Cancer diagnosis & prognosis最新文献

Background/aim: Neurofibromatosis type 1 (NF1) is a tumor predisposition syndrome characterized by neoplasms originating from nerve sheath cells. The autosomal dominant hereditary disease also affects numerous developmental and metabolic processes, for example in the bones. The aim of the study was to document the diagnosis and treatment of an NF1 patient who had developed a space-occupying lesion at the base of the skull with noticeable mandibular changes.

Case report: The patient, who presented for her initial examination as a teenager, had an asymmetrical lower face. The deformation of the lower jaw mainly affected the left ramus and was associated with a deviation of the chin region toward the affected side. MRI revealed a diffuse plexiform neurofibroma (PNF) on the left side, which spread within the dystrophic pterygoid muscles. Over a treatment interval of 21 years, the patient developed numerous PNF in various regions of the body. The extent of the skull base tumor and the degree of muscular dystrophy remained constant during this period. Similarly, the mandibular dysplasia already noted during the initial examination remained unchanged.

Conclusion: Although mandibular dysplasias associated with PNF are rare findings in patients with NF1, they often have a characteristic pattern and may remain unchanged for decades. Knowledge of tumor-associated mandibular dysplasia in patients with NF1 is essential for the differential diagnosis of tumors in this region which can become malignant.

Background/aim: Cholangiocarcinoma (CCA) is a malignant tumor with high mortality and recurrence rates after treatment. The discovery of prognostic markers is, therefore, essential for improving patient outcomes after treatment. This study aimed to investigate the prognostic value of membranous and cytoplasmic PD-L1 expression, individually and in combination. In addition, the combination of PD-L1 expression and chemotherapeutic status was also explored.

Patients and methods: The expression of PD-L1 was examined in 200 CCA patients using immunohistological staining, and its correlation with clinicopathological data was investigated using the Chi-squared test. Overall survival (OS) and recurrence-free survival (RFS) investigations were performed using Kaplan-Meier (log-rank) and Cox-regression analysis.

Results: The results demonstrated that high PD-L1 expression in the membrane and low expression in the cytoplasm had a correlation with intrahepatic CCA and lymph node metastasis. Furthermore, these patients had shorter OS and RFS compared to other groups of patients. Moreover, when the expression of PD-L1 was combined with chemotherapeutic status, the result demonstrated that patients who had high expression of PD-L1 in the membrane with low expression of PD-L1 in the cytoplasm and did not receive adjuvant chemotherapy showed significantly shorter OS and RFS compared to other patients. This could be an independent prognostic factor for RFS and OS with HR 1.889 and 1.990, respectively.

Conclusion: PD-L1 expression levels can serve as a valuable predictor of outcomes in CCA patients, especially when evaluated alongside chemotherapeutic status.

Background/aim: Immune checkpoint inhibitors (ICIs) have become central in the treatment of non-small cell lung cancer (NSCLC). The occurrence of immune-related adverse events (irAEs) is a critical issue in the management of patients with NSCLC receiving ICIs. Recent studies have suggested that patients who develop irAEs may have a better prognosis than those who do not. However, the most problematic cases involved the development of severe irAEs. This study aimed to investigate the clinical impact of severe irAEs (grade ≥3) in patients with NSCLC treated with ICIs.

Patients and methods: We analyzed 122 patients from a prospective database of consecutive patients with NSCLC who received first-line ICI-containing treatment between November 2018 and October 2024. Patients were classified into two groups: 48 treated with anti-programmed death-ligand 1 (anti-PD-L1) therapy and 74 treated with anti-programmed death-1 (anti-PD-1) therapy. We retrospectively compared the incidence of severe irAEs between the two groups and evaluated the clinical outcomes of severe irAEs on the survival.

Results: Among 122 patients, 24 (19.7%) experienced severe irAEs. The incidence of severe irAEs was significantly higher among patients treated with anti-PD-1 than among those treated with anti-PD-L1. The incidence of irAE-related death was also higher in the anti-PD-1 group than in the anti-PD-L1 group, with pneumonitis accounting for most of these fatalities (87.5%). There were no significant differences in the progression-free or overall survival between patients with and without severe irAEs. A multivariable analysis showed that the use of anti-PD-1 therapy was associated with a worse overall survival.

Conclusion: Treatment with anti-PD-1 was associated with an increased risk of severe irAEs. The incidence of severe irAEs was not associated with an improved survival rate.

Background/aim: Methionine addiction (Hoffman effect) is a fundamental and general cancer hallmark targetable by methionine restriction, using methionine-depleted media or diet, or recombinant methioninase (rMETase). Our previous studies showed differential sensitivity of HCT-116 colon-cancer cells and Hs27 normal fibroblasts to rMETase in co-culture. The present study aimed to demonstrate the rescue conditions of cancer cells by methionine replenishment in the co-cultures of HCT-116 and Hs27 cells after rMETase treatment.

Materials and methods: Equal numbers of HCT-116 colon-cancer cells and Hs27 normal fibroblasts were co-cultured in 6-well plates in Dulbecco's modified Eagle's medium (DMEM). Two days after seeding, co-cultures were treated with rMETase at the HCT-116 IC50 (0.46 U/ml) or left untreated as controls. Growth of each cell type in co-culture was evaluated by phase-contrast microscopy on days 2, 4, 6, 8, 10, and 12 after treatment to assess the response to rMETase. On day 12, the existing medium in all wells was replaced with fresh DMEM containing methionine (methionine replenishment). Regrowth of HCT-116 and Hs27 was then assessed by phase-contrast microscopy 3, 6, and 9 days later.

Results: In the untreated control group, HCT-116 cancer cells rapidly proliferated, and progressively overtook the Hs27 fibroblasts and predominated by day 12. In the rMETase-treated group, viable HCT-116 cells progressively decreased and were almost undetectable by day 12, whereas Hs27 cells remained viable throughout the observation period. After day-12 replenishment of methionine, previously rMETase-treated co-cultures showed reappearance of viable HCT-116 cells by day 3 and dominance over Hs27 cells by day 9.

Conclusion: Continuous treatment with rMETase is necessary to maintain inhibition of cancer cells and normal-cell dominance in co-culture with cancer cells. These results have clinical implications indicating that methionine restriction must be continually maintained to inhibit cancer.

Background/aim: Total gastrectomy is the cornerstone treatment for gastric cancer, particularly in patients with proximal or large tumors. For early-stage gastric cancer, laparoscopic total gastrectomy (LTG) has demonstrated comparable short- and long-term outcomes to those of open total gastrectomy (OTG), while reports on advanced gastric cancer (AGC) are limited. We aimed to compare the short- and long-term outcomes of patients with AGC who underwent LTG or OTG.

Patients and methods: This study included consecutive patients with AGC who underwent LTG or OTG with lymph node dissection at our institution from January 2002 to June 2024. Propensity score matching was conducted at a 1:1 ratio to reduce bias.

Results: A total of 158 patients were enrolled (LTG: 39; OTG: 119). Of these, 64 were paired by propensity score matching. The clinical tumor invasion depth was balanced, but the pathological depth was significantly deeper in the LTG group. The number of patients with lymph node metastasis did not differ. The median operative time was longer for LTG (512.5 min) than for OTG (267 min), whereas LTG resulted in significantly less blood loss (125 g vs. 411 g). Postoperative morbidity (≥Clavien‒Dindo grade 3) was comparable (LTG: 12.5%, OTG: 9.4%). The LTG group had a significantly shorter median hospital stay (11 days vs. 17 days). There were no significant differences in overall or recurrence-free survival between the groups.

Conclusion: LTG is a feasible and safe approach for AGC, offering comparable short- and long-term outcomes to OTG.

Background/aim: Urothelial cancer (UC) is the most common malignancy of the urinary tract, and outcomes in advanced disease remain poor. Comprehensive genomic profiling has revealed rare but potentially actionable alterations, including mesenchymal-epithelial transition factor (MET) exon 14 skipping events, which are well established in non-small cell lung cancer but rarely described in UC. We hereby report a case of high-grade plasmacytoid UC harboring a novel MET exon 14 skipping alteration and discuss its potential clinical relevance.

Case report: A 78-year-old man presented with pelvic pain and hematuria. Imaging showed irregular thickening of the bladder wall with bilateral ureterovesical junction and distal ureter involvement and rectal invasion, consistent with unresectable stage IVA (cT4N0) plasmacytoid UC. He received carboplatin-gemcitabine followed by maintenance avelumab. Next-generation sequencing of tumor tissue identified a novel intronic MET splice-site alteration, NM_000245.4: c.2942-22_2942-19delCTTT, at high variant allele frequency, predicted to cause exon 14 skipping; this result was confirmed on an independent panel, and no additional driver variants were detected.

Conclusion: This case broadens the spectrum of MET exon 14 skipping events in UC by documenting a novel intronic c.2942-22_2942-19delCTTT alteration in plasmacytoid carcinoma. It underscores the importance of routine genomic profiling in advanced and histologically rare UC to uncover targetable alterations and supports consideration of MET-directed therapies or enrollment in tumor-agnostic trials for selected patients, while highlighting the need for further functional and clinical validation.

Background/aim: Consensus on the most informative inflammatory marker for prognosis in biliary tract cancer (BTC) is lacking. The aim of this study was to comprehensively evaluate preoperative inflammatory indices and develop a prognostic nomogram complementary to TNM staging.

Patients and methods: A total of 247 patients with resected BTC were retrospectively analyzed. Eight inflammatory indices, including prognostic nutritional index (PNI) and C-reactive protein-to-albumin ratio (CAR), were assessed alongside non-TNM clinicopathological variables. Least absolute shrinkage and selection operator (LASSO) regression identified overall survival-associated variables for multivariable Cox regression and nomogram construction. Model performance was evaluated using Kaplan-Meier analysis, concordance (C-) index, time-dependent area under the curve (tdAUC), decision curve analysis (DCA), and calibration plots, with bootstrap validation.

Results: LASSO selected PNI and CAR; CAR remained independently significant. The nomogram incorporated CAR and five clinicopathological factors: body mass index ≥25 kg/m2, carbohydrate antigen 19-9 >37 U/ml, moderate/poor differentiation, perineural invasion, and residual tumor status. Patients were stratified by nomogram score into four risk groups showing distinct survival differences. Notably, 50.6% of TNM Stage I-II were reclassified as higher risk, 16.1% of Stage III-IV as lower risk. The nomogram achieved C-index 0.722 versus 0.659 for TNM (p=0.022), with superior tdAUCs, clinical benefit on DCA, and good calibration. Consistent prognostic performance was observed across BTC subtypes and TNM stages.

Conclusion: CAR demonstrated superiority over other inflammatory indices in resected BTC. This CAR-based nomogram complements TNM staging, offering enhanced prognostic stratification for patients with heterogeneous outcomes within the same anatomical stage.

Background/aim: Oral uracil-tegafur (UFT) therapy as adjuvant chemotherapy (ACT) has demonstrated efficacy and is widely used for patients with completely resected early-stage non-small cell lung cancer (NSCLC). However, most previous clinical trials have enrolled patients aged ≤75 years, and evidence regarding the safety of UFT in older patients remains limited. This study aimed to evaluate the safety of adjuvant UFT therapy in older patients.

Patients and methods: We retrospectively analyzed 101 patients who underwent curative lung resection and were pathologically diagnosed with stage IA3 or IB NSCLC (TNM 8th edition) at our department between January 2017 and January 2023. Patients were stratified into older (aged ≥75 years) and younger (aged <75 years) groups, and the administration rate of UFT therapy was compared. Among patients who received UFT, dose, treatment duration, completion rate of 24 months, and incidence of adverse events were further evaluated.

Results: The older group included 42 patients (42%). The UFT administration rate was 63% in the younger group and 62% in the older group, with no statistically significant difference. UFT dose, completion rate of 24 months, and incidence of adverse events in older patients appeared not to be inferior to those in younger patients. However, in the standard-dose group (400 mg daily), the older group tended to have a lower completion rate and a higher incidence of adverse events.

Conclusion: Adjuvant UFT therapy was generally safe in patients aged ≥75 years. Nevertheless, dose adjustments may be necessary in older patients. In a super-aging society, these findings underscore the importance of considering not only chronological age but also each patient's overall condition when making decisions regarding adjuvant UFT therapy.

Background/aim: Pancreatic neuroendocrine tumors (PanNETs) are heterogeneous neoplasms for which surgical resection remains the only potentially curative therapy. However, preoperative diagnostic accuracy - particularly tumor grading - often varies, complicating treatment decisions. This study evaluated diagnostic concordance between preoperative assessments and postoperative pathology, as well as surgical outcomes and prognostic factors in patients undergoing pancreatectomy for PanNETs.

Patients and methods: We retrospectively reviewed the clinical records of 32 patients who underwent surgical resection for PanNETs. Patient demographics, tumor characteristics, surgical procedures, and postoperative outcomes were analyzed. Preoperative imaging and cytology-based diagnoses were compared with final pathological findings to evaluate diagnostic concordance. Prognostic factors were assessed using Kaplan-Meier survival analysis.

Results: Histological grading of resected specimens showed G1 in 53%, G2 in 41%, and G3/NEC in 6%, with a 38% discordance rate from preoperative biopsy. Lymphatic, venous, and perineural invasions were identified in 16%, 44%, and 13% of cases. Lymph node metastasis occurred in 22%. Among 30 patients with follow-up >12 months, eight developed recurrence, most commonly in the liver. The 3-year and 5-year disease-free survival (DFS) rates were 78% and 69%, while overall survival (OS) rates were 96% and 91%. Tumor number >2 and histologic grade G3 were significantly associated with reduced DFS (p<0.05). Lymphatic invasion and metachronous liver metastasis were significantly associated with reduced OS (p<0.01 and p<0.05, respectively). Histological grading mismatch was not associated with survival outcomes.

Conclusion: Pancreatectomy for PanNETs is a safe and effective treatment with favorable long-term outcomes. Histological factors such as tumor grade, lymphatic invasion, and tumor number significantly predict recurrence and survival.

Background/aim: Liquid biopsy (LB) has demonstrated value in managing non-small cell lung cancer (NSCLC) and is widely used for monitoring disease progression in multiple cancers. While the role of baseline circulating tumor DNA (ctDNA) is not yet fully understood, emerging evidence suggests that LB should be integrated into NSCLC management, as pre-treatment ctDNA levels show a strong prognostic association with clinical outcomes. This systematic review and meta-analysis evaluated the diagnostic accuracy of molecular methods including PCR-based assays and next-generation sequencing (NGS) in detecting epidermal growth factor receptor (EGFR) mutations by comparing LB and tissue biopsy in treatment-naive patients with NSCLC.

Materials and methods: A systematic search of MEDLINE and LILACS identified studies comparing matched LB and tissue biopsy in treatment-naive patients with NSCLC using polymerase chain reaction (PCR) or NGS. Sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated using a random-effects model.

Results: Twelve studies with 1,314 patients met the inclusion criteria. Most participants were male (59.5%), had adenocarcinoma (82.2%), and stage IV disease (77%). Pooled sensitivity and specificity for NGS in LB were 69% [95% confidence interval (CI)=0.62-0.75] and 90% (95%CI=0.84-0.94), respectively. Regarding real time quantitative polymerase chain reaction (RT-qPCR) sensitivity was 56% (95%CI=0.46-0.65) and specificity 89% (95%CI=0.66-0.97). NGS yielded a PLR of 6.9 and NLR of 0.34; RT-qPCR had a PLR of 5.1 and NLR of 0.49.

Conclusion: NGS outperforms RT-qPCR in sensitivity and PLR for EGFR mutation detection via LB in patients with NSCLC prior to treatment, reinforcing its potential as a diagnostic tool.