Advances in the Diagnosis and Treatment of Appendiceal Mucinous Neoplasms

Primary appendiceal neoplasms represent a relatively low percentage of all gastrointestinal cancers. A subset of these neoplasms, those of epithelial origin, are characterised by the production of a considerable amount of mucus, which is referred to as appendiceal mucinous neoplasms (AMN). Appendiceal mucinous neoplasms (AMN) have a low incidence, are easily misdiagnosed, depend on postoperative examination for confirmation of the diagnosis, are prone to form a “diagnosis”, and have a high incidence of the disease. Furthermore, they are prone to form peritoneal pseudomyxoma peritonei (PMP), are controversial in surgical decision-making, are prone to recurring after surgery alone, and are tricky to manage clinically. In this paper, we review the pathological characteristics, diagnosis and treatment of appendiceal mucinous tumours in the light of recent literature reports, with a view to providing certain references for the clinical diagnosis and treatment of this disease. .

Surgical management of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms are a rare and complex group of neoplastic lesions that develop from pancreatic islet cells.Their incidence has dramatically increased during the last two decades.Due to its complex nature and pathophysiological behaviour,surgical management continues to evolve.Surgery remains the cornerstone of treatment for most non-functional and functional pancreatic neuroendocrine tumours,while lymphadenectomy remains a controversial subject.Different techniques,such as pancreas-preserving and minimally invasive approaches,continue to evolve and offer the same overall outcomes as open surgery.This comprehensive review describes in detail the current and most up-todate classification and staging of pancreatic neuroendocrine tumours,explores the rationale for nonsurgical and surgical management,and focuses on surgical treatment and more specifically,on minimally invasive approaches.

Spoon-assisted autologous particulate bone graft harvesting technique

Particulate bone plays a crucial role in various oral and maxillofacial surgical procedures,including reconstruction,implantation,and craniofacial surgery.Autologous bone and deproteinized bovine bone xenografts are the two primary resources used for such procedures,with the former demonstrating superior cost-effectiveness and reduced comorbidity rates,particularly in cases involving donor zones.However,a significant challenge lies in acquiring uniformly sized autologous particulate bone specimens,with existing tools often yielding coarse particles at a high cost.Consequently,commercial bone xenograft solutions are frequently favored despite lower standards.This technical note introduces a novel technique for swiftly,safely,and efficiently obtaining autologous particulate bone specimens.The procedure involves the use of a motor handpiece fitted with a micro drill and surgical spoon to collect the bone particles.The continuous irrigation with saline maintains a clear surgical field during the milling process.The collected bone particles are then transferred to a metal capsule for further use.This technique offers a promising solution to the challenge of inconsistent particle size associated with harvesting using traditional methods,providing surgeons with a reliable and efficient method of obtaining autologous particulate bone samples.

Solid pseudopapillary tumor of the pancreas:A systematic review of clinical,surgical and oncological characteristics of 1384 patients underwent pancreatic surgery

Background:Pancreatic solid pseudopapillary tumors(SPTs)are rare clinical entity,with low malignancy and still unclear pathogenesis.They account for less than 2%of exocrine pancreatic neoplasms.This study aimed to perform a systematic review of the main clinical,surgical and oncological characteristics of pancreatic SPTs.Data sources:MEDLINE/PubMed,Web of Science and Scopus databases were systematically searched for the main clinical,surgical and oncological characteristics of pancreatic SPTs up to April 2021,in accordance with the preferred reporting items for systematic reviews and meta-analyses(PRISMA)standards.Primary endpoints were to analyze treatments and oncological outcomes.Results:A total of 823 studies were recorded,86 studies underwent full-text reviews and 28 met inclusion criteria.Overall,1384 patients underwent pancreatic surgery.Mean age was 30 years and 1181 patients(85.3%)were female.The most common clinical presentation was non-specific abdominal pain(52.6%of cases).Mean overall survival was 98.1%.Mean recurrence rate was 2.8%.Mean follow-up was 4.2 years.Conclusions:Pancreatic SPTs are rare,and predominantly affect young women with unclear pathogenesis.Radical resection is the gold standard of treatment achieving good oncological impact and a favorable prognosis in a yearly life-long follow-up.

Risk of appendiceal neoplasm in patients with appendix disorders

The most common appendicular disease is acute appendicitis,with a lifetime risk of 7%–8%.Complicated cases,which can occur in 2%–7%of patients,can signi-ficantly impact the severity of the condition and may require different manage-ment approaches.Nonoperative management with possible delayed appende-ctomy has been suggested for selected patients,however,there is a non-negligible risk of missing an underlying malignancy,which is reported to be as high as 11%.Diagnostic work-up is paramount to achieve optimal treatment with good results.

Demineralized Bone Matrix Fibers plus Allograft Bone for Multilevel Posterolateral Spine Fusion: A Game Changer?

Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been used to avoid the morbidity and insufficient quantity associated with harvesting autologous bone. The primary objective of this retrospective study was to determine whether, in patients with increased risk of operative nonunion related to multilevel fusion, adding DBM fibers to mineralized bone allograft resulted in better fusion than using allograft alone. The secondary objectives were to evaluate how adding DBM fibers affects functional disability, low back pain, intraoperative blood loss and the nonunion rate. Methods: This retrospective study involved a chart review of consecutive patients who underwent multilevel lumbar spinal fusion and were operated on by a single surgeon. The patients were divided into two groups: 14 patients received mineralized bone allograft (control group) and 14 patients received a combination of mineralized bone allograft and DBM (experimental group). Patients were reviewed at a mean of 16.4 ± 2.2 months after surgery at which point CT scans were analyzed to determine whether fusion had occurred;Oswestry disability index (ODI) and pain were also evaluated. Results: A mean of 5 levels [min 2, max 13] were fused in these patients. Posterolateral fusion as defined by the Lenke classification was not significantly different between groups. The experimental DBM group had a significantly better composite fusion score than the control group (P Discussion: Adding DBM fibers to allograft bone during multilevel posterolateral spinal fusion was safe and produced better composite fusion than using allograft only as an autograft extender.

Implementing P-15/ABM Bone Graft as a Standardized Technique for Lumbar Fusion Approaches

Introduction: Lumbar fusion as low back pain treatment continues to be a challenge because of the multiple techniques and materials available, most popular techniques include Transforaminal lumbar interbody fusion (TLIF), Lateral lumbar interbody fusion (LLIF) and Anterior lumbar interbody fusion (ALIF). Successful lumbar fusion is associated with better clinical outcomes, and it is enhanced and targeted through the use of bone graft materials as an osteogenic cell binding peptide P-15, bound to an anorganic bone mineral (ABM). This peptide improves bone formation when used in fixation devices in a targeted and limited way to the implant surface by activating osteoblast precursor cells;by the osteogenic, osteoinductive and osteoconductive stimuli. The main objective of this study is to standardize the lumbar fusion process in the 3 techniques and achieve a more efficient and predictable lumbar fusion, evaluating results with radiological and clinical scales. Material and Methods: Patients underwent lumbar fusion with the use of P-15 Osteogenic Cell Binding Peptide, bound to an anorganic bone mineral (P-15/ABM) bone graft (5 cc) in three different techniques (TLIF, LLIF, ALIF), achieving a total of 100 lumbar levels. Radiological outcomes included fusion rates per Hounsfield Units at computed tomography (CT) scan and Lenke scale. Clinical outcomes were evaluated via the Oswestry Disability Index (ODI), Short Form Performance (SPF-36) and Visual Analog Scale (VAS and VASs) for pain and satisfaction. Results: 67 patients completed the 12 months follow-up, showing no differences in fusion rates between techniques. (Computed Tomography Hounsfield Units) CTHU reaches more than 200 UH at 3 months follow-up and continues fusion process till 12-month follow-up. Clinical scales showed no disability at ODI, improvement at VAS and VASs scales, absence of health restrictions at SPF-36 score since 6 months follow up. Conclusion: Bone graft volume of 5 cc is adequate for achieving successful lumbar fusion, regardless of the surgical technique employed.

Clinicopathologic characteristics and prognosis of gastroenteropancreatic neuroendocrine neoplasms: a multicenter study in South China

Background: Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) are a heterogeneous group of rare tumors. Many issues in terms of epidemiologic features, pathogenesis, and treatment of GEP-NENs are still under discussion. Our study aimed to analyze the clinicopathologic characteristics and prognosis of Chinese patients with GEP-NENs.Methods: Complete clinicopathologic data and survival information of 1183 patients with GEP-NENs treated between 2005 and 2015 were collected from five medical centers in Guangdong Province, China. Patient survival was estimated using the Kaplan–Meier method and analyzed using the log-rank test; prognostic factors were analyzed using the Cox proportional hazards model.Results: The most common tumor location was the rectum(37.4%), followed by the pancreas(28.1%), stomach(20.7%), small intestine(7.2%), appendix(3.4%), and colon(3.3%). After initial definitive diagnosis, 1016(85.9%) patients underwent surgery. The 1-, 3-, and 5-year overall survival(OS) rates for the entire cohort were 87.9%, 78.5%, and 72.8%, respectively. The 3-year OS rates of patients with G1, G2, and G3 tumors were 93.1%, 82.7%, and 43.1%, respectively(P < 0.001). The 3-year OS rates of patients with stage I, II, III, and IV tumors were 96.0%, 87.3%, 64.0%, and 46.8%, respectively(P < 0.001). Patients with distant metastasis who underwent palliative surgery had a longer survival than those who did not(P = 0.003). Similar survival benefits of palliative surgery were observed in patients with neuroendocrine tumor(P y, M category, and sur= 0.031) or neuroendocrine carcinoma(P gery were found to be independent prog= 0.046). In multivariate analysis, age, grade, N categornostic factors.Conclusions: Patients with GEP-NENs who are women, younger than 50 years old, have smaller tumor size, have lower tumor grade, have lower T/N/M category, and who undergo surgery can have potentially longer survival time. Our data showed that surgery can improve the prognosis of GEP-NEN patients with distant metastasis. However, randomized controlled trials need to be conducted to establish the optimal criteria for selecting patients to undergo surgery.

Current perspectives on pancreatic serous cystic neoplasms:Diagnosis, management and beyond

Pancreatic cystic neoplasms have been increasingly recognized recently. Comprising about 16% of all resected pancreatic cystic neoplasms, serous cystic neoplasms are uncommon benign lesions that are usually asymptomatic and found incidentally. Despite overall low risk of malignancy, these pancreatic cysts still generate anxiety, leading to intensive medical investigations with considerable financial cost to health care systems. This review discusses the general background of serous cystic neoplasms, including epidemiology and clinical characteristics, and provides an updated overview of diagnostic approaches based on clinical features, relevant imaging studies and new findings that are being discovered pertaining to diagnostic evaluation. We also concisely discuss and propose management strategies for better quality of life.

Differences between main-duct and branch-duct intraductal papillary mucinous neoplasms of the pancreas

In the last decade,intraductal papillary mucinous neoplasms(IPMNs) have become commonly diagnosed.From a morphological standpoint,they are classified in main-duct IPMNs(MD-IPMNs) and branch-duct IPMNs(BD-IPMNs),depending on the type of involvement of the pancreatic ductal system by the neoplasm.Despite the fact that our understanding of their natural history is still incomplete,recent data indicate that MD-IPMNs and BD-IPMNs show significant differences in terms of biological behaviour with MD-IPMNs at higher risk of malignant degeneration.In the present paper,clinical and epidemiological characteristics,rates of malignancy and the natural history of MD-IPMNs and BD-IPMNs are analyzed.The profile of IPMNs involving both the main pancreatic duct and its side branches(combined-IPMNs) are also discussed.Finally,general recommendations for management based on these differences are given.

Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis

BACKGROUND To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3%(25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8;heterogeneity: P = 0.126;I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2;95%CI: 1.8-161.1;heterogeneity: P = 0.165;I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2;95%CI: 0.3-11.6;heterogeneity: P = 0.304;I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3;95%CI: 0.1-1.1;heterogeneity: P = 0.173;I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5- year disease-specific survival rates reported;hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Update on surgical treatment of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms(PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential(neurendocrine tumors PNETs) or overt(neuroendocrine carcinomas PNECs) malignant,but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimallyinvasive approaches which should be tailored to the individual patient. Generally,surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs,indications for tumor resection are much wider than for pancreatic adenocarcinoma,in many cases due to the relatively benign tumor biology. Thus,patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands,even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However,poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly singlecenter series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable,ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review,we summarize recent advances in the surgical treatment of PNENs.

Efficacy of fascia iliaca compartment nerve block as part of multimodal analgesia after surgery for femoral bone fracture

BACKGROUND: Fascia iliaca compartment nerve block(FICNB) has been an established technique for postoperative analgesia after surgery for femoral bone fracture. FICNB is technically easy, effective for postoperative pain control after operation for femoral bone fracture and decreases the complications induced by systemic analgesic drugs. The severity of postoperative pain is affected by genetics, cultural and social factors across the world. In this study we assessed the efficacy of fascia iliaca compartment nerve block when it is used as part of multimodal analgesia after surgery for femoral bone fracture.METHODS: An institution-based case control study was conducted from September, 2013 to May, 2014. All patients who had been operated on under spinal anesthesia for femoral bone fracture were included. The patients divided into a FICNB group(n=20) and a control group(n=20). The FICNB group was given 30 mL of 0.25% bupivacaine at the end of the operation. Postoperative pain was assessed within the f irst 24 hours, i.e. at 15 minutes, 2 hours, 6 hours, 12 hours and 24 hours using 100 mm visual analogue scale(VAS), total analgesic consumption, and the time for the f irst analgesic request.RESULTS: VAS pain scores were reduced within the f irst 24 hours after operation in the FICNB group compared wtih the control group. VAS scores at 2 hours were taken as median values(IQR) 0.00(0.00) vs.18.00(30.00), P=0.001; at 6 hours 0.00(0.00) vs. 34.00(20.75), P=0.000; at 24 hours 12.50(10.00) vs. 31.50(20.75), P=0.004; and at 12 hours(17.80±12.45) vs.(29.95±12.40), P=0.004, respectively. The total analgesic consumption of diclofenac at 12 and 24 hours was reduced in the FICNB group, and the time for the fi rst analgesic request was signifi cantly prolonged(417.50 vs. 139.25 minutes, P=0.000).CONCLUSIONS: A single injection for FICNB could lead to postoperative pain relief, reduction of total analgesic consumption and prolonged time for the fi rst analgesic request in the FICNB group after surgery for femoral bone fracture. We recommend FICNB for analgesia after surgery for femoral bone fracture and for patients with femoral bone fracture at the emergency department.

Efficacy of topical vs intravenous tranexamic acid in reducing blood loss and promoting wound healing in bone surgery:A systematic review and meta-analysis

BACKGROUND Tranexamic acid(TXA)has been used as an anti-fibrinolytic drug for over half a century and has received much attention in recent decades.AIM To evaluate the efficacy of topical vs intravenous TXA in reducing blood loss and promoting wound healing in bone surgery.METHODS From the electronic resources,PubMed,Cochrane Library,Embase,ISI,and Scopus were used to perform a literature search over the last 10 years between 2010 and 2020.EndNote™X8 was used for managing the electronic resource.Searches were performed with mesh terms.The data were retracted blindly by two independent reviewers.Random effects were used to deal with potential heterogeneity and I2 showed heterogeneity.Chi-square(I2)tests were used to quantify the extent of heterogeneity(P<0.01 was considered statistically significant).The efficacy of topical TXA in reducing blood loss and promoting wound healing in bone surgery was compared with intravenous TXA and placebo.RESULTS According to the research design,1360 potentially important research abstracts and titles were discovered in our electronic searches,and 18 papers remained in agreement with our inclusion criteria.It was found that TXA reduced 277.51 mL of blood loss compared to placebo,and there was no significant difference between topical TXA and IV TXA in reducing blood loss in bone surgery.Our analyses also showed that TXA significantly reduced blood transfusion compared to placebo and there was no significant difference between topical TXA and IV TXA.CONCLUSION The use of both topical and intravenous TXA are equally effective in reducing blood loss in bone surgery,which might be beneficial for wound healing after surgery.

Effectiveness of enhanced recovery after surgery in the perioperative management of patients with bone surgery in China

BACKGROUND Enhanced recovery after surgery(ERAS)was introduced in China in 2007.Over time,the scope of ERAS has expanded from abdominal surgery to orthopedics,urology and other fields.Continuous development and research has contributed to progress of ERAS in China.In 2019,to promote the application of ERAS in bone tumor surgery,we formed the“Consensus of Experts on Perioperative Management of Accelerated Rehabilitation in Major Surgery of Bone Tumors in China”.AIM To evaluate the effect of enhanced recovery after bone tumor surgery in perioperative management in China.METHODS One hundred and seven patients who underwent bone tumor surgery at the Second Affiliated Hospital of Xi’an Jiaotong University between May 2019 and April 2021 were randomized into a study group(53 cases)and a control group(54 cases).The study group adopted the ERAS protocol and the control group adopted conventional care.Main outcome measures included postoperative length of stay(LOS),postoperative complications,mortality,and 30-d readmission rates.Secondary outcomes included postoperative visual analog scale(VAS)score of pain,number of blood transfusions,drainage volume in 24 h after operation,patient satisfaction 30 d after discharge,VAS score at 30 d after discharge,and daily standing walking time.RESULTS There were no significant differences in the baseline data,clinical features and surgical site between the two groups.The LOS in the study group with the ERAS protocol was 7.72±3.34 d compared with 10.28±4.27 d in the control group who followed conventional care.The incidence of postoperative nausea and vomiting(PONV)in the study group was 19%and 37%in the control group.The VAS scores of pain on postoperative day 1(POD1)and POD3 in the study group were 4.79±2.34 and 2.79±1.53 compared with 5.28±3.27 and 3.98±2.27 in the control group.The drainage volume in 24 h after the operation was 124.36±23.43 mL in the study group and 167.43±30.87 mL in the control group.The number of blood transfusions in the study group was also lower.The patient satisfaction rate was higher in the study group than in the control group.CONCLUSION The ERAS protocol in the perioperative period of bone tumor surgery can decrease LOS,PONV,and postoperative pain,blood transfusion and 24-h drainage,improve patient satisfaction and accelerate recovery.

Endoscopic submucosal dissection for colorectal neoplasms

Although endoscopic submucosal dissection(ESD) gains acceptance as one of the standard treatments for esophageal and stomach neoplasms in Japan,it is still in the developing stage for colorectal neoplasms.In terms of indications,little likelihood of nodal metastasis and technical resectability are principally considered.Some of intramucosal neoplasms,carcinomas with minute submucosal invasion,and carcinoid tumors,which are technically unresectable by conventional endoscopic treatments,may become good candidates for ESD,considering substantial risks and obtained benefits.ESD as a staging measure to obtain histological information of the invasion depth and lymphovascular infiltration is acceptable because preoperative prediction is difficult in some cases.In terms of techniques,advantages of ESD in comparison with other endoscopic treatments are to be controllable in size and shape,and to be resectable even in large and fibrotic neoplasms.The disadvantages may be longer procedure time,heavier bleeding,and higher possibility of perforation.However,owing to refinement of the techniques,invention of devices,and the learning curve,acceptable technical safety has been achieved.Colorectal ESD is very promising and become one of the standard treatments for colorectal neoplasms in the near future.

European vs 2015-World Health Organization clinical molecular and pathological classification of myeloproliferative neoplasms

The BCR/ABL fusion gene or the Ph^1-chromosome in the t(9;22)(q34;q11)exerts a high tyrokinase acticity,which is the cause of chronic myeloid leukemia(CML).The1990 Hannover Bone Marrow Classification separated CML from the myeloproliferative disorders essential thrombocythemia(ET),polycythemia vera(PV)and chronic megakaryocytic granulocytic myeloproliferation(CMGM).The 2006-2008 European Clinical Molecular and Pathological(ECMP)criteria discovered 3variants of thrombocythemia:ET with features of PV(prodromal PV),"true"ET and ET associated with CMGM.The 2008 World Health Organization(WHO)-ECMP and 2014 WHO-CMP classifications defined three phenotypes of JAK2^(V617F)mutated ET:normocellular ET(WHO-ET),hypercelluar ET due to increased erythropoiesis(prodromal PV)and ET with hypercellular megakaryocytic-granulocytic myeloproliferation.The JAK2^(V617F)mutation load in heterozygous WHO-ET is low and associated with normal life expectance.The hetero/homozygous JAK2^(V617F)mutation load in PV and myelofibrosis is related to myeloproliferative neoplasm(MPN)disease burden in terms of symptomaticsplenomegaly,constitutional symptoms,bone marrow hypercellularity and myelofibrosis.JAK2 exon 12mutated MPN presents as idiopathic eryhrocythemia and early stage PV.According to 2014 WHO-CMP criteria JAK2 wild type MPL^(515)mutated ET is the second distinct thrombocythemia featured by clustered giant megakaryocytes with hyperlobulated stag-horn-like nuclei,in a normocellular bone marrow consistent with the diagnosis of"true"ET.JAK2/MPL wild type,calreticulin mutated hypercellular ET appears to be the third distinct thrombocythemia characterized by clustered larged immature dysmorphic megakaryocytes and bulky(bulbous)hyperchromatic nuclei consistent with CMGM or primary megakaryocytic granulocytic myeloproliferation.

Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives

Although gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have always been considered rare tumors,their incidence has risen over the past few decades.They represent a highly heterogeneous group of neoplasms with several prognostic factors,including disease stage,proliferative index(Ki67),and tumor differentiation.Most of these neoplasms express somatostatin receptors on the cell surface,a feature that has important implications in terms of prognosis,diagnosis,and therapy.Although International Guidelines propose algorithms aimed at guiding therapeutic strategies,GEP-NEN patients are still very different from one another,and the need for personalized treatment continues to increase.Radical surgery is always the best option when feasible;however,up to 80%of cases are metastatic upon diagnosis.Regarding medical treatments,as GEP-NENs are characterized by relatively long overall survival,multiple therapy lines are adopted during the lifetime of these patients,but the optimum sequence to be followed has never been clearly defined.Furthermore,although new molecular markers aimed at predicting the response to therapy,as well as prognostic scores,are currently being studied,their application is still far from being part of daily clinical practice.As they represent a complex disease,with therapeutic protocols that are not completely standardized,GEP-NENs require a multidisciplinary approach.This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.

PVSG and WHO vs European Clinical,Molecular and Pathological Criteria for prefibrotic myeloproliferative neoplasms

The Polycythemia Vera Study Group(PVSG),World Health Organization(WHO) and European Clinical,Molecular and Pathological(ECMP) classifications agree upon the diagnostic criteria for polycythemia vera(PV) and advanced primary myelofibrosis(MF). Essential thrombocythemia(ET) according to PVSG and 2007/2008 WHO criteria comprises three variants of JAK2V617 F mutated ET when the ECMP criteria are applied. These include normocellular ET,hypercellular ET with features of early PV(prodromal PV),and hypercellular ET due to megakaryocytic,granulocytic myeloprolifera-tion(ET.MGM). Evolution of prodromal PV into overt PV is common. Development of MF is rare in normocellular ET(WHO-ET) but rather common in hypercellular ET.MGM. The JAK2V617 F mutation burden in heterozygous mutated normocellular ET and in heterozygous/homozygous or homozygous mutated PV and ET.MGM is of major prognostic significance. JAK2/MPL wild type ET associated with prefibrotic primary megakaryocytic and granulocytic myeloproliferation(PMGM) is characterized by densely clustered immature dysmorphic megakaryocytes with bulky(bulbous) hyperchromatic nuclei,which are never seen in JAK2V617 F mutated ET,and PV and also not in MPL515 mutated normocellular ET(WHO-ET). JAK2V617 mutation burden,spleen size,LDH,circulating CD34+ cells,and pre-treatment bone marrow histopathology are mandatory to stage the myeloproliferative neoplasms ET,PV,PMGM for proper prognosis assessment and therapeutic implications. MF itself is not a disease because reticulin fibrosis and reticulin/collagen fibrosis are secondary responses of activated polyclonal fibroblasts to cytokines released from the clonal myeloproliferative granulocytic and megakaryocytic progenitor cells in ET.MGM,PV and PMGM.

CONGENITAL EXPRESSION OF mdr-1 GENE IN FRESH CANCER TISSUES FROM SEVERAL HIGH-INCIDENCE NEOPLASMS WITHOUT PREOPERATIVE CHEMOTHERAPY

Objective: The purpose of the present study is to detect characteristics of primary expression of mdr 1 gene in several neoplasms which has high morbidity in clinic. Methods: 151 resected samples, which are pathologically malignant and clinically untreated before operation, were obtained from Anyang Cancer Hospital. All of them were investigated with RT PCR for the expression of mdr 1 gene and correlated each other. Besides, we evaluated the advantages of RT PCR in this study. Results: The mdr 1 gene expression rate of these 151 samples, including cancers of stomach and gastric cardia (n=51), esophagus (n=46), colorectum (n=16), breast (n=15), thyroid (n=10), lung (n=9), uterine cervix (n=4), was 33.3%, 37%, 31.3%, 13.2%, 40%, 55%, 0%, respectively. Conclusion: Compared with other methods, RT PCR for studying mdr 1 gene expression had certain advantages in simplicity, reliability, and accuracy. Overexpression of mdr 1 gene in these neoplasms suggested that cases should be distinguished before treatment according to MDR of tumor and to choose effective drugs for individual cancer patient.