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"Yu, Jesse"
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Association of Pre-operative Geriatric Nutritional Risk Index With Complete Adjuvant Chemotherapy and Prognosis Post-pancreatectomy
2024
The Geriatric Nutritional Risk Index (GNRI) predicts prognosis in various cancers. This study examined the correlation between GNRI, complete adjuvant chemotherapy (AC), and prognosis in patients with resected pancreatic cancer.
We retrospectively evaluated 123 patients with pancreatic cancer who underwent pancreatectomies at our institute between January 2010 and December 2020. Kaplan-Meier and Cox regression methods were used to assess survival. Factors associated with complete AC were identified using logistic regression analysis.
Among the 123 patients with pancreatic cancer, 93 (75.6%) initiated AC, and 55 (44.7%) completed AC. In multivariate analysis, the pre-operative GNRI was an independent prognostic factor for overall survival (OS) [hazard ratio=1.63, 95% confidence interval (CI)=1.01-2.63; p=0.046]. Additionally, pre-operative GNRI was an independent predictor of complete AC (odds ratio=0.38, 95%CI=0.17-0.83; p=0.015). In the high (≥98) and low GNRI (<98) groups, patients who underwent complete AC had significantly longer OS than those who did not (p<0.001, respectively). However, the patients in the low GNRI group who underwent complete AC had no significant difference in OS compared to those in the high GNRI group who did not undergo complete AC (p=0.523).
Pre-operative GNRI may predict complete AC and prognosis in resected pancreatic cancer.
Journal Article
Optimizing Treatment Strategy for Oligometastases/Oligo-Recurrence of Colorectal Cancer
2023
Colorectal cancer (CRC) is the third most common cancer, and nearly half of CRC patients experience metastases. Oligometastatic CRC represents a distinct clinical state characterized by limited metastatic involvement, demonstrating a less aggressive nature and potentially improved survival with multidisciplinary treatment. However, the varied clinical scenarios giving rise to oligometastases necessitate a precise definition, considering primary tumor status and oncological factors, to optimize treatment strategies. This review delineates the concepts of oligometastatic CRC, encompassing oligo-recurrence, where the primary tumor is under control, resulting in a more favorable prognosis. A comprehensive examination of multidisciplinary treatment with local treatments and systemic therapy is provided. The overarching objective in managing oligometastatic CRC is the complete eradication of metastases, offering prospects of a cure. Essential to this management approach are local treatments, with surgical resection serving as the standard of care. Percutaneous ablation and stereotactic body radiotherapy present less invasive alternatives for lesions unsuitable for surgery, demonstrating efficacy in select cases. Perioperative systemic therapy, aiming to control micrometastatic disease and enhance local treatment effectiveness, has shown improvements in progression-free survival through clinical trials. However, the extension of overall survival remains variable. The review emphasizes the need for further prospective trials to establish a cohesive definition and an optimized treatment strategy for oligometastatic CRC.
Journal Article
Oligometastasis of Gastric Cancer: A Review
2024
The concept of oligometastasis is not yet fully established in the field of gastric cancer. However, metastatic lesions that are localized, technically resectable at diagnosis, present a certain response to preoperative chemotherapy, and present favorable survival outcomes with local treatments, sometimes in combination with chemotherapy, are recognized as oligometastasis in the field of gastric cancer. Oligometastasis is noted in European Society for Medical Oncology guidelines and Japanese gastric cancer treatment guidelines, and local treatment is mentioned as one of the pivotal treatment options for oligometastasis. Solitary liver metastasis or a small number of liver metastases; retroperitoneal lymph node metastasis, especially localized para-aortic lymph node metastasis; localized peritoneal dissemination; and Krukenberg tumor are representative types of oligometastasis in gastric cancer. The AIO-FLOT3 trial prospectively evaluated the efficacy of multimodal treatments for gastric cancer with oligometastasis, including surgical resection of primary and metastatic lesions combined with chemotherapy, confirming favorable survival outcomes. Two phase 3 studies are ongoing to investigate the efficacy of surgical resection combined with perioperative chemotherapy compared with palliative chemotherapy. Thus far, the evidence suggests that multimodal treatment for oligometastasis of gastric cancer is promising.
Journal Article
Phase II Study of Preoperative Chemoradiotherapy With S-1 Plus Oxaliplatin for Locally Advanced Rectal Cancer (PerSeUS-RC01)
by
IWATA, YOSHINORI
,
TANAKA, CHIHIRO
,
YAWATA, KAZUNORI
in
Antineoplastic Combined Chemotherapy Protocols - pharmacology
,
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
,
Cancer therapies
2021
We report the end results of a study evaluating the safety and efficacy of preoperative chemoradiotherapy with S-1 plus oxaliplatin.
Eligible patients had histopathologically confirmed locally advanced rectal carcinoma (LARC; cT3-T4, any N). They received oral S-1 (80 mg/m
/day on days 1-5, 8-12, 22-26, and 29-33) and oxaliplatin by infusion (50 mg/m
/day on days 1, 8, 22, and 29) along with radiotherapy (1.8 Gy/day, total dose: 45 Gy/25 fractions). A chemotherapy gap was included in the third week of radiotherapy. The study endpoint was pathological response rate (Grade 2, 3). Secondary endpoints included rates of pathologic complete response (pCR), R0 resection, disease-free survival (DFS), overall survival (OS), local and distant recurrence, and safety and relative dose intensity.
The study enrolled 23 patients at three Centres in Gifu, Japan. All patients received chemoradiotherapy, and 22 underwent surgery. Rates of pathological response, R0 resection, and pathological down-staging were 56.5% (13/23), 95.7% (22/23), and 63.6% (14/22), respectively. There were no grade 4 adverse events, but grade 3 events occurred in 21.7% of patients. The cumulative 3-year local recurrence rate was 8.7%. Distant metastasis occurred in 10 (43.5%) patients, 2 (8.7%) from local recurrence and 2 from secondary pancreatic cancer and lung cancer. There were 8 patients with lung metastasis, 2 with liver metastasis, one with ovarian metastasis, and one with bone metastasis. Three-year rates of DFS and OS were 51.1% (median follow-up 34.3 months) and 91.1% (45.2 months), respectively.
The study showed high pathological response rate without severe toxicity and good follow-up results. Unexpectedly, however, this regimen could not control local recurrence and distant metastasis. Nevertheless, adding oxaliplatin to preoperative chemoradiotherapy with S-1 in patients with LARC appears feasible and may safely result in better local control than standard treatment. The study suggests adding treatment with induction chemotherapy in consideration of CEA level and N factor.
Journal Article
Prognostic impact of severe neutropenia in colorectal cancer patients treated with TAS-102 and bevacizumab, addressing immortal-time bias
by
Kobayashi, Ryo
,
Iihara, Hirotoshi
,
Kiyama, Shigeru
in
Bevacizumab
,
Bias
,
Biomedical and Life Sciences
2023
Background
Several studies have reported an association between severe neutropenia and long-term survival in patients treated with trifluridine-tipiracil (TAS-102). Because some of these studies failed to address immortality time bias, however, their findings should be interpreted with caution. Additionally, the association between severe neutropenia and survival in patients receiving TAS-102 in combination with bevacizumab (Bmab) remains unclear.
Patients and methods
We conducted a single-center retrospective cohort study in patients with colorectal cancer who received Bmab + TAS-102. We compared overall survival (OS) between patients who developed grade ≥ 3 neutropenia during the treatment period and those who did not. To account for immortal time bias, we used two approaches, time-varying Cox regression and landmark analysis.
Results
Median OS was 15.3 months [95% CI: 14.1–NA] in patients with grade ≥ 3 neutropenia and 10.0 months [95% CI: 8.1–NA] in those without. In time-varying Cox regression, onset grade ≥ 3 neutropenia was significantly related to longer survival after adjustment for age and modified Glasgow Prognostic Score. Additionally, 30-, 60-, 90-, and 120-day landmark analysis showed that grade ≥ 3 neutropenia was associated with longer survival after adjustment for age and modified Glasgow Prognostic Score, with respective HRs of 0.30 [0.10–0.90], 0.65 [0.30–1.42], 0.39 [0.17–0.90], and 0.41 [0.18–0.95].
Conclusion
We identified an association between long-term survival and the development of severe neutropenia during the early cycle of Bmab + TAS-102 using an approach that addressed immortality time bias.
Journal Article
Association of Preoperative and Postoperative Plasma Syndecan-1 and Colorectal Cancer Outcome
by
MORI, RYUTARO
,
HAYASHI, HIROKATSU
,
FUTAMURA, MANABU
in
Atherosclerosis
,
Biomarkers
,
Biomarkers, Tumor - blood
2024
A three-dimensional network constructed using glycocalyx (GCX) extends throughout the cancer cell nest in human colorectal cancer (CRC). GCX was found to be closely related to cancer. We examined the prognostic correlation and potential of syndecan-1 (SDC1), a representative proteoglycan of GCX, as a biomarker.
We analyzed SDC1 in the transcriptomic profiles of a major publicly available CRC cohort from The Cancer Genome Atlas (TCGA) using a computational algorithm. We investigated serum SDC1 levels preoperatively and on postoperative day seven in 48 patients with stage I-III CRC who underwent surgery during July-December 2019 at Gifu University Hospital.
For TCGA, no significant differences existed between the high and low SDC1 expression groups regarding disease-free, disease-specific, and overall survival for stage I-III, and only overall survival for stage IV was significantly different. In our study, among the 48 patients, 17 (no recurrence), 13 (1 recurrence), and 18 (10 recurrences) had stage I-III, respectively. Preoperative and postoperative day 7 SDC1 levels for patients with stage I-III were 10.7±2.3 and 9.9±3.1 ng/ml (p=0.40), 11.1±1.7 and 10.1±0.8 ng/ml (p=0.07), and 10.3±2.0 and 9.5±1.4 ng/ml (p=0.15), respectively. In stage II and III, patients were divided into two groups according to differences between preoperative and postoperative SDC1 levels (SDC1pre-pro). SDC1pre-pro ≤0 group significantly prolonged disease-free survival compared with SDC1pre-pro >0 group (p=0.048).
Dynamic change in serum SDC1 levels serves as a prognostic biomarker for stage II and III colorectal cancer.
Journal Article
Achieving and Sustaining Universal Health Coverage: Fiscal Reform of the National Health Insurance in Taiwan
The paper discusses the expansion of the universal health coverage (UHC) in Taiwan through the establishment of National Health Insurance (NHI), and the fiscal crisis it caused. Two key questions are addressed: How did the NHI gradually achieve universal coverage, and yet cause Taiwanese health spending to escalate to fiscal crisis? What measures have been taken to reform the NHI finance and achieve moderate success to date? The main argument of this paper is that the Taiwanese Government did try to implement various reforms to save costs and had moderate success, but the path-dependent process of reform does not allow increasing contribution rates significantly and thereby makes sustainability challenging.
Journal Article
Fusion surgery in robot-assisted esophagectomy: stepwise learning curves across the da Vinci™ and hinotori™ platforms
by
Matsumoto, Keita
,
Asai, Ryuichi
,
Mitsui, Noriki
in
Cameras
,
Care and treatment
,
Comparative analysis
2026
Background
Robot-assisted minimally invasive esophagectomy (RAMIE) provides superior precision, three-dimensional visualization, and enhanced instrument dexterity compared to conventional approaches. The “Fusion Surgery” concept, which emphasizes dynamic cooperation between console and bedside surgeons, has the potential to improve operative efficiency and facilitate technical skill acquisition. This study used stepwise learning curves in RAMIE to explore the feasibility and initial experience with the da Vinci™ and hinotori™ robotic platforms.
Methods
We retrospectively analyzed 30 patients with esophageal cancer who underwent RAMIE using the Fusion Surgery approach between June 2024 and November 2025. The first 25 consecutive procedures were performed with the da Vinci system, followed by five with the hinotori system, all by the same surgical team. Thoracic lymphadenectomy was standardized into lower, middle, and upper mediastinal segments. Learning curves were assessed using cumulative sum (CUSUM) analysis of console operation time. Intraoperative blood loss and postoperative hospital stay were evaluated as secondary outcomes.
Results
The median total console operation time was 210 min. Middle mediastinal dissection time was significantly shorter with the hinotori system than with the da Vinci system (46 vs. 76 min,
p
= 0.010), whereas upper and lower mediastinal dissections showed favorable trends. CUSUM analysis demonstrated progressive improvement across all mediastinal levels. Upper mediastinal console time continued to decrease after transition to the hinotori system, middle mediastinal dissection showed marked improvement following the transition, and lower mediastinal dissection exhibited a steady downward trend from the initial cases. These findings indicate cumulative learning and effective transfer of technical skills across robotic platforms.
Conclusions
The Fusion Surgery approach may support gradual improvement in RAMIE performance across all mediastinal levels. Transitioning from the da Vinci to the hinotori robotic system did not interrupt the learning curve, supporting smooth continuation of surgical proficiency on a new platform. Fusion Surgery may provide a robust and adaptable framework for sustained technical advancement in RAMIE.
Journal Article
Urine-based nematode chemotaxis assay (N-NOSE) as a predictor of recurrence after curative surgery for resectable pancreatic cancer: preliminary data and single center experience
2025
Background
Pancreatic cancer (PC) remains one of the most lethal malignancies, with high recurrence rates even after curative-intent surgery. Current surveillance tools, including imaging and serum carbohydrate antigen 19–9, have limitations in specificity and sensitivity. N-NOSE is a urine-based assay using the chemotactic behavior of
Caenorhabditis elegans
to detect cancer-associated volatile organic compounds. This study prospectively evaluated the prognostic value of N-NOSE in patients undergoing curative surgery for resectable PC.
Methods
Twenty-four patients with resectable PC, all treated with preoperative gemcitabine plus S-1 chemotherapy followed by curative-intent pancreatectomy, were enrolled. The chemotaxis index was measured at three time points: before treatment, after preoperative chemotherapy, and postoperatively. Recurrence within two years was assessed. Univariate and multivariate logistic regression analyses were performed to identify predictors of recurrence, and recurrence-free survival was analyzed using Kaplan–Meier methods.
Results
During the two-year follow-up, 13 patients (54.2%) experienced recurrence. Univariate analysis identified pre-treatment platelet-to-lymphocyte ratio > 1.53 (
p
= 0.04), pathological lymph node metastasis (
p
= 0.04), and pre-treatment N-NOSE positivity (
p
= 0.007) as significant predictors. Multivariate analysis confirmed pre-treatment N-NOSE positivity as the only independent predictor (odds ratio: 3.10 × 10⁷; 95% CI: 11.38–;
p
= 0.03). In patients who recurred, the chemotaxis index increased significantly after surgery (
p
= 0.02), while remaining stable in non-recurrent cases.
Conclusions
Pre-treatment N-NOSE positivity and postoperative increases in chemotaxis index were associated with recurrence after curative-intent surgery for resectable PC. This simple, non-invasive urine assay shows promise as a novel prognostic biomarker to enable earlier detection of recurrence, refine postoperative surveillance, and support personalized patient management.
Journal Article
Novel drug combination nanoparticles exhibit enhanced plasma exposure and dose-responsive effects on eliminating breast cancer lung metastasis
by
Griffin, James I.
,
Zhu, Linxi
,
Wu, Yan
in
Animals
,
Antineoplastic Agents - blood
,
Antineoplastic Agents - chemistry
2020
Early diagnosis along with new drugs targeted to cancer receptors and immunocheckpoints have improved breast cancer survival. However, full remission remains elusive for metastatic breast cancer due to dose-limiting toxicities of heavily used, highly potent drug combinations such as gemcitabine and paclitaxel. Therefore, novel strategies that lower the effective dose and improve safety margins could enhance the effect of these drug combinations. To this end, we developed and evaluated a novel drug combination of gemcitabine and paclitaxel (GT). Leveraging a simple and scalable drug-combination nanoparticle platform (DcNP), we successfully prepared an injectable GT combination in DcNP (GT DcNP). Compared to a Cremophor EL/ethanol assisted drug suspension in buffer (CrEL), GT DcNP exhibits about 56-fold and 8.6-fold increases in plasma drug exposure (area under the curve, AUC) and apparent half-life of gemcitabine respectively, and a 2.9-fold increase of AUC for paclitaxel. Using 4T1 as a syngeneic model for breast cancer metastasis, we found that a single GT (20/2 mg/kg) dose in DcNP nearly eliminated colonization in the lungs. This effect was not achievable by a CrEL drug combination at a 5-fold higher dose (i.e., 100/10 mg/kg GT). A dose-response study indicates that GT DcNP provided a therapeutic index of ~15.8. Collectively, these data suggest that GT DcNP could be effective against advancing metastatic breast cancer with a margin of safety. As the DcNP formulation is intentionally designed to be simple, scalable, and long-acting, it may be suitable for clinical development to find effective treatment against metastatic breast cancer.
Journal Article