No salvage treatment strategy has been established for relapsed or refractory primary central nervous system lymphoma (PCNSL). We compared treatment outcomes of patients who underwent salvage chemotherapy with or without autologous stem cell transplantation (ASCT). We retrospectively analyzed PCNSL patients who were histologically diagnosed with diffuse large B-cell lymphoma. All patients relapsed after high-dose methotrexate (MTX)-based chemotherapy, or were refractory to high-dose MTX. Patients were treated with salvage chemotherapy, such as ICE/D (ifosfamide, carboplatin, etoposide, and dexamethasone) or high-dose MTX. High-dose chemotherapy containing thiotepa and busulfan followed by ASCT was performed if patients were eligible for ASCT after salvage treatment. Forty-five patients (35 relapsed and 10 refractory) received ICE/D or high-dose MTX. Despite the important difference that ICE/D was used predominantly for early relapsed or refractory patients, the two salvage treatments produced similar overall response rates [84.4 % (38/45) for ICE/D and 81.3 % (13/16) for high-dose MTX re-treatment]. Eighteen patients underwent ASCT, whereas 27 patients received salvage chemotherapy alone. The median progression-free survival of patients who underwent ASCT (19.5 months) was significantly better than that of patients who did not receive ASCT (6.7 months, P = 0.023). Multivariate analysis showed that refractoriness to initial treatment and no ASCT were significantly associated with poor survival outcome. Our study suggested that the combination of ifosfamide, carboplatin, etoposide, and dexamethasone may represent a feasible salvage treatment option for relapsed or refractory PCNSL, and that high-dose chemotherapy containing thiotepa and busulfan followed by ASCT may be effective for patients with a favorable toxicity profile.
Objective: We evaluated the prognostic value of tumor deposit (TD) counts and incorporated them with the number of positive lymph nodes to develop a revised nodal staging. Summary Background Data: The current American Joint Committee on Cancer (AJCC) staging on colon cancer includes the TDs only for nodenegative patients, as N1c, and their counts are not considered. Methods: We included consecutive patients with stage III colorectal cancer who underwent curative resections between January 2010 and December 2019. The patients were grouped as TD 0, TD 1, TD 2, or TD ≥3 based on their TD counts. Disease-free survival and overall survival were compared. Results: Of 2446 eligible stage III patients, 658 (26.9%) had TDs. Among them, 500 (76.0%) patients concurrently had positive lymph nodes (LNs). TD counts were significantly related to worse disease-free survival (DFS) and overall survival regardless of pT stages or the number of positive LNs. The patients were restaged based on the integrated number of TD counts and positive LNs. The N3 stage, which had ≥10 integrated TDs and positive LNs, was newly classified. Among the patients who completed 6 months of adjuvant chemotherapy, those upstaged to N2 from an initial stage of N1 experienced significantly worse DFS than those confirmed as N1 in the revised N staging. The newly N3-staged patients showed significantly worse DFS than the patients initially staged as N2. Conclusions: Revised N staging using the integrated number of TD counts and positive LNs could predict DFS more accurately than current staging. It would also draw greater attention to the patients with highrisk stage III colon cancer staged as N3.
Purpose: The impact of postoperative complications on long-term oncologic outcome after radical colorectal cancer surgery is controversial. The aim of this study was to examine the risk factors and oncologic outcomes of surgery-related postoperative complication groups.Methods: From January 2010 to December 2010, 310 patients experienced surgery-related postoperative complications after radical colorectal cancer surgery. These stage I–III patients were classified into 2 subgroups, minor (grades I, II) and major (grades III, IV) complication groups, according to extended Clavien-Dindo classification system criteria. Clinicopathologic differences between the 2 groups were analyzed to identify risk factors for major complications. The diseasefree survival rates of surgery-related postoperative complication groups were also compared.Results: Minor and major complication groups were stratified with 194 patients (62.6%) and 116 patients (37.4%), respectively. The risk factors influencing the major complication group were pathologic N category and operative method. The prognostic factors associated with disease-free survival were preoperative perforation, perineural invasion, tumor budding, and receiving neoadjuvant therapy. With a median follow-up period of 72.2 months, the 5-year disease-free survival rates were 84.4% in the minor group and 78.5% in the major group, but there was no statistical significance between the minor and major groups (P = 0.392).Conclusion: Advanced cancer and open surgery were identified as risk factors for increased surgery-related major complications after radical colorectal cancer surgery. However, severity of postoperative complications did not affect disease-free survival from colorectal cancer.
Background: Propofol is considered to protect against immunosuppression and has lower inflammatory responses in the perioperative period than volatile agents. We evaluated whether the anesthetic agent is associated with cancer outcomes. Methods: We retrospectively reviewed 2616 patients who underwent colorectal cancer surgery under general anesthesia between 2016 and 2018 (follow-up closure: July 2021) at a single institution. Patients received propofol-based total intravenous anesthesia or sevoflurane-based inhalational anesthesia. After propensity score matching, the postoperative neutrophil-lymphocyte ratio (NLR) was compared as primary outcome, and clinical outcomes were evaluated. Results: After 1:2 propensity matching, 717 patients were given propofol anesthesia and 1410 patients were given sevoflurane anesthesia. In the matched cohort, preoperative NLR was not significantly different between propofol and sevoflurane anesthesia (mean (95% CI)2.3 (1.8 to 2.8) and 2.2 (1.9 to 3.2); p = 0.72). NLR was significantly lower in propofol anesthesia at postoperative day two and five (mean difference (95% CI) 0.71 (0.43 to 0.98); p = 0.000 and 0.52 (0.30 to 0.74); p = 0.000). Urinary retention showed a higher incidence after propofol anesthesia (4.9% vs. 2.6%; p = 0.008). Other postoperative complications and overall/recurrence-free survival were not different in the two groups. Discussion: Although propofol anesthesia showed lower postoperative NLR than sevoflurane anesthesia, there was no association with clinical outcomes.
We evaluated the predictive value of semiquantitative volumetric parameters derived from sequential PET/CT and developed a nomogram to predict pathological complete response (pCR) in patients with rectal cancer treated by neoadjuvant chemoradiotherapy (nCRT). From April 2008 to December 2013, among the patients who underwent nCRT, those who were taken sequential PET/CT before and after nCRT were included. MRI-based staging and semiquantitative parameters of PET/CT including standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were evaluated before and after nCRT. Multivariable analysis was performed to select significant predictors to construct a nomogram. Sensitivity, specificity, accuracy, and area under the receiver operating characteristics curve (AUC) of the model were evaluated to determine its performance. Among 137 eligible patients, 17 (12.4%) had pCR. All post-PET/CT parameters showed significant differences between pCR and non-pCR groups. Patients were randomly assigned to a training group (91 patients) and a validation group (46 patients). In multivariable analysis with the training group, post-CEA, post-MRI T staging, post-SUVmax, and post-MTV were significantly associated with pCR. There was no significant pre-nCRT variable for predicting pCR. Using significant predictors, a nomogram was developed. Sensitivity, specificity, accuracy, and AUC of the nomogram were 0.882, 0.808, 0.848, and 0.884 with the training group and 0.857, 0.781, 0.783, and 0.828 with the validation group, respectively. This model showed the better performance than other predictive models that did not contain PET/CT parameters. A nomogram containing semiquantitative post-PET/CT could effectively select candidates for organ-sparing strategies.
HALS is considered a safe and feasible approach for rectal cancer treatment that enables the preservation of the advantages of conventional laparoscopic surgery.
Since effective immunotherapeutic agents such as immune checkpoint blockade to treat cancer have emerged, the need for reliable preclinical cancer models that can evaluate and discover such drugs became stronger than ever before. The traditional preclinical cancer model using a cancer cell line has several limitations to recapitulate intra-tumor heterogeneity and in-vivo tumor activity including interactions between tumor-microenvironment. In this review, we will go over various preclinical cancer models recently discovered including patient-derived xenografts, humanized mice, organoids, organotypic-tumor spheroids, and organ-on-a-chip models. Moreover, we will discuss the future directions of preclinical cancer research.
In vitro culture of patient-derived tumor cells offers many advantages in the development of novel therapies for colorectal cancer. Although various culture systems have been developed, the long-term expansion of patient-derived tumor cells remains challenging. The present results suggested that tumor cells isolated from colorectal cancer patient-derived xenografts can be efficiently immortalized in conditioned medium from irradiated feeder cells containing Y-27632, a rho-associated coiled-coil containing protein kinase (ROCK) inhibitor. Patient-derived tumor cells proliferated rapidly, reaching 90-95% confluence in ~6 days. Short tandem repeat analysis suggested that these tumor tissues and cultured cells presented 13 identical short tandem repeat loci, including Amelogenin, Penta E, Penta D, D2S1338 and D19S433. Their epithelial phenotype was confirmed by staining for epithelial cell adhesion molecule and cytokeratin 20, whereas vimentin was used as a mesenchymal marker. When cells were transferred to 3D cultures, they continued to proliferate, forming well-defined tumor spheroids. Expression levels of human telomerase reverse transcriptase and C-Myc mRNA were increased in cultured cells. Finally, immortalized cells were used for the screening of 65 anticancer drugs approved by the Food and Drug Administration, allowing the identification of gene-drug associations. In the present study, primary culture models of colorectal cancer were efficiently established using a ROCK inhibitor and feeder cells, and this approach could be used for personalized treatment strategies for patients with colorectal cancer.
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