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 were evaluated by the ratio of the variant allele frequency (VAF) 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 vs 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.

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Background: Circulating tumor DNA (ctDNA) test has not yet been an established tool for monitoring cancer. Sensitive, yet affordable methods should allow frequent ctDNA monitoring that can assist in clinical management. Patients and Methods: This prospective observational study was conducted in a total of 36 patients with Stage I to IV esophageal squamous cell cancer (ESCC) were enrolled between September 1, 2015 and February 28, 2018. We investigated whether frequent ctDNA monitoring during treatment followed by routine surveillance by digital PCR (dPCR) using tumor-specific mutations offers clinical validity in daily practice for ESCC patients. Results: Mutation screening of tumors from analyzable 35 patients using a specifically-designed "SCC panel" revealed 221 mutations with variant allele frequency (VAF) >2%. VAF of ctDNA was informative in 34 patients surveillance by dPCR using 58 mutations (1-3 per patient). A total of 569 plasma samples at 332 time points for ctDNA testing were evaluated. In pretreatment plasma, the average VAF was higher in advanced stages than earlier stages (P < .0001); tumor volume was also higher for higher VAF (r = 0.71). The ctDNA-positive rate in the pretreatment plasma of stage II or higher was 85.2% (23/27) whereas 85.7% (6/7) stage I were below the detection limit. Ninety-one % (10/11) patients whose ctDNA increased during chemotherapy showed disease progression. Among patients who recurred, ctDNA elevated with a median lead time of 149 days to the imaging diagnosis. Patients with decreased ctDNA within 3 months of initial treatment (n = 10) showed significantly better outcomes than did patients with ctDNA-positive (n = 11; P < .0001, HR 0.10, 95% CI, 0.03-0.30). Conclusions: Our results indicate that frequent tumor burden monitoring using a small number of tumor-specific ctDNAs by dPCR enables prediction of relapse and chemotherapeutic efficacy, as well as relapse-free corroboration in management of ESCC patients.

Highlights Primary malignant melanoma of the esophagus (PMME) is a rare disease with a poor prognosis. There are few reports of treatment with the anti-programmed cell death 1 antibody, nivolumab for PMME. We report a case of retroperitoneal recurrence of PMME successfully treated with nivolumab.

BackgroundGastrointestinal stromal tumors (GISTs) grow relatively slowly and without specific symptoms; therefore, they are typically incidental findings. We report a rare gastric GIST in the mediastinum associated with chest discomfort and an esophageal hiatal hernia.Case presentationAn 81-year-old woman with chest discomfort was admitted to the hospital, where barium esophagography showed a sliding esophageal hiatal hernia and a tumor of the lower esophagus and gastric wall. Esophagogastroscopy confirmed the presence of a huge submucosal tumor that extended from the lower esophagus to the gastric fundus. According to computed tomography, the mediastinal mass measured 12.7 cm and had heterogeneous low-density areas. A submucosal gastric tumor, which we suspected to be a GIST, was diagnosed in association with an esophageal hiatal hernia. Using thoracolaparotomy, we performed a total gastrectomy, a lower esophagectomy, and a Roux-en-Y reconstruction with the jejunum. The presumptive diagnosis was confirmed through immunohistochemical examination; immunostaining yielded results positive for CD34 and c-kit. The patient was discharged from the hospital 13 days after surgery with no complications and remained disease-free at follow-up 24 months after surgery.ConclusionsGIST should be considered in the differential diagnosis of tumors growing in the mediastinum.

Purpose:We recently reported a noninvasive method for the assessment of right ventricular (RV) operating stiffness that is obtained by dividing the atrial-systolic descent of the pulmonary artery-RV pressure gradient (PRPGDAC) derived from the pulmonary regurgitant velocity by the tricuspid annular plane movement during atrial contraction (TAPMAC). Here, we investigated whether this parameter of RV operating stiffness, PRPGDAC/TAPMAC, is useful for predicting the prognosis of patients with heart failure (HF). Methods:We retrospectively included 127 hospitalized patients with HF who underwent an echocardiographic examination immediately pre-discharge. The PRPGDAC/TAPMAC was measured in addition to standard echocardiographic parameters. Patients were followed until 2 years post-discharge. The endpoint was the composite of cardiac death, readmission for acute decompensation, and increased diuretic dose due to worsening HF.Results: 58 patients (46%) experienced the endpoint during follow-up. Univariable and multivariable Cox regression analyses demonstrated that the PRPGDAC/TAPMAC was associated with the endpoint. In a Kaplan-Meier analysis, the event rate of the greater PRPGDAC/TAPMAC group was significantly higher than that of the lesser PRPGDAC/TAPMAC group. In a sequential Cox analysis for predicting the endpoint's occurrence, the addition of PRPGDAC/TAPMAC to the model including age, sex, NYHA functional classification, brain natriuretic peptide level, and several echocardiographic parameters including tricuspid annular plane systolic excursion significantly improved the predictive power for prognosis. Conclusion:A completely noninvasive index of RV operating stiffness, PRPGDAC/TAPMAC, was useful for predicting prognoses in patients with HF, and it showed an incremental prognostic value over RV systolic function.

BACKGROUND & AIMS: This study investigated whether a circulating tumor DNA (ctDNA) assay using digital PCR (dPCR) could provide early relapse detection and disease-free corroboration at molecular level during postoperative surveillance of colorectal cancer (CRC). METHODS: The ctDNA dynamics of 52 patients with CRC measured by dPCR targeting 87 individual tumor-specific mutations (1-5 per patient) were compared with results for conventional surveillance using serum tumor markers and computed tomography scanning (CTS). The data were collected between March 2016 and June 2018. RESULTS: A total of 1,526 prospectively collected plasma samples from 867 timepoints were analyzed. The average number of ctDNA assays per patient was 16.4 and the median follow-up was 1,503 days (range 322-1,951 days). Among patients with Stage II or higher disease who underwent curative resection as their initial surgery (n=47), patients who were ctDNA-positive during the postoperative period (n= 9) showed a higher risk of relapse than those who had sustained ctDNA-negative results (n=38) (hazard ratio 56.3, 95%CI 7.8-407.0, P < 0.0001). Elevated ctDNA levels were observed in nine of 10 clinical-relapse patients (11 of 13 events) with an average lead time from a ctDNA-positive time-point to clinical relapse of 191.9 days (range 0-376 days). Given periodic CTS surveillance with ctDNA, 218 (57.1%) CTSs were presumed to be unnecessary for clinical relapse detection and a ctDNA assay would still provide a lead time of 307 days (range 45-582 days). CONCLUSION: Our findings suggest that the ctDNA assay can reduce the frequency of CTS for relapse diagnosis during postoperative surveillance of CRC.

Highlights ECS is a rare tumor often treated in the same manner as esophageal cancer. ECS often presents as a polypoid tumor continuous with the superficial lesion. We encountered an ECS case in which a polypoid lesion sloughed off before surgery. Polypoid tumor exfoliation in ECS may lead to an incorrect diagnosis.