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.

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.

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.

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.

Comprehensive treatment of advanced primary live cancer with intraperitoneal chemotherapy or in combination with other therapies:therapeutic observation of 72 cases

Objective： To evaluate the effect of intraperitoneal chemotherapy or in combination with other therapies in patients with advanced primary liver cancer. Methods： 72 patients with advanced primary liver cancer with no indication for surgery received intraperitoneal chemotherapy in combination with other therapies including transcatheter arterial chemoembolization （TACE）, radiofrequency catheter ablation （RFA）, percutaneous ethanol injection therapy （PELT） and radiotherapy. Of them, 29 cases were complicated with hilar or retroperitoneal multiple lymph node metastases, 14 with portal vein embolus, 15 with intrapedtoneal and diaphragmatic metastases, 6 with chylous ascites, one with cancerous ascites, and 7 with suspected cancerous ascites （referring to large amounts of ascites without hypoproteinemia while exfoliative cytology of the ascites was positive）. The mean maximum tumor size was 8.2 cm in diameter. Liver function at the initial treatment was Child A in 53 cases, and Child B in 19 cases. I ntrapedtoneal chemotherapy was performed in all these patients. The intraperitoneal chemotherapy protocols included： 5-FU 0.5-0.75 g/d for 10-15 consecutive days, with a total dosage of 5-12.5 g, and at the last day of chemotherapy 10 mg mitomycin （MMC） or 100 mg carboplatin was injected. For 7 cases of cholangiocarcinoma, Gemzar 800-1000 mg was administered additionally. A majority of all these patients received another one or two therapy methods followed by intraperitoneal chemotherapy. TACE was performed in the patients with multiple tumors or nodule more than 5 cm in diameter in the liver, RFA or PElT with nodule fewer than 4 in number and 5 cm or less than 5 cm in diameter and radiotherapy, only for metastases, with metastatic lymph nodes, localized metastasis within the abdominal cavity or portal vein embolus. Interval time between two methods was one month or so. Two months after the sequential therapy, repeated treatment would be given if general medical condition and liver function were perfect at that time. Results： The median survival time of the group was 13.97 ± 6.27 months. The 1- and 2-year survival rates were 59.7% and 30.6% respectively. The mean survival time of the patients with liver function Child A was 15.91 ± 5.49 months, and that of the patients with Child B was 8.55 ± 5.09 months. The difference was statistically significant （P 〈 0.05）. Conclusion： Intraperitoneal chemotherapy or in combination with other therapies in patients with advanced primary liver cancer with metastases to abdominal cavity is an effective method. It can prolong the survival time and improve life quality for a certain percentage of patients with advanced pnmary liver cancer.

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.

Prevention of metastasis to liver by using 5-FU intraperitoneal chemotherapy in nude mice inoculated with human colonic cancer cells

AIMS Using a new approach of regional adjuvant chemotherapy to prevent cancer cells hepatic metasta- sis after radical surgery of large bowel cancer. METHODS A model of liver with metastasis of hu- man colonic cancer (HCC) cells in nude mice was used to observe the effect in prevention of metastasis of HCC cells inoculated via spleen applied with early postoper- ative intraperitoneal (IP) chemotherapy using large dose of 5-FU. RESULTS The incidence of metastasis to liver was decreased by 40%,the mean number of metastatic liv- er nodules in each animal was reduced by 50.89% and the mean survival times of each animal was prolonged by 48.21% by using 5-FU 40 mg/NS 40 ml/kg IP for two consecutive days as compared with the controls. CONCLUSIONS IP is a new and more effective re- gional adjuvant chemotheraputic approach in the pre- vention of liver metastasis HCC cells after radical surgery of large bowel cancer.

The value of postoperative hepatic regional chemotherapy in prevention of recurrence after radical resection of primary liver cancer

INTRODUCTIONIn China,primary liver cancer (PLC) ranks secondin cancer mortality since the 1990s.In the field ofPLC treatment,surgical resection remains the best,which includes large PLC resection,small PLCresection,re-resection of subclinical recurrence,aswell as cytoreduction and sequential resection forunresectable PLC.However,recurrence

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.

Targeted IL-24 gene therapy inhibits cancer recurrence after liver tumor resection by inducing tumor cell apoptosis in nude mice

BACKGROUND: Interleukin-24 (IL-24) is a novel candidate tumor suppressor that induces tumor cell apoptosis experimentally in a variety of human malignant cells including liver cancer cells. The present study was conducted to investigate the potential effect of recombinant adeno-associated virus (rAAV)-mediated IL-24 gene therapy on tumor recurrence and metastasis by inducing tumor cell apoptosis in a hepatocellular carcinoma (HCC) model in nude mice. METHODS: We established a recurrent and metastatic HCC model in nude mice and constructed an rAAV vector carrying alpha-fetoprotein (AFP) promoter for expressing the IL-24 gene (rAVV/AFP/IL-24). The vector was administered by regional injection (liver incisal margin). AFP was detected by radiation immunoassay. Histological evaluation of tumor recurrence and metastasis was performed for the liver and lung. The effect of tumor cell apoptosis was confirmed by TUNEL analysis. RESULTS: IL-24 gene therapy prevented tumor recurrence and metastasis, as evidenced by marked decreases in the number of metastatic tumor nodules and tumor volume in the liver and lung. At the same time, serum AFP concentration decreased markedly in the IL-24 group compared with the control or rAAV groups (P<0.05). IL-24 gene therapy inhibited tumor recurrence and metastasis as evidenced by the induction of tumor cell apoptosis. CONCLUSION: The results demonstrated that targeted IL-24 gene therapy was effective in the prevention of postoperative recurrence and metastasis in an HCC nude mice model by induction of tumor cells apoptosis with potential minimum tumor burden.

Neo-adjuvant therapy for hepatocellular carcinoma before liver transplantation:Where do we stand?

Liver transplantation (LT) for hepatocellular carcinoma (HCC) within Milan criteria is a widely accepted optimal therapy. Neo-adjuvant therapy before transplantation has been used as a bridging therapy to prevent dropout during the waiting period and as a down-staging method for the patient with intermediate HCC to qualify for liver transplantation. Transarterial chemoembolization and radiofrequency ablation are the most commonly used method for locoregional therapy. The data associated with newer modalities including drug-eluting beads, radioembolization with Y90, stereotactic radiation therapy and sorafenib will be discussed as a tool for converting advanced HCC to LT candidates. The concept &#x0201c;ablate and wait&#x0201d; has gained the popularity where mandated observation period after neo-adjuvant therapy allows for tumor biology to become apparent, thus has been recommended after down-staging. The role of neo-adjuvant therapy with conjunction of &#x0201c;ablate and wait&#x0201d; in living donor liver transplantation for intermediate stage HCC is also discussed in the paper.

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.

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.

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.

Efficacy of neoadjuvant chemotherapy for initially resectable colorectal liver metastases:A retrospective cohort study

BACKGROUND The liver is the most common metastatic site of colorectal cancer.Hepatectomy is the mainstay of treatment for patients with colorectal liver metastases(CRLMs).However,there are cases of early recurrence after upfront hepatectomy alone.In selected high-risk patients,neoadjuvant chemotherapy(NAC)may improve longterm survival.AIM To determine the efficacy of NAC for initially resectable CRLMs.METHODS Among 644 patients who underwent their first hepatectomy for CRLMs at our institution,297 resectable cases were stratified into an upfront hepatectomy group(238 patients)and a NAC group(59 patients).Poor prognostic factors for upfront hepatectomy were identified using multivariate logistic regression analysis.Propensity score matching was used to compare clinical outcomes between the upfront hepatectomy and NAC groups,according to the number of poor prognostic factors.Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test.RESULTS Preoperative carcinoembryonic antigen levels(≥10 ng/mL)(P=0.003),primary histological type(other than well/moderately differentiated)(P=0.04),and primary lymph node metastases(≥1)(P=0.04)were identified as independent poor prognostic factors for overall survival(OS)in the upfront hepatectomy group.High-risk status was defined as the presence of two or more risk factors.After propensity score matching,50 patients were matched in each group.Among high-risk patients,the 5-year OS rate was significantly higher in the NAC group(13 patients)than in the upfront hepatectomy group(18 patients)(100%vs 34%;P=0.02).CONCLUSION NAC may improve the prognosis of high-risk patients with resectable CRLMs who have two or more risk factors.

Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.

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.

Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

A comparative study of different interventional therapies for primary liver cancer

IM To compare the therapeutic effect of three types of interventional management for pimary liver cancer.METHODS 468 patients with primary liver cancer were randomly allocated to three groups: 138 cases with chemotherapy alone using mitomycin C, adriamycin and 5FU (group A); 158 with chemoembolization using lipiodol (group B); and 172 with chemoembolization using lipiodol and gelfoam (group C). All patients were angiographically and sonographically followed up.RESULTS ① 675% patients in group C had the AFP value decreased by more than 50%, which was much higher than 433% ingroup B and 322% in group A; ② The tumor size reduced by ≥50% in 203% of group A, 412% of group B and 448% of group C. There was obvious difference between groups A and group B or C (P<001); ③ The oneyear and threeyear survival rates were 205%±36% and 19%±24% for group A, 513%±44% and 101%±49% for group B, and 630%±24% and 139%±50% for group C respectively. There was obvious difference among the three groups (P<005); ④ The mean survival time for patients in groups A, B and C were 96 months, 161 months and 179 months, respectively.CONCLUSION Chemoembolization with lipiodol and gelfoam is the most effective therapy for primary liver cancer in this study. The position of the embolization should be the far and middle sections of the hepatic artery, and the proximal section should be reserved as the route of the next intraarterial chemoembolization.

Outcomes associated with the intention of loco-regional therapy prior to living donor liver transplantation for hepatocellular carcinoma

BACKGROUND Loco-regional therapy for hepatocellular carcinoma(HCC) during the period awaiting liver transplantation(LT) appears to be a logical approach to reduce the risk of tumor progression and dropout in the waitlist.Living donor LT(LDLT)offers a flexible timing for transplantation providing timeframe for well preparation of transplantation.AIM To investigate outcomes in relation to the intention of pre-transplantation locoregional therapy in LDLT for HCC patients.METHODS A total of 308 consecutive patients undergoing LDLTs for HCC between August2004 and December 2018 were retrospectively analyzed.Patients were grouped according to the intention of loco-regional therapy prior to LT,and outcomes of patients were analyzed and compared between groups.RESULTS Overall,38 patients(12.3%) were detected with HCC recurrence during the follow-up period after LDLT.Patients who were radiologically beyond the University of California at San Francisco criteria and received loco-regional therapy as down-staging therapy had significant inferior outcomes to other groups for both recurrence-free survival(RFS,P < 0.0005) and overall survival(P= 0.046).Moreover,patients with defined profound tumor necrosis(TN) by locoregional therapy had a superior RFS(5-year of 93.8%) as compared with others(P= 0.010).CONCLUSION LDLT features a flexible timely transplantation for patient with HCC.However,the loco-regional therapy prior to LDLT does not seem to provide benefit unless a certain effect in terms of profound TN is noted.