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Background The neutrophil/lymphocyte ratio (NLR) has been reportedly associated with prognosis in cancer patients by influencing both cancer progression and chemosensitivity. However, the correlation between NLR and the outcome of neoadjuvant chemotherapy (NAC) in breast cancer patients remains unclear. Methods NLR was evaluated in 177 patients with breast cancer treated with NAC with 5-fluorouracil, epirubicin, and cyclophosphamide, followed by weekly paclitaxel and subsequent curative surgery. The correlation between NLR and prognosis, including the efficacy of NAC, was evaluated retrospectively. Results NLR ranged from 0.5 to 10.6. Fifty-eight patients with low NLR (<3.0) had a higher pathological complete response (pCR) rate ( p  < 0.001) and were more frequently diagnosed with ER-negative/progesterone receptor (PR)-negative/HER2-negative (triple-negative) breast cancer (TNBC; p  < 0.001) compared with patients with high NLR (≥3.0). Among TNBC patients who achieved pCR, disease-free survival ( p  = 0.006) and overall survival ( p  < 0.001) were significantly longer in patients with low NLR than in those with high NLR. Low NLR was associated with a significantly favorable prognosis in TNBC patients who achieved pCR, according to univariate analysis ( p  = 0.044, hazard ratio = 0.06). Conclusions Low NLR may indicate high efficacy and favorable outcome after NAC in patients with TNBC.

Background/Aim: Blood transfusion and a large amount of intraoperative blood loss (IBL) have been reported to have a negative impact on long-term survival via immunosuppression. In recent years, thanks to the spread of laparoscopic surgery and the development of surgical devices, the average amount of IBL has decreased, as has the need for perioperative blood transfusion. Under such conditions, the prognostic significance of the amount of IBL is unclear. The aim of this study was to assess the impact of the amount of IBL on long-term survival. Patients and Methods: A total of 277 patients who underwent laparoscopic surgery for stage II/III colorectal cancer were enrolled. Results: The median amount of IBL was 30 ml, and 16 patients received blood transfusion. The overall survival rates were significantly better in the low-IBL (≤100 ml) group than in the high-IBL (>100 ml) group regardless of the blood transfusion. As the amount of IBL increased, the decline rate of the peripheral lymphocyte count increased. Conclusion: A large amount of IBL was associated with poor long-term survival, regardless of blood transfusion, in patients with colorectal cancer.

Background The lymphocyte-to-monocyte ratio (LMR) has been used as a parameter reflecting systemic inflammation in several tumors, and is reportedly associated with prognosis in cancer patients. In this study, we evaluated the predictive value of LMR for progression and chemosensitivity in breast cancer patients treated with preoperative chemotherapy. Methods LMR was evaluated in 239 patients with breast cancer treated with neoadjuvant chemotherapy (NAC) with 5-fluorouracil, epirubicin, and cyclophosphamide, followed by weekly paclitaxel with or without trastuzumab, and subsequent curative surgery. The correlations between LMR and clinicopathological features, prognosis, and pathological complete response (pCR) rate of NAC were evaluated retrospectively. We also evaluated the predictive value of neutrophil-to-lymphocyte ratio (NLR), and compared the predictive values of LMR and NLR. Results We set 6.00 as the cut-off level for LMR based on the receiver operating characteristic (ROC) curve. A total of 119 patients (49.8%) were classified in the high-LMR group and 120 (50.2%) were classified in the low-LMR group. The low-LMR group had significantly worse disease-free survival rate (DFS) in all patients ( p  = 0.005) and in triple-negative breast cancer patients ( p  = 0.006). However, there was no significant correlation between LMR and pCR. Multivariate analysis showed that low LMR was an independent risk factor for DFS ( p  = 0.008, hazard ratio = 2.245). However, there was no significant difference in DFS ( p  = 0.143, log-rank) between patients in the low- and high-NLR groups. Conclusions LMR may be a useful prognostic marker in patients with breast cancer.

Although the phase III SUNLIGHT trial has demonstrated the survival benefit of the addition of bevacizumab (Bmab) to trifluridine/thymidine phosphorylase inhibitor (FTD/TPI), neutropenia, which frequently occurs during FDT/TPI + Bmab therapy, is a concern for clinicians. As TPI is excreted by the kidneys, the risk of adverse events is likely to be high in patients with an impaired renal function. This study aimed to investigate the relationship between renal impairment and the incidence of chemotherapy-induced neutropenia during FTD/TPI + Bmab therapy using real-world data. We retrospectively reviewed the medical records of 69 patients with metastatic colorectal cancer (mCRC) who were treated with FTD/TPI + Bmab for more than 28 days. Patients with renal impairment with an eGFR of 30–44 mL/min/1.73 m 2 were defined as the G3b group. Seven patients (10.1%) were classified into the G3b group. Patients in the G3b group had an approximately 24% higher incidence of grade ≥ 3 neutropenia in comparison to others (71.4% vs. 46.8%), and the incidence of grade 4 neutropenia in the G3b group was significantly higher than that in others (42.9% vs. 9.7%, p  = 0.042). The G3b group frequently developed grade ≥ 3 neutropenia within 30 days of the initiation of FTD/TPI + Bmab therapy. However, the duration required for neutrophil count to recover to ≥ 1500/mm 3 and the treatment effects of the G3b group were comparable to those observed in other patients. Clinicians should pay extra attention to patients with a decreased renal function who are treated with FTD/TPI + Bmab therapy, but no special measures are required for patients with an eGFR ≥ 30 mL/min/1.73 m 2 as no marked differences were observed in neutrophil count recovery.

Numerous reports indicate that tumor-infiltrating lymphocytes (TILs) are a prognostic factor in various cancers and that they must be good biomarkers. However, the methods of evaluating TILs differ in each study; thus, there is not yet a standardized methodology for evaluating TILs. The purpose of this study is to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in patients with colorectal cancer (CRC) using the new method proposed by the International TILs Working Group in breast cancer and to standardize the method of evaluating TILs in CRC. We retrospectively reviewed a database of 160 patients with Stage II or III CRC. The density of TILs was assessed by measuring the area occupied by mononuclear cells over the stromal area on hematoxylin and eosin (H-E)-stained sections. We set 42% as the cut-off percentage of the area occupied by TILs according to the receiver operating characteristic curve, and we classified patients into the high-TILs and the low-TILs groups. The rates of relapse-free survival (RFS) and overall survival (OS) in the high-TILs group were significantly higher than those in the low-TILs group. A multivariate analysis showed that the density of TILs was independently associated with RFS and OS. Moreover, the density of TILs assessed by an observer was significantly associated with the density of TILs assessed by the automated imaging software program. The new method for evaluating TILs, which was recommended by the International TILs Working Group in breast cancer, might be a useful predictive factor in colorectal cancer patients.

Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker. TILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively. Of the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a multivariate analysis of recurrence in TNBC patients, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063). The results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.

Purpose HER2 expression is crucial in breast cancer classification and treatment. Traditionally, tumors were categorized as HER2-positive or HER2-negative, but HER2-low (IHC 1 + or 2 + without ISH amplification) has emerged as a new classification. Among HER2-negative cases, HER2-ultralow (≤ 10% faint HER2 staining) and HER2-null (completely HER2-negative) have been proposed. While differences between HER2-low and HER2-zero tumors are studied, little is known about the clinical and prognostic characteristics of HER2-ultralow breast cancer . This study aimed to clarify the clinical characteristics, immune microenvironment, treatment response, and prognosis of HER2-ultralow tumors, with HER2-null and HER2-low tumors analyzed as comparators . Methods A retrospective analysis of 244 HER2-negative breast cancer patients treated with neoadjuvant chemotherapy (NAC) at Osaka Metropolitan University Hospital (2007–2018) classified tumors into HER2-low (41.0%), HER2-ultralow (36.1%), and HER2-null (23.0%). Clinicopathological features , tumor-infiltrating lymphocyte (TIL) counts , pathological complete response (pCR) , and prognostic outcomes (disease-free survival [DFS] and overall survival [OS]) were evaluated . Results HER2-ultralow tumors showed significantly higher estrogen receptor (ER) positivity compared with HER2-null tumors (51.8% vs. 19.6%, p < 0.001), and also tended to have higher progesterone receptor positivity (p = 0.048). In contrast, HER2-null tumors were associated with younger age (median 50.0 vs. 56.0 years, p = 0.004) and higher TIL density (50.0% vs. 36.8%, p = 0.016). The overall pCR rate was 27.9%. DFS showed no significant differences among the three groups (p = 0.087), but OS was significantly worse in HER2-null compared with Not HER2-null tumors (p = 0.026, HR = 0.454). HER2-ultralow cases demonstrated an intermediate prognosis between HER2-low and HER2-null (OS comparison with HER2-null,>p= 0.101). Conclusion HER2-ultralow tumors represent a distinct subgroup characterized by higher hormone receptor positivity , whereas HER2-null tumors were associated with younger age, higher TIL density, and poorer survival. These findings emphasize the clinical significance of refining HER2-negative subclassification to distinguish HER2-ultralow , while acknowledging limitations of sample size and retrospective design .

Purpose Human epidermal growth factor receptor 2 (HER2)-low breast cancer has been recognized as a distinct biological subset within HER2-negative breast cancer. This study aimed to examine the differences in sentinel lymph node metastasis (SLNM) rates and prognosis between HER2-low and HER2-zero breast cancers. Methods This retrospective study evaluated 965 estrogen receptor-positive, HER2-negative breast cancer patients who underwent sentinel lymph node biopsy at Osaka Metropolitan University Hospital. Clinicopathological characteristics, SLNM rates, and prognostic outcomes were compared between patients with HER2-low and with HER2-zero breast cancers. Results The SLNM rate was significantly higher in the HER2-low group than in the HER2-zero group ( p  = 0.039). However, disease-free survival (DFS), recurrence-free interval (RFI), overall survival, and breast cancer-specific survival were not significantly different between the two groups. In subgroup analysis excluding macrometastases, DFS and RFI were significantly longer in the HER2-low breast cancer group. Conclusion HER2-low breast cancer exhibits a higher SLNM rate, suggesting unique biological behavior. However, its overall prognosis remains similar to that of HER2-zero breast cancer, with potential prognostic advantages in select subgroups.

The peripheral blood platelet-lymphocyte ratio (PLR) has been proposed as an indicator for evaluating systemic inflammatory responses in cancer-bearing patients. While some reports suggest a correlation between PLR and prognosis, few studies have examined the relationship between PLR and sensitivity to chemotherapy. We conducted a study on whether PLR could serve as a predictor of the therapeutic effects of neoadjuvant chemotherapy (NAC). PLR was evaluated in 177 breast cancer patients treated with the NAC 5-fluorouracil, epirubicin and cyclophosphamide, followed by weekly paclitaxel and subsequent curative surgery. The correlation between PLR and prognosis, and between PLR and the efficacy of NAC, were evaluated retrospectively. The low PLR group had significantly more patients > 56 years old (p = 0.001) and postmenopausal women (p = 0.001) than the high PLR group. The low PLR group also had a higher pathologic complete response (pCR) rate (p = 0.019). On examining the correlation with prognosis, the low-PLR group was found to have significantly longer disease-free survival (p = 0.004) and overall survival (p = 0.032) than the high PLR group. Multivariate analysis also revealed that lymph node metastasis (p = 0.043, hazard ratio = 4.40) and a high PLR (p = 0.005, hazard ratio = 2.84) were independent, unfavorable prognostic factors. For patients with breast cancer treated with NAC, a low PLR indicated high chemotherapy sensitivity, suggesting that PLR could serve as a predictive marker of the therapeutic effect of NAC.

PurposeTo demonstrate how artificial intelligence (AI) can expand radiologists’ capacity, we visualized the features of invasive ductal carcinomas (IDCs) that our algorithm, developed and validated for basic pathological classification on mammograms, had focused on.Materials and methodsIDC datasets were built using mammograms from patients diagnosed with IDCs from January 2006 to December 2017. The developing dataset was used to train and validate a VGG-16 deep learning (DL) network. The true positives (TPs) and accuracy of the algorithm were externally evaluated using the test dataset. A visualization technique was applied to the algorithm to determine which malignant findings on mammograms were revealed.ResultsThe datasets were split into a developing dataset (988 images) and a test dataset (131 images). The proposed algorithm diagnosed 62 TPs with an accuracy of 0.61–0.70. The visualization of features on the mammograms revealed that the tubule forming, solid, and scirrhous types of IDCs exhibited visible features on the surroundings, corners of the masses, and architectural distortions, respectively.ConclusionWe successfully showed that features isolated by a DL-based algorithm trained to classify IDCs were indeed those known to be associated with each pathology. Thus, using AI can expand the capacity of radiologists through the discovery of previously unknown findings.