Background
Although neuroendocrine tumors (NETs) are rare, the number of patients with NET is increasing. However, in Japan, there have been no epidemiological studies on NET since 2005; thus, the ...prevalence of NET remains unknown.
Methods
We reported the epidemiology of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) pancreatic neuroendocrine tumors (PNETs) and gastrointestinal neuroendocrine tumors (GI-NETs) in Japan in 2005. Here, we conducted the second nationwide survey on patients with GEP-NETs who received treatment in 2010.
Results
A total of 3,379 patients received treatment for PNETs in 2010, representing a 1.2-fold increase in the number of patients from 2005 to 2010. The prevalence was estimated to be 2.69/100,000, with an annual onset incidence of 1.27/100,000 in 2010. Non-functioning tumor (NF)-PNETs comprised 65.5 % of cases followed by insulinoma (20.9 %) and gastrinoma (8.2 %). Interestingly, the number of patients with NF-PNETs increased ~1.8 fold since 2005. A total of 19.9 % of patients exhibited distant metastasis at initial diagnosis; 4.3 % had complications with multiple endocrine neoplasia type 1 (MEN-1), and only 4.0 % had NF-PNETs associated with MEN-1. Meanwhile, an estimated 8,088 patients received treatment for GI-NETs, representing a ~1.8-fold increase since 2005. The prevalence was estimated to be 6.42/100,000, with an annual onset incidence of 3.51/100,000. The locations of GI-NETs varied: foregut, 26.1 %; midgut, 3.6 %; and hindgut, 70.3 %. Distant metastasis and complications with MEN-1 were observed in 6.0 and 0.42 % at initial diagnosis, respectively. The frequency of carcinoid syndrome in patients with GI-NETs was 3.2 %.
Conclusion
We clarified the epidemiological changes in GEP-NETs from 2005 to 2010 in Japan.
The worldwide prevalence and incidence of neuroendocrine neoplasms (NEN) have been increasing recently, although few studies have analyzed data on the current situation of NENs in Japan. Here, the ...Japan Neuroendocrine Tumor Society (JNETS) planned to investigate the recent incidence and distribution of these tumors using data from the national cancer registry started in 2016. This study examined the incidence and distribution of primary sites as well as rate of advanced disease from this population-based registry.
A retrospective, population-based study using data from the national cancer registry in Japan (NCR) was conducted to evaluate patients with gastro-entero-pancreatic NEN (GEP-NEN) in 2016. Associated population data were used to determine annual age-adjusted incidences.
A total of 6735 individuals were diagnosed with GEP-NEN in Japan in 2016. Annual onset incidence was 0.70/100,000 for pancreatic NEN and 2.84/100,000 for gastrointestinal NEN. NEN in the ileum accounted for only 1% of total GEP-NENs in Japan. Most NENs in the esophagus or lungs were neuroendocrine carcinomas (NECs), while the majority of those in the duodenum, ileum, appendix and rectum were grade 1 neuroendocrine tumors (NETs). Median age at initial diagnosis was in between 60 to 65. Tumors in the duodenum, appendix and rectum were mostly limited to local, while those in the esophagus, stomach and colon tended to show distant metastasis. In Japan, initial treatment for GEP-NENs was resection even if the tumor was NEC.
This is the first report of a national registry-based incidence and distribution of GEP-NEN in Japan. These data will serve as an important first step to determining the exact etiology and trends for this pathology in Japan.
Background There have been few epidemiological studies on gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Japan. Methods We examined the epidemiology of GEP-NETs pancreatic endocrine ...tumors (PETs) and gastrointestinal neuroendocrine tumors (GI-NETs) in Japan in 2005 using a nationwide stratified random sampling method. Results A total of 2,845 individuals received treatment for PETs. Prevalence was estimated as 2.23/100,000 with an annual onset incidence of 1.01/100,000. Non-functioning tumor (NF)-PET constituted 47.4%, followed by insulinoma (38.2%) and gastrinoma (7.9%). Distant metastases were reported in 21% patients with NF-PETs and occurred more frequently as tumor size increased (>2 cm). Multiple endocrine neoplasia type 1 (MEN-1) was detected in 10% of PETs but only in 6.1% of NF-PETs. NF-PETs were detected incidentally by physical examination in 24% patients. In 2005, an estimated 4,406 patients received treatment for GI-NETs. Prevalence was estimated as 3.45/100,000, with an annual onset incidence of 2.10/100,000. The locations of GI-NETs varied: foregut, 30.4%; midgut, 9.6%; and hindgut, 60.0%. Distant metastases were observed in 6%. Lymph node metastases occurred more frequently as tumor size increased (>1 cm). The frequency of MEN-1 complications was 1%. Physical examination revealed GI-NETs in 44% patients. The frequency of symptomatic GI-NETs was 3.4%. Interestingly, 77.1% of patients with foregut GI-NETs had type A gastritis. Conclusion Our results show there are large differences in GEP-NETs between Japan and Western nations, primarily due to differences in the presence of MEN-1 in NF-PETs and the location, symptomatic status, and prevalence of malignancy in GI-NETs.
Several new developments have occurred in the field of pancreatic neuroendocrine neoplasm (PNEN) recently in Japan. First, the utility of chromogranin A (CgA), useful for the diagnosis and monitoring ...of the treatment response of neuroendocrine neoplasm (NEN), has been demonstrated in Japan. For PNEN diagnosis and treatment, grading and correct histological diagnosis according to the WHO 2010 classification is important. Regarding the histological diagnosis, the advent of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has enabled correct pathological diagnosis and suitable treatment for the affected tissue. Furthermore, EUS-FNA has also facilitates the assessment of the presence or absence of gene mutations. In addition, patients who have a well-differentiated neuroendocrine tumor (NET) showing a Ki-67 index of higher than 20 % according to the WHO 2010 classification, have also been identified, and their responses to treatment were found to be different from those of patients with poorly differentiated neuroendocrine carcinoma (NEC). Therefore, the concept of NET G3 was proposed. Additionally, somatostatin receptor type 2 is expressed in several cases of NET, and somatostatin receptor scintigraphy (
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In-octreoscan) has also been approved in Japan. This advancement will undoubtedly contribute to the localization diagnosis, the identification of remote metastasis, and assessments of the treatment responses of PNEN. Finally, regarding the treatment strategy for PNEN, the management of liver metastasis is important. The advent of novel molecular-targeted agents has dramatically improved the prognosis of advanced PNEN. Multimodality therapy that accounts for the tumor stage, degree of tumor differentiation, tumor volume, and speed of tumor growth is required.
Background/Purpose
Hepatic resection is considered the treatment of choice for neuroendocrine liver metastases (NELM). However, the safety and efficacy of resection have not been fully evaluated ...using a large cohort. The aim of the present study was to collect real‐world data regarding hepatic resections for NELM.
Methods
A retrospective, multicenter survey was conducted. The background characteristics of patients undergoing an initial hepatic resection for NELM, the operative details, pathological findings, and patient outcomes were investigated.
Results
A total of 222 patients were enrolled from 30 institutions. The primary tumor site was the pancreas in 58.6%, and the presentation of NELM was synchronous in 63.1% of the cases. Concomitant resection of the primary tumor and liver metastases was performed for 66.4% of the synchronous metastases, and the 90‐day morbidity and mortality rates were 12.6% and 0.9%, respectively. The operations resulted in R2 resections in 26.1% of the cases, and 83.4% of the patients experienced recurrence after R0/1 resections. However, the patients were treated using multiple modalities after R2 resection or recurrence, and the overall survival rate was relatively favorable, with 5‐year and 10‐year survival rates of 70.2%, and 43.4%, respectively. Univariable and multivariable analyses identified the tumor grading (G3) of the primary tumor as a significant prognostic factor for both the recurrence‐free and overall survivals.
Conclusions
The present data confirmed the safety of the surgical resection of NELM. Although recurrences were frequent, the survival outcomes after resection were favorable when a multi‐disciplinary treatment approach was used.
Highlight
On behalf of the Japanese Neuroendocrine Tumor Society, Aoki and colleagues investigated the status of treatment for neuroendocrine liver metastasis. The results of 222 enrolled patients confirmed the safety of surgical resection of neuroendocrine liver metastasis together with the primary tumor. Although recurrences were frequent, survival outcomes after resection were favorable.
Background
Neuroendocrine neoplasm (NEN) is a comparatively rare tumor that has been considered indolent. Due to these characteristics, detailed epidemiological data have not been analyzed in Japan. ...To elucidate the present status of NEN diagnosis and treatment in Japan, we started a registry cohort study in January 2015.
Methods
Patients pathologically diagnosed with NENs of the pancreas, gastrointestinal tract, lungs, bronchi, or thymus after January 2012 were enrolled in this registry after the date of ethics review committee approval in each hospital or institute. Follow-up was continued for enrolled patients.
Results
During 5 years of enrollment between January 2015 and December 2019, a total of 1526 participants from 63 departments were enrolled in this registry (mean, 305.2 participants/year), covering approximately 5.8% of the annual incidence of NENs in Japan. For pancreatic NEN, 41.9% of patients had metastasis and the dominant metastatic site was the liver, at twice the rate of lymph node metastasis in the current registry. In contrast, the frequency of lymph node metastasis from gastrointestinal (GI)-NEN was similar to that of the liver. The distribution of WHO 2019-based grades varied according to the primary site. Low-to-intermediate grade (G1–G2) was dominant for duodenal, jejunal/ileal, rectal, and pancreatic NENs, whereas high grade (G3 or NEC) was dominant for esophageal, stomach, and colon NENs. For PanNENs, G3 and NEC accounted only for 1.6% and 2.9%, respectively.
Conclusions
These cohort data provide crucial information for clinical research to clarify the characteristics of NENs in Japan.
Background
Neuroendocrine tumors (NETs) are believed to be relatively rare and to follow a generally indolent course. However, liver metastases are common in NET patients and the outcome of NET liver ...metastasis is poor. In Western countries, streptozocin (STZ) has been established as a first-line anticancer drug for unresectable NET; however, STZ cannot be used in daily practice in Japan. The aim of the present study was to determine the status of STZ usage in Japan and to evaluate the effectiveness and safety of STZ chemotherapy in Japanese NET patients.
Methods
A retrospective multi-center survey was conducted. Five institutions with experience performing STZ chemotherapy participated in the study. The patient demographics, tumor characteristics, context of STZ chemotherapy, and patient outcome were collected and assessed.
Results
Fifty-four patients were enrolled. The main recipients of STZ chemotherapy were middle-aged patients with pancreatic NET and unresectable liver metastases. The predominant regimen was the weekly/bi-weekly intravenous administration of STZ combined with other oral anticancer agents. STZ monotherapy was used in one-fourth of the patients. The median progression-free and overall survival periods were 11.8 and 38.7 months, respectively, and sustained stable disease was obtained in some selected patients. The adverse events profile was mild and tolerable.
Conclusions
Our survey showed the clinical benefit and safety of STZ therapy for Japanese patients with unresectable NET. Therefore, we recommend that STZ, which is the only cytotoxic agent available against NET, should be used in daily practice in Japan.
Background
Glomus tumors are subcutaneous tumors arising from glomus bodies, thermoregulatory components of the skin. These tumors could occur in visceral organs where glomus bodies are not normally ...present. Herein, we report a case of primary pancreatic glomus tumor with aggressive direct invasion into the superior mesenteric vein (SMV). To the best of our knowledge, this is the second case report of a glomus tumor arising in the pancreas.
Case presentation
A 46-year-old woman was referred to our hospital due to vomiting with epigastric and back pain. Dynamic-CT revealed a well-circumscribed hypervascular mass, measuring 37 mm in its maximal diameter involving the pancreatic head. Both CT and endoscopic ultrasonography (EUS) revealed direct invasion into the SMV and radiologically suspected tumor thrombus. Biopsy sample obtained by EUS-guided fine needle aspiration revealed proliferation of small cells, round-to-oval tumor cells with round nuclei and scant cytoplasm. A histological diagnosis of pancreatic neuroendocrine tumor, G1 was initially considered. Therefore, subtotal stomach-preserving pancreatoduodenectomy using Child-II reconstruction was subsequently performed. Her SMV was resected and reconstructed due to extensive tumor involvement. Subsequent histopathological analysis revealed solid tumor cells proliferation that comprised oval-shaped nuclei and scant cytoplasm around disorganized or slit-shaped vessels in hematoxylin–eosin-stained slides. Immunohistochemical analysis then demonstrated positive immunoreactivity for smooth muscle actin, vimentin, and CD34, but negative for chromogranin A, synaptophysin, CD56, and signal transducer and activator of transcription 6. Based on these histological findings of resected specimens, the lesion was subsequently diagnosed as a primary pancreatic glomus tumor harboring direct invasion into the SMV. Her postoperative course was uneventful and annual surveys for the following 4 years post-op detected no clinical signs of recurrence.
Conclusions
We report a very rare case of glomus tumor of the pancreas accompanied by venous invasion. Curative surgical resection is the best treatment option for pancreatic glomus tumors. Although pancreatic glomus tumor is rare, it should be taken into consideration in the differential diagnosis of a pancreatic solid tumor with hypervascularity.
Abstract
Background
This phase I/II study was conducted to evaluate the efficacy, safety and pharmacokinetics of streptozocin (STZ) in Japanese patients with unresectable or metastatic ...gastroenteropancreatic neuroendocrine tumors.
Methods
Twenty-two patients received up to 4 cycles of intravenous STZ at either 500 mg/m2 once daily for 5 consecutive days every 6 weeks (daily regimen) or at 1000–1500 mg/m2 once weekly for 6 weeks (weekly regimen). Tumor response was evaluated using the modified RECIST criteria ver. 1.1, and adverse events were assessed by grade according to the National Cancer Institute CTCAE (ver. 4.0).
Results
Fourteen (63.6%) patients completed the study protocol. No patients had complete response; partial response in 2 (9.1%), stable disease in 17 (77.3%), non-complete response/non-progressive disease in 2 (9.1%) and only 1 (4.5%) had non-evaluable disease. Excluding the latter, the response rate in the daily and weekly regimens was 6.7% (1/15) and 16.7% (1/6), respectively, with an overall response rate of 9.5% (2/21). However, the best overall response in each patient showed that the disease control rate was 100%.
Adverse events occurred in all 22 patients, including 17 grade 3 adverse events in 11 patients; however, no grade 4 or 5 adverse events were reported. Prophylactic hydration and antiemetic treatment reduced the severity and incidence of nephrotoxicity, nausea and vomiting. Plasma STZ concentrations decreased rapidly after termination of infusion, with a half-life of 32–40 min. Neither repeated administration nor dose increases affected pharmacokinetic parameters.
Conclusions
STZ may be a useful option for Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors.
In a phase I/II study, streptozocin in a daily or weekly regimen was effective and well-tolerated in 22 Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors.
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