Prognostic value of an echocardiographic index reflecting right ventricular operating stiffness in patients with heart failure.

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.

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.

Efficacy of enhanced prehabilitation for patients with esophageal cancer undergoing esophagectomy.

BACKGROUND: Several studies have demonstrated that prehabilitation helps reduce the incidence of postoperative complications. In this study, we investigated the safety and efficacy of enhanced prehabilitation (EP) in the hospital for patients with esophageal cancer. METHODS: We retrospectively reviewed the data of 48 consecutive patients who underwent radical esophagectomy with gastric tube reconstruction between September 2015 and June 2019. EP program had been introduced in August 2017. In the EP group, patients received the EP program during hospitalization 7 days before surgery in addition to conventional perioperative rehabilitation. The EP program consisted of aerobic exercise and muscle strength training in the morning and afternoon. Operative outcomes were compared between patients who received EP (EP group; 23 patients) and patients who did not receive EP (control group; 25 patients). RESULTS: The preoperative (EP group vs. control group, 492.9 ± 79.7 vs. 418.9 ± 71.8 m, p < 0.001) and postoperative (EP group vs. control group, 431.5 ± 80 vs. 378 ± 68.7 m, p < 0.001) 6-min walk distance was significantly higher in the EP group than in the control group. The respiratory complications rate was significantly lower in the EP group (4.3%) than in the control group (36%) (p = 0.007). The incidence of atelectasis was particularly significantly lower in the EP group (0%) than in the control group (24%) (p = 0.012). CONCLUSIONS: EP was performed safely for patients before esophagectomy. EP improved the exercise tolerance of the patients before esophagectomy and might be useful in preventing respiratory complications.

Primary esophageal malignant melanoma successfully treated with anti-PD-1 antibody for retroperitoneal recurrence after esophagectomy: A case report.

INTRODUCTION: Primary malignant melanoma of the esophagus (PMME) is a rare disease with a poor prognosis. Here, we report a case of retroperitoneal recurrence of PMME successfully treated with the anti-programmed cell death 1 antibody, nivolumab. PRESENTATION OF CASE: A 70-year-old male with dysphagia was referred to our hospital. Esophagogastroscopy showed an elevated tumor in the lower thoracic esophagus. A histopathological examination of the biopsy revealed poorly differentiated squamous cell carcinoma. The patient was diagnosed with clinical T3N1M0 stage III esophageal squamous cell carcinoma and was treated with neoadjuvant chemotherapy followed by radical esophagectomy. A postoperative histopathological examination revealed that atypical cells with a brown pigment were scattered in the tumor. Immunohistochemical staining demonstrated positive expression of human melanoma black 45, melan A, and S100. A pathological diagnosis of PMME was confirmed. Sixteen months after surgery, abdominal computed tomography revealed solitary retroperitoneal recurrence in the lateral portion of the ascending colon. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) showed hypermetabolic accumulation with a maximum standardized uptake value of 5.8. The patient was treated with nivolumab (240 mg) every two weeks. After eight courses of nivolumab, abnormal accumulation of the retroperitoneal mass disappeared on PET, and this therapeutic effect continued for 20 months. CONCLUSIONS: Nivolumab was effective for recurrence of PMME in our case. There are few reports of treatment with nivolumab for PMME. Further studies are necessary to establish the usefulness of nivolumab for PMME in the future.

Esophageal carcinosarcoma in which the sarcomatous element has sloughed off: A case report.

INTRODUCTION: Most esophageal carcinosarcoma (ECS) tumors present as a polypoid tumor that is continuous with the superficial lesion and suspended by a pedicle. Here, we report a case of ECS in which a polypoid lesion sloughed off before surgery. PRESENTATION OF CASE: A 76-year-old man with dysphagia was admitted to our hospital. Esophagogastroscopy revealed a 20-mm polypoid tumor continuous with a superficial lesion and attached to the lesion by a thin pedicle in the mid-thoracic esophagus. Histopathological examination of the endoscopic biopsy showed that the superficial lesion was a moderately differentiated squamous cell carcinoma and that the polypoid tumor contained a sarcomatous element. He was diagnosed with ECS and underwent radical esophagectomy with three-field lymph node dissection. In the resected specimen, no polypoid tumor was found, and only a superficial lesion was observed. The histopathological findings revealed only squamous cell carcinoma, and the pathological diagnosis was esophageal squamous cell carcinoma, pT1bN0M0, pathological stage I. The patient was discharged from the hospital 22 days after surgery and did not experience any complications. He is currently alive and remained cancer-free for three years since surgery was performed. DISCUSSION: Due to the distinctive configuration in which the polypoid lesion was connected to the superficial cancerous lesion by a very thin pedicle, researchers suggested that the polypoid tumor, which consisted of a sarcomatous element, was sloughed off before surgery. CONCLUSION: We encountered a rare case of ECS in which the sarcomatous element sloughed off prior to surgical resection.

Feasibility of totally laparoscopic pylorus-preserving gastrectomy with intracorporeal gastro-gastrostomy for early gastric cancer: a retrospective cohort study.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) has been accepted as a function-preserving surgery for the treatment of early gastric cancer in East Asian countries. Therefore, this study aimed to evaluate the feasibility and safety of totally laparoscopic PPG (TLPPG) with intracorporeal anastomosis. METHODS: A total of 43 patients with early gastric cancer underwent laparoscopy-assisted PPG (LAPPG) with extracorporeal anastomosis between May 2006 and November 2012. The operative outcomes of 22 patients who underwent TLPPG between November 2012 and February 2019 were evaluated, and data were compared with that of the LAPPG group. RESULTS: No significant difference in the operative time was observed between the two groups. Blood loss was lower in the TLPPG group (18.5 mL) than in the LAPPG group (30.7 mL, p = 0.008), and the length of abdominal incision was shorter in the TLPPG group (3.8 cm) than in the LAPPG group (4.7 cm, p < 0.001). No significant difference in the complication rate was observed between the two groups (13.6% in the TLPPG vs. 9.3% in the LAPPG group, p = 0.594). No anastomosis-related complications occurred in either group. No significant between-group difference was observed in the delayed gastric emptying (TLPPG, 9.1 vs. LAPPG, 7%, p = 0.762). The initiation of postoperative fluid (TLPPG, 1.0 day vs. LAPPG, 3.0 days, p < 0.001) and meal (TLPPG, 3.0 days vs. LAPPG, 4.0 days, p < 0.001) intake was earlier in the TLPPG group than in the LAPPG group. No significant between-group difference was observed in the postoperative hospital stay. CONCLUSIONS: The findings of this study suggest that TLPPG with intracorporeal reconstruction not only is as feasible and safe as LAPPG for the treatment of patients with early gastric cancer but also provides certain advantages such as reduced blood loss and wound size.

[A Thoracic Aortic Dissection Case during Treatment with Ramucirumab plus Nab-Paclitaxel].

Ramucirumab(RAM)plus nab-paclitaxel(nab-PTX)therapy is a regimen that is recommended for the second round of chemotherapy in recurrent, progressive gastric cancer. We report the first case of a thoracic aortic dissection developed during RAM plus nab-PTX therapy. A 59-year-old male who had undergone a proximal gastrectomy for esophagogastric junction cancer had a recurrence of cancer 6 years later(metastasis to the para-aortic lymph node and left adrenal gland, local recurrence, and multiple bone metastases). He was treated with RAM plus nab-PTX therapy for second-line chemotherapy. On day 9 of the third cycle, he experienced sudden, severe neck pain and visited the outpatient emergency department. Computed tomography detected a Stanford type-A thoracic aortic dissection. However, the patient suffered from a myocardial infarction before the operation, and died. This is the first report of an aortic dissection associated with RAM. Clinicians must be aware of this complication.

Giant gastrointestinal stromal tumor of the mediastinum associated with an esophageal hiatal hernia and chest discomfort: a case report.

BACKGROUND: Gastrointestinal 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 PRESENTATION: An 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. CONCLUSIONS: GIST should be considered in the differential diagnosis of tumors growing in the mediastinum.

Interactions of the antitumor macrolide aplyronine A with actin and actin-related proteins established by its versatile photoaffinity derivatives.

The antitumor and apoptogenic macrolide aplyronine A (ApA) is a potent actin-depolymerizing agent. We developed an ApA acetylene analog that bears the aryldiazirine group at the C34 terminus, which formed a covalent bond with actin. With the use of the photoaffinity biotin derivatives of aplyronines A and C, Arp2 and Arp3 (actin-related proteins) were specifically purified as binding proteins along with actin from tumor cell lysate. However, Arp2 and Arp3 did not covalently bind to aplyronine photoaffinity derivatives. Thus, actin-related proteins might indirectly bind to ApA as the ternary adducts of the actin/ApA complex or through the oligomeric actin.