BACKGROUND/AIM:A substantial proportion of patients with cancer experience clinically relevant psycho-oncological distress. In addition to clinic-based screening, mobile approaches are receiving increasing attention for standardized assessment. However, evidence in patients with musculoskeletal sarcoma remains limited. PATIENTS AND METHODS:Forty-five patients with sarcoma underwent smartphone-based distress screening using a cancer-specific questionnaire (QSC-R10) at two time points (T1 and T2). At T1, patients also completed the System Usability Scale (SUS) and additional acceptability items. RESULTS:Mean QSC-R10 scores decreased significantly from T1 to T2 (p=0.034). Patients with recurrent disease showed significantly higher distress at follow-up (p=0.012). Usability was high (SUS: 83.78±12.68), and overall acceptance was high. CONCLUSION:Smartphone-based distress screening is feasible and well accepted in patients with musculoskeletal sarcoma and may improve the identification of psycho-oncological needs through repeated, real-world assessments.
BACKGROUND/AIM:Circadian rhythms regulate DNA repair, cell-cycle control, apoptosis, pigmentation, barrier function, and immune surveillance in skin, and their disruption may increase susceptibility to ultraviolet-induced carcinogenesis. MATERIALS AND METHODS:This narrative review synthesizes mechanistic, experimental, epidemiologic, and translational studies on circadian rhythm disruption and skin neoplasms, with emphasis on melanoma and nonmelanoma skin cancer. RESULTS:Core clock genes such as CLOCK, BMAL1, PER, and CRY orchestrate daily oscillations in cutaneous physiology, including nucleotide excision repair and inflammatory signaling. Experimental studies show that ultraviolet (UV) exposure during circadian phases with low DNA repair capacity produces more persistent lesions and more tumors, while human meta-analytic evidence suggests a modest increase in melanoma risk among shift workers. Evidence for basal cell carcinoma and squamous cell carcinoma is less consistent, likely because of differences in UV exposure, occupation, and confounding by behavior. CONCLUSION:Circadian disruption is a plausible modifier of skin cancer risk, particularly for melanoma, through effects on UV DNA repair, immune surveillance, melatonin signaling, and tumor biology. Further prospective studies using objective circadian biomarkers and dermatology-specific endpoints are needed.
BACKGROUND/AIM:Kita-Kyushu Lung Cancer antigen-1 (KK-LC-1) is a cancer-testis antigen that represents a promising target for treatment with T-cell receptor (TCR) gene-engineered T cells. This study aimed to evaluate the utility of immunohistochemical detection of KK-LC-1 in resected lung adenocarcinoma specimens. PATIENTS AND METHODS:We reviewed the medical records of 110 patients who underwent curative resection for lung adenocarcinoma. The original monoclonal antibody against KK-LC-1, Kmab34B3, was evaluated in this study. Overall survival (OS) and recurrence-free survival (RFS) were compared based on KK-LC-1 positivity and epidermal growth factor receptor (EGFR) mutation. Cox regression analyses were performed to identify prognostic factors. RESULTS:Thirty-nine patients (35%) were positive for KK-LC-1. KK-LC-1 positivity was significantly associated with larger invasive tumor size, advanced pathological stage, lymphatic invasion, vascular invasion, and lymph node metastasis. No significant difference in OS was observed between KK-LC-1-positive and -negative patients (5-year OS: 79.8% vs. 94.0%, p=0.07). However, KK-LC-1-positive patients had significantly poorer RFS than KK-LC-1-negative patients (5-year RFS: 67.7% vs. 85.5%, p=0.020). In multivariate analysis, KK-LC-1 positivity was not an independent predictor of RFS (hazard ratio=1.230, p=0.63). EGFR mutation analysis was available for 89 patients, of whom 45 (50.5%) harbored EGFR mutations. In the EGFR mutation-positive subgroup, KK-LC-1-positive patients had significantly poorer OS than KK-LC-1-negative patients (5-year OS: 77.0% vs. 100%, p=0.026). RFS also tended to be poorer in KK-LC-1-positive patients, although the difference did not reach statistical significance (5-year RFS: 66.6% vs. 88.4%, p=0.055). CONCLUSION:KK-LC-1 positivity was significantly associated with pathological high-grade tumors and poor RFS in patients with lung adenocarcinoma. Moreover, KK-LC-1 may serve as a prognostic factor for lung adenocarcinoma, and KK-LC-1-positive patients may be suitable candidates for TCR reconstitution therapy.
Sun exposure is widely recognized as a major etiologic factor in cutaneous melanoma. However, melanomas also occur in skin areas unexposed to the sun, such as the palmoplantar surface. Although the risk factors and mutational processes underlying acral melanoma remain poorly understood, these tumors frequently occur at sites of increased mechanical stress on the hand and foot, suggesting that mechanical stress may contribute to the development of plantar melanoma. Furthermore, mechanical forces regulate skin homeostasis, especially during skin development, regeneration, and wound healing. In plantar acral melanoma, mechanical stress associated with weight-bearing activity has been linked to nuclear membrane instability, which may explain the frequent occurrence of plantar acral melanoma at higher mechanical stress points. In this review, we discuss the role of mechanical stress in melanoma pathogenesis and provide an overview of mechanobiological mechanisms involved in melanoma progression and aggressiveness. Insights from these investigations may guide future research and improve the management of acral melanoma.
BACKGROUND/AIM:While thermal ablation has emerged as a less invasive alternative for colorectal liver metastases (CRLM), evidence directly comparing repeat hepatectomy and ablation after prior resection remains limited. This study aimed to compare survival and short-term outcomes between the two strategies using propensity-adjusted analyses with multiple imputation. PATIENTS AND METHODS:A total of 150 patients with recurrent CRLM after initial resection who underwent repeat hepatectomy (n=94) or ablation (n=56) were retrospectively enrolled. Outcomes included overall survival (OS), local tumor progression-free survival (LTPFS), distant progression-free survival (DPFS), and perioperative outcomes. Propensity score matching (PSM) was applied, and Inverse probability of treatment weighting (IPTW) was additionally used as a sensitivity analysis. Estimates were pooled across imputed datasets. RESULTS:In pooled PSM analyses, ablation showed comparable OS to repeat hepatectomy [hazard ratio (HR)=1.330, p=0.370] and comparable DPFS (HR=1.310, p=0.299). However, ablation was associated with significantly worse LTPFS (HR=4.540, p=0.004). For short-term outcomes, ablation resulted in shorter hospital stay (4.6 versus 15.5 days, p<0.001) and lower incidence of Clavien-Dindo grade ≥IIIa complications (0% versus 19.5%, p=0.033). These findings were consistent in IPTW analyses. CONCLUSION:Repeat hepatectomy and ablation for intrahepatic recurrence after resection of colorectal metastases showed comparable OS, with a trade-off between superior local control and reduced perioperative burden. When both options are feasible, ablation may represent a reasonable alternative to repeat hepatectomy for patients prioritizing lower treatment burden.
BACKGROUND/AIM:Pancreatic adenocarcinoma (PAAD) is characterized by a desmoplastic, profoundly immunosuppressive tumor microenvironment (TME). Adhesion G protein-coupled receptors (aGPCRs) regulate cell-matrix interactions and immune modulation, yet their specific roles in PAAD remain poorly understood. This study aimed to identify novel tumor-specific aGPCRs and define their functional and immunological landscape. MATERIALS AND METHODS:Transcriptomic profiles from The Cancer Genome Atlas (TCGA)-PAAD (n=178+4) and the Genotype-Tissue Expression (GTEx)-Pancreas (n=165) cohorts were integrated. Following rigorous batch-effect correction via multi-factor generalized linear modeling, we performed differential expression analysis, biological validation, and functional enrichment (KEGG, GSEA). Immune infiltration was quantified using marker-gene signature scoring, and prognostic weight was assessed via age-adjusted Cox proportional hazards regression. RESULTS:We identified a highly distinct aGPCR dysregulation signature characterized by the massive upregulation of ADGRG7 (log2FC=+3.46, p adj=1.92×10-5) and ADGRF1 (log2FC=+2.36, p adj=4.10×10-5) alongside the depletion of the macrophage marker ADGRE1. Survival analyses revealed an uncoupling of diagnostic specificity from prognostic weight; unlike ADGRG6, neither ADGRG7 nor ADGRF1 acted as standalone prognostic predictors, suggesting they are uniformly essential neoplastic drivers. Within the PAAD "immune desert," ADGRG7 positively correlated with residual Th1 niches, whereas ADGRF1 exhibited a distinct myeloid-exclusion phenotype. CONCLUSION:ADGRG7 and ADGRF1 are foundational, highly tumor-specific aGPCRs within the PAAD microenvironment. Their unique immune correlation profiles and uniform expression highlight them as promising diagnostic biomarkers and actionable therapeutic targets for overcoming TME-mediated immunosuppression.
BACKGROUND/AIM:Esophageal squamous cell carcinoma (ESCC) exhibits substantial heterogeneity in its tumor immune microenvironment (TIME). We aimed to establish an integrated spatial immune phenotyping framework incorporating immune infiltration, spatial distribution, and suppressive-effector immune balance. PATIENTS AND METHODS:A total of 139 patients with surgically resected ESCC were retrospectively analyzed, including a discovery cohort (n=89) and an external validation cohort (n=50). Whole-slide histopathological evaluation and immunohistochemistry were used to assess spatial immune-cell infiltration. Tumors were classified according to total tumor-infiltrating lymphocyte (TIL) level, the intratumoral-to-stromal TIL ratio, and stromal suppressive-to-effector immune balance. TCGA-ESCA transcriptomic data were analyzed to characterize the identified phenotypes. RESULTS:Stromal TILs significantly exceeded intratumoral TILs (p<0.001). Increased intratumoral immune infiltration and enrichment of suppressive immune-cell populations were associated with aggressive clinicopathological features. Four immune phenotypes were identified: immune-cold, immune-excluded, CD8-effector infiltrated, and suppressive-infiltrated. The suppressive-infiltrated phenotype showed the poorest overall survival in both the discovery (p=0.010) and validation cohorts (p=0.008). In the pooled cohort, Type IV status remained independently associated with worse overall survival after adjustment for major clinicopathological factors [hazard ratio (HR)=2.64, 95% confidence interval (CI)=1.20-5.79, p=0.015]. Adding Type IV status improved prognostic performance (C-index: 0.650 to 0.673; likelihood-ratio test, p=0.018). Transcriptomic analyses demonstrated increased immune checkpoint activity, T-cell exhaustion, and stromal activation signatures in the suppressive-infiltrated phenotype (all p<0.05). CONCLUSION:Integrated assessment of immune infiltration, spatial distribution, and suppressive-effector balance identified clinically distinct immune phenotypes in ESCC. The suppressive-infiltrated phenotype represents a high-risk immune microenvironmental subgroup independently associated with poor survival.
BACKGROUND/AIM:Several studies have reported the clinical value of prognostic markers in patients with hepatocellular carcinoma (HCC). However, no study has examined the clinical significance of the Cirrhosis Outcome Risk Estimator (CORE) risk score on outcomes. This study aimed to investigate the impact of CORE risk score on survival in patients undergoing hepatectomy for HCC. PATIENTS AND METHODS:This single-center retrospective study included 639 patients who underwent hepatectomy for HCC between January 2004 and December 2023. Clinical parameters were compared between the low (≤2.4) and high (>2.4) CORE score groups. Multivariate analyses were performed to assess the impact of the CORE risk score on outcomes. RESULTS:Patients in the high CORE score group had significantly worse 5-year overall (58.9% vs. 80.4%; p<0.001) and recurrence-free (32.9% vs. 52.5%; p<0.001) survival rates than the low CORE score group. Multivariable analyses indicated high CORE risk score as an independent prognostic factor for poor overall [hazard ratio (HR)=1.84; 95% confidence interval (CI)=1.38-2.43; p<0.001] and recurrence-free (HR=1.38; 95%CI=1.09-1.75; p=0.007) survival. CONCLUSION:The CORE risk score, an easily accessible screening test, may be a reliable predictor of survival in patients undergoing hepatectomy for HCC.
BACKGROUND/AIM:In patients with acute abdominal pain (AAP), the accuracy of artificial intelligence (AI) models in the diagnosis of acute appendicitis (AA) has been rarely reported so far. PATIENTS AND METHODS:A cohort of 1333 AAP patients, including 697 women (52.3%) and 636 men (47.7%), was included in the study. The clinical symptoms (n=22), signs (n=14) and laboratory tests (n=3) were recorded in each pa tient. The most significant diagnostic predictors were used to construct diagnostic formulas (DFs) to be applied for AA diagnosis. Hierarchical summary receiver operating characteristics (HSROC) models were used to calculate the summary sensitivity and specificity estimates for each data set (history-taking, diagnostic findings and tests as well as DFs). RESULTS:In HSROC analysis, the area under the curve (AUC) values for i) clinical history-taking, ii) diagnostic findings and tests, and iii) DFs were as follows: i) AUC=0.550 [95% confidence interval (CI)=0.500-0.590]; ii) AUC=0.731 (95% CI=0.690-0.770), and for iii) AUC=0.958 (95% CI=0.940-0.986). The differences between these AUC values (roc-comp) were all statistically significant: between i) and ii) p<0.0001; between i) and iii) p<0.0001; between ii) and iii) p<0.0001. CONCLUSION:The diagnostic accuracy (DA) of DFs is superior to both the clinical history-taking and clinical findings (with tests), and therefore the use of these AI-based models should be an important part of the diagnostic algorithm of AA among patients presenting with AAP.
BACKGROUND/AIM:Giant cell tumors of the bone (GCTB) involving the sacroiliac joint are uncommon and pose significant surgical challenges due to their proximity to major neurovascular structures and the complexity of stabilizing the pelvic. We describe a case of sacroiliac joint GCTB successfully managed with preoperative denosumab, piecemeal tumor resection, and spinopelvic reconstruction. CASE REPORT:A 34-year-old woman presented with progressive gluteal pain and swelling. Imaging demonstrated an osteolytic lesion extending from the left sacrum to the ilium with extraosseous soft-tissue involvement. Histopathology confirmed the GCTB diagnosis. To facilitate resection and reduce intraoperative blood loss, denosumab (120 mg monthly) was administered for five months, resulting in marked peripheral ossification on computed tomography. The tumor was resected via a posterior approach with preservation of the S1-S3 nerve roots. Spinopelvic reconstruction was achieved using L4-S2 fixation, S2 alar-iliac screws, artificial bone graft, and unsintered hydroxyapatite/poly-L-lactide mesh. The postoperative course was uneventful, and no neurological deficits were observed. Follow-up computed tomography at three months and one year demonstrated stable instrumentation, preserved graft integrity, and no evidence of local recurrence. CONCLUSION:Preoperative denosumab followed by posterior tumor resection and spinopelvic reconstruction provided excellent short-term tumor control and functional recovery in this patient with sacroiliac joint GCTB. Given the high recurrence risk associated with pelvic lesions, continued long-term surveillance is essential.
BACKGROUND/AIM:Poor prognosis of brain tumors is partly related to the blood brain barrier (BBB) to hydrophilic anticancer drugs. Early studies demonstrated that intracranial injection of vital dyes bypassed BBB in cats. We investigated if intraventricular infusion of gemcitabine can circumvent the blood-brain barrier and achieve therapeutically relevant drug concentrations within the brain and cerebrospinal fluid. MATERIALS AND METHODS:Brain diffusion of the vital hydrophilic Bleu Patente dye was studied after intracranial or intravenous injection in guinea pig, or after a 24 h protracted intraventricular infusion in sheep. Gemcitabine, a hydrophilic anticancer drug, was quantified by high-performance liquid chromatography. Viability of human glioblastoma cells was studied in vitro. Cells were maintained in drug-free fresh culture medium for 72 h after drug exposure before an assay with Crystal Violet. Tolerance of a single 24 h intraventricular infusion of gemcitabine was evaluated in sheep. RESULTS:Bleu Patente diffused into brain of guinea pigs after an intracranial injection, whereas brain remained unstained after an intravenous administration. After a 24 h intraventricular infusion, dye penetrated deeply into the cerebral cortex of sheep. Brain concentration of gemcitabine was higher following intracranial injection than after intravenous administration in guinea pigs. At the end of a 24 h intraventricular infusion of 20 mg gemcitabine in sheep, mean concentrations reached 1,415 microg/l in cerebrospinal fluid and 850 microg/kg in brain. These concentrations exceeded the IC90 values of gemcitabine for A172, U87-MG, and U118-MG human glioblastoma cell lines. Tolerance of a single 24 h intraventricular infusion of 20 mg gemcitabine was good in sheep. CONCLUSION:We hypothesize that intraventricular injections allow the hydrophilic drugs to circumvent BBB by using the glymphatic system. Given high concentrations in the cerebrospinal fluid and brain, and given its good tolerability, we propose to study protracted intraventricular infusion of gemcitabine in patients with refractory primary, secondary brain tumors, and meningeal metastasis.
BACKGROUND/AIM:Although melanoma represents only approximately 1% of skin cancers, it causes the majority of skin-cancer deaths. In its early stages, melanoma can be treated successfully with surgery alone, yet a meaningful proportion of patients still present with advanced disease. Geographic variation in demographic and socioeconomic profiles of patients with melanoma across U.S. regions remains poorly characterized. Assessment of regional disparities in patient composition and stage at diagnosis is necessary for the advancement of targeted public health strategies. This study examined geographic variation in demographic, socioeconomic, and clinical characteristics among U.S. patients with melanoma. PATIENTS AND METHODS:We conducted a cross-sectional analysis of patients diagnosed with melanoma between 2004 and 2020 using the National Cancer Database (NCDB). Patients were assigned to one of six U.S. geographic regions based on reporting facility location. Descriptive analyses were performed to evaluate age, sex, race and ethnicity, insurance type, income, urban-rural residence, and American Joint Committee on Cancer (AJCC) stage at diagnosis. RESULTS:Among 986,555 patients (mean age, 65.3 years; 60.1% male), substantial socioeconomic variation was identified across regions. Uninsured rates were highest in the Southwest (3.4%) and Southeast (2.4%). Lower-income households (<$63,000) predominated in the Southwest (75.9%) and Southeast (67.9%). Advanced-stage (III-IV) disease at diagnosis was most common in the Southwest (13.0%) and least common in the Northeast (7.6%). The cohort was predominately White (99.1%). CONCLUSION:Substantial geographic variation exists in the demographic and socioeconomic profile of patients with melanoma, which may correlate to meaningful differences in stage at diagnosis and, given melanoma's strongly stage-dependent prognosis, potentially survival outcomes as well. These disparities likely reflect structural inequities in screening access, insurance coverage, and healthcare infrastructure. Region-specific interventions, including Medicaid expansion, increased access to dermatologic care, public awareness campaigns, and targeted screening, are warranted to improve outcomes nationwide.
BACKGROUND/AIM:Robot-assisted minimally invasive esophagectomy (RAMIE) has swiftly gained global acceptance for the management of esophageal cancer; however, the associated learning curve may negatively impact patient outcomes. This study aimed to evaluate differences in surgical outcomes between the initial and subsequent periods and to assess the impact of accumulated experience in RAMIE in clinical practice. PATIENTS AND METHODS:We retrospectively reviewed 130 consecutive patients who underwent RAMIE at our institution. The initial period comprised the first 20 procedures performed by each of three surgeons (n=60), and the remaining procedures constituted the later period (n=70). Operative and postoperative outcomes were compared between the two periods, and factors associated with major postoperative complications were evaluated using logistic regression analysis. RESULTS:Operative performance demonstrated significant improvement in the later period. Total, thoracic, and robotic operative times were significantly shorter (all p<0.001), and the number of thoracic dissected lymph nodes (LNs) was significantly higher (p=0.02). Thoracic blood loss exhibited a decreasing trend (p=0.07). Clinical outcomes also improved, with a significantly lower overall complication rate (p=0.04), reduced severity of postoperative complications (p=0.02), and a lower incidence of major complications (p=0.005) during the later period. No mortality was recorded, and the length of postoperative hospital stay did not differ significantly between the two periods. Multivariate analysis identified the later period as an independent factor associated with a reduced risk of major complications (odds ratio=0.30; 95% confidence interval=0.12-0.75; p=0.01). CONCLUSION:Accumulated experience with RAMIE is correlated with improved operative time, enhanced LN dissection, and a reduction in postoperative complications, thereby supporting its continued safe and effective implementation following the initial learning curve.
BACKGROUND/AIM:Chemotherapy administered near death is a recognized quality indicator of end-of-life cancer care intensity. However, simple clinical signals to prompt treatment reassessment and coordinate planned end-of-life care remain unclear in advanced gastric cancer. This study evaluated the interval from last chemotherapy to death and explored factors associated with near-end-of-life chemotherapy and failure to transition to a planned end-of-life care setting. PATIENTS AND METHODS:This single-center retrospective study included 53 patients with advanced or recurrent gastric cancer who had complete data regarding final chemotherapy, mortality, and concurrent laboratory findings. The primary endpoint was chemotherapy administration within 30 days of death. A planned end-of-life care setting was defined as a scheduled transition to a palliative care unit, institutional care, or home-based care with visiting nursing support. RESULTS:The median interval from last chemotherapy to death was 67 days, with 15 patients (28.3%) receiving chemotherapy within 30 days of death. Serum albumin at final chemotherapy was significantly lower in these patients compared to those treated >30 days before death (2.5 vs. 3.2 g/dl, p<0.001), with an optimal cutoff of 2.9 g/dl. Patients receiving chemotherapy ≤30 days before death were less likely to transition to a planned end-of-life care setting (60.0% vs. 91.4%, p=0.015) and more likely to experience emergency hospitalization or sudden clinical deterioration (46.7% vs. 11.4%, p=0.010). Furthermore, albumin ≤2.9 g/dl and C-reactive protein (CRP) >1.0 mg/dl were associated with failure to transition to a planned care setting. CONCLUSION:Low serum albumin at final chemotherapy may serve as a practical clinical trigger for reassessing treatment continuation and facilitating timely end-of-life care planning in advanced or recurrent gastric cancer.
BACKGROUND/AIM:The efficacy of durvalumab consolidation therapy after chemoradiotherapy (PACIFIC regimen) for patients with epidermal growth factor receptor (EGFR) mutation-positive locally advanced unresectable non-small cell lung cancer (NSCLC) remains unclear. Additionally, data on failure patterns, including in-field recurrence (IFR) and out-of-field recurrence (OFR), are limited. PATIENTS AND METHODS:In this retrospective study, 83 patients with locally advanced unresectable NSCLC treated with the PACIFIC regimen were analyzed. Of them, 10 patients had tumors harboring EGFR mutations. Progression-free survival (PFS), overall survival (OS), and the cumulative incidences of IFR and OFR were evaluated. RESULTS:The median follow-up time was 26.6 months. The 2-year PFS rate was 23% [95% confidence interval (CI)=7-78%] in the EGFR mutation-positive group and 53% (95%CI=42-66%) in the EGFR mutation-negative group (p=0.15). The 2-year cumulative incidence of OFR was significantly higher in the EGFR mutation-positive group (77%, 95% CI=49-100%) than in the EGFR mutation-negative group (26%, 95%CI=16-37%) (hazard ratio=2.90, 95%CI=1.29-6.51, p=0.01). On exploratory multivariate analysis, EGFR mutation positivity, Eastern Cooperative Oncology Group performance status 2-4, and PD-L1 expression <1% were significantly associated with OFR. No significant differences in IFR, OS, and adverse events were observed between the groups. CONCLUSION:Although IFR and safety profiles were comparable between the two groups, EGFR mutation positivity was associated with a higher incidence of OFR. These exploratory findings highlight the limitations of durvalumab consolidation and support the shift toward alternative systemic strategies, such as osimertinib, in patients with EGFR mutation-positive locally advanced unresectable NSCLC.
BACKGROUND/AIM:This study aimed to identify clinical predictors associated with early discontinuation of eribulin therapy in patients with unresectable or recurrent breast cancer. PATIENTS AND METHODS:We retrospectively reviewed data for 63 patients with breast cancer starting eribulin therapy between August 2011 and December 2022 at a single institution. Patients with missing data for hormone receptor/human epidermal growth factor receptor 2 (HER2) status or baseline hematological parameters were excluded. Data were collected on demographics, tumor subtype, comorbidities, concomitant medications, and baseline complete blood count. The primary outcome was time to treatment discontinuation for any reason. Cox proportional hazards models were used to identify predictors of discontinuation, stratified by reason: progressive disease (PD) or adverse events (AE). RESULTS:The median age was 62 years; 69.8% were hormone receptor-positive and 15.9% HER2-positive. During follow-up, 61 out of 63 patients (96.8%) discontinued treatment. Discontinuation was due to PD in 69.8%, AE in 17.5%, and other causes in 9.5%. Considering all reasons, multivariate analysis identified a neutrophil-to-lymphocyte ratio (NLR) ≥3.5 [hazard ratio (HR)=1.97, p=0.020] as an independent predictor of discontinuation. Multivariate analysis identified dyslipidemia (HR=3.59, p=0.009) as independent predictors of PD-related discontinuation, whilst antidepressant use (HR=0.22, p=0.049) was associated with a lower risk of discontinuation. Univariate analysis showed that oral glucocorticoid use was associated with a higher risk of AE-related discontinuation (HR=4.79, p=0.013). CONCLUSION:High NLR and dyslipidemia were associated with early discontinuation of eribulin therapy. These findings highlight the need for individualized treatment strategies based on baseline risk factors.
BACKGROUND/AIM:This study evaluated the clinical significance of baseline lymphocyte-to-monocyte ratio (LMR) and its early dynamic changes as an on-treatment biomarker in patients with advanced hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (Ate/Bev), with stratification by alpha-fetoprotein (AFP) status. PATIENTS AND METHODS:We retrospectively reviewed 108 patients with advanced HCC treated with first-line Ate/Bev. Baseline LMR and LMR at six weeks (LMR 6w) were calculated. Patients were classified into high/low groups (cutoff: 3.69) and dynamic change groups [increased (Up) vs. decreased (Down)]. Overall survival (OS) and objective response rate (ORR) were assessed according to baseline AFP levels (cutoff: 20 ng/ml). RESULTS:High baseline LMR significantly correlated with longer OS (median not reached vs. 17.3 months, p<0.001). Notably, patients with increased LMR at six weeks (Up group) demonstrated significantly superior OS compared to the Down group (33.6 vs. 18.9 months, p=0.018) and a higher ORR (46.0% vs. 26.0%, p=0.037). The High+Up cohort achieved the most favorable prognosis. In stratified analyses, these prognostic and predictive values of early LMR dynamics were prominently observed in AFP-negative patients (p<0.05), but were attenuated in AFP-positive individuals. CONCLUSION:Early dynamic increase in LMR serves as a powerful, cost-effective on-treatment biomarker for Ate/Bev therapy in advanced HCC. Integrating systemic immune dynamics with tumor biology provides superior risk stratification, particularly for AFP-negative patients.
BACKGROUND/AIM:Patients with familial adenomatous polyposis (FAP) can develop multiple adenomatous polyps in the gastrointestinal tract, including the duodenum and large intestine. Few studies have reported surgical techniques for pancreaticoduodenectomy (PD) after prophylactic colorectal surgery, although this is technically challenging. CASE REPORT:We describe the surgical technique used in a 46-year-old man with FAP who underwent PD for a papillary adenoma after prophylactic total colectomy. After resection of the specimen, the jejunal limb was elevated via the Treitz route (retro-remnant mesocolic plane) for pancreaticojejunostomy and hepaticojejunostomy. Subsequently, gastrojejunostomy was performed via an isoperistaltic route. To the best of our knowledge, this is the first study to present the technical aspects of PD after total colectomy, focusing on the jejunal limb route during reconstruction. CONCLUSION:The present study highlights the clinical course of a patient who underwent PD after prophylactic total colectomy for FAP. As a functional mesocolic plane is absent in patients who have undergone prophylactic total colectomy, special considerations of the jejunal limb route are required in PD after prophylactic colorectal surgery. This approach may be an optional and feasible strategy for successful PD after prophylactic colorectal surgery.
Neurofibromatosis type 1 (NF1) is characterized by the development of neurofibromas, including cutaneous neurofibromas and plexiform neurofibromas (PNFs). Despite more than a century of clinical recognition, the terminology used to describe these tumors remains inconsistent across disciplines, particularly in pathology, radiology, and clinical practice. This lack of standardized nomenclature complicates communication, diagnostic assessment, risk stratification, and therapeutic decision-making. In this multidisciplinary consensus paper, experts from the German NF Working Group sought to harmonize current terminology for NF1-associated neurofibromas, with particular emphasis on PNF, and to relate this terminology to diagnostic procedures, clinical course, and treatment considerations. A new structured terminology of NF integrating anatomic and histological descriptions is proposed. Using a modified Delphi process, the group developed consensus statements addressing the definition and classification of neurofibromas and their relevance for imaging, pathology, surgery, biopsy, and medical treatment. A unified terminology is especially important in the era of targeted therapy, as MEK inhibitors have emerged as a promising treatment option for selected patients with NF1-associated PNF. Establishing a shared conceptual framework may improve interdisciplinary communication, support more consistent clinical decision-making, and provide a stronger basis for future recommendations on the use of MEK inhibitors in NF1.
BACKGROUND/AIM:Immune checkpoint inhibitor-based combination therapies are standard treatment options for unresectable hepatocellular carcinoma (HCC). However, conventional endpoints such as objective response rate, progression-free survival, and overall survival may not fully capture response dynamics, including depth of response (DpR), time to response, and duration of response. This study descriptively evaluated response dynamics in patients with unresectable HCC treated with durvalumab plus tremelimumab or atezolizumab plus bevacizumab. PATIENTS AND METHODS:This retrospective single-center study included 148 patients with unresectable HCC who received durvalumab-tremelimumab (n=53) or atezolizumab-bevacizumab (n=95). A reduction of ≥50% in target lesion diameter was defined as DpR50. Because of baseline imbalances and differences in observation period, the analysis was only descriptive and hypothesis-generating. RESULTS:Fifty-three patients received durvalumab-tremelimumab and 95 received atezolizumab-bevacizumab. The overall response rate was 35.8% for the durvalumab-tremelimumab group and 27.4% for the atezolizumab-bevacizumab group, whereas the disease control rates were 54.7% and 71.6%, respectively. DpR50 was observed in 26.4% and 11.6% of patients, respectively. The median times to response were 2.3 and 3.3 months, and the median durations of response were 22.3 and 10.0 months, respectively. Durable response lasting ≥6 months occurred in 24.5% and 15.8% of all treated patients, respectively. The median PFS was 5.2 and 7.0 months, and median OS was 17.0 and 22.0 months, respectively. CONCLUSION:Therapy with durvalumab-tremelimumab was associated with deeper and more durable tumor shrinkage in selected responders, whereas atezolizumab-bevacizumab provided broader disease control mainly through stable disease. These findings should be interpreted as hypothesis-generating.
