Nationwide questionnaire survey on pediatric pancreatic tumors in Japan

BACKGROUND Pediatric pancreatic tumors are rare and account for<0.1%of all childhood cancers.The primary treatment for pancreatic tumors is surgical resection.However,because of the lack of knowledge regarding pediatric pancreatic tumors,no comprehensive treatment plans for pediatric pancreatic tumors have been developed.AIM To compared the clinical features,treatment methods,and prognosis of pediatric pancreatic tumors in Japan with those in other countries.METHODS Questionnaires were sent to 213 pediatric surgical units in Japan.Pancreatic tumors that were not surgically treated were excluded from the survey.The primary survey investigated the number of patients aged 0-18 years who underwent pancreatic tumor surgery and the type of tumors managed during the 22-year study period(from January 1,2000 to December 31,2021)by post card.The secondary survey assessed the clinical images,treatment methods,and tumor outcomes via email.RESULTS The primary survey enrolled 228 patients.In the secondary survey,213 patients were eventually enrolled.The most common type of pancreatic tumor was solid pseudopapillary neoplasm(SPN)[n=164(77.0%)],followed by pancreatoblastoma[n=16(7.5%)],pancreatic endocrine tumor[n=14(6.6%)],non-epithelial tumor[n=9(4.2%)],pancreatic tumor[n=7(3.3%)],and metastatic pancreatic tumor[n=3(1.4%)].Overall,123(57.7%)patients underwent distal pancreatectomy,of whom 49 underwent laparoscopic surgery.Forty-four(20.7%)patients underwent enucleation,of whom eight underwent laparoscopic surgery.Thirty-two(15.0%)patients underwent pancreaticoduodenectomy,of whom one underwent laparoscopic surgery.All patients with SPN,including those with distant metastases and recurrent disease,survived.CONCLUSION SPN was more common in Japan than in other countries.Regardless of the histological type,resection is the most effective treatment for pediatric pancreatic tumors.

Laparoscopic spleen-preserving total pancreatectomy for the treatment of low-grade malignant pancreatic tumors:Two case reports and review of literature

BACKGROUND Function-preserving pancreatectomy can improve the long-term quality of life of patients with benign or low-grade malignant tumors,such as intraductal papillary mucinous neoplasms(IPMNs)and mucinous cystic neoplasms.However,there is limited literature on laparoscopic spleen-preserving total pancreatectomy(LSpTP)due to technical difficulties.CASE SUMMARY Patient 1 was a 51-year-old male diagnosed with IPMN based on preoperative imaging,showing solid nodules in the pancreatic head and diffuse dilation of the main pancreatic duct with atrophy of the distal pancreas.We performed L-SpTP with preservation of the splenic vessels,and the postoperative pathology report revealed IPMN with invasive carcinoma.Patient 2 was a 60-year-old male with multiple cystic lesions in the pancreatic head and body.L-SpTP was performed,and intraoperatively,the splenic vein was injured and required ligation.Postoperative pathology revealed a mucinous cystic tumor of the pancreas with low-grade dysplasia.Both patients were discharged on postoperative day 7,and there were no major complications during the perioperative period.CONCLUSION We believe that L-SpTP is a safe and feasible treatment for low-grade malignant pancreatic tumors,but more case studies are needed to evaluate its safety,efficacy,and long-term outcomes.

Obstructive jaundice caused by secondary pancreatic tumor from malignant solitary fibrous tumor of pleura:A case report

A 77-year-old man on systemic chemotherapy against postoperative bilateral multiple lung metastases of malignant solitary fibrous tumor of the pleura suffered from pruritus and jaundice. Blood examination showed elevated levels of hepatobiliary enzymes. Abdominal computed tomography showed a tumor with peripheral enhancement in the pancreatic head, accompanied with the dilatation of intra- and extra-hepatic bile ducts. He was diagnosed as having obstructive jaundice caused by a pancreatic head tumor. The pancreatic head tumor was presumably diagnosed as the metastasis of malignant solitary fibrous tumor of the pleura, because the findings on the pancreatic head tumor on abdominal CT were similar to those on the primary lung lesion of malignant solitary fibrous tumor of the pleura. The pancreatic tumor grew rapidly after the implantation of metallic stent in the inferior part of the common bile duct. The patient died of lymphangitis carcinomatosa of the lungs. Autopsy revealed a tumor that spread from the pancreatic head to the hepatic hilum. Microscopically, spindle-shaped cells exhibiting nuclear atypicality or division together with collagen deposition were observed. Immunohistochemically the pancreatic head tumor cells were negative for staining of α-smooth muscle actin （α-SMA） or CD117, but positive for vimentin, CD34 and CD99. These findings are consistent with those on malignant solitary fibrous tumor of the pleura. We report the first case of obstructive jaundice caused by a secondary pancreatic tumor from malignant solitary fibrous tumor of the pleura.

Molecular alterations in pancreatic tumors

Genetic alterations in pancreatic tumors can usually be classified in:(1)Mutational activation of oncogenes;(2)Inactivation of tumor suppressor genes;and(3)Inactivation of genome maintenance genes controlling the repair of DNA damage.Endoscopic ultrasound-guided fine-needle aspiration has improved preoperative diagnosis,but the management of patients with a pancreatic lesion is still challenging.Molecular testing could help mainly in solving these“inconclusive”specimens.The introduction of multi-gene analysis approaches,such as next-generation sequencing,has provided a lot of useful information on the molecular characterization of pancreatic tumors.Different types of pancreatic tumors(e.g.,pancreatic ductal adenocarcinomas,intraductal papillary mucinous neoplasms,solid pseudopapillary tumors)are characterized by specific molecular alterations.The aim of this review is to summarize the main molecular alterations found in pancreatic tumors.

Surgery for pancreatic tumors in the midst of COVID-19 pandemic

The spread of the new coronavirus(COVID-19)infection in 2020 has had a significant impact on the treatment of cancer worldwide.During the COVID-19 pandemic,the biggest challenge for pancreatic surgeons is the difficulty in providing oncological care.In this review article,from the standpoint of surgeons,we explain the concept of triaging of patients with pancreatic tumors under the COVID-19 pandemic,and the actual impact of COVID-19 on the treatment of patients with pancreatic tumors.The most vital points in selecting the best therapeutic approach for patients with pancreatic tumors during this pandemic are(1)Oncologists need to tailor the treatment plan based on the COVID-19 phase,tumor malignant potential,and patients’comorbidities;and(2)Optimal treatment for pancreatic cancer should be planned according to the condition of each patient and tumor resectability based on national comprehensive cancer network resectability criteria.To choose the best therapeutic approach for patients with pancreatic tumors during this pandemic,we need to tailor the treatment plan based on elective surgery acuity scale(ESAS).Newly established ESAS for pancreatic tumor and flowchart indicating the treatment strategy of pancreatic cancer,are feasible to overcome this situation.

Central pancreatectomy:a new technique for resection of selected pancreatic tumors

BACKGROUND:Pancreatic tumors located in the neck region usually require pancreaticoduodenectomy or splenopancreatectomy.For small benign tumors enucleation is not usually feasible due to their size and localization;then pancreatectomy is often needed.Central pancreatectomy consists of a limited resection of the midportion of the pancreas and can be offered in benign and low-grade malignant tumors of the neck of the pancreas.The study aimed to evaluate whether central pancreatectomy has a place in pancreatic surgery. METHODS:In this study,which covered a period of 14 months,we performed central pancreatectomy in four selected patients.Preoperative evaluation and operative frozen section biopsy in indicated cases allowed proper selection for the procedure.Operative details,complications and follow-up were recorded. RESULTS:Four patients,two with serous cystadenoma,and one with an islet cell tumor,and one with a hydatid cyst, were identified for the procedure.The mean tumor size was 3 cm,the mean operative time was 217.5 minutes,and the mean blood loss was 382.5 ml.There was no morbidity or mortality in this series.No endocrine or exocrine deficiency was observed in any patient during a mean follow-up of 22.7 months. CONCLUSIONS:Central pancreatectomy is a procedure that offers excellent results in benign and low-grade malignant tumors.It preserves functional elements(endocrine and exocrine)of the pancreas and also eliminates the infective and hematological effects of splenectomy.Thus,central pancreatectomy should be included in the armamentarium of pancreatic surgery,and in order to obtain good results,proper indications and adequate experience are recommended.

Evidence-Based Dampness-Heat ZHENG(Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG(syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG(DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

Pregnancy Complicated With a Giant Pancreatic Tumor and Decompensation of Liver Cirrhosis:A Case Report and Literature Review

Pregnancy with solid pseudopapillary tumor of the pancreas(SPTP)is rare.Because pregnancy hormones may cause tumor progression,the management and treatment of SPTP need to balance the safety of pregnant women and fetuses with surgical treatment.We reported a case of a giant pancreatic tumor diagnosed during pregnancy that was considered to be SPTP.Examinations also showed hepatitis B virus infection and severe decompensation of liver cirrhosis.Medical termination of pregnancy was performed.The patient has lived with the tumor until now without surgery.We retrieved the published case reports,summarized the clinical characteristics of pregnancy with SPTP,and explored its management during the perinatal period.Most patients with SPTP have a good prognosis with good maternal and fetal outcomes,and it is important to choose an appropriate treatment method and timing.However,pregnancy combined with decompensated liver cirrhosis needs to be terminated in a timely manner because of its high-risk status.

Advancements in medical treatment for pancreatic neuroendocrine tumors:A beacon of hope

This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors(pan-NETs),emphasizing tailored approaches for specific subtypes.Cytoreductive surgery and somatostatin analogs(SSAs)play pivotal roles in managing tumors,while palliative options such as molecular targeted therapy,peptide receptor radionuclide therapy,and chemotherapy are reserved for SSA-refractory patients.Gastrinomas,insul-inomas,glucagonomas,carcinoid tumors and VIPomas necessitate distinct thera-peutic strategies.Understanding the genetic basis of pan-NETs and exploring immunotherapies could lead to promising avenues for future research.This review underscores the evolving landscape of pan-NET treatment,offering renewed hope and improved outcomes for patients facing this complex disease.

Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

Pancreatic neuroendocrine tumors:Are tumors smaller than 2 cm truly indolent?

BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related symptoms.Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for malignancy.However,it is unclear whether managing these small tumors expectantly is truly safe.AIM To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm or<2 cm)in surgically treated patients.METHODS This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,Colombia.To assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery department.Qualitative variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion.RESULTS The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),respectively.Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter.The recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 cm.Patient survival was additionally comparable between the two tumor groups.CONCLUSION Tumor size does not dictate prognosis;lymph node and lymphovascular involvement affect mortality,which high-lights that histopathological factors-rather than tumor size-may play a role in management.

Close relationship between mediators of inflammation and pancreatic cancer:Our experience

In this editorial,we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer.Cancer of the pancreas remains one of the deadliest cancer types.The highest incidence and mortality rates of pancreatic cancer are found in developed countries.Trends of pancreatic cancer incidence and mortality vary considerably worldwide.A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease.Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche.In this editorial,we highlight the foundational studies that have driven our understanding of these processes.In our experimental center,we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer.We focused on the role of mast cells(MCs).MCs contain pro-angiogenic factors,including tryptase,that are associated with increased angiogenesis in various tumors.In this editorial,we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue.The assessment includes the density of c-Kit receptor-positive MCs,the density of tryptase-positive MCs,the area of tryptasepositive MCs,and angiogenesis in terms of microvascularization density.

Prediction of the lymphatic,microvascular,and perineural invasion of pancreatic neuroendocrine tumors using preoperative magnetic resonance imaging

BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous studies.There was no previous study reported the relationship between magnetic resonance imaging(MRI)parameters and LMPI.AIM To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs(NFPNETs).METHODS A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study.The patients were divided into group 1(n=34,LMPI negative)and group 2(n=27,LMPI positive).The clinical characteristics and qualitative MRI features were collected.In order to predict LMPI status in NF-PNETs,a multivariate logistic regression model was constructed.Diagnostic performance was evaluated by calculating the receiver operator characteristic(ROC)curve with area under ROC,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accuracy.RESULTS There were significant differences in the lymph node metastasis stage,tumor grade,neuron-specific enolase levels,tumor margin,main pancreatic ductal dilatation,common bile duct dilatation,enhancement pattern,vascular and adjacent tissue involvement,synchronous liver metastases,the long axis of the largest lymph node,the short axis of the largest lymph node,number of the lymph nodes with short axis>5 or 10 mm,and tumor volume between two groups(P<0.05).Multivariate analysis showed that tumor margin(odds ratio=11.523,P<0.001)was a predictive factor for LMPI of NF-PNETs.The area under the receiver value for the predictive performance of combined predictive factors was 0.855.The sensitivity,specificity,PPV,NPV and accuracy of the model were 48.1%(14/27),97.1%(33/34),97.1%(13/14),70.2%(33/47)and 0.754,respectively.CONCLUSION Using preoperative MRI,ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.

Neuroendocrine tumors of the gastro-entero-pancreatic system

Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms, although their prevalence has increased substantially over the past three decades. Moreover, there has been an increased clinical recognition and characterization of these neoplasms. They show extremely variable biological behavior and clinical course. Most NETs have endocrine function and secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome; however, many are clinically silent until late presentation with mass effects. Investigation and management should be individualized for each patient, taking into account the likely natural history of the tumor and general health of the patient. Management strategies include surgery for cure or palliation, and a variety of other cytoreductive techniques, and medical treatment including chemotherapy, and biotherapy to control symptoms due to hormone release and tumor growth, with somatostatin analogues (SSAs) and alphainterferon. New biological agents and somatostatintagged radionuclides are under investigation. Advances in the therapy and development of centers of excellence which coordinate multicenter studies, are needed to improve diagnosis, treatment and therefore survival of patients with GEP NETs.

Isolation and biological analysis of tumor stem cells from pancreatic adenocarcinoma

AIM: To explore the method of isolation and biological analysis of tumor stem cells from pancreatic adenocarcinoma cell line PANC-1. METHODS: The PANC-1 cells were cultured in Dulbecco modified eagle medium F12 (1:1 volume) (DMEM-F12) supplemented with 20% fetal bovine serum (FBS). Subpopulation cells with properties of tumor stem cells were isolated from pancreatic adenocarcinoma cell line PANC-1 according to the cell surface markers CD44 and CD24 by flow cytometry. The proliferative capability of these cells in vitro were estimated by 3-[4,5-dimehyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) method. And the tumor growth of different subpopulation cells which were injected into the hypodermisof right and left armpit of nude mice was studied,and expression of CD44 and CD24 of the CD44+CD24+ cell-formed nodules and PANC-1 cells were detected by avidin-biotin-peroxidase complex (ABC) immunohistochemical staining. RESULTS: The 5.1%-17.5% of sorted PANC-1 cells expressed the cell surface marker CD44,57.8% -70.1% expressed CD24,only 2.1%-3.5% of cells were CD44+ CD24+. Compared with CD44-CD24-cells,CD44+CD24+ cells had a lower growth rate in vitro. Implantation of 104 CD44-CD24-cells in nude mice showed no evidenttumor growth at wk 12. In contrast,large tumors were found in nude mice implanted with 103 CD44+CD24+ cells at wk 4 (2/8),a 20-fold increase in tumorigenic potential (P < 0.05 or P < 0.01). There was no obvious histological difference between the cells of the CD44+CD24+ cell-formed nodules and PANC-1 cells. CONCLUSION: CD44 and CD24 may be used as the cell surface markers for isolation of pancreatic cancer stem cells from pancreatic adenocarcinoma cell line PANC-1. Subpopulation cells CD44+CD24+ have properties of tumor stem cells. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy,it may be a very promising target for new drug development.

An automated deep learning based pancreatic tumor diagnosis and classification model using computed tomography images

Purpose-The advancements of deep learning(DL)models demonstrate significant performance on accurate pancreatic tumor segmentation and classification.Design/methodology/approach-The presented model involves different stages of operations,namely preprocessing,image segmentation,feature extraction and image classification.Primarily,bilateral filtering(BF)technique is applied for image preprocessing to eradicate the noise present in the CT pancreatic image.Besides,noninteractive GrabCut(NIGC)algorithm is applied for the image segmentation process.Subsequently,residual network 152(ResNet152)model is utilized as a feature extractor to originate a valuable set of feature vectors.At last,the red deer optimization algorithm(RDA)tuned backpropagation neural network(BPNN),called RDA-BPNN model,is employed as a classification model to determine the existence of pancreatic tumor.Findings-The experimental results are validated in terms of different performance measures and a detailed comparative results analysis ensured the betterment of the RDA-BPNN model with the sensitivity of 98.54%,specificity of 98.46%,accuracy of 98.51% and F-score of 98.23%.Originality/value-The study also identifies several novel automated deep learning based approaches used by researchers to assess the performance of the RDA-BPNN model on benchmark dataset and analyze the results in terms of several measures.

Rapid transformation of branched pancreatic duct-derived intraductal tubulopapillary neoplasm into an invasive carcinoma: A case report

BACKGROUND Intraductal tubulopapillary neoplasm(ITPN)is a rare disease accounting for approximately 3%of all intraductal pancreatic tumors,with intraductal papillary mucinous neoplasm(IPMN)being one of the most common differential diagnoses.Both ITPN and IPMN display slow growth.A branched pancreatic duct type is commonly observed in IPMN,whereas ITPN derived from the branched pancreatic duct has been reported in a limited number of cases;hence,its pathogenesis remains unclear.CASE SUMMARY Here,we present the case of a patient with ITPN localized in a branched pancreatic duct,with poorly controlled irritable bowel syndrome.A contrastenhanced computed tomography scan of the abdomen incidentally revealed a 5-mm oligemic nodule-like change in the body of the pancreas.Endoscopic ultrasound(EUS)indicated a 10-mm hypoechoic mass without any cystic structures that had grown within 2 mo.EUS-guided fine needle aspiration was performed for definitive diagnosis,and the findings suggested ductal papillary carcinoma.Distal pancreatectomy was performed,and the tumor was pathologically diagnosed as ITPN with an invasive cancerous component,pT3N1aM0,pStage IIB(International Cancer Control,8^(th) edition).The patient underwent treatment with postoperative adjuvant chemotherapy(S-1 monotherapy);however,relapse was observed 1 year and 10 mo after surgical resection,and subsequent treatment involving a combination of chemotherapy and radiotherapy was administered.Maintenance therapy has since facilitated a stable disease state.CONCLUSION Regardless of the microscopic size of the neoplasm,early diagnosis of ITPN with EUS-guided fine needle aspiration and surgical resection are crucial.

Hyperthermia combined with chemotherapy vs chemotherapy in patients with advanced pancreatic cancer:A multicenter retrospective observational comparative study

BACKGROUND Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy(CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electrohyperthermia(mEHT) is a new hyperthermia technique that induces immunogenic death or apoptosis of pancreatic cancer cells in laboratory experiments and increases tumor response rate and survival in pancreatic cancer patients, offering beneficial therapeutic effects against this severe type of cancer.AIM To assess survival, tumor response and toxicity of mEHT alone or combined with CHT compared with CHT for the treatment of locally advanced or metastatic pancreatic cancer.METHODS This was a retrospective data collection on patients affected by locally advanced or metastatic pancreatic cancer(stage Ⅲ and IV) performed in 9 Italian centers, members of International Clinical Hyperthermia Society-Italian Network. This study included 217 patients, 128(59%) of them were treated with CHT(no-mEHT) and 89(41%) patients received mEHT alone or in association with CHT. mEHT treatments were performed applying a power of 60-150 watts for 40-90 min, simultaneously or within 72 h of administration of CHT.RESULTS Median patients’ age was 67 years(range 31-92 years). mEHT group had a median overall survival greater than non-mEHT group(20 mo, range 1.6-24, vs 9 mo, range 0.4-56.25, P < 0.001). mEHT group showed a higher number of partial responses(45% vs 24%, P = 0.0018) and a lower number of progressions(4% vs 31%, P < 0.001) than the no-mEHT group, at the three months follow-up. Adverse events were observed as mild skin burns in 2.6% of mEHT sessions.CONCLUSION mEHT seems safe and has beneficial effects on survival and tumor response of stage Ⅲ-IV pancreatic tumor treatment. Further randomized studies are warranted to confirm or not these results.

Pancreatic neuroendocrine tumors:A review of serum biomarkers,staging,and management

Pancreatic neuroendocrine tumors(pNETs)are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading,clinical staging,and presence of symptoms related to hormonal secretion.With regard to diagnosis,remarkable advances have been made:Chromogranin A is recommended as a general marker for pNETs.But other new biomarker modalities,like circulating tumor cells,multiple transcript analysis,microRNA profile,and cytokines,should be clarified in future investigations before clinical application.Therefore,the currently available serum biomarkers are insufficient for diagnosis,but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs.Surgical resection is still the only curative therapeutic option for localized pNETs.However,a debulking operation has also been proven to be effective for controlling the disease.As for drug therapy,steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor,while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs.Great progress has been achieved in the combination of systematic therapy with local control treatments.The optimal timing of local control intervention,planning of sequential therapies,and implementation of multidisciplinary care remain pending.