First-line pemetrexed and carboplatin plus anlotinib for epidermal growth factor receptor wild-type and anaplastic lymphoma kinase-negative lung adenocarcinoma with brain metastasis: A case report and review of the literature.

RATIONALE: Brain metastasis (BM) is a serious complication in non-small cell lung cancer (NSCLC) patients. Pemetrexed is one of the preferred agents in nonsquamous NSCLC with BM; however, the traditional chemotherapy demonstrated limited efficacy partly due to drug resistance and the blood-brain barrier. PATIENT CONCERNS: A 52-year-old male non-smoker was admitted for irritating cough, chest distress, and back pain. DIAGNOSES: Epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative primary lung adenocarcinoma with an asymptomatic solitary BM (cTxNxM1b, IVA). INTERVENTIONS: Pemetrexed (500 mg/m of body surface area) and carboplatin (area under the curve of 5) were firstly administered every 3 weeks for 3 cycles, followed by pemetrexed/carboplatin plus anlotinib (12 mg daily; 2 weeks on and 1 week off) for another 3 cycles. Then maintenance anlotinib monotherapy was continued for a year, without unacceptable adverse events. OUTCOMES: The BM was slightly enlarged after 3 cycles of pemetrexed/carboplatin; however, a complete remission was achieved after the combination therapy. His intracranial progression-free survival was more than 2 years. LESSONS: Pemetrexed/carboplatin plus anlotinib could be considered for the treatment of epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative lung adenocarcinoma with BM. Further well-designed trials are warranted to verify this occasional finding.

S-1 plus apatinib followed by salvage esophagectomy for irinotecan-refractory small cell carcinoma of the esophagus: A case report and review of the literature.

RATIONALE: Small cell carcinoma of the esophagus (SCCE) is an uncommon but lethal disease characterized by dismal prognosis. Only 10% of advanced SCCE patients survive longer than 1 year. Resection is a choice for limited-stage cases, whereas the optimal treatment regimen for primary SCCE is yet to be elucidated. To the best of our knowledge, the efficacy of S-1 plus apatinib for irinotecan-refractory SCCE has not been reported before. PATIENT CONCERNS: A 61-year old, previously healthy male was admitted for dysphagia and fatigue. Endoscopic biopsy revealed a tumor in the middle third of the esophagus. Further exams including abdomen computed tomography excluded distant metastasis. DIAGNOSES: Primary SCCE (pT1bN1M0, IIB) was established after salvage operation. INTERVENTIONS: The tumor was enlarged after 1 cycle of first-line chemotherapy using irinotecan plus cisplatin, which indicated drug resistance. Second-line oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval) for a month showed efficacy, as shown by decreased serum neuron-specific enolase and stable of the esophageal lesion. Thereafter, salvage minimally invasive Ivor-Lewis esophagectomy and 2-field lymph node dissection was performed, followed by oral apatinib plus S-1 at the prior dosage for 6 months. In addition, maintenance therapy using low-dose apatinib (250 mg daily) plus S-1 (40 mg, twice daily for 4 weeks with a 2-week interval) were administered for another 6 months. Then the patient was followed up irregularly at the outpatient clinic. OUTCOMES: The adverse events including hand-foot syndrome, hypertension, vomiting, leukopenia, impaired hepatic function, and fatigue were mainly tolerable. Forty months after the operation, he was readmitted for back pain and disseminated bone metastases appeared in magnetic resonance images. His progression-free survival could not be obtained precisely, and his overall survival was longer than 40 months up to September 2019. LESSONS: S-1 plus apatinib followed by a timely esophagectomy with curative intent might be an alternative option for chemotherapy-refractory SCCE in selected patients. Better evidence is warranted.

S-1 plus apatinib as first-line palliative treatment for stage IVB gastroesophageal junction adenocarcinoma: A case report and review of the literature.

RATIONALE: Apatinib has been proven to significantly prolong the survival of the patients with advanced chemotherapy-refractory gastric cancer. To date, studies on apatinib plus S-1 as first-line palliative therapy for metastatic gastroesophageal junction (GEJ) cancer are rare. PATIENT CONCERNS: A 61-year-old female patient was admitted with dysphagia, significant loss of body weight, and poor performance status. DIAGNOSES: Endoscopic biopsy revealed the diagnosis of poorly-differentiated GEJ adenocarcinoma, and the patient was clinically staged as T3NxM1G3 (IVB). INTERVENTIONS: She had received 4 cycles of palliative therapy using oral apatinib (425 mg daily) plus S-1 (40 mg twice daily for 4 weeks, with a 2-week drug-free interval), followed by maintenance low-dose apatinib (250 mg daily) plus S-1 at the same dosage thereafter. OUTCOMES: Her progression-free survival was nearly 5 months, and the overall survival was >11 months up to now. The adverse events were tolerable. LESSONS: Apatinib plus S-1 might be an alternative option for late-stage GEJ cancer. However, high-quality trials are warranted before the recommendation of this therapeutic regimen.

Association of serum cystatin C levels with mortality in patients with acute type A aortic dissection.

Increased serum cystatin C levels are related to the prognosis of cardiovascular diseases. This study aims to investigate the effect of admission serum cystatin C levels on short- and long-term mortality in patients with acute type A aortic dissection (ATAAD). From 2010 to 2014, 136 consecutive patients with ATAAD were enrolled and followed up. Clinical data and laboratory assays including were measured. During a median follow-up of 198.7 days, the short-term mortality (30-days) was 20.6%, whereas the long-term death rate was 10.2%. We identified that the expression of cystatin C and high-sensitivity C-reactive protein (hs-CRP) in the dying patients was higher than in the surviving patients (P < 0.01). Hs-CRP (HR = 1.41, 95% CI: 1.03-2.59, P = 0.037) was an independent risk factor of short-term death determined by univariate and multivariate Cox analyses. No impact of cystatin C was observed on the short-term mortality. For long-term mortality, cystatin C (HR = 1.49, 95% CI: 1.10-7.36, P = 0.013) was identified as an independent predictor at above the cut-off value ≥ 1.10 mg/L. ROC analysis showed the AUC values of cystatin C and hs-CRP were 0.772 (95% CI, 0.692-0.839) and 0.640 (95% CI, 0.574-0.739), respectively, in the prediction of long-term death. The combined AUC value of cystatin C and hs-CRP was 0.883 (95% CI, 0.826-0.935; P < 0.01). Taken together, high cystatin C levels (≥ 1.10 mg/L) on admission are independently associated with the long-term mortality in patients with ATAAD.