A novel approach to rescue immune escape in oral squamous cell carcinoma: Combined use of interferon-γ and LY294002

Major histocompatibility complex (MHC) class I molecules have been found to be downmodulated in many tumors. The antigen-processing machinery (APM) genes, especially transporters associated with antigen processing (TAP)-1 and tapasin play important roles in the processing of class I antigens. In this study, we investigated the expression of TAP-1 and tapasin in oral squamous cell carcinoma (OSCC); the result indicated significant down-regulation in the expression of these genes. Interferon (IFN)-γ treatment was applied. After the addition of IFN-γ, unexpectedly, the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway was activated, which induced the proliferation of tumor cells. With the combined application of LY294002 (specific inhibitor of AKT signaling) and IFN-γ, tumor cell apoptosis was induced and the expression of TAP-1 and tapasin was still up-regulated. Hence, our method is a novel and efficient approach to use IFN-γ for rescuing the cells from immunosurveillance.     

Adjuvant intraoperative post-dissectional tumor bed chemotherapy—A novel approach in treating midgut neuroendocrine tumors

Background

Midgut neuroendocrine tumor (NET) patients are often diagnosed at an advanced stage with extensive mesenteric lymph node and liver metastasis. Even with skillful surgical dissection, macro and microscopic residual disease at the dissection site remains a possibility. We hypothesize these potential tumor residuals in mesenteric lymph node dissection beds can be eliminated safely by a local application of 5-fluorouracil (5-FU). We describe a novel technique invented by the author to treat these micro and macro residuals.

Methods

Retrospectively, charts of 62 consecutive midgut NET patients with boggy mesenteric lymphadenopathy who underwent cytoreductive debulking surgeries from 1/2007 to 12/2009 were reviewed. A total of 32 patients received an intraoperative application of 5-FU saturated gelfoam strips secured into the mesenteric defect following the extensive lymphadenectomy. A total of 30 untreated patients served as a control.

Results

The 5-year survival after cytoreductive surgeries was 22/32 (68.8%) for the treated group, vs. 20/30 (66.7%) for the control. Six patients (6/32, 18.8%) among the study group required additional debulking surgeries, vs. 16 patients (16/30, 53.3%) in the control group. Upon reoperation, loco-regional recurrence was noted in 9 of the 16 patients (56.3%) in the control group, vs. only 2/6 (33.3%) of treated patients. Overall, local recurrence rate is 6.25% (2/32) in the treated group vs. 30% (9/30) in the control group. Post-op complication rates are similar in the two arms.

Conclusions

Intraoperative application of chemotherapy is a safe and effective adjuvant to reduce local recurrence and the need of reoperation by the tumoricidal or tumorstatic effects of 5-FU on any potential microscopic residual disease after extensive cytoreductive surgeries in advanced stage NET patients with mesenteric lymph node metastasis. It provides patients with sustained, slow releasing, high dose of 5-FU within the surgical bed with a negligible side effect profile. Further studies are required to evaluate its effect on long term survival.     

Sequential treatment in disseminated well- and intermediate-differentiated pancreatic neuroendocrine tumors: Common sense or low rationale?

Fortunately, the landscape of the systemic treatment for grade 1 and 2 pancreatic neuroendocrine tumors has changed in the last decade with at least four different alternatives approved in the field. Chemotherapy, somatostatin analogues, sunitinib and everolimus remind valid options according to the most referenced international guidelines. However, and although this is something done in the routine practice, there is a lack of evidence for the use of any of these strategies after failure to the others. Moreover, further sequential alternatives in third or fourth line have never been tested prospectively. The need for a better understanding of the rationale to sequence different systemic options is even greater in non-pancreatic neuroendocrine tumors since available therapies are scarce. Sequential strategies in other solid tumors have led to a clear improvement in overall survival. This is also believed to occur in neuroendocrine tumors but no clear data on it has been delivered yet. We postulate that the different mode of action of the systemic options available for the treatment of neuroendocrine tumors may avoid the complete resistance of one option after the other and that sequential use of these agents will be translated into a longer overall survival of patients. Prospective and randomized trials that seek for the activity of drugs after failure to another systemic alternatives are highly needed in this field of neuroendocrine tumors.     

Management and outcome of children with neuroendocrine tumors of the appendix in Spain: Is there room for improvement?

Purpose

Neuroendocrine tumors (NETs) are, after lymphomas, the most frequent gastrointestinal tumors in children, mainly located in the appendix. Best management remains unclear, given the absence of pediatric guidelines. We present the first Spanish series of pediatric patients with NETs.

Patients and methods

Retrospective study of all pediatric patients (<18 years) with NET treated in four oncology reference institutions in Spain between 1994 and 2015.

Results

Seventeen patients were included. All patients presented with acute abdomen. TNM stage was T1a (82%) and T1b (12%). Extension study was heterogenous, with only 4 patients undergoing an OctreoScan. Four patients met criteria for second surgery (affected surgical margins or mesoappendix invasion), but it was only performed in two. Despite the diverse management, none of the patients relapsed during follow-up.

Conclusions

The disparity in diagnostic tests, second surgery criteria and follow-up shown in this study highlights the need for specific pediatric guidelines.

     

Solid neuroendocrine carcinomas of the breast: metastases or primary tumors?

Neuroendocrine breast carcinomas are rare but may represent either metastatic or primary lesions. So far, clinical and preoperative histopathological examinations do not distinguish properly between a primary or metastatic breast tumor. Due to any possible consequences following an appropriate treatment, markers which may be helpful for such a distinguishment are needed. We addressed this study in order to evaluate the immunohistochemical expression of GCDFP-15 and mammaglobin in a subset of pure neuroendocrine breast carcinomas (n = 9) and compared the expression profile with a cohort of non-mammary neuroendocrine tumors (n = 99). We observed in our study that solid neuroendocrine breast carcinomas are characterized by the expression of estrogen and progesterone receptors as well as GCDFP-15 and/or mammaglobin. GCDFP-15 was expressed in 6 out of 9 cases, mammaglobin was positive in 4 out of 9 tumors. In contrast, neuroendocrine tumors of the non-mammary cohort expressed neither GCDFP-15 nor mammaglobin. We conclude that mammaglobin and GCDFP-15 as markers of epithelial breast origin may work as a new and reliable diagnostic tool to distinguish primary endocrine tumors of the breast from a metastatic neuroendocrine disease. This is of utmost importance, especially for surgical management.     

Activation of protein kinase A (PKA) signaling mitigates the antiproliferative and antiinvasive effects of α-difluoromethylornithine in breast cancer cells

We have shown that α-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, the first and rate-limiting enzyme in polyamine synthesis, has significant antiproliferative and antiinvasive effects in breast cancer cells. We have also reported that these antitumor effects are associated with activation of multiple signaling pathways, including STAT-3, STAT-1, Jun-N-Terminal kinase (JNK), and Mitogen activated protein kinase (MAPK), the latter being found to mediate its antiinvasive action in MDA-MB-435 cells. The present experiments were designed to test the effect of DFMO on the protein kinase A (PKA) pathway and determine its biological significance. We found that DFMO administration (1 mM) to MDA-MB-435 breast cancer cells significantly increased cAMP response element (CRE)-binding protein (CREB) phosphorylation as well as the transactivation of pCRE-luc, a CREB-dependent promoter activated by PKA. To determine the significance of this biochemical effect of DFMO, we used the PKA inhibitor H89 which, as expected, suppressed in a dose-dependent manner (1 and 10 μM) basal and DFMO-induced CREB phosphorylation in our system. Administration of H89 alone was able to suppress proliferation of MDA-MB-435 cells when used at a concentration (10 μM) shown to completely block basal CREB phosphorylation. At concentrations of 0.5 and 1 μM, H89 treatment, while having no antiproliferative effect of its own, potentiated in a dose-dependent fashion the growth inhibitory action of a suboptimal concentration of DFMO (0.01 mM). Ten micromoles of H89 reduced invasiveness of MDA-MB-435 cells in matrigel by ∼40% (an effect similar to that of 1 mM DFMO). The combination treatment further reduced invasiveness by ∼80% (P < 0.01 versus the individual treatments). H89 treatment (10 μM) partially reduced DFMO-induced phosphorylation of STAT-3 but not that of STAT-1, Extracellular regulated kinase (ERK), and JNK. In conclusion, our results indicate that PKA signaling exerts proproliferative and proinvasive effects in our experimental system. Therefore, its activation by DFMO represents a compensatory mechanism which should be blocked in order to maximize the antitumor action of the drug. Our data are also consistent with the notion that STAT-3 activation by DFMO is at least in part mediated through the PKA pathway.     

Advances in the treatment of primary brain tumors: Dawn of a new era?

The prognosis for patients with malignant primary brain tumors has been poor, and until recently, there was little evidence that chemotherapy was beneficial. The publication of the phase III trial comparing the combination of temozolomide with external beam radiation therapy with radiation therapy alone demonstrated a clear survival benefit for the combination regimen. These results, along with improvements in clinical trial design and outcome assessment, advances in our understanding of glioma tumor biology, and recognition of critical drug-drug interactions, have provided a foundation for developing better treatments for these cancers.     

No synergistic activity of epirubicin and interferon-α2b in the treatment of hepatocellular carcinoma

Single-agent activity for anthracyclines reflected by response rates of 10%–30% has been reported in patients with advanced hepatocellular carcinoma (HCC). Preclinical data indicate that -interferon could enhance the cytotoxic activity of the anthracycline Adriamycin or its analog epirubicin. In a phase I/II study, 31 patients with biopsy-proven inoperable HCC were treated with interferon-2b given s. c. at a dose of 3×10⁶ units/m² per day for 5 days per week plus weekly epirubicin given at 25 mg/m² as an i. v. bolus. The protocol called for 4 consecutive weeks of treatment followed by 1 week off treatment. In all, 15 patients had been previously treated; 6 patients had failed hormonal therapy (tamoxifen), 5 patients had failed prior anthracycline treatment, and 4 patients had received chemoembolization of the tumor and had subsequently progressed. A total of 30 patients were evaluable for response. In all, 1 patient (3%) achieved a partial response for 8+ months and 11 patients (35%) achieved stabilization of disease. Six patients had a fall in alpha-fetoprotein (AFP) values of >50% during therapy. The median survival for all patients was 9.5 months (range, 3–34+ months). The main side effects were hematological toxicity and fever, both of which were considered tolerable. As an indicator of the immunostimulatory effects of interferon, an elevation in serum markers of inflammation [C-reactive protein (CRP), ₂-microglobulin] was found in 15%–20% of patients. All patients had measurable Mx protein production during therapy, but these effects were not correlated to the clinical response. The clinical response rate achieved in this trial indicates that the combination of interferon and epirubicin, at least when used on the schedule reported herein, is not superior to treatment with either agent alone for patients with advanced HCC. However, single patients achieved a prolonged progression-free interval (8–10+ months) on this therapy, and it may therefore be an option for patients who have failed prior hormonal or single-agent anthracycline therapy.     

Outcome after surgical treatment of suspected gastrointestinal stromal tumors involving the duodenum: Is limited resection appropriate?

INTRODUCTION: Present surgical opinion is divided regarding the optimal method for the treatment of duodenal gastrointestinal stromal tumor (GIST) with some supporting the selective use of limited resection (LR) versus others who prefer pancreaticoduodenectomy (PD). METHODS: A retrospective review of 22 patients who underwent surgery for suspected GIST involving the duodenum. RESULTS: There were 15 GISTs, 1 leiomyosarcoma and 6 other non-GIST benign submucosal tumors. Seven patients underwent LR and seven underwent PD for GIST. The median follow-up was 42 (range, 2-174) months. Patients who underwent LR versus PD had similar mean disease-specific survival [144 (95% CI, 92-196) vs. 130 (95% CI, 82-127) months, P = 0.808] and recurrence rates (14% vs. 29%, P = 0.515). All recurrences occurred at distant sites. Comparison between LR versus PD demonstrated that LR was associated with a significantly shorter operation time [125 (range, 50-305) vs. 350 (range, 210-465) min., P = 0.001] but similar morbidity rate (23% vs. 43%, P = 0.357). Comparison between GIST and other benign tumors demonstrated that size was the only statistically significant distinguishing factor [8.5 (range, 2.5-18.0) vs. 2.5 (range, 1.5-8.0) cm, P = 0.014]. CONCLUSION: Benign non-GIST tumors may be distinguished from duodenal GIST as they are smaller in size. LR is a viable treatment option for suspected GIST involving the duodenum.     

Is treatment with interferon-α effective in all patients with metastatic renal carcinoma? A new approach to the investigation of interactions

The first analysis of the MRC RE01 trial in metastatic renal carcinoma identified a 28% reduction in the hazard of death for patients treated with interferon-alpha compared with medroxyprogesterone acetate (MPA). No subgroup was identified in which treatment with interferon-alpha was more or less effective than MPA. We used a new approach based on fractional polynomials to investigate the updated data from this trial for the possible interaction of treatment with prognostic factors. In the spirit of hypothesis generation, we considered 10 possible prognostic variables, of which white cell count (WCC) was found to influence the effectiveness of interferon treatment. In patients treated with MPA, there was no prognostic effect of WCC, whereas, in patients treated with interferon, the risk of dying increased significantly with WCC level. We defined subgroups of patients based on WCC levels and estimated a hazard ratio of 0.53 in favour of interferon in patients with WCC <6.5 x 10(9), whereas for patients with WCC >10 x 10(9) the risk appears to be similar between the treatment groups, or even slightly raised in the interferon group. Since our results are derived from flexible statistical models, they may be interpreted as a new hypothesis and require validation in independent data.     

Inorganic phosphate in the development and treatment of cancer: A Janus Bifrons?

Inorganic phosphate (Pi) is an essential nutrient to living organisms. It is required as a component of the energy metabolism, kinase/phosphatase signaling and in the formation and function of lipids, carbohydrates and nucleic acids and, at systemic level, it plays a key role for normal skeletal and dentin mineralization. Pi represents an abundant dietary element and its intestinal absorption is efficient, minimally regulated and typically extends to approximately 70%. Maintenance of proper Pi homeostasis is a critical event and serum Pi level is maintained within a narrow range through an elaborate network of humoral interactions and feedback loops involving intestine, kidney, parathyroid gland and bone, and depends on the activity of a number of hormones, including parathyroid hormone, 1,25-dihydroxy vitamin D, and fibroblast growth factor 23 as major regulators of Pi homeostasis. Notably, Pi intake seemingly continues to increase as a consequence of chronic high-phosphorus (P) diets deriving from the growing consumption of highly processed foods, especially restaurant meals, fast foods, and convenience foods. Several recent reports have generated significant associations between high-P intake or high-serum Pi concentration and morbidity and mortality. Many chronic diseases, including cardiovascular diseases, obesity and even cancer have been proposed to be associated with high-P intakes and high-serum Pi concentrations. On the other hand, there is also evidence that Pi can have antiproliferative effects on some cancer cell types, depending on cell status and genetic background and achieve additive cytotoxic effects when combined with doxorubicin, illustrating its potential for clinical applications and suggesting that up-regulating Pi levels at local sites for brief times, might contribute to the development of novel and cheap modalities for therapeutic intervention in some tumours. Overall, the influence of Pi on cell function and the possible relationship to cancer have to be fully understood and investigated further.     

Chemotherapy for advanced non-pancreatic well-differentiated neuroendocrine tumours of the gastrointestinal tract,a systematic review and meta-analysis: A lost cause?

BackgroundChemotherapy is well-established in the treatment of patients with well-differentiated neuroendocrine tumours (NETs) arising from the pancreas (pNETs); however, its role in patients with gastrointestinal non-pancreatic NETs (non-pNETs) is uncertain. This systematic review assesses the evidence for the role of chemotherapy in well-differentiated non-pNET patients.MethodsEligible studies (identified using MEDLINE) were those reporting response and/or survival data for patients with well-differentiated non-pNETs receiving systemic chemotherapy. The primary end-point was overall-response (OR) rate; secondary end-points were progression-free survival (PFS), overall survival (OS), disease-stabilization (DS) and disease-control (DC) rates.ResultsOf 6434 studies screened, 20 were eligible: one randomised phase III trial, 2 randomised phase II studies, 10 single-arm phase II trials and 7 retrospective analyses including a total of 264 patients (median of 11 patients per study, range 6–49); and employing multiple chemotherapy schedules. The mean “median PFS” and “median OS” were 16.9 months (95%-confidence interval (CI) 3.8–30.04) and 32.2 months (95%-CI 10.4–54.2), respectively. The non-weighted mean OR, DS and DC rates were 11.5% (95%-CI 5.8–17.2), 56.5% (95%-CI 38.1–74.9) and 70.7% (95%-CI 54.9–86.5), respectively. In studies including both pNETs and non-pNET patients, meta-analysis showed a lower OR-rate in the non-pNET patients when compared to pNETs [odds ratio (OR) 0.35 (95% CI 0.18–0.66)]; however significance was lost when high-risk bias studies were excluded in a sensitivity analysis [OR 0.45 (95% CI 0.19–1.07); p-value 0.07].ConclusionStudies were of evidence level-C with heterogeneous populations and treatments; and small patient numbers. Well-designed, prospective studies are needed to adequately evaluate the role of chemotherapy in this setting.     

Expression of phosphoprotein enriched in astrocytes 15 kDa (PEA-15) in astrocytic tumors: a novel approach of correlating malignancy grade and prognosis

Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) is a multifunctional protein that was first identified in brain astrocytes and that has subsequently been shown to be expressed in different tissues. Despite its many important roles, the clinical significance of PEA-15 expression levels in astrocytic tumors has yet to be properly defined. We studied the PEA-15 expression pattern of 65 patients [diagnosed according to World Health Organization (WHO) criteria] with diffuse astrocytoma (WHO grade II), anaplastic astrocytoma (grade III), and glioblastoma (grade IV). PEA-15 expression levels were immunohistochemically measured and categorized as no, low, or high expression. All tumors expressed PEA-15 in our study. Twenty-three (35.4%) and 42 (64.6%) tumors expressed low and high PEA-15 levels, respectively. In grade II astrocytoma (diffuse astrocytoma) and grade III astrocytoma (anaplastic astrocytoma), 100% and 88.9% of patients expressed high PEA-15 levels, respectively, while a smaller number (50%) of patients with grade IV astrocytoma (glioblastoma) expressed high PEA-15 levels. PEA-15 expression level was inversely associated with WHO grade (P = 0.0006). Next, we evaluated prognosis and PEA-15 expression levels in 43 patients with high-grade astrocytomas based on the following parameters: age, gender, WHO grade, surgical resection extent, MIB-1 labeling index (LI), and PEA-15 expression level. Multivariable analyses revealed that high PEA-15 expression level displayed a significant correlation with longer overall survival (OS) in high-grade astrocytomas (P = 0.0024). Patients with total resection survived significantly longer (P = 0.0044) than those with lower resection extent, while patients with MIB-1 labeling index ≤25% indicated significant (P = 0.0434) correlation with OS as well. In conclusion, PEA-15 expression level was inversely associated with WHO grade and may serve as an important prognostic factor for high-grade astrocytomas.     

Is the prevalence of colonic neuroendocrine tumors increased in patients with inflammatory bowel disease?

Inflammatory bowel disease (IBD) patients may bear an increased neuroendocrine tumor (NET) risk. These tumors are mostly reported as coincidental findings during surgery. We aimed to determine the prevalence of colonic NET in a Dutch nationwide IBD cohort and calculate the prevalence rate ratios (PRR) compared with the general Dutch population. Our second aim was to investigate whether a high bowel surgery rate in IBD could result in a high PRR for NET. The Dutch Pathology Registry (PALGA) was searched to identify all IBD patients with colonic NET in The Netherlands between 1991 and 2011. We determined the prevalence and PRR of colonic NET in a 20‐year period. For our second aim, we compared NET prevalence in colonic resection specimens between IBD cases and non‐IBD controls (diverticulitis and ischemia). We identified 51 IBD patients who developed colonic NET resulting in a prevalence of 60.4–89.3 per 100,000 patients in a 20‐year period with a PRR of 2.8–4.1. However, adjusted for resection type, sex and age, a higher NET prevalence was shown in diverticulitis (OR 5.52, 95% CI 3.47–8.78) and ischemia (OR 1.97, 95% CI 1.09–3.58) compared with IBD. Our key finding is that NET are more prevalent in IBD patients compared with the general population (PRR 2.8–4.1). This might be attributed to a high rate of incidental NET as IBD patients frequently undergo intestinal surgery. A lower adjusted NET prevalence in colonic resection specimens for IBD compared to ischemia and diverticulitis supports this hypothesis.     

Appendectomy or right hemicolectomy in the treatment of appendiceal carcinoid tumors?

AIMS AND BACKGROUND: Carcinoids of the appendix continue to be of interest, despite their low incidence. There is still considerable controversy surrounding these tumors, especially with regard to the role of right hemicolectomy in the surgical management. The aim of this work was to explicate the current therapeutic knowledge and to review the criteria for the indications of appendectomy or hemicolectomy. METHODS: The records of patients who underwent appendectomies from 1990 to 2000 were analyzed. Seven patients were included in the study. The clinical data were reviewed for demographic details, tumor size, localization in the appendix, histological patterns and surgical procedures. All patients underwent appendectomy including removal of the mesenteriolum, and in one of them a right hemicolectomy was performed 3 weeks later. The mean follow-up was 7 years (range, 4-14). Follow-up data included symptoms, urinary 5-hydroxyindoleacetic acid, ultrasound examination, computerized tomography, and octreotide scanning. RESULTS: Seven patients (0.9% of all appendectomies) were reported to have carcinoid tumors of the appendix. They were 3 men and 4 women with a mean age of 29 years. All patients were admitted for appendicitis. None suffered from the carcinoid syndrome. The site of the tumor was the apex of the appendix in 4 cases, the body in 2 cases and the base in 1 case. Mean tumor diameter was 8 mm (range, 5-29 mm); in 6 patients it was <2 cm. Treatment was appendectomy in all cases; additional right hemicolectomy was necessary in one case because of a tumor of more than 2 cm with invasion of the mesoappendix and lymph nodes. The 7-year survival rate is 100%. Six patients are without disease, while 1 patient (the one who underwent a right hemicolectomy) developed metastases in the liver 6 years after the operation. This patient, who was treated with a liver resection, is still alive. CONCLUSIONS: According to current guidelines, an appendectomy may be performed for small carcinoid tumors (<1 cm). Reasons for more extensive surgery than appendectomy are tumor size >2 cm, lymphatic invasion, lymph node involvement, spread to the mesoappendix, tumor-positive resection margins, and cellular pleomorphism with a high mitotic index. The criteria that direct us towards major (hemicolectomy) or minor surgery (appendectomy) are controversial. Tumor size is still considered the most important prognostic factor, with a presumed increase in the risk of metastasis for tumors greater than 2.0 cm. The accepted treatment of such tumors is a right hemicolectomy. However, there is no evidence demonstrating a survival benefit for right hemicolectomy over simple appendectomy in patients with carcinoids greater than 2.0 cm in diameter.     

Computed tomography in the size measurement of gastric gastrointestinal stromal tumors: Implication to risk stratification and “wait-and-see” tactics

IntroductionThis study aimed to compare the radiologic size of gastric gastrointestinal stromal tumors (GISTs) on computed tomography (CT) with the pathologic size in a Chinese population, and elucidate the potential significance of the CT size in the preoperative risk stratification.Materials and methodsThe study enrolled 314 patients treated by endoscopic/surgical resection of gastric lesions that proved postoperatively to be GISTs. Bland-Altman analysis and intraclass correlation coefficient (ICC) were adopted to assess the size agreement between CT and pathology. Independent predictors of risk category underestimation and the optimal cut-off value of CT size were determined by logistic regression analysis and the receiver operating characteristic (ROC) curve.ResultsCT underestimated gastric GISTs size by 0.30 cm [95% confidence interval (CI): (?0.42, - 0.19); p < 0.001]. In the subgroup analysis, the size underestimation was 0.10 cm in GISTs ≤ 5 cm [95% CI: (?0.19, ?0.01); p = 0.024]; and 0.75 cm in GISTs >5 cm [95% CI: (?1.05, 0.45), p < 0.001].Though ICC values showed well reliability for the corresponding pathologic size, with 0.95 in all size, 0.86 in size ≤ 5 cm, and 0.92 in size >5 cm respectively. Risk underestimation by CT imaging mainly occurred in gastric GISTs with smaller size (≤5 cm; p = 0.010) and lower mitotic index (≤5 per 50 high-power fields; p = 0.011). CT size of 3.65 cm was defined as an absolute cut-off to differentiate intermediate/high-risk patients from low-risk group, with 87.5% sensitivity at a specificity of 57.8%.ConclusionPreoperative CT underestimated the mean size by 0.30 cm in gastric GISTs. A CT size of 3.65 cm would facilitate the selection of potential intermediate/high-risk patients, instant intervention should be encouraged in the absence of contraindications.     

Correction to “Efficacy and safety of endoscopic resection in treatment of small gastric stromal tumors: A state-of-the-art review”

We corrected the name of our institution in this study. The correct name should be “Department of Gastroenterology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen 518000, Guangdong Province, China.     

Efficacy and adverse effects of olanzapine in the treatment of moderate to severe refractory neuropathic pain

Objective The aim of the study was to investigate the efficacy and adverse effects of olanzapine in the treatment of moderate to severe refractory neuropathic pain.Methods Forty patients with digestive system cancer were enrolled,who had moderate to severe refractory neuropathic pain;the patients were treated with olanzapine for 2 weeks at a daily dosage of 5 mg to 10 mg per night according to patients’response and tolerability,combined with conventional analgesic therapy.Pain intensity was evaluated by using a Numeral Rating Scale(NRS)at baseline,3 days,and 2 weeks after therapy.The Pittsburg Sleep Quality Index(PSQI)was evaluated at baseline and 2 weeks after therapy.Data on adverse events were recorded.The dosage of conventional analgesics was adjusted over time based on the severity of pain.Results The mean pain score decreased by 2.575±1.318(P<0.000)at 3 days and by 3.400±1.614(P<0.000)at 2 weeks;30%of the patients experienced significant pain relief at 3 days and 50%at 2 weeks.The PSQI decreased by 4.725±2.828(P<0.000)at 2 weeks.The adverse events induced by olanzapine included sleepiness,weight gain,dizziness,fatigue,dry mouth,and constipation;all the side effects were mild.Conclusion When combined with conventional analgesic therapy,olanzapine was effective in relieving pain and sleep disturbance,and was well-tolerated among patients with refractory neuropathic pain.