Muscle loss 6 months after surgery predicts poor survival of patients with non-metastatic colorectal cancer.

Background: Muscle loss is a common characteristic of cancer-related malnutrition and a predictor of poorer prognosis in oncological patients. This study evaluated the association between altered body composition 6 months after surgery and the prognosis in patients with non-metastatic colorectal cancer. Materials and methods: A total of 314 patients who underwent elective curative surgery were enrolled in the study. The third lumbar CT images on preoperative and 6-months postoperative were collected to calculate the skeletal muscle index (SMI), visceral adiposity index (VATI), and subcutaneous adiposity index (SATI). Sarcopenia was defined by the cut-off values reported in the literature, and risk factors affecting overall survival (OS) and disease-free survival (DFS) in CRC were analyzed using Cox regression models. Results: Eighty-two of 314 patients (26.1%) with CRC were diagnosed with sarcopenia before surgery, the preoperative sarcopenia was not significantly associated with the prognosis of CRC patients. There were significant differences in frequency of complications between patient groups according to sarcopenia (41.5 vs. 21.4%, p = 0.004). The Postoperative LOS (11.21 ± 3.04 vs. 8.92 ± 2.84, p < 0.001) was longer in the sarcopenia group than in the non-sarcopenia group, and 30-d readmission (24.4 vs. 6.0%, p < 0.001) was higher in the sarcopenia group compared to the non-sarcopenia group. In multivariate analysis, 6-months SMI loss > 10% after surgery was independently associated with poorer OS [hazard ratio (HR) = 3.74; 95% confidence interval (CI) 1.96 to 7.12; P < 0.001] and DFS (HR = 3.33; 95% CI, 1.71 to 6.47; P < 0.001). SMI changes were moderately correlated with changes in body mass index (BMI) (R = 0.47, P < 0.001). Conclusion: 6-months muscle loss after surgery may affect overall and disease-free survival and was an independent predictor of prognosis in patients with CRC.

Forkhead Box S1 mediates epithelial-mesenchymal transition through the Wnt/ß-catenin signaling pathway to regulate colorectal cancer progression.

BACKGROUND: Recent studies have shown that the fox family plays a vital role in tumorigenesis and progression. Forkhead Box S1 (FOXS1), as a newly identified subfamily of the FOX family, is overexpressed in certain types of malignant tumors and closely associated with patient's prognosis. However, the role and mechanism of the FOXS1 in colorectal cancer (CRC) remain unclear. METHOD: FOXS1 level in CRC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the relationship between FOXS1 expression and clinicopathological features in 136 patients in our unit. The expression of FOXS1 was knocked down in CRC cells using small interfering RNA (siRNA) technology. Cell proliferation was assessed by CCK8 assay, colony formation, and 5-Ethynyl-20-deoxyuridine (EdU) incorporation assay. Flow cytometry detected apoptosis and wound healing, and Transwell assays determined cell migration and invasion. Western blotting was used to detect the levels of proteins associated with the Wnt/ß-catenin signaling pathway. Then, we used short hairpin RNA (shRNA) to knock down FOXS1 to see the effect of FOXS1 on the proliferation, migration, invasion, and metastasis of CRC cells in vivo. Finally, we investigated the impact of Wnt activator LiCl on the proliferation, migration, invasion, and metastasis of CRC cells after FOXS1 knockdown. RESULT: Compared to those in normal groups, FOXS1 overexpressed in CRC tissues and CRC cells (P < 0.05). Upregulation of FOXS1 association with poor prognosis of CRC patients. si-FOXS1 induced apoptosis and inhibited proliferation, migration, invasion, the epithelial-mesenchymal transition (EMT), and the Wnt/ß-catenin signaling pathway in vitro; sh-FOXS1 inhibited the volume and weight of subcutaneous xenografts and the number of lung metastases in vivo. LiCl, an activator of Wnt signaling, partially reversed the effect of FOXS1 overexpression on CRC cells. CONCLUSION: FOXS1 could function as an oncogene and promote CRC cell proliferation, migration, invasion and metastasis through the Wnt/ßcatenin signaling pathway, FOXS1 may be a potential target for CRC treatment.

The effect of prophylactic thoracic duct ligation during esophagectomy on the incidence of chylothorax and survival of the patients: an updated review.

BACKGROUND: The role of thoracic duct ligation (TDL) during esophagectomy remains controversial. This review aimed to elucidate the effect of TDL on chylothorax and survival of the patients after esophagectomy for cancer. METHODS: We searched articles from PubMed, Web of Science, Scopus, Cochrane, and Google Scholar till May 2020 according to the PRISMA guidelines using the terms of [Oesophagectomy OR esophagectomy] AND [chylothorax] AND [thoracic duct ligation]. Only those compared the incidence of chylothorax in patients who ligated or resected the thoracic duct (ligation group) or preserved the thoracic duct (preservation group) were selected. RESULTS: First, 15 studies including one randomized controlled trial were collected for meta-analysis regarding post-esophagectomy chylothorax. Of these, 3658 patients underwent TDL and 4638 cases preserved the thoracic duct. Both groups showed similar chylothorax rate (odd ratios 0.73 in favor of ligation group; 95% confidence interval [CI] 0.50-1.07, p = 0.11). Second, four studies providing survival information were included for another meta-analysis, and the patients in preservation group demonstrated better 5-year overall survival compared to those in ligation group (odds ratio 1.25; 95% CI 1.08-1.44, p = 0.002). CONCLUSIONS: The present review provided updated evidence opposing prophylactic TDL during esophagectomy for lowering chylothorax. Considering the harmful effect of TDL on survival of the patients, further well-designed trials should be considered in selected cases under strict supervision.

Contralateral spontaneous rupture of the esophagus following severe emesis after non-intubated pulmonary wedge resection.

BACKGROUND: Non-intubated thoracoscopic lung surgery has been reported to be technically feasible and safe. Spontaneous rupture of the esophagus, also known as Boerhaave's syndrome (BS), is rare after chest surgery. CASE PRESENTATION: A 60-year-old female non-smoker underwent non-intubated uniportal thoracoscopic wedge resection for a pulmonary nodule. Ultrasound-guided serratus anterior plane block was utilized for postoperative analgesia. However, the patient suffered from severe emesis, chest pain and dyspnea 6 h after the surgery. Emergency chest x-ray revealed right-sided hydropneumothorax. BS was diagnosed by chest tube drainage and computed tomography. Besides antibiotics and tube feeding, a naso-leakage drainage tube was inserted into the right thorax for pleural evacuation. Finally, the esophagus was healed 40d after the conservative treatment. CONCLUSIONS: Perioperative antiemetic therapy is an indispensable item of fast-track surgery. Moreover, BS should be kept in mind when the patients complain of chest distress following emesis after thoracic surgery.

Late-onset anastomotic leak following sweet esophagectomy: A case report and review of the literature.

RATIONALE: Late-onset anastomotic leak (AL) is an uncommon but potentially lethal complication after esophagectomy. PATIENT CONCERNS: A 74-year-old male patient was readmitted due to chest distress and chills about 3 months after initial esophagectomy for cancer. DIAGNOSES: The previous endoscopic biopsy revealed primary esophageal squamous cell carcinoma, and sweet esophagectomy with gastric conduit reconstruction was therefore performed. The patient developed AL 3 months after the surgery. INTERVENTIONS: Naso-leakage extraluminal drainage tube was utilized because the symptoms of the patient were aggravated 1 month after the chest tube drainage since his second admission for AL. OUTCOMES: Twenty-one days after naso-leakage extraluminal drainage, the computed tomography images showed the healing of the leakage. Then the patient was discharged from the hospital. LESSONS: Late-onset AL should be kept in mind when the patient complained of chest distress and fever during the follow up after esophagectomy. In addition, naso-leakage extraluminal drainage could be considered for the treatment of AL. Further trials for better evidence are warranted.

Extralobar pulmonary sequestration with elevated serum neuron-specific enolase: A case report and review of the literature.

RATIONALE: Pulmonary sequestration (PS) presenting with elevated serum tumor markers is rare, and it might be misdiagnosed as malignancy. PATIENT CONCERNS: A 26-year-old asymptomatic male patient was admitted because the x-ray showed an intrathoracic lesion. Meanwhile, the serum neuron-specific enolase (NSE) was elevated. Three-dimensional computed tomography angiography revealed an isolated feeding vessel arising from the aorta. DIAGNOSES: Extralobular PS was confirmed by computed tomography angiography and postoperative pathological staining. INTERVENTIONS: Two-port thoracoscopic resection of the sequestrated lobe was performed. OUTCOMES: The serum NSE decreased to within the normal range and persisted during the follow up of 10 months. LESSONS: A thorough work-up should be considered for the PS patients presenting with abnormal serum NSE. Detailed knowledge regarding the relationship between NSE and PS necessitates further studies.

Salvage camrelizumab plus apatinib for relapsed esophageal neuroendocrine carcinoma after esophagectomy: a case report and review of the literature.

The current evidence regarding immunotherapy plus targeted therapy in esophageal neuroendocrine carcinoma (NEC) is lacking. Camrelizumab is a programmed cell death protein 1 inhibitor. Apatinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. A 50-year-old female was initially diagnosed as primary esophageal NEC. Neoadjuvant chemotherapy and Ivor Lewis esophagectomy were performed (ypT3N0M0, stage Ⅱ). Twenty months after the surgery, an isolated mediastinal lymph node recurrence of NEC was recorded. The specimen revealed a positive expression of vascular endothelial growth factor and programmed cell death ligand 1. The diseased lymph node was slightly enlarged after two cycles of first-line paclitaxel liposome and S-1. Second-line apatinib and S-1 for 2 months also resulted in progressive disease. Subsequently, third-line camrelizumab plus apatinib was continued for 5 months. The patient demonstrated a progression-free status for more than 10 months following the combination therapy. Meanwhile, relevant studies of camrelizumab in gastric or esophageal cancer were briefly reviewed. Based on the current evidence, camrelizumab is a promising agent for esophageal cancer. More prospective trials are warranted before a definite recommendation could be drawn.

Ganglioneurofibroma arising within the extralobar pulmonary sequestration.

BACKGROUND: Neurogenic tumor arising within the pulmonary sequestration (PS) is rare. CASE PRESENTATION: A 42-year-old asymptomatic female was referred to our hospital for work-up of extralobar PS. The independent feeding artery from the thoracic aorta was confirmed by three-dimensional computed tomography angiography (3D-CTA). Uniportal thoracoscopic resection of the sequestrated lung with mediastinal lymph node sampling was performed successfully. Ganglioneurofibroma within the PS was diagnosed as the specimen revealed positive expression of SRY-related HMG-box 10 protein, neuron-specific enolase, S-100, chromogranin A and synuclein. Tumor recurrence was not recorded 1 year after the surgery. CONCLUSION: Preoperative 3D-CTA is useful to identify the aberrant vessels of PS. An elaborate diagnostic work-up after a timely resection is necessary for subsequent management and follow-up plan.

Anti-PD-1 antibody camrelizumab plus doxorubicin showed durable response in pulmonary sarcomatoid carcinoma: Case report and literature review.

WHAT IS KNOWN AND OBJECTIVE: Pulmonary sarcomatoid carcinoma (PSC) is characterized by dismal prognosis and resistance to platinum-based chemotherapy. The immune checkpoint inhibitors showed promising efficacy in the treatment of PSC. Camrelizumab is a programmed cell death protein 1 inhibitor; however, current evidence of its efficacy in PSC is lacking. CASE SUMMARY: A 47-year-old female non-smoker presented with central-type masses in the right upper and lower lobes. PSC (cT4N2M0, stage IIIB) with positive expression of programmed death ligand-1 was diagnosed. First-line camrelizumab plus doxorubicin and cisplatin was introduced, followed by camrelizumab monotherapy due to grade 4 leukopenia and thrombocytopenia during the combination therapy. The lesions indicated a partial remission which endured for more than 20 months. WHAT IS NEW AND CONCLUSION: Camrelizumab plus doxorubicin and cisplatin regimen is a promising option for PSC patients. Further high-quality trials are warranted.

Association between low-fat enteral nutrition after esophagectomy and a lower incidence of chyle leakage: A call for more and better evidence.

OBJECTIVE: Reliable methods to prevent chyle leakage after esophagectomy are needed. This retrospective study was performed to evaluate the correlation between low-fat nutrition and the incidence of chyle leakage after esophagectomy. METHODS: This multicenter retrospective case-control study involved patients who underwent Ivor Lewis esophagectomy from December 2012 to August 2017. Tube feeding was started on postoperative day 1 with a normal fat-containing formula (control group, 203 patients) or low fat-containing formula (241 patients). RESULTS: The patients in the control group and low-fat group had a similar incidence of chyle leakage (7 [3.4%] vs. 19 [9.4%], respectively) and anastomotic leakage (4 [2.0%] vs. 11 [5.4%], respectively). The multivariate logistic regression indicated that high-volume surgeon experience (performance of ≥100 esophagectomies per year) was correlated with a lower incidence of chyle leakage (odds ratio, 0.280; 95% confidence interval, 0.110-0.712), whereas low-fat nutrition was correlated with an increased risk of anastomotic leakage (odds ratio, 5.995; 95% confidence interval, 1.201-29.925). CONCLUSION: Prophylactic low-fat enteral nutrition following esophagectomy might not decrease the risk of chyle leakage. More and better evidence is needed.

The effect of early oral feeding after esophagectomy on the incidence of anastomotic leakage: an updated review.

OBJECTIVE: Early oral feeding (EOF) is considered to be an important component of enhanced recovery after surgery (ERAS), but raises the concern of increased risk of anastomotic leakage (AL) in patients receiving esophagectomy. This review aimed to elucidate the correlation of EOF and the incidence of AL after esophageal resection. METHODS: We searched PubMed, Web of Science, Scopus, Cochrane Library and Google Scholar from their inception to February 2020 for published articles that compared AL after EOF (oral feeding initiated within postoperative day [POD] 3) vs. conventional feeding regimen (nil-by-mouth with enteral tube nutrition support, until oral feeding since POD 4 and beyond) following esophagectomy. RESULTS: A total of 11 full articles were included in this review, including 5 registered randomized controlled trials (RCTs) and 6 observational studies that compared EOF with conventional care after esophagectomy. Meta-analysis was not possible due to significant heterogeneity, bias, and small sample sizes. Among the 11 included studies, 9 (including the 5 RCTs) showed that EOF did not increase AL rate, whereas the other 2 retrospective studies indicated that delayed oral feeding resulted in fewer AL. CONCLUSIONS: EOF after esophagectomy probably does not increase the incidence of AL, and it is a promising strategy in line with the essence of ERAS. However, more and better evidence from high-quality RCTs are still needed.

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.

A rare case of cavitary lung cancer complicated with mycotic pneumonia and bullous emphysema: A case report and review of the literature.

RATIONALE: The accurate diagnosis and staging of cavitary lung cancer is challenging but essential for the choice of therapy; therefore, the differential diagnosis of cystic pulmonary lesions needs to be elucidated. PATIENT CONCERNS: A patient was admitted with multifocal thin-walled cystic lesions in chest computed tomography. DIAGNOSES: The patient had been diagnosed as heterogeneous bullous emphysema pathologically about 3 years ago. His diagnosis turned out to be metastatic cavitary lung cancer complicated with fungal pneumonia this time. INTERVENTIONS: The patient underwent lung volume reduction surgery during his first hospitalization. Concurrent systemic chemotherapy and whole brain radiotherapy were administered after the diagnosis of cystic lung cancer. OUTCOMES: The patient was lost to follow-up after the chemoradiotherapy. LESSONS: Cavitary lung cancer should always be kept in mind during differential diagnosis of pulmonary cystic lesions. Pathological diagnosis by biopsy and surgery could be considered to avoid delayed treatment of malignancy.

[Correlations of GRIM-19 and its target gene product STAT3 to malignancy of human colorectal carcinoma].

BACKGROUND & OBJECTIVE: GRIM-19 (gene associated with retinoid-interferon-induced mortality-19) gene is a specific protein to inhibit signal transducers and activators of transcription 3 (STAT3). STAT3 and its pathway are involved in modulating cell proliferation, apoptosis, differentiation, and mediating malignant transformation of cells. This study was to investigate the expression of GRIM-19 and its target gene STAT3 in human colorectal carcinoma tissues, and explore their roles in the tumorigenesis of colorectal carcinoma. METHODS: The expression of GRIM-19, STAT3 and its activated form p-STAT3 in 40 specimens of colorectal carcinoma, adjacent tissue, and normal tissue was determined by immunohistochemistry and Western blot. The correlations of the expression of GRIM-19, STAT3, and p-STAT3 to various clinicopathologic characteristics of colorectal carcinoma were analyzed statistically. The mRNA expression and gene mutation of GRIM-19 in colon cancer cell line SW480 and 23 specimens of colorectal carcinoma, adjacent tissue, and normal tissue were detected by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. RESULTS: The expression of both STAT3 and p-STAT3 were up-regulated in colorectal carcinoma. The mRNA and protein expression of GRIM-19 was obviously lower in colorectal carcinoma than in normal tissues. The expression of GRIM-19 was correlated to clinical stage and cell differentiation of colorectal cancer (P< 0.05). GRIM-19 expression in colorectal cancer was negatively correlated to STAT3 and p-STAT3 expression (Chi2 = 9.95, P = 0.00; Chi2 = 5.10, P = 0.02). No mutation of GRIM-19 gene was detected in colorectal carcinoma tissues. CONCLUSIONS: The low expression or absence of GRIM-19 may play an important role in the tumorigenesis of colorectal carcinoma. The high expression of STAT3 and the low expression of GRIM-19 co-exist in colorectal carcinoma, and may be related to malignant transformation and abnormal proliferation of cells.