[The impact of the dosage of intraoperative opioids on postoperative survival outcomes in patients with pancreatic cancer].

Objective: To investigate the impact of the dosage of intraoperative opioids on postoperative survival of pancreatic cancer patients who underwent pancreatectomy. Methods: The clinical data of 95 patients with pancreatic cancer who underwent pancreatectomy at Harbin Medical University Cancer Hospital from September 2013 to August 2018 were retrospectively collected. Dosage of intraoperative opioid medications was converted to fentanyl equivalent dose. Patients were divided into high-dose group (fentanyl consumption ≥2.21 mg, n=46) and low-dose group (fentanyl consumption<2.21 mg, n=49) according to the median intra-operative fentanyl equivalents. The relapse-free survival (RFS) and overall survival (OS) between the two groups were compared. Cox proportional hazards regression model was used to analyze the impact of important covariates on RFS and OS. Results: RFS of patients in low-dose group at 1, 3 and 5 years was 75.5%, 26.5% and 15.2% respectively. OS of patients in low-dose group at 1, 3 and 5 years was 77.6%, 32.5% and 24.4% respectively. RFS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 23.9% and 12.0% respectively. OS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 37.0% and 15.0%. There was no significant difference in RFS and OS between the two groups (all P>0.05). Multivariate Cox analysis showed that dosage of intraoperative fentanyl was not associated with RFS (HR=1.205, 95%CI: 0.737-1.970, P=0.456) or OS (HR=1.062, 95%CI: 0.634-1.778, P=0.818). Conclusion: Dosage of intraoperative opioid has no effect on RFS and OS in pancreatic cancer patients undergoing pancreatectomy.

Prognostic factor from MR spectroscopy in rat with astrocytic tumour during radiation therapy.

OBJECTIVE: To investigate the relationship between the tumour volume and metabolic rates of astrocytic tumours using MR spectroscopy (MRS) during radiation therapy (RT). METHODS: 12 healthy male Sprague-Dawley® rats (Sprague-Dawley Animal Company, Madison, WI) were used, and a tumour model was created through injecting C6 tumour cells into the right caudate nuclei of the rats. Tumours grew for 18 days after the injection and before the imaging study and radiation treatment. MRS was performed with two-dimensional multivoxel point-resolved spectroscopy sequence using a GE Signa VH/i 3.0-T MR scanner (GE Healthcare, Milwaukee, WI) equipped with rat-special coil. RT was given on the 19th day with a dose of 4 Gy in one single fraction. The image examinations were performed before RT, and on the 4th, 10th, 14th and 20th days after treatment, respectively. GE FuncTool software package (GE Healthcare) was used for post-processing of spectrum. RESULTS: Metabolic ratios of serial MRS decrease progressively with time after RT. Choline-containing components (Cho)/creatine and creatine phosphate (Cr) ratios immediately prior to RT differed significantly from those on the 10th, 14th and 20th days after RT; both Cho/N-acetyl aspartate (NAA) ratios and NAA/Cr ratios immediately prior to RT differed significantly from those on the 14th and 20th days after RT. A positive correlation between changes of tumour volume and changes of Cho/Cr, lipid and lactate/Cr and glutamate plus glutamine/Cr ratio was observed on the 4th day after RT. CONCLUSION: MRS provides potential in monitoring tumour response during RT, and the imaging biomarkers predict the response of astrocytic tumours to treatment. ADVANCES IN KNOWLEDGE: MRS is combined with both tumour size and Ki-67 labelling index to access tumour response to radiation.

Over-expression of NYGGF4 (PID1) inhibits glucose transport in skeletal myotubes by blocking the IRS1/PI3K/AKT insulin pathway.

INTRODUCTION: Defects in insulin-stimulated glucose uptake in muscle are the important early events in the pathogenesis of insulin resistance. NYGGF4 (also named PID1) is a recently discovered gene which is suggested to be associated with obesity-associated insulin resistance. In this study, we aimed to investigate the effects of NYGGF4 on glucose uptake and insulin signaling in rat skeletal muscle cells. METHODS: Rat L6 myoblasts were transfected with either an empty vector or an NYGGF4-expressing vector and induced to differentiate into mature L6 skeletal myotubes. Glucose uptake was determined by measuring uptake of 2-deoxy-d-[(3)H] glucose. Immunoblotting was performed to detect the translocation of insulin-sensitive glucose transporter 4 (GLUT4). Immunoblotting was also used to measure phosphorylation and total protein levels of the insulin signaling proteins including insulin receptor (IR), insulin receptor substrate 1 (IRS1), Akt, extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38, and c-Jun-N-terminal kinase (JNK). RESULTS: NYGGF4 over-expression in L6 skeletal myotubes reduced insulin-stimulated glucose uptake and impaired insulin-stimulated GLUT4 translocation. It also diminished insulin-stimulated tyrosine phosphorylation of IRS1 and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, p38, or JNK. CONCLUSIONS: Over-expression of NYGGF4 inhibits glucose transport in skeletal myotubes by blocking the IRS1/PI3K/AKT insulin pathway. These observations highlight the potential role of NYGGF4 in glucose homeostasis and the development of insulin resistance in obesity.

[The pathological changes of nasopharyngeal carcinoma cases treated by stereotactic radiosurgery].

OBJECTIVE: To study the pathological changes of nasopharyngeal carcinoma cases after the treatment of stereotactic radiosurgery. METHOD: 15 cases with recurrent or residual squamous cell carcinoma of nasopharynx diagnosed as T1-4 N0M0 were selected, which had undergone previous radiotherapy. The patients were treated by Gamma Knife while the isodose curve was 50% and the margin dose was 20 Gy. The nasopharynx biopsy was performed before the treatment and 1, 3, 6, 12 months after the treatment. The biopsy specimen was taken to make a pathological examination. RESULT: 1. Before the Gamma Knife treatment, carcinoma cell could be seen in the tissue; 2. 1-3 months after the treatment, cell necrosis and acute inflammation cell infiltration could be seen in the target; 3. 6-12 months after the treatment, infiltration of chronic inflammation cell, proliferation of fibrous tissue and capillary could be found in the target. CONCLUSION: This research implies that the short-term pathological changes after the treatment of stereotactic radiosurgery can be defined as two phases: The first phase occurs from 1 to 3 months after the treatment called necrosis period. The second phase occurs from 6 to 12 months after the Gamma Knife treatment named as absorption period.

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Gamma knife radiosurgery for torsion spasm. Report of two cases.

The authors report on two patients who underwent radiosurgery for torsion spasm and evaluate the efficiency of gamma knife radiosurgery (GKS) as an alternative treatment. The first patient was a 33-year-old woman with severe right-sided lower-limb torsion dystonia. The second patient was a 20-year-old man with right-sided upper-limb torsion dystonia. The target was located at the anterior portion of the ventrolateral nucleus. The maximum doses were 150 Gy and 145 Gy, respectively. Double isocenters with a 4-mm collimator were used. Follow up lasted for 18 months and 8 months, respectively. Both patients had excellent clinical improvement 2 to 3 months after GKS, respectively. The authors believe that GKS may be a safe and efficient treatment for torsion spasm.

Radiosurgery for growth hormone-producing pituitary adenomas.

OBJECT: The authors sought to evaluate the effect of gamma knife radiosurgery (GKS) on growth hormone (GH)-producing pituitary adenoma growth and endocrinological response. METHODS: From 1993 to 1997, 79 patients with GH-producing pituitary adenomas were treated with GKS. Seventy-six patients had acromegaly. Sixty-eight patients were treated with GKS as the primary procedure. The tumor margin was covered with a 50 to 90% isodose and the margin dose was 18 to 35 Gy (mean 31.3 Gy). The dose to the visual pathways was less than 10 Gy except in one case. Sixty-eight patients (86%) were followed for 6 to 52 months. Growth hormone levels declined with improvement in acromegaly in all cases in the first 6 months after GKS. Normalization of the hormone levels was achieved in 23 (40%) of 58 patients who had been followed for 12 months and in 96% of cases for more than 24 months (43 of 45), or more than 36 months (25 of 26), respectively. With the reduction of GH hormone levels, 12 of 21 patients with hyperglycemia regained a normal blood glucose level (p < 0.001). The tumor shrank in 30 (52%) of 58 patients who had been followed for 12 months (p < 0.01), 39 (87%) of 45 patients for more than 2 years (p = 0.02), and 24 (92%) of 26 patients for more than 36 months. In the remainder of patients tumor growth ceased. CONCLUSIONS: Gamma knife radiosurgery for GH-producing adenomas showed promising results both in hormonal control and tumor shrinkage. A margin dose of more than 30 Gy would seem to be effective in improving the clinical status, reducing high blood glucose levels, and normalizing hypertension.

Gamma knife radiosurgery for cavernous hemangiomas.

OBJECT: The authors analyzed the outcome of 53 patients with cavernous hemangiomas who underwent gamma knife radiosurgery (GKS) and evaluated the benefit of the treatment. METHODS: From 1994 to 1995, 57 patients were treated with GKS for cavernous hemangiomas. The mean margin dose to the lesions was 20.3 Gy (range 14.5-25.2 Gy) and the prescription isodose was 50 to 80%. The mean follow-up period was 4.2 years. Four patients were lost to follow up. In 18 of 28 patients whose chief complaint was seizures, there was a decrease in seizure frequency. Five of 23 patients with hemorrhage suffered rebleeding 4 to 39 months after GKS. Seventeen patients in whom the hemangiomas were located at the frontal or parietal lobe had neurological disability and in five this was severe. Two patients underwent resection of their hemangioma after GKS. Three experienced visual problems. Follow-up imaging demonstrated shrinkage of the lesion in 19 patients. CONCLUSIONS: A higher margin dose (> 16 Gy) may be associated with a reduction in the incidence of rebleeding after GKS. Higher dosage and severe brain edema after GKS may decrease the frequency and intensity of seizures at least temporarily. Gamma knife radiosurgery may play a role in protection against hemorrhage and in reduction of the rate of seizure in selected cases with the appropriate dose.

Stereotactic Gamma thalamotomy for the treatment of parkinsonism.

From September 1994 to June 1995, eight patients with intractable parkinsonism underwent gamma thalamotomy in our hospital. All of these patients were male, with an average age of 59.3 years. The duration of the disease from initial diagnosis was 2-10 years (mean 6.8 years). All had failed or had serious side effects with antiparkinsonian medicine. Seven cases had tremor-dominant symptoms, while the other had mainly rigidity. Six cases had bilateral symptoms. Computed tomography or magnetic resonance imaging (MRI) was undertaken prior to treatment in all cases to exclude focal brain lesions. Stereotactic MRI was taken with the Leksell frame in place and both T1- and T2-weighted images were obtained. The targets were located in the area of Vim/Voa/Vop based on the Schaltenbrand atlas. In seven cases, two plugged 4-mm-collimator shots were used. The maximum dose was 160 Gy in six cases and 180 Gy in one case. In another case, a single 4-mm-collimator shot was used, and a maximum dose of 160 Gy was delivered to the target center. The border of the internal capsule was outside the 20-30% isodose line. We intended the 50% isodose line to have an oval-shaped region with the use of two shots and should correspond to the shape of Vim. Follow-up data were available for six patients (mean: 4.5 months, range: 2-9 months). Tremor disappeared in three cases and improved in the other three. In one of these six cases, the tremor disappeared just 3 days after gamma thalamotomy. Rigidity improved in four of these six cases. In only one patient, treated with a maximum dose of 180 Gy, was there any contralateral limb weakness, which developed 3 months after treatment and has been recovering gradually. Follow-up MRI T2-weighted images in this case showed that the diameter of the lesion was larger than intended and there was a region of diffuse edema in the thalamus and upper brain stem. No other complications occurred in this series.

Changes of T cell subsets in peripheral blood of patients with Schistosomiasis japonica and their relation to interleukin-1.

T cell subsets in peripheral blood were phenotyped in 56 patients with different stages of Schistosomiasis japonica, including 17 with acute, 14 with chronic and 25 with advanced infection. The activity of interleukin-1 (IL-1) produced by peripheral blood mononuclear cells (PBMC) induced by lipopolysaccharide (LPS) in vitro was simultaneously detected in these three groups of patients. It was found that the percentages of CD3+ (total T cell), CD4+ (helper/inducer T cell) and CD8+ (suppressor/cytotoxic T cell) T cell and the level of IL-1 were significantly increased in the group of acute Schistosomiasis japonica. In the groups of chronic and advanced Schistosomiasis japonica, the proportion of CD3+ T cell, the ratio of CD3+/CD4+ and the level of IL-1 were remarkably reduced, and the percentage of CD8+ T cell was increased. The rate of CD4+ T cell was obviously decreased in cases patients with advanced Schistosomiasis japonica. The percentage of CD4+ T cell was positively correlated to the level of IL-1 in the three groups of patients. These results indicate that T cell subsets and IL-1 may play an important role in the immunoregulation of Schistosomiasis japonica.

Changes in T cell subsets and T suppressor cell function and their relationship in human schistosomiasis japonica.

The function of spontaneous T suppressor cell (STs) of peripheral blood was examined in 56 patients with schistosomiasis japonica at various stages. The subsets of T cell were simultaneously phenotyped in 46 cases. The percentages of CD3+ (pan T cell), CD4+ (helper/inducer T cell) and CD8+ (suppressor/cytotoxic T cell) in patients with acute schistosomiasis japonica were significantly higher than those in the normal controls. In patients with chronic and advanced schistosomiasis japonica, the percentage of CD8+ T cell and the function of STs were greatly increased, but the percentage of CD3+ T cell and the ratio of CD4+/CD8+ were obviously reduced. All of these markers changed more significantly in patients with advanced schistosomiasis japonica. The percentage of CD8+ T cell in patients with acute schistosomiasis japonica was negatively correlated with the function of STs. In patients with chronic and advanced schistosomiasis japonica the percentage of CD8+ T cell was correlated positively and the ratio of CD4+/CD8+ negatively with the function of STs. The results indicated that the cellular immunity was significantly increased in cases of acute schistosomiasis japonica and decreased in those with chronic or advanced schistosomiasis japonica. The increased CD8+ T cell may be principally cytotoxic T cells in patients with acute schistosomiasis japonica, but suppressor T cells in patients with chronic and advanced schistosomiasis japonica. The subsets of T cells and the function of T suppressor cells may play an important role in the immunoregulation of schistosomiasis japonica.

Immunohistochemical detection of HBsAg and HBcAg in the liver of patients with schistosomiasis japonica complicated by hepatocellular carcinoma.

In liver biopsies from 21 patients with schistosomiasis japonica complicated by hepatocellular carcinoma (HCC), 69 patients with advanced schistosomiasis japonica, and 25 patients with HCC, HBsAg and HBcAg were investigated with peroxidase-antiperoxidase technique. The positive rate of HBAg (i.e. HBsAg and/or HBcAg) in the liver of patients with schistosomiasis japonica complicated by HCC was significantly higher than in the group of advanced schistosomiasis japonica, but similar to that in cases of HCC. The location of carcinoma cells in the liver was not related to the distribution of Schistosoma ova in patients with schistosomiasis japonica complicated by HCC. The results indicated that the complication with hepatitis B virus infection may be one of the major factors involved in the development of HCC in patients with schistosomiasis japonica.

Changes in the level of IL-2, T cell subsets and the function of T suppressor cells in patients with schistosomiasis japonica.

The level of interleukin-2 (IL-2) produced by peripheral blood mononuclear cells in vitro, T cell subsets and the function of T suppressor cells (Ts) in patients with schistosomiasis japonica were investigated. It was found that the level of IL-2 induced by schistosomal antigens was significantly high and positively related to the percentage of CD4+ cells. In the groups of chronic and advanced schistosomiasis japonica, the level of IL-2 induced by schistosomal antigens was markedly lower than that in the group of acute schistosomiasis japonica, but significantly higher than that in the group of normal controls. The IL-2 level was negatively related to the percentage of CD8+ T cells and the ratio of CD4+/CD8+. The level of IL-2 induced by PHA was greatly reduced in the group of advanced schistosomiasis japonica. The changes in the level of IL-2 and its relationship with T cell subsets and the function of Ts are also discussed.