weeks, followed by a higher dose of 8 mg/kg every two weeks until disease progression or unacceptable toxicity. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR) and secondary endpoints included ORR in patients with left-sided tumor, disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety.
FINDINGS
From February 12, 2018 to December 1, 2019, a total of 110 patients aged between 26 and 77 years (median: 55; interquartile range [IQR]: 47-63) with fluorouracil, oxaliplatin, and irinotecan refractory RAS and BRAF wild-type mCRC were enrolled from 22 hospitals in China. As the data cut-off date on May 15, 2020, the IRC-assessed ORR and DCR was 31% (34/110, 95% confidence interval [CI] 22-40%) and 75% (82/110, 95% CI 65-82%), respectively. Thirty one percent (34/110) patients achieved confirmed partial response (PR). The median PFS and median OS were 5.1 months (95% CI 3.4-5.2) and 16.2 months (95% CI 11.1-not available [NA]), respectively. The most common ≥ grade 3 treatment-related adverse events (TRAEs) were hypomagnesemia (17%, 19/110) and acneiform dermatitis (11%, 12/110). No deaths occurred. Genomic analysis suggested positive association between MYC amplification and patients' response (P = 0.0058). RAS/RAF mutation and MET amplification were the most frequently detected resistance mechanisms. Patients with high circulating tumor DNA (ctDNA) at baseline or without ctDNA clearance at the 7th week after the first dose of SCT200 administration before receiving SCT200 had worse PFS and OS.
INTERPRETATION
SCT200 exhibited promising clinical efficacy and manageable safety profiles in RAS and BRAF wild-type mCRC patients progressed on fluorouracil, irinotecan and oxaliplatin treatment. The baseline ctDNA and ctDNA clearance status at the 7th week after the first dose of SCT200 administration before receiving SCT200 could be a potential prognostic biomarker for RAS and BRAF wild-type mCRC patients with SCT200 therapy.
FUNDING
This study was sponsored by Sinocelltech Ltd., Beijing, China and partly supported by the National Science and Technology Major Project for Key New Drug Development (2019ZX09732001-006, 2017ZX09304015).
Topics: Adult; Aged; Humans; Middle Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Colorectal Neoplasms; ErbB Receptors; Fluorouracil; Genomics; Irinotecan; Oxaliplatin; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Rectal Neoplasms
PubMed: 38217945
DOI: 10.1016/j.ebiom.2024.104966 -
Stem Cell Research & Therapy Oct 2023The aim of the study was to evaluate the efficacy and safety of allogeneic umbilical cord-derived mesenchymal stem cells (TH-SC01) for complex perianal fistula in... (Clinical Trial)
Clinical Trial
OBJECTIVES
The aim of the study was to evaluate the efficacy and safety of allogeneic umbilical cord-derived mesenchymal stem cells (TH-SC01) for complex perianal fistula in patients with Crohn's disease (CD).
METHODS
This was an open-label, single-arm clinical trial conducted at Jinling Hospital. Adult patients with complex treatment-refractory CD perianal fistulas (pfCD) were enrolled and received a single intralesional injection of 120 million TH-SC01 cells. Combined remission was defined as an absence of suppuration through an external orifice, complete re-epithelization, and absence of collections larger than 2 cm measured by magnetic resonance imaging (MRI) at 24 weeks after cell administration.
RESULTS
A total of 10 patients were enrolled. Six patients (60.0%) achieved combined remission at 24 weeks. The number of draining fistulas decreased in 9 (90.0%) and 7 (70.0%) patients at weeks 12 and 24, respectively. Significant improvement in Perianal Crohn Disease Activity Index, Pelvic MRI-Based Score, Crohn Disease Activity Index, and quality of life score were observed at 24 weeks. No serious adverse events occurred. The probability of remaining recurrence-free was 70% at week 52.
CONCLUSION
The study demonstrated that local injection of TH-SC01 cells might be an effective and safe treatment for complex treatment-refractory pfCD after conventional and/or biological treatments fail (ClinicalTrials.gov ID, NCT04939337).
TRIAL REGISTRATION
The study was retrospectively registered on www.
CLINICALTRIALS
gov (NCT04939337) on June 25, 2021.
Topics: Adult; Humans; Crohn Disease; Hematopoietic Stem Cell Transplantation; Mesenchymal Stem Cells; Pilot Projects; Quality of Life; Rectal Fistula; Treatment Outcome
PubMed: 37904247
DOI: 10.1186/s13287-023-03531-0