Changed resting-state connectivity of anterior insular cortex affects subjective pain reduction after knee arthroplasty: A longitudinal study.

The mechanism of chronic knee osteoarthritis (OA) pain and postoperative pain due to knee arthroplasty has not been elucidated. This could be involved neuroplasticity in brain connectivity. To clarify the mechanism of chronic knee OA pain and postoperative pain, we examined the relationship between resting-state functional connectivity (rs-FC) and clinical measurements in knee OA before and after knee arthroplasty, focusing on rs-FCs with the anterior insular cortex (aIC) as the key region. Fifteen patients with knee OA underwent resting-state functional magnetic resonance imaging and clinical measurements shortly before and 6 months after knee arthroplasty, and 15 age- and sex-matched control patients underwent an identical protocol. Seed-to-voxel analysis was performed to compare the clinical measurements and changed rs-FCs, using the aIC as a seed region, between the preoperative and postoperative patients, as well as between the operative and control patients. In preoperative patients, rs-FCs of the aIC to the OFC, frontal pole, subcallosal area, and medial frontal cortex increased compared with those of the control patients. The strength of rs-FC between the left aIC and right OFC decreased before and after knee arthroplasty. The decrease in rs-FC between the left aIC and right OFC was associated with decreased subjective pain score. Our study showed a correlation between longitudinally changed rs-FC and clinical measurement before and after knee arthroplasty. Rs-FC between the aIC and OFC have the potential to elucidate the mechanisms of knee OA pain and postoperative pain due to knee arthroplasty.

Usefulness of synthetic MRI for differentiation of IDH-mutant diffuse gliomas and its comparison with the T2-FLAIR mismatch sign.

INTRODUCTION: The T2-FLAIR mismatch sign is a characteristic imaging biomarker for astrocytoma, isocitrate dehydrogenase (IDH)-mutant. However, investigators have provided varying interpretations of the positivity/negativity of this sign given for individual cases the nature of qualitative visual assessment. Moreover, MR sequence parameters also influence the appearance of the T2-FLAIR mismatch sign. To resolve these issues, we used synthetic MR technique to quantitatively evaluate and differentiate astrocytoma from oligodendroglioma. METHODS: This study included 20 patients with newly diagnosed non-enhanced IDH-mutant diffuse glioma who underwent preoperative synthetic MRI using the Quantification of Relaxation Times and Proton Density by Multiecho acquisition of a saturation-recovery using Turbo spin-Echo Readout (QRAPMASTER) sequence at our institution. Two independent reviewers evaluated preoperative conventional MR images to determine the presence or absence of the T2-FLAIR mismatch sign. Synthetic MRI was used to measure T1, T2 and proton density (PD) values in the tumor lesion. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance. RESULTS: The pathological diagnoses included astrocytoma, IDH-mutant (n = 12) and oligodendroglioma, IDH-mutant and 1p/19q-codeleted (n = 8). The sensitivity and specificity of T2-FLAIR mismatch sign for astrocytoma were 66.7% and 100% [area under the ROC curve (AUC) = 0.833], respectively. Astrocytoma had significantly higher T1, T2, and PD values than did oligodendroglioma (p < 0.0001, < 0.0001, and 0.0154, respectively). A cutoff lesion T1 value of 1580 ms completely differentiated astrocytoma from oligodendroglioma (AUC = 1.00). CONCLUSION: Quantitative evaluation of non-enhanced IDH-mutant diffuse glioma using synthetic MRI allowed for better differentiation between astrocytoma and oligodendroglioma than did conventional T2-FLAIR mismatch sign. Measurement of T1 and T2 value by synthetic MRI could improve the differentiation of IDH-mutant diffuse gliomas.

Feasibility, safety, and efficacy of intraoperative magnetic resonance imaging-guided hepatectomy for small hepatocellular carcinoma: A retrospective study.

Advancements in diagnostic modalities, such as enhanced magnetic resonance imaging, provide increased opportunities for identifying small hepatocellular carcinoma that is undetectable on preoperative ultrasonography. Whether it is acceptable to leave these lesions untreated is uncertain. This study aimed to evaluate the safety and efficacy of intraoperative magnetic resonance imaging-guided hepatectomy using new navigation systems. This study was conducted between July 2019 and January 2023. We retrospectively studied the clinicopathological features and prognoses of patients with small hepatocellular carcinoma who underwent curative intraoperative magnetic resonance imaging-guided hepatectomy. We evaluated 23 patients (median age, 75 years), among whom 20 (87.0%) were males. Seven (30.4%) and 15 (65.2%) patients had liver cirrhosis and a history of hepatectomy, respectively. The median size of the target lesions was 9 mm, with a median distance of 6 mm from the liver surface. Despite being undetectable preoperatively on contrast-enhanced ultrasonography, all lesions were identified using intraoperative magnetic resonance imaging. Based on pathological findings, 76.0% of the lesions were malignant. The complete resection rate was 100%, and tumor-free margins were confirmed in 96.0% of the patients. Intraoperative magnetic resonance imaging-guided hepatectomy is safe and effective in identifying and resecting small hepatocellular carcinoma lesions that are undetectable on preoperative ultrasonography.

New-onset of rheumatic diseases following COVID-19 vaccination: the report of three cases and a literature review.

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.

Successful Treatment of Diffuse Large B-cell Lymphoma Involving Multiple Renal and Bone Infiltrations Presenting with Giant Cell Arteritis-like Manifestations: A Case Report.

We herein report a case of diffuse large B-cell lymphoma (DLBCL) involving multiple renal and bone infiltrations presenting with giant cell arteritis-like (GCA)-like manifestations. One month prior, the present patient had left-sided temporal headache, jaw claudication, and renal failure. The patient was diagnosed with DLBCL based on a renal biopsy. After rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus intrathecal methotrexate/cytarabine/prednisone and rituximab, high-dose methotrexate, and cytarabine (R-MA) chemotherapy, the patient's clinical manifestations improved, and complete remission was achieved. DLBCL rarely but occasionally presents with GCA-like manifestations or multiple renal and bone infiltrations, highlighting the need for prompt and aggressive combination chemotherapy.

New-onset Immune-mediated Necrotizing Myopathy and Trigeminal Neuropathy after SARS-CoV-2 mRNA Vaccination in a Patient with Rheumatoid Arthritis and Sjögren's Syndrome.

We present the case of a 42-year-old woman with rheumatoid arthritis and Sjögren's syndrome treated with adalimumab who developed immune-mediated necrotizing myopathy (IMNM) and trigeminal neuropathy after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Trigeminal neuralgia and elevated serum creatine kinase levels emerged 12 days post-vaccination, followed by myalgia in the femoral muscles. IMNM was histologically diagnosed. The pathogenesis may involve molecular mimicry between the SARS-CoV-2 spike glycoprotein and autologous tissues triggered by vaccination. This case emphasizes the association between SARS-CoV-2 vaccination, tumor necrosis factor inhibitor, IMNM, and trigeminal neuropathy, as well as the importance of monitoring immune-mediated adverse events following SARS-CoV-2 vaccination in patients with autoimmune disease.

Frequency of lymph node metastasis according to tumor location in clinical T1 early gastric cancer: supplementary analysis of the Japan Clinical Oncology Group study (JCOG0912).

BACKGROUND: The frequency of lymph node metastases per lymph node site in early gastric cancer has not been well clarified from the data based on prospective studies. This exploratory analysis aimed to determine the frequency and location of lymph node metastases in clinical T1 gastric cancer using the data from JCOG0912 to investigate the validity of the extent of standard lymph node dissection defined in Japanese guidelines. METHODS: This analysis included 815 patients with clinical T1 gastric cancer. The proportion of pathological metastasis was identified for each lymph node site per tumor location (middle third and lower third) and four equal parts of the gastric circumference. The secondary aim was identification of the risk factor for lymph node metastasis. RESULTS: Eighty-nine patients (10.9%) had pathologically positive lymph node metastases. Although the overall frequency of metastases was low (0.3-5.4%), metastases were widely located in each lymph node sites when primary lesion was in the middle third of the stomach. No. 4sb and 9 showed no metastasis when primary lesion was in the lower third of the stomach. Lymph node dissection of metastatic nodes resulted in a 5-year survival in more than 50% of patients. A tumor greater than 3 cm and a T1b tumor were associated with lymph node metastasis. CONCLUSIONS: This supplementary analysis demonstrated that nodal metastasis from early gastric cancer is widely and disorderly not depending on the location. Thus, systematic lymph node dissection is necessary to cure the early gastric cancer.

Gastroblastoma mimics the embryonic mesenchyme of the foregut: a case report.

BACKGROUND: Gastroblastoma is a rare gastric tumor composed of epithelial and spindle cell components. The characteristic MALAT-GLI1 fusion gene has only been identified in 5 reported cases. We report the morphological characterization of gastroblastoma with the MALAT1-GLI1 fusion gene in a young Japanese woman. CASE PRESENTATION: A 29-year-old Japanese woman visited Iwate Medical University Hospital with upper abdominal pain. Computed tomography revealed a tumor in expansive lesions involving the gastric antrum. Histologically, we observed a biphasic morphology composed of epithelial and spindle cell components. The epithelial components appeared as slit-like glandular structures with tubular or rosette-like differentiation. The spindle cell components consisted of short spindle-shaped oval cells. Immunohistochemical (IHC) analysis revealed that the spindle cell component was positive for vimentin, CD10, CD56, GLI1, and HDAC2, and focally positive for PD-L1. The epithelial component was positive for CK AE1/AE3, CAM5.2, and CK7, and negative for CK20 and EMA. Both components were negative for KIT, CD34, DOG1, SMA, desmin, S100 protein, chromogranin A, synaptophysin, CDX2, and SS18-SSX. The MALAT-GLI1 fusion gene was detected molecularly. CONCLUSIONS: We report the following new findings with this case: (i) gastric tumors mimic the gastrointestinal mesenchyme in the embryonic period; (ii) nuclear expression of PD-L1 and HDAC2 were observed in the spindle cell component of a gastroblastoma. We speculate that histone deacetylase (HDAC) inhibitors may offer a promising treatment option for gastroblastoma.

Risk model for mortality associated with esophagectomy via a thoracic approach based on data from the Japanese National Clinical Database on malignant esophageal tumors.

PURPOSE: Postoperative complications after esophagectomy can be severe or fatal and impact the patient's postoperative quality of life and long-term outcomes. The aim of the present study was to develop the best possible model for predicting mortality and complications based on the Japanese Nationwide Clinical Database (NCD). METHODS: Data registered in the NCD, on 32,779 patients who underwent esophagectomy via a thoracic approach for malignant esophageal tumor between January, 2012 and December, 2017, were used to create a risk model. RESULTS: The 30-day mortality rate after esophagectomy was 1.0%, and the operative mortality rate was 2.3%. Postoperative complications included pneumonia (13.8%), anastomotic leakage (13.2%), recurrent laryngeal nerve palsy (11.1%), atelectasis (4.9%), and chylothorax (2.5%). Postoperative artificial respiration for over 48 h was required by 7.8% of the patients. Unplanned intubation within 30 postoperative days was performed in 6.2% of the patients. C-indices evaluated using the test data were 0.694 for 30-day mortality and 0.712 for operative mortality. CONCLUSIONS: We developed a good risk model for predicting 30-day mortality and operative mortality after esophagectomy based on the NCD. This risk model will be useful for the preoperative prediction of 30-day mortality and operative mortality, obtaining informed consent, and deciding on the optimal surgical procedure for patients with preoperative risks for mortality.

Abatacept ameliorates both glandular and extraglandular involvements in patients with Sjögren's syndrome associated with rheumatoid arthritis: Findings from an open-label, multicentre, 1-year, prospective study: The ROSE (Rheumatoid Arthritis with Orencia Trial Toward Sjögren's Syndrome Endocrinopathy) and ROSE II trials.

OBJECTIVE: To clarify the efficacy and safety of intravenous abatacept for glandular and extraglandular involvements in Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). MATERIALS AND METHODS: We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials). The primary endpoint was the remission rate as measured by SDAI at 52 weeks. The secondary endpoints included the changes in the Saxon's test, Schirmer's test, ESSDAI and ESSPRI. Adverse events and adherence rates were also analyzed. RESULTS: 68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled. SDAI decreased significantly from 23.6 ± 13.2 at baseline to 9.9 ± 9.5 at 52 weeks. Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly at 24 weeks. Tear volume increased significantly at 52 weeks. Both ESSDAI and ESSPRI were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients. CONCLUSION: Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in SS associated with RA.

Encapsulating Peritoneal Sclerosis in Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Systemic Sclerosis.

We encountered a 57-year-old Japanese woman with encapsulating peritoneal sclerosis (EPS) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis. The patient was admitted to our hospital because of ascites retention. Administration of tocilizumab, an anti-interleukin-6 receptor antibody, for her RA reduced the refractory ascites remarkably; however, she developed sudden acute gastrointestinal bleeding and died a year later. On autopsy, sclerotic thickening of the peritoneum showed diffuse infiltration of podoplanin-positive fibroblast-like cells, and a diagnosis of EPS was made. EPS rarely occurs in SLE, and tocilizumab may be a new treatment candidate for EPS.

Arm heating to relieve Raynaud's phenomenon in systemic sclerosis: A single-arm multicentre prospective clinical trial.

OBJECTIVES: Raynaud's phenomenon, one of the major symptoms of systemic sclerosis (SSc), is difficult to treat. Although it is empirically considered that warming is a beneficial technique, there is no supportive evidence. We conducted a multicentre study to evaluate whether continuous heating of the arm alleviates Raynaud's phenomenon in SSc. METHODS: A pair of disposable warmers was applied to the upper arm near the elbow of patients with SSc. Two weeks of non-warmer application were followed by 2 weeks of warmer application, which was repeated twice. The Raynaud Condition Score (RCS), number of episodes, and duration of Raynaud's phenomenon were recorded. The differences in the mean RCS, frequency, and duration of Raynaud's phenomenon between the warmer application and non-application periods were analysed. RESULTS: Twenty-eight patients were included in the analysis. The average RCS was 1.98 and 2.66 during the warmer application and non-application periods, respectively. The change between the two periods was statistically significant by paired t-test. In addition, the frequency and total duration of Raynaud's phenomenon in the warmer application period were significantly lower than those in the non-application period. CONCLUSIONS: Heating of the upper arm near the elbow is effective in alleviating Raynaud's phenomenon in SSc.

Intra- and inter-examination reproducibility of T2 mapping for temporomandibular joint assessment at 3.0 T.

T2 mapping allows quantification of the temporomandibular joint (TMJ) ultrastructural degeneration. The study aimed to assess intra- and inter-examination reproducibility of T2 mapping for TMJ evaluation at 3.0 Tesla (T). Seventeen volunteers, regardless of temporomandibular disorder (TMD) diagnosis, received magnetic resonance (MR) examination at 3.0 T. T2 mapping was performed twice (> 5 min between sessions without repositioning) on 12 volunteers to ensure intra-examination reproducibility. Nine volunteers underwent two examinations (> 6 months) to ensure inter-examination reproducibility. The regions of interest (ROIs) of the articular disc and retrodiscal tissue were manually selected and calculated. The mean T2 values of the articular disc and retrodiscal tissue were 25.3 ± 3.0 and 30.0 ± 4.1 ms, respectively. T2 mapping showed excellent intra-examination intraclass correlation coefficients (ICCs) for both articular disc (0.923) and retrodiscal tissue (0.951). Very strong correlations (r) were observed in both articular disc (0.928) and retrodiscal tissue (0.953) (P < .001). Inter-examination reproducibility also demonstrated that the ICCs were excellent (0.918, 0.935) on both ROIs. T2 values between first and second examinations were strongly correlated (r = 0.921, 0.939) (P < .001). In conclusion, T2 mapping seems to be a promising tool for TMJ assessment, regardless of the TMJ condition.

Native Myocardial T1 Value in Predicting 1-Year Outcomes in Patients with Nonischemic Dilated Cardiomyopathy Experiencing Recent Heart Failure.

The evidence for the clinical implications, especially the short-term utility, of native myocardial T1 value (T1native) on cardiac magnetic resonance (CMR) in nonischemic dilated cardiomyopathy (NIDCM) is scant. We investigated the potential of T1native to assess left ventricular (LV) myocardial characteristics and predict 1-year outcomes in patient with NIDCM experiencing recent heart failure (HF).Forty-five patients with NIDCM and HF symptoms within 3 months underwent CMR with cine, non-contrast T1 mapping, and late gadolinium enhancement (LGE). T1native per patient was defined as an averaged T1 value of 5 short-axis slices of base-to-apex LV myocardium. The appearance of LGE was visually examined. T1native correlated with the LV end-diastolic dimension normalized to height (LVEDD) (r = 0.38, P = 0.0103), ejection fraction (r = -0.39, P = 0.009), and serum N-terminal pro-brain natriuretic peptide levels (r = 0.48, P = 0.001), whereas the presence and segmental extent of LGE correlated only with LVEDD. In the 1-year follow-up cohort, the optimal cutoffs of T1native for predicting LV reverse remodeling (LVRR) and combined cardiac events (cardiac death, ventricular tachycardia/fibrillation, heart failure hospitalization) were 1366 ms and 1377 ms, respectively. In multivariate analysis, T1native < 1366 ms and T1native > 1377 ms remained significant predictors of LVRR (odds ratio, 11.3) and cardiac events (hazard ratio, 15.3), respectively, whereas the presence and segmental extent of LGE did not.T1native in patients with NIDCM experiencing recent HF may offer a promising strategy for assessing LV myocardial characteristics and predicting 1-year LVRR and cardiac events.

Evaluation of subscapularis tendon tears of the anterosuperior aspect using radial-sequence magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging (MRI) is widely used to diagnose subscapularis tendon tears; however, it is difficult to assess the anterosuperior aspect of these tears. Radial-sequence MRI can reveal the fiber components of the anterosuperior aspect, from perpendicular, by overcoming the partial volume effect. We aimed to classify the insertion of subscapularis tendon tears on radial-sequence MRI and determine the effectiveness of radial-sequence MRI for subscapularis tendon tear assessments. METHODS: We retrospectively investigated 196 patients (mean age, 66.7 ± 9.0 years; 118 men, 78 women) who underwent 1.5 T MRI before arthroscopic rotator cuff repair. Radial-sequence MRI findings of the anterosuperior aspect insertion of the subscapularis tendon were classified into five grades, and intraoperative findings compared with preoperative conventional MRI and radial-sequence MRI. We calculated sensitivity, specificity, accuracy, and positive and negative predictive values. Interobserver and intraobserver reliability for radial-sequence MRI classification was calculated using kappa (κ). RESULTS: Conventional MRI sensitivity of subscapularis tendon tears was 45.3%; specificity, 95.8%; accuracy, 82.1%; positive predictive value, 80.0%; and negative predictive value, 82.5%. Radial-sequence MRI sensitivity was 92.5%; specificity, 88.1%; accuracy, 89.3%; positive predictive value, 74.2%; and negative predictive value, 96.9%. Sensitivity (P < .001), accuracy (P = .04), specificity (P = .02), and negative predictive values (P < .001) in radial-sequence MRI were significantly higher than those in conventional MRI. Intraobserver and interobserver reliabilities for radial-sequence MRI classification were κ = 0.78 and 0.65, respectively, corresponding to high reproducibility, and defined as good. CONCLUSION: We provide evidence that radial-sequence MRI is an effective tool to evaluate subscapularis tendon tears, especially before surgery.

Effects of Proximal Gastrectomy and Various Clinical Factors on Postoperative Quality of Life for Upper-third Gastric Cancer Assessed using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45): A PGSAS NEXT Study.

BACKGROUND: It is important to determine the effect of clinical factors on several domains (symptoms, living status, and quality of life [QOL]) after gastrectomy to establish individualized therapeutic strategies. This study was designed to determine the factors-particularly surgical method-that influence certain domains after gastrectomy for proximal gastric cancer by using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45) questionnaire. METHODS: We conducted a nationwide study of PGSAS-45 questionnaire responses retrieved from 1950 (82.5%) patients from 70 institutions who had undergone gastrectomy for gastric cancer. Of these, 1,538 responses for proximal gastric cancer (1020 total gastrectomies and 518 proximal gastrectomies [PGs]) were examined. RESULTS: PG significantly and favorably affected four main outcome measures (MOMs): elderly affected 10 MOMs, male sex affected 4 MOMs, longer postoperative period affected 8 MOMs, preservation of the vagus nerve affected 1 MOM, adjuvant chemotherapy affected 1 MOM, clinical stage affected 2 MOMs, and more extensive lymph node dissection affected 2 MOMs. However, the laparoscopic approach had an adverse effect on MOMs and combined resection of other organs had no favorable effect on any MOMs. CONCLUSIONS: This PGSAS NEXT study showed that it is better to perform PG for proximal gastric cancer, even for patients with advanced cancer, to obtain favorable postoperative QOL if oncological safety is guaranteed. Because the MOMs of PGSAS-45 are positively and negatively influenced by various background factors, it also is necessary to provide personalized care for each patient to prevent deterioration and further improve symptoms, living status, and QOL postoperatively.

Prediction of the peritoneal recurrence via the macroscopic diagnosis of the serosal invasion in patients with gastric cancer: Supplementary analysis of JCOG0110.

BACKGROUND: Indications for adjuvant chemotherapy for advanced gastric cancer are determined based on the pathological diagnosis. However, macroscopic diagnoses have been reported as predictors of peritoneal recurrence and survival. This study investigated the predictability of peritoneal recurrence and survival based on macroscopically (sT) and pathologically (pT) diagnosed serosal invasion to identify more sensitive predictors of peritoneal recurrence. METHODS: This study included 396 patients who underwent R0 resection without adjuvant chemotherapy with S-1 in the JCOG0110 study. Tumor depth limited to the subserosa (SS) was defined as serosal invasion negative (T-), while tumors with serosal invasion (SE, SI) were defined as serosal invasion positive (T+). The predictability of peritoneal recurrence based on sT and pT was evaluated using the Fine and Gray model. Cox regression analyses were performed for overall survival (OS) and relapse-free survival (RFS) with sT or pT as covariates. FINDINGS: A total of 150 patients (37.9%) were sT+ and 82 (26.3%) were pT+. Sixty-two patients (15.7%) were sT+/pT+, 88 (22.2%) were sT+/pT-, 20 (5.1%) were sT-/pT+, and 226 (57.1%) were sT-/pT-. Both sT and pT were found to be independent predictors of peritoneal recurrence, OS, and RFS. The 5-year RFS rates of sT+/pT+, sT+/pT-, sT-/pT+, and sT-/pT-patients were 45.2%, 63.6%, 55.0%, and 81.8%, respectively. CONCLUSION: Intraoperatively diagnosed macroscopic serosal invasion showed a similar predictive value for peritoneal recurrence as pathologically diagnosed serosal invasion. The establishment of a novel staging system incorporating macroscopic serosal invasion is recommended.

Prognostic biomarker study in patients with clinical stage I esophageal squamous cell carcinoma: JCOG0502-A1.

We undertook genomic analyses of Japanese patients with stage I esophageal squamous cell carcinoma (ESCC) to investigate the frequency of genomic alterations and the association with survival outcomes. Biomarker analysis was carried out for patients with clinical stage T1bN0M0 ESCC enrolled in JCOG0502 (UMIN000000551). Whole-exome sequencing (WES) was performed using DNA extracted from formalin-fixed, paraffin-embedded tissue of ESCC and normal tissue or blood sample. Single nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs) were identified. We then evaluated the associations between each gene alteration with a frequency of 10% or more and progression-free survival (PFS) using a Cox regression model. We controlled for family-wise errors at 0.05 using the Bonferroni method. Among the 379 patients who were enrolled in JCOG0502, 127 patients were successfully analyzed using WES. The median patient age was 63 years (interquartile range, 57-67 years), and 78.0% of the patients ultimately underwent surgery. The 3-year PFS probability was 76.3%. We detected 20 genes with SNVs, indels, or amplifications with a frequency of 10% or more. Genomic alterations in FGF19 showed the strongest association with PFS with a borderline level of statistical significance of P = .00252 (Bonferroni-adjusted significance level is .0025). Genomic alterations in FGF4, MYEOV, CTTN, and ORAOV1 showed a marginal association with PFS (P < .05). These genomic alterations were all CNAs at chromosome 11q13.3. We have identified new genomic alterations associated with the poor efficacy of ESCC (T1bN0M0). These findings open avenues for the development of new potential treatments for patients with ESCC.

Laparoscopic distal pancreatectomy for metastatic melanoma originating from the choroidal membrane: a case report.

BACKGROUND: Metastatic melanoma originating from the choroidal membrane is extremely rare. Here, we report a case of laparoscopic distal pancreatectomy for malignant melanoma that developed after heavy-particle therapy for malignant choroidal melanoma. CASE PRESENTATION: A 43-year-old Japanese woman underwent 70 Gy heavy-particle radiotherapy for a right choroidal malignant melanoma. Positron emission tomography-computed tomography examination was performed 4 years after treatment, when contrast accumulation was observed on the posterior wall of the stomach. Endoscopic ultrasonography and computed tomography showed a mass with contrast enhancement in contact with the stomach wall. Based on the imaging findings, a gastrointestinal stromal tumor of the posterior wall of the lower gastric corpus with extramural growth was suspected. Laparoscopic surgery was performed under general anesthesia. A black-pigmented tumor originating from the pancreas was discovered. Following an intraoperative diagnosis of metastasis of malignant melanoma, a laparoscopic distal pancreatectomy was performed. The pathological diagnosis was pancreatic metastasis of malignant melanoma. The patient was treated with adjuvant immune checkpoint inhibitors and chemotherapy after surgery, which led to long-term survival. CONCLUSIONS: Including this case, only eight case reports on pancreatic resection for metastatic ocular malignant melanoma have been reported. The ocular malignant melanoma with distant metastasis has a poor prognosis. Therefore, in our case, careful follow-up is required. A single pancreatic metastasis from a malignant melanoma of the choroid can be successfully managed by laparoscopic radical resection of the pancreas, and molecularly targeted adjuvant chemotherapy.

Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer.

We investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC). We compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses was evaluated by the ratio of the variant allele frequency of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis. Total positive and negative objective responses (ORs) were defined as either >50 or ≤50% reductions, respectively, in the total tumor volume at the end of first-line chemotherapy. Mutation screening of 43 tumors from 42 patients revealed 96 mutations. The pretreatment dPCR-ctDNA data were informative in 38 patients, using 70 selected mutations (1-3 per patient). The areas under the curve (AUCs) for the post-/pre-volume and post-/pre-ctDNA levels used in predicting the total OR were 0.85 and 0.88, respectively. The optimal cutoff value of post-/pre-ctDNA was 0.13. In 20 patients with post-/pre-volume ≥50%, the total OR could be predicted by the post-/pre-ctDNA with high accuracy; the AUC by post-/pre-ctDNA was higher than that by post-/pre-volume (0.85 versus 0.76, respectively). Patients with low post-/pre-ctDNA (n = 18) had a significantly better overall survival rate than those with high post-/pre-ctDNA (n = 20; P = 0.03). Early ctDNA changes after an initial cycle of chemotherapy predict later responses to treatment with high accuracy in ESCC patients.