Enzymatic Fat Dissolution Improves Detection of Small Lymph Nodes in Colon Cancer Surgery.

Background Accurate lymph node evaluation is essential for staging colon cancer and guiding postoperative treatment decisions. In this study, we compared the efficacy of a simple enzymatic fat dissolution method with the conventional method for lymph node sampling from specimens after colon cancer surgery. Methods We enrolled 58 patients who underwent elective laparoscopic surgery for colon adenocarcinoma between May 2018 and May 2021 at Fukuoka University Hospital in Fukuoka, Japan. The specimens from these patients were treated using fat dissolution and were compared with specimens from 58 patients for which conventional manual palpation was used. Results A significantly greater number of lymph nodes were detected by the fat dissolution method compared with the conventional method (average per patient, 27.5 vs. 22.6, P = 0.02). In particular, the between-group difference was significant for lymph nodes measuring <5 mm (average per patient, 26.1 vs. 20.9; P = 0.01). Multivariate analysis showed that, compared with the conventional method, the fat dissolution method was significantly associated with the identification of lymph node metastasis. The positive rate of lymph nodes ≥10 mm in diameter was markedly higher along the inferior mesenteric artery than the ileocolic artery (100% vs. 52.6%). Conclusions The use of the fat dissolution method led to an increase in the number of small lymph nodes detected. Rates of metastasis according to lymph node size may depend on the lymph node station.

A pilot study on the safety and efficacy of neoadjuvant chemo­adoptive immunotherapy for locally advanced rectal cancer.

The safety and efficacy of combination therapy of immune cell therapy and chemotherapy [chemo-adoptive immunotherapy (CAIT)] for patients with stage IV or recurrent colorectal cancer have been reported. In the present study, the safety and efficacy of neoadjuvant CAIT were investigated for preoperative therapy of locally advanced rectal cancer. The study included patients with cT3/T4 or cN (+) rectal adenocarcinoma scheduled for curative surgery. Six patients who consented to participate in the current study were selected as subjects. Neoadjuvant CAIT involves administration of activated autologous lymphocytes, αß T cells, and mFOLFOX6 every 2 weeks for six courses, followed by surgery 4-6 weeks thereafter. Common Terminology Criteria for Adverse Events grade 3 neutropenia was observed in one patient. Neoadjuvant CAIT and curative surgery were performed on all the patients. The confirmed response rate was 67%. Downstaging was confirmed in five patients (83%). Regarding histological effects, two patients were grade 1a and four were grade 2. Regarding immunological reactions, both CD4+ and CD8+ T cell infiltration rates increased after treatment in three patients on tumor-infiltrating lymphocyte (TIL) analysis. In peripheral blood analysis, the total lymphocyte count was maintained in all patients, and the CD8+ T cell count increased by ≥3 times on the pretreatment count in two patients but may not be associated with changes in TILs. During the median postoperative follow-up duration of 24 months, liver and lung metastases occurred in one patient, but all patients survived. In conclusion, neoadjuvant CAIT (αß T cells + mFOLFOX6) can be safely administered for the treatment of advanced rectal cancer. Verification of the efficacy of comprehensive immune cell therapy, especially the induction of antitumor immunity for the prevention of recurrence, will be maintained. The current study is registered with the Japan Registry of Clinical Trials (jRCT; ID, jRCTc030190248; January 21, 2019).

Effect of heating insufflation tube of AirSeal system on laparoscopic surgery.

The AirSeal system (CONMED, NY, USA) can outstandingly keep pneumoperitoneum stable. However, water droplets form on the access port, impairing the performance of comfortable surgical procedures because of the resultant wet surgical field. This study was performed to clarify the mechanism of water droplet formation and to prevent it. Condensation was observed on the AirSeal system. A heater was wrapped around the tri-lumen tube, and the heating effect was assessed. The simulator experiments revealed that condensation formed in the tri-lumen tube and on the wall of the access port. The accumulated weight of the condensation on the wall of the access port was 41.6 g in the Heated group, 138.2 g in the Control group, and 479.4 g in the Cooled group. In the clinical assessment, the accumulated volume of the condensation attached to the inside wall was significantly smaller in the Heated group than in the Unheated group (111.7 g vs. 332.9 g, respectively). We clarified that the volume of condensation attached to the wall of the access port depended on the temperature of the tri-lumen tube. The clinical study revealed that the condensation on the access port was reduced by heating the tri-lumen tube. The development of a novel heating device for the insufflation tube would be effective and useful.

Demonstration of equivocal anti-glomerular basement membrane antibody positivity as a non-specific reaction through multiple immunologic assays in a case of pediatric asymptomatic hematuria.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) antibody is essential for the diagnosis of anti-GBM disease. The major epitope consists of the α3 subunits of type IV collagen non-collagenous domain (α 3(IV)NC1). There have been only a few reports of patients false-positive for anti-GBM antibody. CASE REPORT: We experienced an 8-year-old boy who presented with asymptomatic hematuria followed by positivity for anti-GBM antibody as evaluated by a commercially available chemiluminescent enzyme immunoassay (CLEIA). While his condition remained stable other than continuing hematuria, his anti-GBM antibody titer increased. Further examination of another anti-GBM antibody assay (fluoroenzyme immunoassay) showed negative results. Thus, evaluation of the accuracy of his positivity for anti-GBM antibody was required. We conducted the following examinations: A) enzyme-linked immunosorbent assay, B) immunoblotting for recombinant α 1-5(IV)NC1, and C) immunohistochemical analysis of normal kidney tissue sections. Specimens used for the analysis were sera in A and IgG from the patient in B and C, respectively. As a result, no anti-GBM antibody was detected in A. In B, no band specific to α 1-5(IV)NC1 was observed. In C, the kidney tissue was not stained. Taken together, these results led us to judge the positive anti-GBM result in CLEIA of our patient to be a non-specific reaction. CONCLUSION: The commercial assays for anti-GBM antibody can lead to false-positive results. We recommend confirmation of anti-GBM antibody positivity through the use of multiple assays in patients demonstrating an atypical clinical course for anti-GBM disease.

Safety evaluation of immune-cell therapy for malignant tumor in the Cancer Immune-cell Therapy Evaluation Group (CITEG).

BACKGROUND AIMS: With the aim of strengthening the scientific evidence of immune-cell therapy for cancer and further examining its safety, in October 2015, our hospital jointly established the Cancer Immune-Cell Therapy Evaluation Group (CITEG) with 39 medical facilities nationwide. METHODS: Medical information, such as patients' background characteristics, clinical efficacy and therapeutic cell types obtained from each facility, has been accumulated, analyzed and evaluated by CITEG. In this prospective study, we analyzed the adverse events associated with immune-cell therapy until the end of September 2022, and we presented our interim safety evaluation. RESULTS: A total of 3839 patients with malignant tumor were treated with immune-cell therapy, with a median age of 64 years (range, 13-97 years) and a male-to-female ratio of 1:1.08 (1846:1993). Most patients' performance status was 0 or 1 (86.8%) at the first visit, and 3234 cases (84.2%) were advanced or recurrent cases, which accounted for the majority. The total number of administrations reported in CITEG was 31890, of which 960 (3.0%) showed adverse events. The numbers of adverse events caused by treatment were 363 (1.8%) of 19661 administrations of αßT cell therapy, 9 of 845 administrations of γδT-cell therapy (1.1%) and 10 of 626 administrations of natural killer cell therapy (1.6%). The number of adverse events caused by dendritic cell (DC) vaccine therapy was 578 of 10748 administrations (5.4%), which was significantly larger than those for other treatments. Multivariate analysis revealed that αßT cell therapy had a significantly greater risk of adverse events at performance status 1 or higher, and patients younger than 64 years, women or adjuvant immune-cell therapy had a greater risk of adverse events in DC vaccine therapy. Injection-site reactions were the most frequently reported adverse events, with 449 events, the majority of which were associated with DC vaccine therapy. Among all other adverse events, fever (228 events), fatigue (141 events) and itching (131 events) were frequently reported. In contrast, three patients had adverse events (fever, abdominal pain and interstitial pneumonia) that required hospitalization, although they were weakly related to this therapy; rather, it was considered to be the effect of treatment for the primary disease. CONCLUSIONS: Immune-cell therapy for cancer was considered to be a safe treatment without serious adverse events.

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

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

Detection of carbon dioxide embolism by transesophageal echocardiography during transanal/perineal endoscopic surgery: a pilot study.

The transanal/perineal (ta/tp) endoscopic approach has been widely used for anorectal surgery in recent years, but carbon dioxide embolism is a possible lethal complication. The frequency of this complication in this approach is not known. In this study, we investigated the frequency of intraoperative (including occult) carbon dioxide embolism using transesophageal echocardiography. Patients who underwent surgery via the ta/tp approach and consented to participate were included. Intraoperative transesophageal echocardiography was used to observe the right ventricular system in a four-chamber view. Changes in end-tidal carbon dioxide (EtCO2), oxygen saturation (SpO2), and blood pressure were taken from anesthesia records. Median maximum insufflation pressure during the ta/tp approach was 13.5 (12-18) mmHg. One patient (4.8%) was observed to have a bubble in the right atrium on intraoperative transesophageal echocardiography, with a decrease in EtCO2 from 39 to 35 mmHg but no obvious change in SpO2 or blood pressure. By lowering the insufflation pressure from 15 to 10 mmHg and controlling bleeding from the veins around the prostate, the gas rapidly disappeared and the operation could be continued. Among all patients, the range of variation in intraoperative EtCO2 was 5-22 mmHg, and an intraoperative decrease in EtCO2 of > 3 mmHg within 5 min was observed in 19 patients (median 5 mmHg in 1-10 times).Clinicians should be aware of carbon dioxide embolism as a rare but potentially lethal complication of anorectal surgery, especially when using the ta/tp approach.

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

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

A Continuous Increase in CXC-Motif Chemokine Ligand 10 in a Case of Anti-Nuclear Matrix Protein-2-Positive Juvenile Dermatomyositis.

Anti-nuclear matrix protein-2 (NXP2) antibody is associated with the severe, chronic myositis phenotype in juvenile dermatomyositis (JDM). Although hyperproduction of type I interferon is considered to play an important role in JDM, sequential changes in biomarkers associated with this pathophysiology have not yet been described in detail. An 8-year-old boy who presented with muscle weakness, heliotrope rash, and Gottron's papules was diagnosed with JDM. With regard to myositis-specific autoantibodies, anti-NXP2 was detected. Although the increase of serum myogenic enzymes was modest at onset, two courses of methyl-prednisolone (mPSL) pulse therapy followed by oral prednisolone and methotrexate were insufficient to initiate remission. Therefore, additional treatment, with intravenous cyclophosphamide (IVCY) and intravenous immunoglobulin (IVIG) was required to obtain a favorable outcome. We also retrospectively evaluated serum concentration of several cytokines: interleukin (IL)-6, soluble tumor necrotizing factor receptor (sTNFR)-1, sTNFR-2, IL-18, and CXC-motif chemokine ligand (CXCL)-10. The cytokine profile of this patient at onset showed a CXCL-10-dominant pattern. Additionally, sequential evaluation of CXCL-10 revealed an aberrantly high level of CXCL-10 persistent despite two courses of mPSL pulse therapy, and the level of this cytokine only gradually decreased after initiation of IVCY and IVIG. The hyperproduction of CXCL-10, presumably reflecting the hyperproduction of type I interferon in the affected tissue, may persist for a certain period, even after the initiation of multiple courses of mPSL pulse therapy. With regard to the fact that anti-NXP2 is associated with subcutaneous calcification, our data suggest the importance of aggressive intervention in cases of anti-NXP2-positive JDM as well as the need for the development of a more pathophysiologically specific treatment.

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

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

Relationship between perioperative oncological evaluation and recurrence using circulating tumor DNA with KRAS mutation in patients with colorectal cancer.

BACKGROUND: The detection of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) by liquid biopsy may have prognostic information. In this perioperative study, we evaluate if there is a relationship between mutant allele frequency (MAF) of Kirsten rat sarcoma viral oncogene homolog (KRAS) and tumor recurrence and how that could be useful in the early detection of recurrence. METHODS: Among 304 cases of colorectal cancer surgery, ctDNA was sampled from the perioperative blood of 84 patients with CRC with KRAS mutation (exon 4 p.A146T, exon 4 p.A146V, exon 2 p.G12A, exon 2 p.G12C, exon 2 p.G12D, exon 2 p.G12S, exon 2 p.G12V, exon 2 p.G13D, exon 3 p.Q61H) and analyzed using the digital polymerase chain reaction system. The median observation period was 26 months. RESULTS: Although the relationship between the perioperative MAF of KRAS and recurrence was not proved, tumor diameter, tumor depth, and stage were correlated with the preoperative MAF of KRAS (p = 0.034, p = 0.002, p = 0.008). However, tumor diameter, tumor depth, and stage did not correlate with MAF of KRAS at postoperative day 30. CONCLUSIONS: In this study, pathological tumor size, tumor depth, and stage were correlated with preoperative MAF of KRAS, but it was unreliable to predict recurrence by detection of ctDNA with KRAS mutation in the perioperative period of colorectal surgery.

Implementation of geriatric assessment and long-term care insurance system by medical professionals in cancer treatment: a nationwide survey in Japan.

BACKGROUND: A questionnaire survey was conducted to assess the implementation status of geriatric assessment in cancer treatment and the potential for collaboration between medical care and the long-term care insurance system. METHODS: Questionnaires were sent to 795 facilities in Japan. The questions were instructed to be answered via an online survey (SurveyMonkey®), which began in September 2020 and closed on 31 October 2020. The questionnaire consisted of 8 questions on the status of geriatric assessment implementation and 15 questions on the long-term care insurance system. RESULTS: In total, 631 departments in 340 (42.8%) of 795 hospitals and clinics provided responses. Approximately 81.5% of the departments did not perform geriatric assessment. The common reasons were lack of knowledge about geriatric assessment (54.0%) and lack of personnel (35.5%). Even if geriatric assessment was conducted, 63.6% of departments did not utilize geriatric assessment results in clinical practice. Approximately 61.7% of respondents were familiar with the long-term care insurance system and 62.9% with the certification process. Moreover, 28% of respondents used certification examination results in treatment planning. CONCLUSIONS: Geriatric assessment is less recognized than the long-term care insurance system, and its results are rarely used in clinical practice. However, 28% of certification examination results are utilized in treatment decision-making. Notably, this survey first showed the incorporation of the long-term care insurance system into the medical care of vulnerable elderly patients with cancer.

A Trial Protocol of Precision Medicine for Patients with RAS Wild Metastatic Colorectal Cancer Using Liquid Biopsy (RAS-liquid Study): A Prospective, Multicenter Observational Study.

BACKGROUND: Anti-epidermal growth factor receptor (EGFR) therapy has been identified to prolong the survival of metastatic colorectal cancer (mCRC) patients without RAS mutations. However, its efficacy is not always consistent for these patients. Genomic profiles of primary tumors and metastases are not always concordant; thus, chemotherapeutic agents can alter the tumor molecular profile. This molecular heterogeneity may explain resistance to anti-EGFR therapy. Liquid biopsy using circulating tumor DNA (ctDNA) is a novel, non-invasive diagnostic tool that can accommodate this molecular heterogeneity, providing a comprehensive, real-time view of the molecular landscape. In this study, we evaluated the predictive value of genomic mutations in ctDNA for primary and acquired resistance to anti-EGFR therapy. METHODS/DESIGN: This study is a prospective, multicenter, observational study of mCRC patients with wild-type tissue RAS treated with cytotoxic agents and anti-EGFR antibodies as first-line therapy. Genomic mutations, including RAS, BRAF, PIK3CA, and EGFR in ctDNA, are assessed via Droplet Digital PCR before starting chemotherapy and every 3 months thereafter until disease progression. The target sample size is estimated to be 100. The primary endpoint is the response rate in patients without RAS mutation in their blood sample before starting chemotherapy. DISCUSSION: This study will clarify the predictive value of baseline RAS mutation in ctDNA for responses to anti-EGFR therapy; the frequency of emerging RAS, BRAF, PIK3CA, and EGFR mutations in ctDNA; and the association with secondary resistance to anti-EGFR therapy in first-line therapy for wild-type tissue RAS mCRC patients.

Intraoperative pressure monitoring of the lower leg for preventing compression-related complications associated with the lithotomy position.

BACKGROUND: Several serious complications are associated with the lithotomy position, including well-leg compartment syndrome and peroneal nerve paralysis. The aims of this study were to identify risk factors for the intraoperative elevation of lower leg pressure and to evaluate the effectiveness of monitoring external pressure during surgery for preventing these complications. METHODS: The study included 106 patients with a diagnosis of sigmoid colon or rectal cancer who underwent elective laparoscopic surgery between June 2019 and December 2020. We divided the posterior side of the lower leg into four parts (upper outside, upper inside, lower outside, lower inside) and recorded the peak pressure applied to each area at hourly intervals during surgery (called "regular points") and when the operating position was changed (e.g., by head-tilt or leg elevation; called "points after change in position"). When the pressure was observed to be higher than 50 mmHg, we adjusted the position of the leg and re-recorded the data. Data on postoperative leg-associated complications were also collected. RESULTS: The pressure was measured at a total of 1125 points (regular, n = 620; after change of position, n = 505). The external pressure on the upper outer side of the right leg (median, 36 mmHg) was higher than that on any other area of the lower leg. The pressure increase to more than 50 mmHg was observed not only during the change of position (27.5%) but also during regular points (22.4%). Bodyweight, strong leg elevation, and low head position were identified as factors associated with increased external pressure. There have been no compression-related complications in 534 cases at our institution since the introduction of intraoperative pressure monitoring. CONCLUSIONS: Several risk factors associated with increased external pressure on the lower leg were identified. Intraoperative pressure monitoring might help reduction of pressure-related complications, needing further and larger prospective data collections.

Oncological evaluation in the perioperative period using cfDNA with BRAF V600E mutation in patients with colorectal cancer.

The detection of circulating cell-free DNA (cfDNA) by liquid biopsy is reported to provide prognostic information in colorectal cancer (CRC). Although the frequency of BRAF V600E mutation in CRC is less than 10%, it is associated with poor responses to conventional chemotherapy. We conducted a prospective study to investigate the relationship between the perioperative mutant allele frequency (MAF) of BRAF V600E and tumor recurrence, and to evaluate the possibility of early detection of recurrence. Among 362 patients who underwent radical resection, cfDNA was extracted from the perioperative blood of 11 CRC patients with BRAF V600E mutation and analyzed using the digital polymerase chain reaction (dPCR) system. The median follow-up time was 22 months, and there were four cases of recurrence. Although there was no correlation between recurrence and the perioperative MAF of BRAF V600E, tumor diameter was correlated with the MAF (p = 0.024), and the MAF increased with time in two patients from whom additional samples were obtained prior to recurrence. In this study, we identified a correlation between the pathological tumor diameter and the MAF, but it was difficult to predict recurrence by measuring cfDNA with BRAF V600E mutation in the perioperative period of radical resection of CRC.

The Pre-treatment Lymphocyte-to-Monocyte Ratio Predicts Efficacy in Metastatic Colorectal Cancer Treated With TAS-102 and Bevacizumab.

BACKGROUND/AIM: Our multicenter phase II TAS-CC3 study demonstrated favorable median progression-free survival (PFS) and overall survival (OS) of 32 metastatic colorectal cancer (mCRC) patients treated with TAS-102 + bevacizumab as 3rd-line treatment. PATIENTS AND METHODS: We investigated the predictive and prognostic values of pre-treatment blood inflammation-based scores, including the neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte ratio (LMR) on disease-control (DC), PFS and OS by a post-hoc analysis. RESULTS: Receiver operating characteristic curve analyses of the 3 inflammation-based scores versus DC showed the best predictive performance for LMR, followed by NLR and PLR. The high-LMR group had a significantly higher DC rate than the low group (87.5 vs. 43.8%). The high-LMR group showed significantly longer survival than the low group (4.9 vs. 2.3 m for median PFS) (21.0 vs. 6.1 m for median OS). CONCLUSION: The pre-treatment LMR is a valid predictive and prognostic biomarker for mCRC patients undergoing TAS-102 and bevacizumab treatment.

[A Case of Internal Jugular Vein Thrombosis Caused by Gravity-Induced Catheter Excursion following Subcutaneous Implantable Central Venous Port Insertion for Colorectal Cancer Treatment].

The patient was a 66-year-old woman. She underwent central venous port insertion as part of postoperative adjuvant chemotherapy for sigmoid colon cancer. At the beginning of the 2 cycle, she experienced discomfort in the neck, and computed tomography was performed. As a result, catheter deviation and a thrombus in the internal jugular vein were observed. It was considered that breast displacement due to gravity caused the catheter deviation and that the position of the tip of the catheter deviating to immediately above the venous valve caused thrombus formation. We examined the factors that may cause catheter deviation.

Safety and effectiveness of high ligation of the inferior mesenteric artery for cancer of the descending colon under indocyanine green fluorescence imaging: a pilot study.

BACKGROUND: Complete mesocolic excision with central vascular ligation is a standard advanced technique for achieving favorable long-term oncological outcomes in colon cancer surgery. Clinical evidence abounds demonstrating the safety of high ligation of the inferior mesenteric artery (IMA) for sigmoid colon cancer but is scarce for descending colon cancer. A major concern is the blood supply to the remnant distal sigmoid colon, especially for cases with a long sigmoid colon. We sought to clarify the safety and feasibility of high ligation of the IMA in surgery for descending colon cancer using indocyanine green (ICG) fluorescence imaging. METHODS: In this prospective single-center pilot study, we examined 20 patients with descending colon cancer who underwent laparoscopic colectomy between April 2018 and September 2019. Following full mobilization and division of the proximal colonic mesentery, we temporarily clamped the root of the IMA and performed ICG fluorescence imaging of the blood flow to the sigmoid colon. The postoperative anastomosis-related complications (primary endpoint) and length of viable remnant colon, and the number of lymph nodes retrieved (secondary endpoints) were evaluated and compared with historical controls who underwent conventional IMA-preserving surgery (n = 20). RESULTS: Blood flow reached 40 (17-66) cm retrograde from the peritoneal reflection, even after IMA clamping. Accordingly, IMA high ligation was performed in all cases. No anastomotic anastomosis-related complications occurred in each group. Retrieved total lymph nodes were higher in number in the ICG-guided group than in the conventional group (p = 0.035). Specifically, more principal nodes were retrieved in the ICG-guided group, compared with the conventional group (p = 0.023). However, the distal margin was not as long compared with the conventional group. CONCLUSION: We demonstrated the safety and feasibility of high ligation of the IMA for descending colon cancer without sacrificing additional distal colon using fluorescence evaluation of blood flow in the remnant colon.

A case of carbon dioxide embolism during the transperineal approach in total pelvic exenteration for advanced anorectal cancer.

The transanal and transperineal endoscopic approaches are useful advanced surgical options for removing rectal and anorectal cancers. Intraoperative carbon dioxide (CO2 ) embolisms, however, have been increasingly reported as potentially fatal complications associated with surgery employing these approaches. We report our experience with a CO2 embolism that was detected because of a sudden drop in end-tidal CO2 with decreasing saturation of percutaneous arterial oxygen during total pelvic exenteration using the transperineal endoscopic approach under pneumopelvis/pneumoperitoneum. Transesophageal echocardiography confirmed that it was a CO2 embolus. We reversed the pneumopelvis and pneumoperitoneum, which alleviated the cardiopulmonary problems, and the surgery then proceeded to achieve R0 resection. The patient was discharged without severe complications other than the CO2 embolism.

Combination of TAS-102 and bevacizumab as third-line treatment for metastatic colorectal cancer: TAS-CC3 study.

BACKGROUND: TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets. METHODS: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1-5 and 8-12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. RESULTS: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred. CONCLUSIONS: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.