Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Ambulatory Radio Iodine Therapy in the Management of Hyperthyroidism in Africa: African Systematic Review and Perspectives in Burkina Faso

Introduction: In hyperthyroidism, selective irradiation of the thyroid gland with radioactive iodine is a radical treatment and an alternative to surgery. The aim of this review is to assess the medium-term efficacy of outpatient treatment of hyperthyroidism with iodine-131 in Africa. Methods: We identified the studies carried out in Africa on outpatient radiation therapy between 2016 and 2020. For each article included, we noted the country concerned and the year of publication, the numbers studied, the socio-demographic characteristics of the patients, the indications for radio iodine therapy, the dose administered, the results of the hormonal dosage 6 months after radiation. Results: 13 retrospective studies were included to constitute a total population of 925 patients. The average age was 40.77 years, the sex ratio of 1/5.4 with a clear female predominance. The 3 main etiologies of hyperthyroidism justifying outpatient radio iodine therapy were Graves’ disease (55.89%), toxic multinodular goiter (22.70%) and toxic adenoma (21.40%). The average dose of iodine 131 administered per course is 13.7 mCi. No short-and medium-term complications were reported. The radio iodine therapy was effective in 86.08% (n = 796) of the patients with extremes of 72% and 100%. Conclusion: Radio iodine therapy is effective in Africa. It is simple, inexpensive on an outpatient basis and well tolerated. The introduction of outpatient radio iodine therapy could improve the management of patients with hyperthyroidism in Burkina Faso.

Radiological findings in non-surgical recurrent hepatocellular carcinoma:From locoregional treatments to immunotherapy

Since hepatocellular carcinoma(HCC)represents an important cause of mortality and morbidity all over the world.Currently,it is fundamental not only to achieve a curative treatment but also to manage in the best way any possible recurrence.Even if the latest update of the Barcelona Clinic Liver Cancer guidelines for HCC treatment has introduced new locoregional techniques and confirmed others as well-established clinical practices,there is still no consensus about the treatment of recurrent HCC(RHCC).Locoregional treatments and medical therapy represent two of the most widely accepted approaches for disease control,especially in the advanced stage of liver disease.Different medical treatments are now approved,and others are under investigation.On this basis,radiology plays a central role in the diagnosis of RHCC and the assessment of response to locoregional treatments and medical therapy for RHCC.This review summarized the actual clinical practice by underlining the importance of the radiological approach both in the diagnosis and treatment of RHCC.

Systematic review of ablative therapy for the treatment of renal allograft neoplasms

BACKGROUND To date,there are no guidelines on the treatment of solid neoplasms in the transplanted kidney.Historically,allograft nephrectomy has been considered the only reasonable option.More recently,nephron-sparing surgery (NSS) and ablative therapy (AT) have been proposed as alternative procedures in selected cases.AIM To review outcomes of AT for the treatment of renal allograft tumours.METHODS We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 Checklist.PubMed was searched in March 2019 without time restrictions for all papers reporting on radiofrequency ablation (RFA),cryoablation (CA),microwave ablation (MWA),high-intensity focused ultrasound (HIFU),and irreversible electroporation (IRE) of solid tumours of the kidney allograft.Only original manuscripts describing actual cases and edited in English were considered.All relevant articles were accessed in full text.Additional searches included all pertinent references.Selected studies were also assessed for methodological quality using a tool based on a modification of the Newcastle Ottawa scale.Data on recipient characteristics,transplant characteristics,disease characteristics,treatment protocols,and treatment outcomes were extracted and analysed.Given the nature and the quality of the studies available (mostly retrospective case reports and small retrospective uncontrolled case series),a descriptive summary was provided.RESULTS Twenty-eight relevant studies were selected describing a total of 100 AT procedures in 92 patients.Recipient age at diagnosis ranged from 21 to 71 years whereas time from transplant to diagnosis ranged from 0.1 to 312 mo.Most of the neoplasms were asymptomatic and diagnosed incidentally during imaging carried out for screening purposes or for other clinical reasons.Preferred diagnostic modality was Doppler-ultrasound scan followed by computed tomography scan,and magnetic resonance imaging.Main tumour types were: papillary renal cell carcinoma (RCC) and clear cell RCC.Maximal tumour diameter ranged from 5 to 55 mm.The vast majority of neoplasms were T1a N0 M0 with only 2 lesions staged T1b N0 M0.Neoplasms were managed by RFA (n = 78),CA (n = 15),MWA (n = 3),HIFU (n = 3),and IRE (n = 1).Overall,3 episodes of primary treatment failure were reported.A single case of recurrence was identified.Follow-up ranged from 1 to 81 mo.No cancer-related deaths were observed.Complication rate was extremely low (mostly < 10%).Graft function remained stable in the majority of recipients.Due to the limited sample size,no clear benefit of a single procedure over the other ones could be demonstrated.CONCLUSION AT for renal allograft neoplasms represents a promising alternative to radical nephrectomy and NSS in carefully selected patients.Properly designed clinical trials are needed to validate this therapeutic approach.

Liver-directed therapies for liver metastases from neuroendocrine neoplasms:Can laser ablation play any role?

Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases(LM)from neuroendocrine neoplasms(NEN),and minimally invasive,liver-directed therapies are gaining increasing interest.Catheter-based treatments are used in disseminated disease,whereas ablation techniques are usually indicated when the number of LM is limited.Although radiofrequency ablation(RFA)is by far the most used ablative technique,the goal of this opinion review is to explore the potential role of laser ablation(LA)in the treatment of LM from NEN.LA uses thinner needles than RFA,and this is an advantage when the tumors are in at-risk locations.Moreover,the multi-fiber technique enables the use of one to four laser fibers at once,and each fiber provides an almost spherical thermal lesion of 12-15 mm in diameter.Such a characteristic enables to tailor the size of each thermal lesion to the size of each tumor,sparing the liver parenchyma more than any other liver-directed therapy,and allowing for repeated treatments with low risk of liver failure.A recent retrospective study reporting the largest series of LM treated with LA documents both safety and effectiveness of LA,that can play a useful role in the multimodality approach to LM from NEN.

Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Advancing the understanding and management of blastic plasmacytoid dendritic cell neoplasm:Insights from recent case studies

We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination.The article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this disease.These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.Furthermore,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission.The editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.

Favorable response after radiation therapy for intraductal papillary mucinous neoplasms manifesting as acute recurrent pancreatitis:A case report

BACKGROUND There has been an increasing number of elderly patients with intraductal papillary mucinous neoplasm(IPMN),who are surgically intolerant and require less invasive treatment options,which are limited.In the present study,we report a case of IPMN presenting with acute recurrent pancreatitis(ARP),in which radiation therapy effectively prevented further attacks of ARP and reduced tumor volume.CASE SUMMARY An 83-year-old man was referred to our hospital with an asymptomatic incidental pancreatic cyst.Endoscopic ultrasound imaging and magnetic resonance cholangiopancreatography revealed a multiloculated tumor in the head of the pancreas,with dilated pancreatic ducts and mural nodules.The patient was diagnosed with mixed-type IPMN,and five years later,he developed ARP.Several endoscopic pancreatic ductal balloon dilatations failed to prevent further ARP attacks.Surgery was considered clinically inappropriate because of his old age and comorbidities.He was referred to our department for radiation therapy targeted at those lesions causing intraductal hypertension and radiation was administered at a dose of 50 Gy.An magnetic resonance imaging scan taken ten weeks after treatment revealed a decrease in tumor size and improvement of pancreatic duct dilatation.Fourteen months later,he remains symptom-free from ARP.CONCLUSION This case highlights the important role of radiation therapy in mitigating the signs and symptoms of ARP in patients with inoperable IPMN.

Clinical observation of 125 I labeled anti alpha fetoprotein antibody radioimmunotherapy in hepatocellular carcinoma *

AIM To observe the therapeutic effects and toxic side reactions of 125 I labeled hourse anti human AFP polyclonal antibodies in immuno targeting therapy against hepatocellular carcinoma (HCC).

A new breakthrough:ESD using a newly developed grasping type scissor forceps for early gastrointestinal tract neoplasms

Endoscopic submucosal dissection(ESD) has allowed the achievement of histologically curative en bloc resection of gastrointestinal neoplasms regardless of size,permitting the resection of previously non-resectable tumors.The ESD technique for treatment of early gastric cancer has spread rapidly in Japan and a few other Asian countries due to its excellent eradication rate compared to endoscopic mucosal resection.Although numerous electrosurgical knives have been developed for ESD,technical difficulties and high complication rates(bleeding and perforation) have limited their use worldwide.We developed the grasping type scissor forceps(GSF) to resolve such ESD-related problems.Our animal and preliminary clinical studies showed that ESD using GSF is a safe(no intraoperative complication) and technically efficient(curative en bloc resection rate 92%) method for dissection of early gastrointestinal tumors.The use of GSF is a promising option for performing ESD on early stage GI tract tumors both safely and effectively.

Radioiodine therapy for castration-resistant prostate cancer following prostate-specific membrane antigen promoter-mediated transfer of the human sodium iodide symporter

Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because of the thyroid-specific expression of the human sodium iodide symporter （hNIS）. Here, we explore the efficacy of a novel form of gene therapy using prostate-specific membrane antigen （PSMA） promoter-mediated hNIS gene transfer followed by radioiodine administration for the treatment of castration-resistant prostate cancer （CRPC）. The androgen-dependent C33 LNCaP cell line and the androgen-independent C81 LNCaP cell line were transfected by adenovirus. PSMA promoter-hNIS （Ad.PSMApro-hNIS） or adenovirus.cytomegalovirus-hNIS containing the cytomegalovirus promoter （Ad.CMM-hNIS） or a control virus. The iodide uptake was measured in vitro. The in vivo iodide uptake by C81 cell xenografts in nude mice injected with an adenovirus carrying the hNIS gene linked to PSMA and the corresponding tumor volume fluctuation were assessed. Iodide accumulation was shown in different LNCaP cell lines after Ad.PSMApro-hNIS and Ad.CMV-hNIS infection, but not in different LNCaP cell lines after adenovirus.cytomegalovirus （Ad.CMV） infection. At each time point, higher iodide uptake was shown in the C81 cells infected with Ad.PSMApro-hNIS than in the C33 cells （P 〈 0.05）. An in vivo animal model showed a significant difference in 1311 radioiodine uptake in the tumors infected with Ad.PSMApro-hNIS, Ad.CMV-hNIS and control virus （P 〈 0.05） and a maximum reduction of tumor volume in mice infected with Ad.PSMApro-hNIS. These results show prostate-specific expression of the hNIS gene delivered by the PSMA promoter and effective radioiodine therapy of CRPC by the PSMA promoter-driven hNIS transfection.

Selective lateral lymph node dissection after neoadjuvant chemoradiotherapy in rectal cancer

BACKGROUND Lateral lymph node metastasis is one of the leading causes of local recurrence in patients with advanced mid or low rectal cancer.Neoadjuvant chemoradiotherapy(NCRT)can effectively reduce the postoperative recurrence rate;thus,NCRT with total mesorectal excision(TME)is the most widely accepted standard of care for rectal cancer.The addition of lateral lymph node dissection(LLND)after NCRT remains a controversial topic.AIM To investigate the surgical outcomes of TME plus LLND,and the possible risk factors for lateral lymph node metastasis after NCRT.METHODS This retrospective study reviewed 89 consecutive patients with clinical stage II-III mid or low rectal cancer who underwent TME and LLND from June 2016 to October 2018.In the NCRT group,TME plus LLND was performed in patients with short axis(SA)of the lateral lymph node greater than 5 mm.In the non-NCRT group,TME plus LLND was performed in patients with SA of the lateral lymph node greater than 10 mm.Data regarding patient demographics,clinical workup,surgical procedure,complications,and outcomes were collected.Multivariate logistic regression analysis was performed to evaluate the possible risk factors for lateral lymph node metastasis in NCRT patients.RESULTS LLN metastasis was pathologically confirmed in 35 patients(39.3%):26(41.3%)in the NCRT group and 9(34.6%)in the non-NCRT group.The most common site of metastasis was around the obturator nerve(21/35)followed by the internal iliac artery region(12/35).In the NCRT patients,46%of patients with SA of LLN greater than 7 mm were positive.The postoperative 30-d mortality rate was 0%.Two(2.2%)patients suffered from lateral local recurrence in the 2-year follow up.Multivariate analysis showed that cT4 stage(odds ratio[OR]=5.124,95%confidence interval[CI]:1.419-18.508;P=0.013),poor differentiation type(OR=4.014,95%CI:1.038-15.520;P=0.044),and SA≥7 mm(OR=7.539,95%CI:1.487-38.214;P=0.015)were statistically significant risk factors associated with LLN metastasis.CONCLUSION NCRT is not sufficient as a stand-alone therapy to eradicate LLN metastasis in lower rectal cancer patients and surgeons should consider performing selective LLND in patients with greater LLN SA diameter,poorer histological differentiation,or advanced T stage.Selective LLND for NCRT patients can have a favorable oncological outcome.

Radiotherapy of 180 cases of operable esophageal carcinoma

AIM To compare the validity of radiotherapy and surgery for operable esophageal carcinoma in 180 patients with pathologically proved esophageal carcinoma who had been accepted for surgery, but for various reasons, were given radical radiation therapy. METHODS The reasons of abandoning surgery in the patients were: poor cardiac function (21), poor pulmonary function (36), poor general condition (9), senility (aged 69～81 years), 32 and refusal by the patient (82). They were treated either by the isocenter technic alone or anteroposterior plus isocenter irradiation to a total dose of 50～70 Gy/5～7wk. RESULTS The 1 , 3 and 5 year survival rates were 64%, 34% and 23%. The 3 and 5 year survival rates showed that lesions in the upper third did better than those in the middle and lower thirds ( P <0 05). The 5 year survival rate by radiation alone (44 5%) of the upper third lesions was slightly better than by surgery. The effect for lesions in the middle third was slightly inferior, and that for the lower third was even poorer than that of surgery. CONCLUSION The result of radiation alone for the operable esophageal carcinoma was similar to that of surgery.

Double-bullet radioimmunotargeting therapy in 31 patients with primary liver cancer

AIM To observe the effect of a double bullet immunotargeting therapy with the merit of chemotherapy and internal radiotherapy for primary liver cancer. METHODS The polyclonal horse antibody against human AFP (anti AFPAb) and the monoclonal murine antibody against human AFP (anti AFPMcAb) were used as carriers, and 131 I and mitomycin C (MMC) as warheads, to form double bullet, ie, 131 I anti AFPMcAb MMC (double bullet 1) and 131 I anti AFPAb MMC (double bullet 2) prepared by the modified chloramine T method. The double bullet targeting therapy was administered by intravenous drip once a month in 31 patients (treatment group) with unresectable primary liver cancer. Among them 4, 17 and 10 patients were administered 1, 2 and 3 times, and the median value of radiation dose (MBq/case) were 193 5±37 74; 651 9±232 4, and 992 0±230 5 respectively. RESULTS The shrinkage of tumor, AFP decrease and 1 and 2 year survival rates were significantly higher than those of the control groups of transarterial infusion (TAI) or transarterial chemoembolization (TACE) at the same time (50 0%, 15/30 vs 30 0%, 9/30, P <0 05; 66 7%, 18/27 vs 28 0%, 7/25, P <0 01 and 50 0%, 34 0% vs 33 0%, 3 3%, P <0 01, respectively). Furthermore, the tumor progression rate (10%) in treatment group was significantly lower than that of control group (40 0%, P <0 01). CONCLUSION Double bullet target therapy has a better effect due to the synergistic effects of antibody, radioisotope, and anticancer agents, thus enhancing the tumor killing effect.

Outcomes of T3a Prostate Cancer with Unfavorable Prognostic Factors Treated with Brachytherapy Combined with External Radiotherapy and Hormone Therapy

Objective To evaluate the outcomes of T3 a prostate cancer with unfavorable prognostic factors treated with permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy.Methods From January 2003 to December 2008,38 patients classified as T3 a prostate cancer with unfavorable prognostic factors were treated with trimodality therapy(brachytherapy + external radiotherapy + hormone therapy).The prescription dose of brachytherapy and external radiotherapy were 110 Gy and 45 Gy,respectively.The duration of hormone therapy was 2-3 years.The endpoints of this study included biochemical failure-free survival(BFFS),distant metastasis-free survival(DMFS),cancer-specific survival(CSS),and overall survival(OS).Survival curves were calculated using the Kaplan-Meier method.The Log-rank test was used to identify the prognostic predictors for univariate analysis.Results The median follow-up was 71 months.The serum pre-treatment prostate-specific antigen(PSA) level ranged from 10.0 to 99.8 ng/ml(mean 56.3 ng/ml),the Gleason score ranged from 5 to 9(median 8),and the percentage of positive biopsy cores ranged from 10% to 100%(mean 65%).The 5-year BFFS,DMFS,CSS,and OS rates were 44%,69%,82%,and 76%,respectively.All biochemical failures occurred within 40 months.The percentage of positive biopsy cores was significantly correlated with BFFS,DMFS,and OS(all P=0.000),and the Gleason score with DMFS(P=0.000) and OS(P=0.001).Conclusions T3 a prostate cancer with unfavorable prognostic factors presents not so optimistic outcome.Hormone therapy should be applied to prolong the biochemical progression-free or metastasis-free survival.The percentage of positive biopsy cores and the Gleason score are significant prognostic factors.

Gastroenteropancreatic neuroendocrine neoplasms:A clinical snapshot

Our understanding about the epidemiological aspects,pathogenesis,molecular diagnosis,and targeted therapies of neuroendocrine neoplasms(NENs)have drastically advanced in the past decade.Gastroenteropancreatic(GEP)NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors.Most NENs are welldifferentiated,and slow growing.Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin,glucagon,vasoactive intestinal polypeptide,gastrin,somatostatin,adrenocorticotropin,growth hormone releasing hormone,parathyroid hormone-related peptide,serotonin,histamine,and 5-hydroxy indole acetic acid(5-HIAA).Biomarkers such as pancreatic polypeptide,human chorionic gonadotrophin subunits,neurotensin,ghrelin,and calcitonin are used in the diagnosis of non-functional NENs.5-HIAA levels correlate with tumour burden,prognosis and development of carcinoid heart disease and mesenteric fibrosis,however several diseases,medications and edible products can falsely elevate the 5-HIAA levels.Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs.Emerging novel biomarkers include circulating tumour cells,circulating tumour DNA,circulating micro-RNAs,and neuroendocrine neoplasms test(NETest)(simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood).NETest has high sensitivity(85%-98%)and specificity(93%-97%)for the detection of gastrointestinal NENs,and is useful for monitoring treatment response,recurrence,and prognosis.In terms of management,surgery,radiofrequency ablation,symptom control with medications,chemotherapy and molecular targeted therapies are all considered as options.Surgery is the mainstay of treatment,but depends on factors including age of the individual,location,stage,grade,functional status,and the heredity of the tumour(sporadic vs inherited).Medical management is helpful to alleviate the symptoms,manage inoperable lesions,suppress postoperative tumour growth,and manage recurrences.Several molecular-targeted therapies are considered second line to somatostatin analogues.This review is a clinical update on the pathophysiological aspects,diagnostic algorithm,and management of GEP NENs.

Indications of external radiotherapy for hepatocellular carcinoma from updated clinical guidelines: Diverse global viewpoints

The etiology and disease patterns of hepatocellular carcinoma(HCC)significantly vary among regions. Modern standard treatments commonly require multidisciplinary approaches, including applications of up-to date medicine and advanced procedures, and necessitate the support of socioeconomic systems. For these reasons, a number of clinical guidelines for HCC from different associations and regions have been presented. External beam radiation therapy was contraindicated for HCC until a few decades ago, but with the development of new technologies, its application has rapidly increased as selective irradiation for tumorous lesions became possible. Most of the guidelines had been opposed or indifferent to radiotherapy in the past, but several guidelines have introduced indications and recommendations for radiotherapy in their updated versions. This review will discuss the characteristics of important guidelines and their contents regarding radiotherapy and will also provide guidance to physicians who are considering applications of locoregional modalities that include radiotherapy.

Advances in medical treatment for pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms(PanNENs)are rare neoplasms with strong heterogeneity that have experienced an increasing incidence rate in recent years.For patients with locally advanced or distant metastatic PanNENs,systemic treatment options vary due to the different differentiations,grades and stages.The available options for systemic therapy include somatostatin analogs,molecularly targeted agents,cytotoxic chemotherapeutic agents,immune checkpoint inhibitors,and peptide receptor radionuclide therapy.In addition,the development of novel molecularly targeted agents is currently in progress.The sequence of selection between different chemotherapy regimens has been of great interest,and resistance to chemotherapeutic agents is the major limitation in their clinical application.Novel agents and high-level clinical evidence continue to emerge in the field of antiangiogenic agents.Peptide receptor radionuclide therapy is increasingly employed for the treatment of advanced neuroendocrine tumors,and greater therapeutic efficacy may be achieved by emerging radiolabeled peptides.Since immune checkpoint inhibitor monotherapies for PanNENs appear to have limited antitumor activity,dual immune checkpoint inhibitor therapies or combinations of antiangiogenic therapies and immune checkpoint inhibitors have been applied in the clinic to improve clinical efficacy.Combining the use of a variety of agents with different mechanisms of action provides new possibilities for clinical treatments.In the future,the study of systemic therapies will continue to focus on the screening of the optimal benefit population and the selection of the best treatment sequence strategy with the aim of truly achieving individualized precise treatment of PanNENs.

Endoscopic techniques for diagnosis and treatment of gastroentero-pancreatic neuroendocrine neoplasms:Where we are

BACKGROUND The correct localization of the primary tumor site and a complete histological diagnosis represent the milestones for the proper management of gastro-enteropancreatic neuroendocrine neoplasms(GEP-NENs).AIM To analyze current evidence on the role of endoscopy in the diagnosis/treatment of GEP-NENs.METHODS An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature(retrospective and prospective studies,systematic reviews,case series)published in the last 15 years,using both medical subject heading(MeSH)terms and free-language keywords:gastro-enteropancreatic neuroendocrine neoplasms;endoscopy;ultrasound endoscopy;capsule endoscopy;double-balloon enteroscopy;diagnosis;therapy;staging.RESULTS In the diagnostic setting,endoscopic ultrasonography(EUS)represents the diagnostic gold standard for pancreatic NENs and the technique of choice for the locoregional staging of gastric,duodenal and rectal NENs.The diagnosis of small bowel NENs(sbNENs)has been improved with the advent of video capsule endoscopy and double-balloon enteroscopy,which allow for direct visualization of the entire small bowel;however,data regarding the efficacy/safety of these techniques in the detection of sbNENs are scanty and often inconclusive.From a therapeutic point of view,endoscopic removal is the treatment of choice for the majority of gastric NENs(type 1/2),for well-differentiated localized nonmetastatic duodenal NENs<1 cm,confined to the submucosa layer and for<10 mm,stage T1–T2,rectal NENs.EUS-guided pancreatic locoregional ablative treatments have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients.CONCLUSION Standard axial endoscopy and EUS still play a pivotal role in several GEP-NENs.Advanced techniques for increasing the rate of R0 resection should be reserved for high-volume referral centers.

A Randomized Clinical Study on Combination of Concurrent Chemo-Radiotherapy and Thalidomide for Middle-Late Esophageal Cancer

OBJECTIVE To evaluate the response rate and tolerance of patients with middle-late esophageal carcinoma, who were treated with concurrent chemoradiotherapy （CCRT） plus thalidomide.METHODS Sixty-five eligible patients with local middle-late esophageal carcinoma were randomly assigned to the treatment group （TG） and the control group （CG）. The 33 patients from the TG were treated with CCRT plus thalidomide （a 60-70 Gy of radiation dose, and 5-FU plus cisplatin; oral administration of thalidomide at a dose of 100 mg/d on the first week and 200 mg/d on the second. Both were taken with water, at bedtime until completion of the radiotherapy. In the CG, 32 patients received CCRT only. The clinical effects and tolerance to the CCRT between the 2 groups were compared.RESULTS The response rates of the therapeutic combination in the TG and CG were 87.9% and 68.7%, respectively. There were no statistical differences in comparing the response rates between the 2 groups （P 〉 0.05）; the local control rates in the TG and CG were 93% and 91%, respectively, and there were no statistical differences between the 2 groups （P 〉 0.05）; the 1-year survival rates of the patients in the TG and CG were 74.0% and 63.0%, respectively, without statistical differences between the 2 groups （P 〉 0.05）. The improvement rates of KPS scoring in the TG and CG were 57.6% and 31.3%, respectively. There were significant differences in comparing the improvement rates between the 2 groups （P 〈 0.05）. The incidence rates of nausea and vomiting were lower in the TG compared to the CG, with a statistical significance between the 2 groups （P 〈 0.05）. However, the incidence rates of constipation, lethargy and fatigue were higher in the TG than in CG, showing a statistically significant difference between the 2 groups （P 〈 0.05）. CONCLUSION CCRT combined with thalidomide in treating esophageal carcinoma may improve the quality of life of the patients, the treatment may also raise patients＇ compliance to chemoradiotherapy, and possibly increase their long-term survival rate. Further studies related to this topic are needed.