Lymphatic flow mapping using near-infrared fluorescence imaging with indocyanine green helps to predict lymph node metastasis intraoperatively in patients with esophageal or esophagogastric junction cancer not treated with neoadjuvant chemotherapy.

BACKGROUND: Lymphatic flow mapping using near-infrared fluorescence (NIR) imaging with indocyanine green (ICG) has been used for the intraoperative prediction of lymph node metastasis in esophageal or esophagogastric junction cancer. However, a consistent method that yields sufficient diagnostic quality is yet to be confirmed. This study explored the diagnostic utility of our newly established lymphatic flow mapping protocol for predicting lymph node metastasis in patients with esophageal or esophagogastric junction cancer. METHODS: We injected 0.5 mL of ICG (500 µg/mL) into the submucosal layer at four peritumoral points on the day before surgery for 54 patients. We performed lymphatic flow mapping intraoperatively using NIR imaging. After determining the NIR status and presence of metastases, evaluable lymph node stations on in vivo imaging and all resected lymph nodes were divided into four categories: ICG+meta+ (true positive), ICG+meta- (false positive), ICG-meta+ (false negative), and ICG-meta- (true negative). RESULTS: The distribution of ICG+ and meta+ lymph node stations differed according to the primary tumor site. Sensitivity and specificity for predicting meta+ lymph nodes among ICG+ ones were 50% (95% CI 41-59%) and 75% (73-76%), respectively. Predicting meta+ lymph node stations among ICG+ stations improved these values to 66% (54-77%) and 77% (74-79%), respectively. Undergoing neoadjuvant chemotherapy was an independent risk factor for having meta+ lymph nodes with false-negative diagnoses (odds ratio 4.82; 95% CI 1.28-18.19). The sensitivity of our technique for predicting meta+ lymph nodes and meta+ lymph node stations in patients who did not undergo neoadjuvant chemotherapy was 79% (63-90%) and 83% (61-94%), respectively. CONCLUSION: Our protocol potentially helps to predict lymph node metastasis intraoperatively in patients with esophageal or esophagogastric junction cancer undergoing esophagectomy who did not undergo neoadjuvant chemotherapy.

Bromodomain protein BRD8 regulates cell cycle progression in colorectal cancer cells through a TIP60-independent regulation of the pre-RC complex.

Bromodomain-containing protein 8 (BRD8) is a subunit of the NuA4/TIP60-histone acetyltransferase complex. Although BRD8 has been considered to act as a co-activator of the complex, its biological role remains to be elucidated. Here, we uncovered that BRD8 accumulates in colorectal cancer cells through the inhibition of ubiquitin-dependent protein degradation by the interaction with MRG domain binding protein. Transcriptome analysis coupled with genome-wide mapping of BRD8-binding sites disclosed that BRD8 transactivates a set of genes independently of TIP60, and that BRD8 regulates the expression of multiple subunits of the pre-replicative complex in concert with the activator protein-1. Depletion of BRD8 induced cell-cycle arrest at the G1 phase and suppressed cell proliferation. We have also shown that the bromodomain of BRD8 is indispensable for not only the interaction with histone H4 or transcriptional regulation but also its own protein stability. These findings highlight the importance of bromodomain as a therapeutic target.

Identification of odontogenic ameloblast associated as a novel target gene of the Wnt/ß-catenin signaling pathway.

The Wnt/ß-catenin signaling pathway plays a key role in development and carcinogenesis. Although some target genes of this signaling have been identified in various tissues and neoplasms, the comprehensive understanding of the target genes and their roles in the development of human cancer, including hepatoma and colorectal cancer remain to be fully elucidated. In this study, we searched for genes regulated by the Wnt signaling in liver cancer using HuH-7 hepatoma cells. A comparison of the expression profiles between cells expressing an active form of mutant ß-catenin and cells expressing enhanced green fluorescent protein (EGFP) identified seven genes upregulated by the mutant ß-catenin gene (CTNNB1). Among the seven genes, we focused in this study on ODAM, odontogenic, ameloblast associated, as a novel target gene. Interestingly, its expression was frequently upregulated in hepatocellular carcinoma, colorectal adenocarcinoma, and hepatoblastoma. We additionally identified a distant enhancer region that was associated with the ß-catenin/TCF7L2 complex. Further analyses revealed that ODAM plays an important role in the regulation of the cell cycle, DNA synthesis, and cell proliferation. These data may be useful for clarification of the main molecular mechanism(s) underlying these cancers.

Combining nutritional status with TNM stage: a physiological update on gastric cancer staging for improving prognostic accuracy in elderly patients.

BACKGROUND: The tumor-node-metastasis (TNM) staging system does not take the patient's physiological status into consideration, reportedly making it insufficient for predicting survival outcomes in frail cancer patients. We assessed the prognostic values of several nutrition- and inflammation-based markers in combination with pTNM stage in gastric carcinoma (GC) patients. METHODS: In total, 1166 patients undergoing GC surgery were studied. The prognostic capabilities of 3 nutritional and 3 systemic inflammatory parameters were examined. We developed new staging systems by adding these markers, individually, to the pTNM stage. We then compared the prognostic capabilities of our new systems with that of pTNM stage alone. We also assessed the prognostic values of these systems by dividing our patient cohort into elderly (≥ 65 years) and non-elderly groups. RESULTS: Our novel staging systems had greater predictive capabilities for overall survival (OS) than pTNM alone. Most notably, survival discrimination was significantly increased for pTNM when it was combined with albumin-based nutritional indices (geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI)). Our new staging systems incorporating GNRI or PNI into pTNM had significantly better predictive capability for OS, especially non-GC mortality, than pTNM alone in elderly GC patients. In the non-elderly patients, the predictive capabilities of the new staging systems for OS differed minimally from that of pTNM. CONCLUSIONS: The predictive capability of pTNM stage was particularly enhanced when this parameter was combined with nutritional markers. Our new approach aids in predicting survival outcomes, especially non-GC-related death, in elderly GC patients.

Optimal settings of near-infrared fluorescence imaging with indocyanine green for intraoperative detection of lymph node metastasis in esophageal cancer.

Lymphatic flow mapping using near-infrared fluorescence (NIR) imaging with indocyanine green (ICG) has been used for intraoperative diagnosis of lymph node metastasis (LNM) in various cancers. Accurate prediction of LNM intraoperatively may allow minimization of the extent of lymphadenectomy. However, a consistent method and diagnostic ability, allowing application of NIR-guided lymphatic flow mapping to esophageal cancer (EC), have not been established due to the multidirectional and complex characteristics of lymphatic flow in the esophagus. Herein, we present a novel NIR-guided surgical technique for predicting lymph node stations potentially containing LNM in EC with high diagnostic accuracy derived from appropriately adjusting the ICG injection setting.

Motile sperm domain containing 1 is upregulated by the Wnt/ß-catenin signaling pathway in colorectal cancer.

Aberrant activation of the Wnt/ß-catenin signaling pathway plays a crucial role in the development and progression of colorectal cancer. Previously, we identified a set of candidate genes that were regulated by this signaling pathway, and the present study focused on motile sperm domain containing 1 (MOSPD1). Immunohistochemical staining revealed that the expression of MOSPD1 was elevated in tumor cells from colorectal cancer tissues compared with in non-tumor cells. Using ChIP-seq data and the JASPAR database, the regulatory region(s) in the MOSPD1 gene as a target of the Wnt/ß-catenin signaling pathway were searched, and a region containing three putative TCF-binding motifs in the 3'-flanking region was identified. Additional analyses using reporter assay and ChIP-quantitative PCR suggested that this region harbors enhancer activity through an interaction with transcription factor 7 like 2 (TCF7L2) and ß-catenin. In addition, chromatin conformation capture assay revealed that the 3'-flanking region interacts with the MOSPD1 promoter. These data suggested that MOSPD1 was regulated by the ß-catenin/TCF7L2 complex through the enhancer element located in the 3'-flanking region. These findings may be helpful for future studies regarding the precise regulatory mechanisms of MOSPD1.

Signature and Prediction of Perigastric Lymph Node Metastasis in Patients with Gastric Cancer and Total Gastrectomy: Is Total Gastrectomy Always Necessary?

BACKGROUND: A growing number of studies suggest that the current indications for partial gastrectomy, including proximal gastrectomy and pylorus-preserving gastrectomy (PPG), may be expanded, but evidence is still lacking. METHODS: We retrospectively analyzed 300 patients with gastric cancer (GC) who underwent total gastrectomy. We analyzed the incidence of pLNMs in relation to tumor location, tumor size and T stage. We further identified predictive factors for perigastric lymph node metastasis (pLNM) in stations 1, 2, 3, 4sa, 4sb, 4d, 5, and 6. RESULTS: No patients with upper-third T1-T2 stage GC had pLNMs in stations 4sa, 4sb, 4d, 5, or 6, but 3.8% of patients with stage T3 had 4d pLNM. No patients with upper-third GC < 4 cm in diameter had pLNMs in 2, 4sa, 4d, 5, or 6, and 2.3% of patients had pLNMs in 4sb. For middle-third GCs, 2.9% of patients with T1 stage had pLNMs in 4sa and 5, but no patients with T2 stage or tumors < 4 cm had pLNMs in 2, 4sa, or 5. The shortest distance from pylorus ring to distal edge of tumor (sDPD) was a new predictive factor for pLNMs in 2, 4d, 5, and 6. CONCLUSIONS: Proximal gastrectomy may be expanded to patients with stage T1-T2 GC and/or tumor diameter < 4 cm in the upper-third stomach, whereas PPG may be expanded to include T1-T2/N0 and/or tumors < 4 cm in the middle-third stomach. A new predictive factor, sDPD, showed good predictive performance for pLNMs, especially in stations 4d, 5, and 6.

Impacts of complications after esophageal cancer surgery on health-related quality of life and nutritional status.

BACKGROUND: The long-term impacts of post-operative complications, especially pulmonary complications and anastomotic leakage, on health-related quality of life (HRQoL), nutritional status and body composition remain to be fully addressed in patients undergoing esophageal cancer surgery. METHODS: Patients who underwent esophagectomy between 2015 and 2019 and survived without recurrence were eligible. HRQoL (European Organization for Research and Treatment of Cancer QLQ-C30 and the QLQ-OES18 questionnaires), nutritional and body composition data were prospectively evaluated before and at 3, 6, 12 and 24 months after surgery. Collected data were compared between patients with post-operative complications and those without. RESULTS: In total, 88 patients were included. Overall complications, anastomotic leakage and pulmonary complications developed in 48 (54.5%), 20 (20.7%) and 18 (20.5%) patients, respectively. Patients with pulmonary complications had significantly more reflux-related symptoms (dry mouth; P = 0.03, coughing; P = 0.047), and more difficulties with eating at 24 months after surgery, as compared to those without such complications. Anastomotic leakage increased pain, speaking problems and dysphagia up to 6 months after surgery. Patients with pulmonary complications had significantly lower prealbumin levels (P = 0.01, 0.02 and 0.008 at 6, 12 and 24 months after surgery, respectively) and lower prognostic nutritional index values over time after surgery than those without these complications. In contrast, anastomotic leakage was not associated with poor nutritional status post-operatively. Body composition was not affected by the occurrence of complications. CONCLUSION: Patients who developed post-operative complications, especially pulmonary complications, had long-lasting negative HRQoL outcomes and poor nutritional status after esophagectomy.

Study protocol of a single-arm phase 2 study evaluating the preventive effect of topical hydrocortisone for capecitabine-induced hand-foot syndrome in colorectal cancer patients receiving adjuvant chemotherapy with capecitabine plus oxaliplatin (T-CRACC study).

BACKGROUNDS: Clinical evidence of the preventive effectiveness of medium-class topical corticosteroids for capecitabine-induced hand foot syndrome (HFS) is limited. Although the pathogenesis and mechanism of HFS are unclear, inflammatory reactions are thought to be involved in HFS development. This study aimed to evaluate the preventive effect of medium-class topical corticosteroids (hydrocortisone butyrate 0.1% topical therapy) for capecitabine-induced HFS in patients with colorectal cancer receiving adjuvant chemotherapy with capecitabine plus oxaliplatin. METHODS: This is a single-center, single-arm, phase 2 study. Patients with colorectal cancer scheduled to receive adjuvant chemotherapy with capecitabine plus oxaliplatin are enrolled, and topical hydrocortisone butyrate 0.1% is applied prophylactically in addition to standard moisturizing therapy. The primary endpoint is the incidence of grade ≥ 2 HFS within three months. The secondary endpoints are the time to onset of HFS, rates of dose reduction, schedule delay, discontinuation caused by capecitabine-induced HFS, and other adverse events. All adverse events are evaluated by clinical pharmacists and attending physicians. DISCUSSION: This study is expected to contribute to the establishment of new supportive care for preventing HFS, not only for colorectal cancer patients receiving adjuvant chemotherapy, but also for various cancer patients receiving capecitabine-based chemotherapy. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCTs031220002. Registered 5 April 2022, https://jrct.niph.go.jp/search Protocol version V.1.0, 16 February 2022.

Optimal criteria for predicting lymph node metastasis in esophageal squamous cell carcinoma by anatomical location using preoperative computed tomography: a retrospective cohort study.

PURPOSE: Predicting lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) is critical for selecting appropriate treatments despite the low accuracy of computed tomography (CT) for detecting LNM. Variation in potential nodal sizes among locations or patients' clinicopathological background factors may impact the diagnostic quality. This study explored the optimal criteria and diagnostic ability of CT by location. METHODS: We retrospectively reviewed preoperative CT scans of 229 patients undergoing curative esophagectomy. We classified nodal stations into six groups: Cervical (C), Right-upper mediastinal (UR), Left-upper mediastinal (UL), Middle mediastinal (M), Lower mediastinal (L), and Abdominal (A). We then measured the short-axial diameter (SAD) of the largest lymph node in each area. We used receiver operating characteristics analyses to evaluate the CT diagnostic ability and determined the cut-off values for the SAD in all groups. RESULTS: Optimal cut-offs were 6.5 mm (M), 6 mm (C, L, and A), and 5 mm (UR and UL). Diagnostic abilities differed among locations, and UR had the highest sensitivity. A multivariate analysis showed poor differentiation to be an independent risk factor for a false-negative diagnosis (p = 0.044). CONCLUSIONS: Optimal criteria and diagnostic abilities for predicting LNM in ESCC varied among locations, and poor differentiation might contribute to failure to detect LNM.

No association between hospital volume and short-term outcomes of some common surgeries: a retrospective cohort study based on a Japanese nationwide database.

PURPOSE: Centralization of high-risk surgeries has become a widespread strategy. However, whether or not the hospital volume affects the outcomes of common surgeries remains unclear. This study explored the association between hospital volume and short-term outcomes of common surgeries, as represented by appendectomy, cholecystectomy, and pneumothorax surgery, by analyzing data from a Japanese nationwide database. METHODS: All hospitals were categorized into four groups (very low-, low-, high-, and very high-volume) according to the annual hospital volume of all gastrointestinal surgeries or all respiratory surgeries in 2017. Patient demographic data and surgical outcomes were evaluated across hospital volume categories. RESULTS: We analyzed 2392 facilities which performed 771,182 gastrointestinal surgeries, and 992 facilities which performed 98,656 respiratory surgeries. Short-term outcomes of patients who underwent appendectomy (n = 50,568), cholecystectomy (n = 104,262), and pneumothorax surgery (n = 11,723) were evaluated. The incidences of postoperative complications, reoperation, and readmission were similar among the groups. Multivariable logistic regression analyses revealed hospital volume to have no association with these short-term outcomes. CONCLUSION: Analyses of a Japanese nationwide database revealed that the hospital volume was not associated with short-term outcomes of appendectomy, cholecystectomy, and pneumothorax surgery. These common surgical procedures may not require centralization into high-volume hospitals.

Survival Prediction Capabilities of Preoperative Inflammatory and Nutritional Status in Esophageal Squamous Cell Carcinoma Patients.

BACKGROUND: Studies have revealed the impacts of various inflammatory and nutritional markers in patients with esophageal squamous cell carcinoma (ESCC). We evaluated the prognostic values of multiple inflammation- or nutrition-based markers, either alone or in combination with pStage, in ESCC patients. METHODS: In total, 360 patients undergoing upfront surgery for ESCC were retrospectively reviewed. The prognostic capabilities of 7 inflammatory and 3 nutritional parameters were investigated. Furthermore, we devised new staging systems by adding these markers to pStage and examined the prognostic abilities of our new approach. Time-dependent receiver operating characteristic curves and the areas under the curve (AUCs) were estimated to compare prognostic capabilities among the parameters. RESULTS: The AUCs for predicting overall survival (OS) of the prognostic nutritional index (PNI), CRP to albumin ration (CAR), lymphocyte to CRP ratio (LCR) and the Naples prognostic score (NPS) were similar to that of pStage. Notably, CAR and LCR showed high predictive capabilities for OS (AUCs; 0.627 and 0.634 for 3-year OS, respectively). New staging systems combining inflammatory or nutritional markers with pStage provided higher AUCs for predicting OS than pStage alone. In particular, NPpStage (NPS and pStage) (P = 0.03), PNpStage (PNI and pStage) (P = 0.03) and LCpStage (LCR and pStage) (P = 0.05) showed significantly higher accuracy for predicting OS than pStage alone. CONCLUSIONS: Various inflammatory or nutritional markers, especially those derived from CRP, are useful for predicting survival outcomes of ESCC patients. The predictive capabilities of these indices were augmented when used in combination with pStage.

A design of forceps-type coincidence radiation detector for intraoperative LN diagnosis: clinical impact estimated from LNs data of 20 esophageal cancer patients.

PURPOSE: To reduce postoperative complications, intraoperative lymph node (LN) diagnosis with 18F-fluoro-2-deoxy-D-glucose (FDG) is expected to optimize the extent of LN dissection, leading to less invasive surgery. However, such a diagnostic device has not yet been realized. We proposed the concept of coincidence detection wherein a pair of scintillation crystals formed the head of the forceps. To estimate the clinical impact of this detector, we determined the cut-off value using FDG as a marker for intraoperative LN diagnosis in patients with esophageal cancer, the specifications needed for the detector, and its feasibility using numerical simulation. METHODS: We investigated the dataset including pathological diagnosis and radioactivity of 1073 LNs resected from 20 patients who underwent FDG-positron emission tomography followed by surgery for esophageal cancer on the same day. The specifications for the detector were determined assuming that it should measure 100 counts (less than 10% statistical error) or more within the intraoperative measurement time of 30 s. The detector sensitivity was estimated using GEANT4 simulation and the expected diagnostic ability was calculated. RESULTS: The cut-off value was 620 Bq for intraoperative LN diagnosis. The simulation study showed that the detector had a radiation detection sensitivity of 0.96%, which was better than the estimated specification needed for the detector. Among the 1035 non-metastatic LNs, 815 were below the cut-off value. CONCLUSION: The forceps-type coincidence detector can provide sufficient sensitivity for intraoperative LN diagnosis. Approximately 80% of the prophylactic LN dissections in esophageal cancer can be avoided using this detector.

Severe thrombocytopenia induced by chemotherapy after total gastrectomy: A report of three cases.

Pancytopenia associated with vitamin B12 and folic acid deficiency has been reported in patients who have undergone total gastrectomy. Therefore, myelosuppression due to chemotherapy following total gastrectomy is considered to be more serious. We encountered three cases of severe thrombocytopenia in patients who received chemotherapy after total gastrectomy. The lowest platelet levels in these patients were 1.7 × 104/mm3, 2.3 × 104/mm3, and 0.9 × 104/mm3, respectively. None of the patients presented with vitamin B12 deficiency, and one patient presented with folic acid deficiency. The association between serum vitamin levels and chemotherapy-related adverse events is controversial. Since folic acid has a shorter half-life (6 hours) and cannot accumulate in the body, unlike vitamin B12 that is stored for a long time in the liver, folic acid deficiency is suspected to be associated with thrombocytopenia induced by post-total gastrectomy chemotherapy. However, serum folic acid levels fluctuate depending on the timing of evaluation and require a few days to evaluate. In conclusion, patients who undergo chemotherapy after total gastrectomy should be monitored for severe thrombocytopenia but serum vitamin B12 levels are not necessarily clinically important. By measuring serum folic acid levels at appropriate times, folic acid deficiency may prove to be a reference for predicting severe thrombocytopenia.

Identifying multiple swollen lymph nodes on preoperative computed tomography is associated with poor prognosis along with pathological extensive nodal metastasis in locally advanced gastric cancer.

BACKGROUND: Advanced gastric cancer with extensive lymph node (LN) metastasis is associated with poor outcomes even after R0 gastrectomy. Although multi-detector row computed tomography (MDCT) is the basis of preoperative LN staging, the diagnostic accuracy of pathologically extensive LN metastasis detection by MDCT remains unsatisfactory. METHODS: We retrospectively evaluated diagnostic accuracy for pN2/3 disease by size and number of depicted LNs on MDCT in a single-center cohort of 421 patients with pT2-4 gastric carcinoma. The positive predictive value (PPV) was determined based on the number and short-axis diameter (SAD) of identified LNs, and oncological outcomes were also evaluated according to clinical LN status and pN categories. RESULTS: The PPV for detecting pN2/3 disease rose with the SAD value cut-off for one LN, reaching 84.6% at 10 mm with no further increase at 15 mm. However, the SAD cut-off value plateaued at 8 mm (91.3%) when at least two measurable LNs were identified on MDCT. Patients with two measurable LNs with SAD≥8 mm had significantly poorer 5-year overall and recurrence-free survival than patients with fewer than two measurable LNs in the pN2-3 disease. On multivariate analysis, two measurable LNs with SAD≥8 mm was an independent prognostic factor for overall and relapse-free survivals. CONCLUSION: Locally advanced gastric cancer with two measurable LNs with SAD≥8 mm on preoperative MDCT is highly associated with pN2/3 disease and poorer outcomes with upfront surgery. This criterion might be a reasonable indicator for identifying candidates for neoadjuvant treatment of advanced gastric cancer.

The type of gastrectomy affects skeletal muscle loss and the long-term outcomes of elderly patients with gastric cancer: a retrospective study using computed tomography images.

PURPOSE: Sarcopenia is common in elderly gastrectomized patients and a known risk factor for postoperative complications and poor overall survival. However, the long-term outcomes of skeletal muscle loss after gastrectomy and the differences in outcomes of different gastrectomy procedures remain unclear. METHODS: The subjects of this retrospective study were 136 patients who underwent various gastrectomy procedures for early gastric cancer, namely: total gastrectomy (TG; n = 20), proximal gastrectomy (PG; n = 16), distal gastrectomy (DG; n = 60), and pylorus-preserving gastrectomy (PPG; n = 40). Skeletal muscle volume (SMV), calculated as the skeletal muscle index (SMI), was measured using cross-sectional computed tomography (CT) scans preoperatively and then 1, 2, and 3 years after gastrectomy. RESULTS: Sarcopenia developed from 2 years onwards in all the patients who underwent TG. The SMI and sarcopenia prevalence after gastrectomy deteriorated over time. Multivariate analysis revealed that TG and PG were significant risk factors for skeletal muscle loss in postoperative years 1 and 3. A decrease in the SMI after TG or PG was most remarkable in elderly patients. CONCLUSIONS: The type of gastrectomy affects skeletal muscle loss in the long term. Elderly patients who undergo TG or PG are at high risk of severe skeletal muscle loss.

Lymphatic invasion is a prognostic factor of pathological N0 esophageal squamous cell carcinoma.

Adjuvant treatment after upfront esophagectomy for esophageal squamous cell carcinoma (ESCC) is indicated only for patients with lymph node metastasis in Japan. However, the recurrence rate after curative resection is high even for node-negative patients; thus, understanding the prognostic factors for patients with node-negative ESCC, which still remains unidentified, is important. Here, we aimed to reveal the prognostic factors for the long-term outcomes of patients with node-negative ESCC. Moreover, we compared the long-term outcomes among high-risk node-negative and node-positive patients. This single-institution retrospective study included 103 patients with pT1b-3N0 ESCC who underwent upfront surgery to identify the population at a high risk of recurrence. To compare overall survival (OS) and recurrence-free survival (RFS) between high-risk node-negative and node-positive patients, 51 node-positive ESCC patients with pStage IIIA or less who had undergone upfront surgery were also included. Univariable and multivariable analyses were performed using the Cox proportional hazard regression model. OS and RFS were compared using the log-rank test. Only lymphatic invasion (Ly+) was associated with worse 3-year OS (hazard ratio, 8.63; 95% confidence interval, 2.09-35.69; P = 0.0029) and RFS (hazard ratio, 4.87; 95% confidence interval, 1.69-14.02; P = 0.0034). The node-negative and Ly+ patients showed significantly worse OS (P = 0.0242) and RFS (P = 0.0114) than the node-positive patients who underwent chemotherapy. Ly+ is the only independent prognostic factor in patients with node-negative ESCC. Patients with node-negative and Ly+ ESCC may benefit from adjuvant treatment.

Chemotherapy-related dysphonia: Similar and differentiating features of six cases.

Dysphonia has been reported with anti-angiogenic chemotherapy agents. Dysphonia in patients with cancer receiving chemotherapy tends to be overlooked in clinical practice since it is non-life-threatening. However, it reduces quality of life. Although inhibition of vascular endothelial growth factor receptor is the reported mechanism of dysphonia, it has not been elucidated. We report 6 cases of patients with dysphonia suspected to be due to panitumumab and nivolumab that have not been reported previously. Peripheral edema, a factor in dysphonia, can be seen with aflibercept, bevacizumab, panitumumab, and nivolumab. Therefore, chemotherapy drugs with peripheral edema may be related to dysphonia.

The first case of gastric leiomyosarcoma developed through malignant transformation of leiomyoma.

Malignant transformation of gastric leiomyoma has not been reported, and therefore it is considered to have virtually no malignant potential. We report a case of gastric leiomyosarcoma arising from leiomyoma. The patient is a 72-year-old man with a submucosal mass measuring 20 mm in diameter, which was incidentally identified by an endoscopic surveillance. A biopsy suggested a diagnosis of leiomyosarcoma, and local excision was performed. Pathological examination revealed that the tumor was composed of two distinct components: typical leiomyoma-like area in the periphery and leiomyosarcoma component exhibiting higher cellularity, prominent nuclear atypia, necrosis, and increased mitosis. Immunohistochemically, in the latter, p53 overexpression, increased Ki-67 labeling index, and attenuated expression of smooth muscle markers were noted. This is the first report to demonstrate the presence of leiomyoma-leiomyosarcoma sequence in the stomach that is well recognized in the uterus. Our observation highlights the potential occurrence of malignant transformation of gastrointestinal leiomyoma.