Comparative efficacy and safety of immunotherapy for patients with advanced or metastatic esophageal squamous cell carcinoma: a systematic review and network Meta-analysis.

BACKGROUND: The study aimed to compare efficacy and safety of various immune checkpoint inhibitors for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC). METHODS: We searched Medline, Web of Science, Cochrane Central Register of Controlled Trials, Embase, Clinical Trials.gov and several international conference databases from January 1, 2000 to December 19, 2021. We conducted Bayesian network meta-analysis to assess the relative effects among treatments. Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate and adverse events. RESULTS: Ten eligible trials with 5250 patients were included. Toripalimab and Camrelizumab plus chemotherapy were preferred to rank first on OS (probability, 61%) and PFS (probability, 37%) in the first-line setting, respectively. In refractory patients, Sintilimab and Camrlizumab were most likely to be ranked first on OS (probability, 37%) and PFS (probability, 94%). The toxicity related to immunotherapy was manageable in clinical trials. Camrelizumab and Nivolumab had the less adverse events of grade 3 or higher in the first and refractory setting, respectively. CONCLUSIONS: This study found that Toripalimab and Camrelizumab plus chemotherapy were likely to be the best option in terms of OS and PFS in the first-line setting for patients with advanced or metastatic ESCC respectively. Sintilimab and Camrelizumab were the preferred options for OS and PFS in refractory patients respectively. The toxicity of immunotherapy was different from conventional chemotherapy, but manageable in patients with ESCC. TRIAL REGISTRATION: PROSPERO registration number: (CRD 42021261554).

Progress in Research on Antitumor Drugs and Dynamic Changes in Skeletal Muscles.

Objective: To review the research progress of reltionship between antitumor drugs and the dynamic changes of the skeletal muscles during treatment phase. Background: Sarcopenia is a common disease in patients with tumors, and it has been agreed that patients with tumors and sarcopenia experience more serious adverse reactions and have a shorter long-term survival after antitumor therapy than patients without sarcopenia. Antitumor drugs whilst beneficial for tumor regression, interferes and synergizes with cancer-induced muscle wasting/sarcopenia, induced myodemia or intramuscular fat and the two conditions often overlap making it difficult to drive conclusions. In recent years, increasing attention has been paid to the dynamic changes in skeletal muscles during antitumor drug therapy. Dynamic changes refer not only measurement skeletal muscle quantity at baseline level, but give more emphasis on the increasing or decreasing level during or end of the whole treatment course. Methods: We retrievaled published English-language original research articles via pubmed, those studies mainly focused on repeated measurements of skeletal muscle index using computed tomography (CT) in cancer patients who received antitumor drug treatment but not received interventions that produced muscle mass change (such as exercise and nutritional interventions). Conclusion: This article will summarize the research progress to date. Most of antineoplastic drug cause skeletal muscle loss during the treatment course, loss of L3 skeletal muscle index is always associated with poor clinical outcomes.

Lysosome-targeted ruthenium(II) complexes induce both apoptosis and autophagy in HeLa cells.

Ruthenium complexes with good biological properties have attracted increasing attention in recent decades. In this work, three ruthenium polypyridine complexes containing 5-fluorouracil derivatives as ligands, [Ru(bpy)2(L)]2+ (Ru1), [Ru(phen)2(L)]2+ (Ru2), [Ru(dip)2(L)]2+ (Ru3) (L = 1-((1,10-phenanthroline-5-amino) pentyl)-5-fluorouracil; bpy = 2,2'-bipyridine; phen =1,10-phenanthroline; dip = 4,7-diphenyl-1,10-phenanthroline), were synthesized and characterized. Based on in vitro cytotoxicity tests, Ru3 (IC50 = 7.35 ± 0.39 µM) showed the best anticancer activity among three compounds in the selected cell lines. It is worth noting that Ru3 also exerts less cytotoxicity on LO2 cell lines, with an IC50 value 5 times higher than that on HeLa cells, indicating its selective activity. Mechanism studies revealed that Ru3 can specifically target lysosomes and induce cell apoptosis in a caspase-dependent manner. Specifically, Ru3 can arrest cell cycle at the G0/G1 phase, increase the intracellular reactive oxygen species (ROS) level, and then damage DNA. In short, Ru3 can eventually cause cell death through the synergy of inducing apoptosis and autophagy, which was further proven by western blot assay results.

Gut microbiota homeostasis restoration may become a novel therapy for breast cancer.

Breast cancer is the most diagnosed cancer in women. It significantly impairs a patient's physical and mental health. Gut microbiota comprise the bacteria residing in a host's gastrointestinal tract. Through studies over the last decade, we now know that alterations in the composition of the gut microbiome are associated with protection against colonization by pathogens and other diseases, such as diabetes and cancer. This review focuses on how gut microbiota can affect breast cancer development through estrogen activity and discusses the types of bacteria that may be involved in the onset and the progression of breast cancer. We also describe potential therapies to curtail the risk of breast cancer by restoring gut microbiota homeostasis and reducing systemic estrogen levels. This review will further explore the relationship between intestinal microbes and breast cancer and propose a method to treat breast cancer by improving intestinal microbes. We aimed at discovering new methods to prevent or treat BC by changing intestinal microorganisms.

Natural history of pathologically confirmed pulmonary subsolid nodules with deep learning-assisted nodule segmentation.

OBJECTIVE: To explore the natural history of pulmonary subsolid nodules (SSNs) with different pathological types by deep learning-assisted nodule segmentation. METHODS: Between June 2012 and June 2019, 95 resected SSNs with preoperative long-term follow-up were enrolled in this retrospective study. SSN detection and segmentation were performed on preoperative follow-up CTs using the deep learning-based Dr. Wise system. SSNs were categorized into invasive adenocarcinoma (IAC, n = 47) and non-IAC (n = 48) groups; according to the interval change during the preoperative follow-up, SSNs were divided into growth (n = 68), nongrowth (n = 22), and new emergence (n = 5) groups. We analyzed the cumulative percentages and pattern of SSN growth and identified significant factors for IAC diagnosis and SSN growth. RESULTS: The mean preoperative follow-up was 42.1 ± 17.0 months. More SSNs showed growth or new emergence in the IAC than in the non-IAC group (89.4% vs. 64.6%, p = 0.009). Volume doubling time was non-significantly shorter for IACs than for non-IACs (1436.0 ± 1188.2 vs. 2087.5 ± 1799.7 days, p = 0.077). Median mass doubling time was significantly shorter for IACs than for non-IACs (821.7 vs. 1944.1 days, p = 0.001). Lobulated sign (p = 0.002) and SSN mass (p = 0.004) were significant factors for differentiating IACs. IACs showed significantly higher cumulative growth percentages than non-IACs in the first 70 months of follow-up. The growth pattern of SSNs may conform to the exponential model. The initial volume (p = 0.042) was a predictor for SSN growth. CONCLUSIONS: IACs appearing as SSNs showed an indolent course. The mean growth rate was larger for IACs than for non-IACs. SSNs with larger initial volume are more likely to grow. KEY POINTS: • Invasive adenocarcinomas (IACs) appearing as subsolid nodules (SSNs), with a mean volume doubling time (VDT) of 1436.0 ± 1188.2 days and median mass doubling time (MDT) of 821.7 days, showed an indolent course. • The VDT was shorter for IACs than for non-IACs (1436.0 ± 1188.2 vs. 2087.5 ± 1799.7 days), but the difference was not significant (p = 0.077). The median MDT was significantly shorter for IACs than for non-IACs (821.7 vs. 1944.1 days, p = 0.001). • SSNs with lobulated sign and larger mass (> 390.5 mg) may very likely be IACs. SSNs with larger initial volume are more likely to grow.

Non-fluoroscopic percutaneous transcatheter closure of atrial septal defects in children under transesophageal echocardiographic guidance.

BACKGROUND: This study sought to investigate the feasibility, safety and effectiveness of transcatheter closure of atrial septal defects (ASDs) under the guidance of transesophageal echocardiography (TEE) in children. METHODS: We reviewed the medical records of patients who underwent percutaneous ASD closure at our center from August 2016 to December 2017. For a total of 88 patients who were identified as having a single-hole defect and were undergoing percutaneous transcatheter ASD closure, a procedure completely guided by TEE was performed. There were 31 male patients and 57 female patients. The patients' mean age was 60.09 ± 36.42 months (13-182 months), and their mean body weight was 20.16 ± 10.04 kg (9-77 kg). Patients were followed up by performing transthoracic echocardiography and obtaining chest X-rays and electrocardiograms. RESULTS: The transcatheter closure of ASDs was successful in all patients. The mean ASD size was 11.58 ± 5.31 mm (3-28 mm), and the mean size of the occlusion device was 16.07 ± 5.29 mm (6-36 mm). The mean procedural times were 13.33 ± 2.82 minutes (6-16 minutes). The mean hospitalization costs were 27,259.66 ± 2507.04 RMB (25,200.00-33,911.45 RMB). The mean postoperative hospital stay was 3.22 ± 0.53 days (3-5 days). Residual shunt, occlusion device shedding or displacement, and pericardial effusion were not observed during or after the operation. CONCLUSION: Percutaneous transcatheter ASD closure completely guided by TEE is a feasible, safe, non-invasive and easy procedure.

Prognostic impact and implications of extracapsular lymph node spread in Borrmann type IV gastric cancer.

The purpose of this study was to evaluate the relationship between extracapsular lymph node spread (ECS) and clinicopathology and its influence on the prognosis in patients with Borrmann type IV gastric cancer. Between 2002 and 2014, clinical data were reviewed from 486 patients with Borrmann type IV gastric cancer who underwent curative resection. Of the 486 patients, lymph node metastasis was found in 456. ECS was detected in 213 (46.7%) patients with lymph node metastasis. A positive lymph node with ECS was significantly correlated with the N category, lymphatic/venous invasion, tumor location, and TNM stage. For the whole patients, the mean OS was 34.7 months, and the 5-year OS rate was 15.5%. The 5-year OS rate of node-negative patients was 48%, for node-positive patients without ECS 18.7%, and for node-positive patients with ECS 5.7% (P = 0.000). In a multivariate analysis, adjusted for tumor location, lymphatic/venous invasion, body mass index (BMI), and TNM stages, ECS remained an independent prognostic factor. For patients with the same N category and TNM stage, those with ECS still had a worse survival rate. Recurrent sites were confirmed in 367 patients. The most frequent recurrent site was the peritoneum. There was a significant difference between ECS+ (N = 150) and ECS- (N = 142) patients (P = 0.008). Our results suggested that ECS was an independent prognostic value for Borrmann type IV gastric cancer patients with curative resection and a subgroup indicated a significantly worse long-term survival for patients with the same N or TNM stages. ECS+ was an adverse factor for peritoneal metastasis.

Surgical treatment of huge hepatocarcinoma with invasion or severe adhesion of diaphragm using the technique of orthotopic liver resection.

BACKGROUND/AIMS: To explore the clinical application and significance of the technique of orthotopic liver resection. METHODOLOGY: From January 2004 to December 2011, five patients with huge hepatocellular carcinoma with invasion or severe adhesion of diaphragm were undergone right semi-liver resection using the technique of orthotopic liver resection. The right hemi-liver was isolated from the first liver portal, second liver portal and third liver portal, then isolated from the normal liver, finally the tumor and the invaded diaphragm were resected or removed from the severe adhesion. The approach to hepatic resection involved routine use of Peng's multifunctional operative dissector, selective control of in and out-flow of liver, control of inferior vena cava (IVC) and liver hanging maneuver, anterior approach, etc. RESULTS: The operations were successfully performed in 5 patients. Operative time was 120, 180, 150, 150 and 160 min, respectively. The amount of blood loss were 350, 350, 400, 450, 600 ml, respectively. Postoperative complications were pleural effusion in 3 cases, and other 2 cases recovered without complications. CONCLUSIONS: Although the technique of orthotopic liver resection has a high technical requirement for surgeons, it provides a surgical method and operative opportunity for the patients whose tumor has invaded diaphragm or has been severe adhesion with diaphragm and conventional liver resection cannot be performed.

Reconstruction of a new pulmonary artery in arterial switch operation.

BACKGROUND: This study was undertaken to evaluate the new method for the reconstruction of the pulmonary artery in arterial switch operation (ASO). METHODS: A total of 108 consecutive infants with congenital heart disease were treated with ASO in our department between January 2004 and June 2012. The new pulmonary arterial root was reconstructed with a fresh autologuos pericardium which was clipped pants-like with continuous mattress suture of 6-0 Prolene thread. Patients were reexamined consecutively at 3 and 6 months and 1, 2 and 6 years after discharge. The pulmonary arterial blood velocity was measured by continuous Doppler during systole. The pulmonary flow of healthy children of same age was also measured in the control group. Simplified Bernoulli formula was used to calculate the pressure gradient via the pulmonary artery for determining whether there was pulmonary stenosis. RESULTS: In this series, 96 infants survived after the surgery and 88 were followed up with a mean peirod of (22±4) months. No pulmonary stenosis was detected with the simplified Bernoulli formula. CONCLUSION: No pulmonary stenosis was detected with the simplified Bernoulli formula.

Neuroprotective capabilities of TSA against cerebral ischemia/reperfusion injury via PI3K/Akt signaling pathway in rats.

BACKGROUND: Hundreds of previous studies demonstrated the cytoprotective effect of trichostatin-A (TSA), a kind of histone deacetylases inhibitors (HDACIs), against cerebral ischemia/reperfusion insult. Meanwhile, phosphatidylinositol-3 kinase/Akt (PI3K/Akt) is a well-known, important signaling pathway that mediates neuroprotection. However, it should be remains unclear whether the neuroprotective capabilities of TSA against cerebral ischemia/reperfusion is mediated by activation of the PI3K/Akt signaling pathway. METHODS: Five groups rats (n = 12 each), with middle cerebral artery occlusion (MCAO) except sham group, were used to investigate the neuroprotective effect of certain concentration (0.05 mg/kg) of TSA, and whether the neuroprotective effect of TSA is associated with activation of the PI3K/Akt signaling pathway through using of wortmannin (0.25 mg/kg). RESULTS: TSA significantly increased the expression of p-Akt protein, reduced infarct volume, and attenuated neurological deficit in rats with transient MCAO, wortmannin weakened such effect of TSA dramatically. CONCLUSIONS: TSA could significantly decrease the neurological deficit scores and reduce the cerebral infarct volume during cerebral ischemia/reperfusion injury, which was achieved partly by activation of the PI3K/Akt signaling pathway via upgrading of p-Akt protein.

Hemangioendothelioma of the right atrial appendage associated with pericardial effusion in an infant.

BACKGROUND: Cardiac hemangioma is a rare cause for pericardial effusion. We present a case of hemangioendothelioma of the right atrial appendage associated with pericardial effusion in an infant. METHODS: The patient was a 49-day-old infant transferred to our department because of the presence of pericardial effusion. Two-dimensional transthoracic echocardiography revealed moderate pericardial effusion and a 24 mm × 16 mm hypoechoic mass located on the right side of the right ventricular outflow tract and in front of the aorta. RESULTS: The infant underwent an exploratory median sternotomy. In the pericardial cavity, 120 mL transudate was observed. A 15 mm × 15 mm encapsulated mass of soft tissue was located in the pericardial cavity and involved the right atrial appendage. The tumor with right atrial appendage was completely removed. Pathological examination revealed wide sessile implant basis of the tumor into the the myocardium of the right atrial appendage, with no affection to the endocardium. Hemangioendothelioma was confirmed histopathologically. Echocardiographic examination 2 years after operation revealed that the infant was free from tumor recurrence. CONCLUSIONS: Pericardial effusion may be caused by hemangioma of the right atrial appendage. The diagnosis of cardiac hemangioma is based on imaging examination and histopathological studies.

[Efficacy of arterial duct stenting in neonatal pulmonary atresia with intact ventricular septum].

OBJECTIVE: To evaluate the feasibility and efficacy of arterial duct stenting in neonates with pulmonary atresia and intact ventricular septum. METHODS: Eleven neonatal pulmonary atresia with intact ventricular septum patients received arterial duct stenting in our hospital from December 2007 to September 2010 were involved in this study. The average age was (8.20 +/- 2.90) days (ranged from 3 to 13 days). The average weight was (3.41 +/- 0.29) kg (ranged from 3.00 to 3.88 kg). The stents were selected according to digital subtracted angiography measurements. After checking for correct position by angiography, the balloon was inflated to expand the stent to desired diameter. Oxygen saturation was monitored, echocardiography was measured and stent diameter and location were observed by chest Xray. Patients were followed up at 1, 3, 6 and 12 months post procedure. RESULTS: Stents were successfully implanted in all 11 patients. The preoperative peripheral oxygen saturation was (63.27 +/- 8.47)%, while increased to (82.73 +/- 5.59)% after alprostadil application and to (86.18 +/- 3.19)% after operation (all P < 0.01). After the operation, the peripheral oxygen saturation was higher than alprostadil application (P < 0.05). The intraoperative narrowest diameter of patent ductus arteriosus was (1.69 +/- 0.37) mm, the length was (16.72 +/- 2.37) mm. The internal diameter of implant stents was 4 mm, the length was (20.18 +/- 3.40) mm. After the operation, surgical B-T shunt operation was performed in one patient due to stent shift and pulse oxygen saturation decrease. One patient died post operation with unknown reason, another patient received stent balloon dilatation due to pulse oxygen saturation decrease at 4 months after the surgery. Pulmonary atresia with intact ventricular septum surgeries were performed in 2 patients at 5 and 7 months after stent implantation. CONCLUSION: The neonatal pulmonary atresia with intact ventricular septum arterial stent implantation was a feasible and effective procedure and this method could be used as preferred treatment in pulmonary atresia and intact ventricular septum for neonates.

Experience in minimally invasive Nuss operation for 406 children with pectus excavatum.

BACKGROUND: This study was to investigate the advantages of thoracoscopy-assisted minimally invasive Nuss operation for the treatment of pectus excavatum (PE) in children. METHODS: A total of 406 patients with PE (female: 93; male: 313) with an average age of 6.8 years (range: 3.5-17.5 years) were included in this study. Associated diseases included congenital heart disease in 9 patients and congenital pulmonary cyst in 2. The Haller index of the patients ranged from 3.35 to 7.23, with an average of 5.17±1.64. Minimally invasive Nuss operation was performed for all the patients. RESULTS: The operations were performed successfully and no operative mortality occurred. The average blood loss during the operation was less than 10 mL and the operating time ranged from 30 to 85 minutes with an average of 45 minutes. The length of hospital stay ranged from 5 to 9 days with an average of 7 days. Struts were implanted in 12 (3.0%) of the 406 patients. Injury of the pericardium occurred in 1 patient during the operation. Early post-operative complications occurred in 9 patients with pneumothorax and 6 patients with pleural effusion, which were cured by puncture or drainage. Poor wound healing occurred in 4 patients (1.0%) and was cured by nutritional support. During a 3-month to 6-year follow-up, 2 patients had scoliosis and 3 patients had displacement of the strut, which was cured by a second Nuss operation. Allergy occurred in 2 patients: the symptoms were improved in 1 patient after conservative treatment, but the strut was removed in advance due to allergy in the other patient. Totally 154 patients (40.0%) underwent operation for strut removal. Excellent repair results were achieved in 387 (95.3%) patients, good repair results in 12 (3.0%), and fair results in 7 (1.7%). CONCLUSIONS: Thoracoscopy-assisted Nuss operation has many advantages including small and masked incision, short operative time, minimal blood loss, fast recovery, less trauma, and satisfactory outcomes of repair. Nuss is a safe and reliable technique for repair of PE.

True thymic hyperplasia in an infant.

True thymic hyperplasia is a very rare entity. We present an instance of idiopathic true massive thymic hyperplasia in a 9-month-old girl with a very large left-sided mediastinal mass noted on diagnostic imaging. Percutaneous biopsy revealed normal thymic tissue. Steroids were administered with no response. Surgery may be required in patients with respiratory distress unresponsive to steroids.

Extracorporeal membrane oxygenation for the treatment of children with severe hemodynamic alteration in perioperative cardiovascular surgery.

BACKGROUND: This article summarizes the use of extracorporeal membrane oxygenation (ECMO) for the treatment of children with severe hemodynamic alteration in perioperative cardiovascular surgery. METHODS: Four children with congenital heart disease (CHD) (3 boys and 1 girl, aged 6 days to 4 years and weighing 2.8-15 kg) associated with severe heart failure and/or hypoxemia were treated with ECMO cardiopulmonary support in perioperative cardiovascular surgery between July 2007 and July 2008. We retrospectively analyzed the medical records of the 4 children. RESULTS: Of the 4 children, 2 survived and 2 died. The survivors were treated with venoarterial (VA) ECMO due to severe low output syndrome after arterial switch operation. They were weaned successfully from 22-hour and 87-hour ECMO support, and discharged 20 days and 58 days after ECMO explantation, respectively. The other boy treated with venovenous ECMO died of severe hypoxemia and metabolic acidosis. The other girl with VSD, treated with VA ECMO because of failure to wean from cardiopulmonary bypass, died from irreversible heart failure 11 hours after ECMO explantation. The main complications in this series included pulmonary hemorrhage, blood tamponade, surgical site bleeding, hemolysis and hyperbilirubinemia. CONCLUSIONS: ECMO is an effective therapy for patients with severe heart failure in the perioperative cardiovascular surgery. The keys to successful ECMO are selection of indications, time to set up ECMO, and good management of complications during ECMO.

[Surgical treatment and prognosis of gastric stump cancer].

BACKGROUND AND OBJECTIVE: Gastric stump cancer (GSC) has unique biological behaviors and poor prognosis. The surgical treatment for GSC is complex. This study was to explore the clinical characteristics of GSC and the effect of operation patterns on long-term survival, and investigate its prognostic factors. METHODS: The clinical data of 81 GSC patients, treated in Zhejiang Cancer Hospital from January 1990 to December 2007, were analyzed. Patients' survival was analyzed by Kaplan-Meier method; the prognosis was analyzed by Cox multivariate regression model. RESULTS: Of the 81 patients, 47 (58.0%) received radical resection, 34 received non-radical operation (including palliative operation, short circuit or fistulation and exploration). The overall 1-, 3-, and 5-year survival rates were 69.1%, 24.3%, and 11.8% in the whole group. The 1-, 3-, and 5-year survival rates were significantly higher in radical resection group than in non-radical operation group (93.6% vs. 35.3%, 42.0% vs. 5.9%, 20.8% vs. 0, P<0.05). Cox multivariate regression analysis showed that clinical stage, pathologic classification, radical resection, peritoneal seeding and liver metastasis were related with the survival of GSC patients. CONCLUSIONS: Radical resection may help to improve the prognosis of GSC. Clinical stage, pathologic classification, radical resection, peritoneal seeding and liver metastasis are independent prognosis factors of GSC.

[An analysis on prognostic factors of hilar cholangiocarcinoma].

OBJECTIVE: To investigate the influencing factors on the prognosis of hilar cholangiocarcinoma. METHODS: The clinical data were retrospectively analyzed in 86 cases of hilar cholangiocarcinoma admitted into our hospital from Jan. 2004 to July. 2008. RESULTS: Of 86 cases with hilar cholangiocarcinoma, the mean survival time was 13.7 +/- 2.3 months, 1-year survival 57.3% and 3-year survival 29.7%. The mean survival time in patients with resection operation (19.4 +/- 2.2 months) was significantly longer than those with no operation (7.2 +/- 1.2 months) (P < 0.05). The mean survival time in patients with non-vascular resection group (23.4 +/- 2.1 months) was significantly longer than those with portal vein resection alone group (15.3 +/- 1.4 months) and hepatic artery resection group (9.3 +/- 0.9 month) (P < 0.05). Cox regression analysis showed that staging, tumor diameter and operative were the dependent prognosis factors while pathologic type, vascular resection and age not the dependent prognosis factors. CONCLUSION: The prognosis of hilar cholangiocarcinoma correlates with operative approach, clinical stage and tumor diameter. A surgeon must be cautious to choose the surgical approach for treatment.

Total anomalous systemic venous drainage to the left atrium.

We present an unusual case of total anomalous systemic venous drainage in which the right superior vena cava, persistent left superior vena cava, inferior vena cava, and coronary sinus were present and unusually connected to the left atrium. Successful surgical correction was achieved, and the patient's recovery was uneventful. Various types of total anomalous systemic venous drainage are discussed, and classification of total anomalous systemic venous drainage is made under the consideration of creation of cardiopulmonary bypass.