Navigating the uncommon: a comprehensive case study of multiple gastroduodenal neuroendocrine tumor

Neuroendocrine tumors (NETs) have varied pathophysiological characteristics, location, clinical presentation, management & outcome. Unfortunately, most NETs are non-functional and therefore, either remain asymptomatic until incidentally detected or present very late with pressure symptoms, adding up to the associated morbidity and mortality. Here we presented a case of a 43-year gentleman, who presented to gastroenterology OPD with chief complaints of heartburn and pain in the upper abdomen for one year. He had an equivocal clinical examination and laboratory parameters. Upper GI endoscopy and computed tomography revealed multiple nodular growths in the D1 segment and pylorus of the stomach. He was successfully managed by wide local excision of D1 and distal stomach (pylorus) followed by Polya gastrojejunostomy reconstruction. Histopathology confirmed well-differentiated NETs, low Ki67, and positive for chromogranin and synaptophysin. This case draws attention to the early age of presentation of multifocal NETs with vague symptoms and equivocal clinical examination. Coexisting gastric NETs with duodenal NETs in itself is very rare, never the less non-functional status and pre-operative diagnostic dilemma. Here, we have also drawn attention to the pros and cons of various diagnostic tools and how their utility can sometimes limit the approach of clinicians, apart from a high index of suspicion.

Síndrome de feocromocitoma-paraganglioma de tipo 5 como causa de hipertensión arterial en una paciente colombiana: reporte de caso / Pheochromocytoma/paraganglioma type 5 syndrome as a cause of secondary hypertension in a Colombian patient: case report

Resumen El feocromocitoma es un tumor derivado de las células de la cresta neural con la capacidad de producir sustancias simpaticomiméticas y, por ende, un cuadro clínico particular. Causa menos del 1 % de los casos de hipertensión arterial sistémica y su incidencia se estima entre 0,4 y 0,6 casos por 100.000 personas cada año, con una supervivencia media de siete años. De todos los tumores sólidos, el feocromocitoma tiene un mayor componente genético, que puede heredarse hasta en el 40 % de los casos. Una vez diagnosticada la enfermedad, se debe definir el tratamiento y el pronóstico, en parte condicionados por las variantes genéticas asociadas, en especial RET, SDHx, VHL y NF1. Se presenta el caso de una mujer joven con dolor abdominal e hipertensión arterial sistémica, a quien se le diagnosticó feocromocitoma. Al secuenciar el exoma, se identificó una variante patogénica extremadamente rara y de reciente descubrimiento: SDHA: c.1A>C (p.Met1Leu). La paciente respondió adecuadamente al tratamiento quirúrgico y continuó en seguimiento sin recurrencias. El abordaje diagnóstico de los pacientes con feocromocitoma comienza con la sospecha clínica, seguida de la medición de determinados metabolitos en sangre y orina, y, finalmente, los estudios de imagenología. Los desarrollos tecnológicos actuales permiten la aplicación de la medicina de precisión en este campo. En este caso de feocromocitoma, se identificó un componente genético importante que no solo afecta al paciente, sino también, a sus familiares. La tamización adecuada del caso índice permite identificar mutaciones y caracterizar mejor la enfermedad.

Abstract Pheochromocytoma is a tumor derived from neural crest cells able to produce sympathomimetic substances and, hence, a particular clinical picture. It is responsible for less than 1% of high blood pressure cases, with an estimated incidence between 0.4 and 0.6 cases per 100,000 people each year, and an average survival of seven years. Pheochromocytoma is a solid tumor with a high genetic component, as heritability can reach 40%. Once diagnosed, its treatment and prognosis are partly conditioned by the associated pathogenic variants that can be documented, especially those related to RET, SDHx, VHL, and NF1 genes. We present the case of a young woman with abdominal pain and high blood pressure, who was found to have a pheochromocytoma. Genetic testing detected a rare and recently discovered pathogenic variant: the SDHA:c.1A>C (p.Met1Leu). The patient responded adequately to the surgical treatment and continued the follow-up without documented recurrences. The diagnostic approach for pheochromocytoma patients must start with a clinical suspicion, followed by metabolite measurement in blood and urine, and finally, imaging. Currently, technology development allows precision medicine applicability. In this case of pheochromocytoma, recent developments in precision medicine resulted in the detection of associated genetic components involving the patient and her family. Adequate screening of the index patient is required for documenting pathogenic variants and better characterizing the disease.

Analysis of cell mutation types of colorectal neuroendocrine tumors / 基础医学与临床

Objective To investigate the mutation types of colorectal neuroendocrine tumors(NETs)and better un-derstand the pathogenesis of colorectal nets.Methods Patients undergoing colorectal NETs surgery were recruited,colorectal NETs and corresponding adjacent cancerous tissues were collected,and whole genome sequencing(WGS)was performed and further deeply analyzed.Results WGS sequencing showed that the mutation types of colorectal NETs included single nucleotide mutations,insertion and deletion mutations(InDel,less than 50 bp in length),copy number variations(CNV),and large structural variations(SV,more than 50 bp in length),such as insertion(INS),deletion(DEL),intra chromosomal translocation(ITX),inter chromosomal translocation(CTX)and inversion(INV).Conclusions A large number of somatic mutations occur in colorectal NETs,especially chro-mosome translocation

Surgical intervention strategies for liver metastasis of neuroendocrine tumors / 临床肝胆病杂志

Neuroendocrine tumors are a group of rare tumor diseases that can occur in various visceral organs of the human body and exhibit significant tumor heterogeneity， and they often lead to secondary tumors mostly involving the liver and carcinoid syndrome. Liver metastasis is an important cause of treatment failure in patients with neuroendocrine tumor， and timely and reasonable surgical interventions that can effectively control disease progression to achieve the disease-free state or the goal of radical treatment and prolong the overall survival of patients has been a focus of research by clinicians and researchers in recent years. With reference to actual clinical work and working experience， this article reviews and discusses the surgical treatment strategies for liver metastasis of neuroendocrine tumors based on related strategies in China and globally and the latest diagnosis and treatment guidelines in China.

Misdiagnosis of intrapancreatic accessory spleen： A report of two cases / 临床肝胆病杂志

Accessory spleen refers to the spleen tissue that exists outside of the normal spleen， with a similar structure to the main spleen and certain functions. Intrapancreatic accessory spleen （IPAS） completely enveloped by the pancreas has an incidence rate of only 2%， and it is easily misdiagnosed in clinical practice due to its atypical clinical symptoms and similar radiological features to pancreatic neuroendocrine tumor， pancreatic solid pseudopapillary tumor， and other pancreatic space-occupying lesions. This article reports the clinical data of two patients with IPAS who were misdiagnosed as pancreatic neuroendocrine tumor and pancreatic solid pseudopapillary tumor， respectively， analyzes the reasons for misdiagnosis， and summarizes the experience in diagnosis and treatment， in order to improve the ability for the differential diagnosis of IPAS in clinical practice.

Enhanced CT intratumor and peritumor CT value ratio for differentiating grade 3 pancreatic neuroendocrine tumor and pancreatic neuroendocrine cancer / 中国医学影像技术

Objective To observe the value of enhanced CT intratumor and peritumor CT value ratio for differentiating grade 3 pancreatic neuroendocrine tumor(PNET)and pancreatic neuroendocrine cancer(PNEC).Methods Totally 39 patients with pancreatic neuroendocrine neoplasm who underwent abdominal CT scanning were retrospectively enrolled and divided into G3 PNET group(n=18)or PNEC group(n=21)according to pathological results.The general data,CT features and CT value ratio of intratumor and peritumor based on arterial phase and portal vein phase enhanced CT were compared between groups.Univariate logistic regression analysis and receiver operating characteristic(ROC)curves were performed to screen the efficient indicator for differentiating G3 PNET and PNEC.Multivariate logistic regression was used to evaluate the differential diagnosis efficacy of the models.Results No significant difference of patients'age,gender,lesion size,location,composition,calcification nor CT value ratio1(CT value of intratumor/CT value from tumor margin to 10 mm tumor margin size)based on arterial phase and portal vein phase was found between groups(all P＞0.05).Significant differences of lesion uniformity,main pancreatic duct dilatation,bile duct dilatation,pancreatic duct invasion,vascular invasion and CT value ratio2(CT value of intratumor/CT value from 10 mm to 20 mm tumor margin size)based on arterial phase and portal vein phase were found between groups(all P＜0.05).and the above parameters were all efficient indicators for differentiating G3 PNET and PNEC.Multivariate logistic regression models were constructed using CT value ratio2 based on arterial phase and portal vein phase,as well as lesion uniformity combined with CT value ratio2 based on arterial phase and portal vein phase,respectively,and the sensitivity,specificity and the area under the curve of the former model was 76.20％,88.90％and 0.899.of the later model was 85.70％,88.90％and 0.926,respectively.Conclusion Enhanced CT intratumor and peritumor CT value ratio was useful for differentiating G3 PNET and PNEC,and the efficiency could be improved through combining CT features.

Progress of studies on DOTATATE-based α/β radionuclide therapy for neuroendocrine neoplasm / 中华核医学与分子影像杂志

Neuroendocrine neoplasm (NEN) is a type of heterogeneous tumor that originates from peptidergic neurons and neuroendocrine cells. The presence of over-expressed somatostatin receptors (SSTR) on the surface of NEN tumor cells has led to the administration of radiolabeled somatostatin analogs (SSA) in combination with over-expressed SSTR, which is called peptide receptor radionuclide therapy (PRRT). The 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacceticacid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE)-based α/β radionuclide therapy is one of the representative therapeutic methods of PRRT. This article reviews the progress of research on α/β radionuclide therapy based on DOTATATE and its related combination therapy, drug toxicity and safety, as well as expectation for modalities with clinical value for NEN treatment.

Value of 18F-FDG and 68Ga-DOTATATE total-body PET/CT imaging in patients with neuroendocrine neoplasms / 中华核医学与分子影像杂志

Objective:To investigate the value of 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) combined with 18F-FDG total-body PET/CT imaging in the diagnosis and heterogeneity assessment of primary foci of neuroendocrine neoplasms (NEN). Methods:Clinical, imaging and pathological data of 39 patients with pathological diagnosis (30 NEN and 9 non-NEN, 18 males and 21 females, age (54.0±11.4) years) who underwent 1/10 activity 18F-FDG and 1/2 activity 68Ga-DOTATATE total-body PET/CT combined imaging in Zhongshan Hospital, Fudan University from August 2020 to March 2023 were retrospectively analyzed. The NEN primary foci were classified as neuroendocrine tumor (NET) G1, G2, G3, and neuroendocrine carcinoma (NEC). Diagnostic efficacy of combined dual-low activity dual-tracer imaging for NEN primary foci and its value for evaluating tumor heterogeneity were analyzed. Results:The sensitivities, specificities, and accuracies of 68Ga-DOTATATE alone and in combination with 18F-FDG total-body PET/CT for the diagnosis of NEN primary foci were 81.2%(26/32), 7/9, 80.5%(33/41) and 90.6%(29/32), 7/9, 87.8%(36/41), respectively. Ten NET G1 and seven NET G2 lesions showed 68Ga-DOTATATE uptake and no 18F-FDG uptake; two NET G2 lesions showed no 68Ga-DOTATATE uptake but 18F-FDG uptake; and two NET G1 and six NET G2 lesions showed both 68Ga-DOTATATE and 18F-FDG uptake. The radiation doses of 68Ga-DOTATATE, 18F-FDG and a single examination of CT were (1.59±0.50), 0.49(0.44, 0.58) and 11.46(10.53, 12.85) mSv, respectively. Conclusion:Combining total-body PET/CT imaging with dual tracers can effectively diagnose NEN primary foci and assess inter-tumor heterogeneity.

Application of 68Ga-NOTA-3P-TATE-RGD PET/CT in the evaluation of neuroendocrine neoplasms / 中华核医学与分子影像杂志

Objective:To investigate the value of PET/CT imaging with 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid-3 polyethylene glycol- D-Phe1-Tyr3-Thr8-octreotide Arg-Gly-Asp (NOTA-3P-TATE-RGD), a dual somatostatin receptor 2- and integrin α vβ 3- targeting tracer, in the evaluation of neuroendocrine neoplasms (NEN). Methods:From April 2021 to February 2022, 35 patients (19 males, 16 females; median age 54(41, 61) years) with histologically confirmed NEN in Peking Union Medical College Hospital were prospectively enrolled. All patients were scanned with both 68Ga-NOTA-3P-TATE-RGD and 68Ga-1, 4, 7, 1 0-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) PET/CT imaging within one week. The differences of the numbers of detected lesions, SUV max and tumor-to-background ratio (TBR) between the two imaging methods were compared by Wilcoxon signed-rank test. Results:Of the 35 patients, the total numbers of lesions detected by 68Ga-NOTA-3P-TATE-RGD and 68Ga-DOTATATE were 1 190 and 1 106, respectively. 68Ga-NOTA-3P-TATE-RGD and 68Ga-DOTATATE both detected 35 primary tumors and performed comparably in detecting lymph node metastases (4(1, 8) vs 4(1, 8); z=-0.45, P=0.655) and bone metastases (5(2, 60) vs 5(2, 66); z=-1.11, P=0.244). However, the number of liver lesions detected by 68Ga-NOTA-3P-TATE-RGD was significantly higher than that by 68Ga-DOTATATE (17(6, 27) vs 8(3, 26); z=-2.31, P=0.021). 68Ga-DOTATATE demonstrated higher SUV max than 68Ga-NOTA-3P-TATE-RGD (15.6(9.9, 24.9) vs 12.7(8.0, 18.4); z=-7.19, P<0.001), while the TBR of liver metastases was significantly lower (3.4(1.8, 5.5) vs 6.1(3.8, 10.8); z=-7.56, P<0.001). Conclusion:68Ga-NOTA-3P-TATE-RGD performs better than 68Ga-DOTATATE in the detection of liver metastases, while is comparable to 68Ga-DOTATATE in detecting lesions of other sites.

Safety and efficacy of 177Lu-DOTATATE for neuroendocrine neoplasms / 中华核医学与分子影像杂志

Objective:To explore the efficacy and adverse effects of 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) in patients with neuroendocrine neoplasms (NEN). Methods:From 2019 to June 2021, 36 patients (26 males, 10 females; age (43.5±12.9) years) with metastatic NEN who were treated with 177Lu-DOTATATE in the Affiliated Hospital of Southwest Medical University were retrospectively analyzed. Toxicities were assessed by using the common terminology criteria for adverse events (CTCAE) version 5.0. Disease progression and tumor response were determined according to the response evaluation criteria in solid tumors (RECIST) version 1.1. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed by Cox proportional-hazards model. Results:Of 36 patients, the median follow-up time was 19.8 months, the median PFS was 24 months, and the median OS was not reached. The WHO grade Ⅲ (hazard ratio ( HR)=3.59, 95% CI: 1.10-11.73, P=0.025; OS: HR=7.85, 95% CI: 1.50-41.10, P=0.004), 18F-FDG positive (PFS: HR=3.05, 95% CI: 1.04-8.93, P=0.033; OS: HR=5.90, 95% CI: 1.04-33.49, P=0.025), and received systemic chemotherapy before peptide receptor radionuclide therapy (PRRT) (PFS: HR=2.79, 95% CI: 1.01-7.73, P=0.039; OS: HR=5.56, 95% CI: 1.01-30.57, P=0.026) were prognostic factors for PFS and OS. Transient side effects included fatigue (27.8%, 10/36), nausea (5.6%, 2/36), and the most common laboratory toxicities were lymphocytopenia (11.1%, 4/36), followed by mild renal toxicity (8.3%, 3/36) and mild liver injury (5.6%, 2/36). Conclusions:PRRT with 177Lu-DOTATATE is an effective and well-tolerated treatment in patients with NEN. PFS and OS are shorter in patients who are WHO grade Ⅲ NEN, 18F-FDG positive, and received systemic chemotherapy before PRRT.

Peptide receptor radionuclide therapy of neuroendocrine neoplasms: current advance and future direction / 中华核医学与分子影像杂志

Neuroendocrine neoplasms (NEN) are heterogeneous tumors originating from neuroendocrine cells, characterized by over expression of somatostatin receptors (SSTR) on the cell surface, with an increasing incidence year by year. In recent years, the peptide receptor radionuclide therapy (PRRT), using radionuclide-labeled somatostatin analogues to combine with SSTR, is developing rapidly and has played an important role in the treatment of NEN. PRRT is considered as a systemic, effective and safe treatment option for metastatic or unresectable SSTR-positive NEN. This article summarizes the method, effectiveness, toxic effect, and treatment measures of PRRT for NEN patients. The future development of PRRT is also discussed in combination with the important advances in recent years.

Clinical and endoscopic features of 179 cases of autoimmune gastritis / 中华消化杂志

Objective:To explore the clinical and endoscopic features of patients with autoimmune gastritis (AIG) and to improve the accuracy of clinical diagnosis of AIG.Methods:From January 3, 2020 to November 25, 2021, the general information (gender, age), laboratory examination indicators and endoscopic findings of 179 AIG patients diagnosed at the Second Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The laboratory examination indicators included hemoglobin, gastrin-17, pepsinogen (PG), anemia combination indicators (ferritin, vitamin B 12), thyroid function indicators (thyroid-stimulating hormone, thyroglobulin antibody and thyroid peroxidase antibody), Helicobacter pylori, and anti-parietal cell antibody and anti-intrinsic factor antibody. Descriptive methods were used for statistical analysis. Results:Among the 179 AIG patients, there were 42 males (23.5%) and 137 females (76.5%), with an average age of (55.23±12.04) years old. The gastrin-17 level of AIG patients was 195.31 ng/L (143.64 ng/L, 273.61 ng/L), PG Ⅰ level and PG Ⅰ/PG Ⅱ ratio were 12.40 μg/L (7.65 μg/L, 19.40 μg/L) and 1.03 (0.66, 1.52), respectively. There were 15.3% (18/118) of the AIG patients with iron deficiency anemia, and 16.1% (19/118) with megaloblastic anemia. The positive rate of anti-parietal cell antibody was 71.8% (51/71), and the positive rate of anti-intrinsic factor antibody was 25.4% (18/71). The serum thyroid-stimulating hormone level increased in 27.3% (15/55) of the patients, and the positive rates of thyroglobulin antibody and thyroid peroxidase antibody were 31.6% (12/38) and 47.4% (18/38), respectively. The positive rate of Helicobacter pylori was 29.7% (38/128). The endoscopic appearance of AIG indicated reverse atrophy, characterized by obvious atrophy in gastric fundus and gastric body mucosa, however the atrophy of gastric antrum was not obvious. Under endoscopy yellow-white turbid mucus, which was difficult to be washed, was found in 67.0% (120/179) of the patients, and under endoscopy the residual gastric fundus glands could be seen in 19.6% (35/179) of the patients. Among 179 AIG patients, 7 cases (3.9%) of neuroendocrine tumor (NET), 7 cases (3.9%) of early gastric adenocarcinoma (including 1 case of poorly differentiated adenocarcinoma), 1 case (0.6%) of adenoma, and 14 cases (7.8%) of hyperplastic polyps were found. Except for the case of poorly differentiated adenocarcinoma undergoing surgery, the others were treated with endoscopic resection. Conclusions:When unexplained iron deficiency anemia, megaloblastic anemia, or reverse atrophy is found, AIG should be considered. AIG patients are at high risk for gastric cancer and NET, and should be closely followed up, and active treatment should be given before anemia and neurological symptoms appear.

Clinical characteristics and prognosis of duodenal neuroendocrine neoplasms / 中华普通外科杂志

Objective:To investigate the clinical characteristics and prognosis of duodenal neuroendocrine neoplasms.Methods:The clinical data of 35 patients with duodenal neuroendocrine neoplasms admitted to Union Hospital, Tongji Medical College, Huazhong University of Science & Technology from Jan 2012 to Dec 2021 were retrospectively analyzed. The differences of clinical characteristics between periampullary and non-periampullary duodenal neuroendocrine neoplasms were analyzed. Kaplan-Meier curve was used for survival analysis, and the clinical factors affecting the prognosis were analyzed.Results:Of the 35 patients, 30 underwent tumor resection, 7 (23%) developed different degree of complications after operation and were improved and discharged after intervention. A total of 5 patients died during the follow-up period. Only 1 of 30 patients who underwent tumor resection died 30 months after operation due to disease progression, and the others had no recurrence or metastasis. Univariate analysis showed that tumor size, tumor grade, and tumor location were associated with the prognosis of patients (all P<0.05), and multivariate analysis showed that patients with tumors located.Away from the ampulla had a significantly better prognosis than those located around the duodenal ampulla ( P<0.01). Conclusions:Patients with duodenal neuroendocrine neoplasms have a good prognosis after complete resection; patients with duodenal neuroendocrine neoplasms located around the ampulla of Vater have a relatively poor prognosis compared with those away from the area of ampulla.

Application of C-type incision to endoscopic submucosal dissection for the treatment of rectal neuroendocrine tumors / 中华消化内镜杂志

Objective:To evaluate the clinical efficacy of C-type endoscopic submucosal dissection (C-ESD) for rectal neuroendocrine tumors (NEN).Methods:The retrospective analysis was performed on data of 55 patients who underwent ESD for rectal NEN at the Department of Endoscopy in Quanzhou First Hospital from January 2018 to July 2021. Patients were divided into the C-ESD group ( n=28) and the conventional ESD group ( n=27). The dissection time, the dissection speed, the number of submucosal injections, the enbloc resection rate, the curative resection rate and the rate of postoperative complications of the two groups were compared. Results:There were no statistically significant differences in basic information between the two groups ( P>0.05). The dissection time was 13.8±4.2 min in the C-ESD group and 19.9±3.9 min in the conventional ESD group with statistically significant difference ( t=5.649, P<0.001). The dissection speed in the C-ESD group was 0.08±0.04 cm 2/min, which was faster than 0.06±0.04 cm 2/min in the conventional ESD group ( t=2.218, P=0.031). The number of submucosal injections in the C-ESD group was less than that in the conventional ESD group [2 (1, 2) VS 3 (2, 3), Z=-8.701, P<0.001]. The lesions were enbloc resected in both groups. The curative resection rate in the C-ESD group was 100.0% (28/28) and 88.9% (24/27) in the conventional ESD group with statistically significant difference ( P=0.011). There were 7 cases of postoperative complications in the conventional ESD group, including 1 delayed bleeding, 5 delayed perforation and 1 muscularis propria injury, while no postoperative complications occurred in the C-ESD group ( P=0.004). Conclusion:C-ESD is a safe and effective treatment strategy for colorectal NEN, which can shorten the dissection time, improve the dissection speed, reduce the number of submucosal injections, improve the curative resection rate, and reduce complications.

Effect of lymph node metastasis on the prognosis of patients with G2 phase stage pancreatic neuroendocrine tumors / 国际外科学杂志

Objective:To investigate the effect of lymph node metastasis on the prognosis of patients with G2 phase stage pancreatic neuroendocrine neoplasm(pNEN).Methods:A retrospective case control study was conducted to analyze the case data of 368 patients with pancreatic neuroendocrine tumors in G2 phase stage from January 1, 2010 to December 31, 2016 in SEER database, including 174 males and 194 females. According to whether lymph nodes were metastatic, they are divided into lymph node non metastatic (N0) group ( n=272) and lymph node metastatic (N1) group ( n=96). The Kaplan-Meier method and Log-rank test were used to compare the overall survival rate (OS) of patients in the N0 and N1 groups. The COX proportional risk model was used to evaluate whether N stage was an independent risk factor affecting prognosis. Count data were expressed as cases and percentage(%), and Chi-square test was used for comparison between the groups. Results:Among all patients, the OS of patients in the N0 group was better than that of patients in the N1 group. The OS of N0 patients at 1, 3, and 5 years was 96.3%, 92.7%, and 85.6%, respectively, while the OS of N1 patients at 1, 3, and 5 years was 92.6%, 82.1%, and 82.1%, respectively ( P=0.014). Multivariate analysis showed that age ( HR=2.245, 95% CI: 1.126-4.475, P=0.022) and N stage ( HR=0.457, 95% CI: 0.237-0.883, P=0.020) were independent prognostic factors for G2 phase pNEN patients. Conclusion:Lymph node metastasis is one of the independent prognostic factors in patients with G2 phase stage pNEN.

Treatment and prognosis of patients of G3 nonfunctional pancreatic neuroendocrine tumors with proliferation index of Ki-67<55% / 中华消化外科杂志

Objective:To investigate the treatment and prognosis of patients of G3 non-functional pancreatic neuroendocrine tumors (pNETs) with proliferation index of Ki-67 <55%.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 15 G3 non-functional pNETs patients with proliferation index of Ki-67<55% who were admitted to Zhongshan Hospital of Fudan University from April 2014 to April 2020 were collected. There were 11 males and 4 females, aged (58±10)years. All patients underwent radical resection of the primary lesion. Obser-vation indicators: (1) treatment; (2) postoperative pathological characteristics; (3) follow-up. Measure-ment data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. The Pearson correlation analysis was used to verify the correlation between variables. Kaplan-Meier method was used to draw survival curve and calculate survival rate. Log-Rank test was used for survival analysis. Results:(1) Treatment. All 15 G3 nonfunctional pNETs patients underwent radical resection of the primary lesion of pancreas, including 5 cases receiving pancreati-coduodenectomy, 10 cases receiving distal pancreatectomy with splenectomy. There were 5 patients with simultaneous liver oligometastasis who underwent combined segmental (lobectomy) hepatectomy. All 15 patients had negative tumor margin, and the operation time and volume of intraoperative blood loss of 15 patients was 120(90,210)minutes and 200(50,300)mL, respectively. None of patient had complications ≥Ⅲ grade of the Clavien-Dindo classification during the postoperative 30 days. Of the 15 patients, there were 5 cases receiving comprehensive treatment based on CAPTEM chemo-therapy (temozolomide combined with capecitabine), 2 cases receiving local interventional therapy, 2 cases receiving CAPTEM chemotherapy, 1 case receiving local interventional therapy combined with molecular targeted therapy, 1 case receiving local interventional therapy combined with long acting somatostatin therapy, 1 cases receiving long acting somatostatin therapy combined with molecular targeted therapy, and 3 cases without postoperative treatment. (2) Postoperative patholo-gical characteristics. The tumor diameter of 15 patients was 3.3(range, 0.5-6.0)cm. There were 2 cases with tumor diameter <2 cm, 13 cases with tumor diameter ≥2 cm. The number of lymph nodes dissected and number of lymph nodes metastatic was 6(4, 10) and 2(1,3) in 15 patients, respectively, including 12 cases with positive lymph node metastasis. Of the 15 patients, there were 5 cases with tumor invasion of adjacent organ, 5 cases with simultaneous liver metastasis, 8 cases with perineural invasion and 8 cases with vascular invasion. There were 3, 7, and 5 patients with stage Ⅱ, stage Ⅲ, and stage Ⅳ of pathological TNM staging, respectively. The proliferation index of Ki-67 and mitotic count was 32%±9% and (11±9)/10 high power field in the primary lesion of 15 patients, respectively, and there was no correlation between proliferation index of Ki-67 and mitotic count ( P>0.05). (3) Follow-up. All 15 patients were followed up after surgery for (55±24)months. The median survival time of 15 patients was 78(range, 43-113)months, with 1-, 3-, 5-year overall survival rate as 100%, 92%, 62%, respectively. During the follow up, 9 of the 15 patients underwent tumor recurrence, with the recurrence time as 20(14, 44)months. There were 8 patients died of tumor recurrence or metastasis. The median survival time was 86(range, 51-120)months in 5 patients receiving comprehensive treatment based on CAPTEM chemotherapy, versus 53(range, 45-60)months in 10 patients receiving other postoperative adjuvant therapy or without postoperative treatment, showing a significant difference between them ( χ2=4.21, P<0.05). Conclusion:The prognosis of patients of G3 nonfunctional pNETs with proliferation index of Ki-67<55% undergoing radical resection combined with postoperative comprehensive treatment based on CAPTEM chemotherapy in better than that of patients receiving other postoperative adjuvant therapy or without posto-perative treatment.

Small cell neuroendocrine carcinoma with adenocarcinoma and high grade squamous intraepithelial neoplasia of the cervix

ABSTRACT Neuroendocrine neoplasm (NEN) of the cervix is a malignant tumor and is classified into low and intermediate-grade neuroendocrine tumor (NET), and high-grade small cell neuroendocrine carcinoma (SCNEC), and large cells neuroendocrine carcinoma (LCNEC). SCNEC of the cervix is an Infrequent tumor with an incidence of less than 1% of all gynecological malignancies. It is characterized by small to medium-sized tumor cells with scant cytoplasm and neuroendocrine differentiation. Most cases of SCNEC of the cervix manifest in pure forms, and only cases show coexisting, non-neuroendocrine component of HPV-associated adenocarcinoma or squamous cell carcinoma. In this report, reviewing the literature, we present one such unique case of SCNEC of the cervix with adenocarcinoma and high-grade squamous intraepithelial neoplasia.

Gastric neuroendocrine tumor: when surgical treatment is indicated? / Tumor neuroendócrino gástrico: quando tratamento cirúrgico está indicado?

ABSTRACT BACKGROUND: Gastric neuroendocrine tumors are a heterogeneous group of neoplasms that produce bioactive substances. Their treatment varies according to staging and classification, using endoscopic techniques, open surgery, chemotherapy, radiotherapy, and drugs analogous to somatostatin. AIMS: To identify and review cases of gastric neuroendocrine neoplasia submitted to surgical treatment. METHODS: Review of surgically treated patients from 1983 to 2018. RESULTS: Fifteen patients were included, predominantly female (73.33%), with a mean age of 55.93 years. The most common symptom was epigastric pain (93.3%), and the mean time of symptom onset was 10.07 months. The preoperative upper digestive endoscopy (UDE) indicated a predominance of cases with 0 to 1 lesion (60%), sizing ≥1.5 cm (40%), located in the gastric antrum (53.33%), with ulceration (60%), and Borrmann III (33.33%) classification. The assessment of the surgical specimen indicated a predominance of invasive neuroendocrine tumors (60%), with angiolymphatic invasion in most cases (80%). Immunohistochemistry for chromogranin A was positive in 60% of cases and for synaptophysin in 66.7%, with a predominant Ki-67 index between 0 and 2%. Metastasis was observed in 20% of patients. The surgical procedure most performed was subtotal gastrectomy with Roux-en-Y reconstruction (53.3%). Tumor recurrence occurred in 20% of cases and a new treatment was required in 26.67%. CONCLUSIONS: Gastric neuroendocrine tumors have a low incidence in the general population, and surgical treatment is indicated for advanced lesions. The study of its management gains importance in view of the specificities of each case and the need for adequate conduct to prevent recurrences and complications.

RESUMO RACIONAL: Os tumores neuroendócrinos gástricos são um grupo heterogêneo de neoplasias produtoras de substâncias bioativas, sendo o seu tratamento variável de acordo com o estadiamento e a classificação, sendo utilizadas técnicas endoscópicas, cirurgias abertas, quimioterapia, radioterapia e fármacos análogos da somatostatina. OBJETIVOS: Identificar e revisar os casos de neoplasia neuroendócrina gástrica submetidos a tratamento cirúrgico. MÉTODOS: Revisão os doentes tratados cirurgicamente de 1983 e 2018. RESULTADOS: Foram incluídos 15 pacientes, com predomínio do sexo feminino (73,33%) e média de idade de 55,93 anos. O sintoma mais comum foi a epigastralgia (93,3%) e o tempo médio do início dos sintomas foi de 10,07 meses. A endoscopia digestiva pré-operatória indicou predomínio de casos com 0 a 1 lesões (60%), de tamanho ≥ 1,5 cm (40%), localizadas em antro gástrico (53,33%), com ulceração (60%), Borrmann 3 (33,33%). A avaliação da peça cirúrgica indicou um predomínio de tumores neuroendócrinos invasivos (60%), com invasão angiolinfática na maioria dos casos (80%). A imuno-histoquímica para cromogranina A foi positiva em 60% dos casos e para sinaptofisina em 66,7%, com índice de Ki-67 predominante entre 0 e 2%. Metástases foram observadas em 20% dos casos. O procedimento cirúrgico mais utilizado foi a gastrectomia subtotal com reconstrução em Y de Roux (53,3%). Recidiva tumoral ocorreu em 20% dos casos e novo tratamento foi necessário em 26,67% dos casos. CONCLUSÕES: Os tumores neuroendócrinos gástricos apresentam baixa incidência na população em geral, e o tratamento cirúrgico está indicado nas lesões avançadas. O estudo de seu manejo ganha importância frente às especificidades de cada caso e a necessidade de conduta adequada para a prevenção de recidivas e complicações.

Liver transplant for metastatic neuroendocrine tumors: a single-center report / Transplante de fígado para tumores neuroendócrinos metastáticos: série de casos

ABSTRACT BACKGROUND: Neuroendocrine tumors are rare neoplasms of uncertain biological behavior. The liver is one of the most common sites of metastases, occurring in 50% of patients with metastatic disease. AIMS: To analyze a clinical series in liver transplant of patients with neuroendocrine tumors metastases. METHODS: A retrospective descriptive study, based on the review of medical records of patients undergoing liver transplants due to neuroendocrine tumor metastases in a single center in northeast Brazil, over a period of 20 years (January 2001 to December 2021). RESULTS: During the analyzed period, 2,000 liver transplants were performed, of which 11 were indicated for liver metastases caused by neuroendocrine tumors. The mean age at diagnosis was 45.09±14.36 years (26-66 years) and 72.7% of cases were females. The most common primary tumor site was in the gastrointestinal tract in 64% of cases. Even after detailed investigation, three patients had no primary tumor site identified (27%). Overall survival after transplantation at one month was 90%, at one year was 70%, and five year, 45.4%. Disease-free survival rate was 72.7% at one year and 36.3% at five years. CONCLUSIONS: Liver transplantation is a treatment modality with good overall survival and disease-free survival results in selected patients with unresectable liver metastases from neuroendocrine tumors. However, a rigorous selection of patients is necessary to obtain better results and the ideal time for transplant indication is still a controversial topic in the literature.

RESUMO RACIONAL: Os tumores neuroendócrinos são neoplasias raras de comportamento biológico incerto. O fígado é um local comum de metástase, ocorrendo em 50% dos pacientes com doença metastática. OBJETIVOS: Analisar casuística de transplante hepático por metástases de tumores neuroendócrinos. MÉTODOS: Estudo descritivo retrospectivo com revisão de prontuários de pacientes submetidos a transplante hepático por metástases de tumores neuroendócrinos em um único centro no Nordeste do Brasil durante 20 anos (janeiro de 2001 a dezembro de 2021). RESULTADOS: Durante o período analisado, foram realizados 2.000 transplantes hepático, sendo 11 indicados por metástases hepáticas de tumores neuroendócrinos. A média de idade ao diagnóstico foi de 45,09±14,36 anos (26-66 anos) e 72,7% dos casos eram do sexo feminino. O local do tumor primário mais comum foi o trato gastrointestinal (64% dos casos). Após detalhada investigação, três pacientes não tiveram o local do tumor primário identificado (27%). A sobrevida global um mês e após um ano do transplante foi de 90 e 70%, respectivamente. A sobrevida após 5 anos foi de 45,4%. A taxa de sobrevida livre de doença foi de 72,7% no primeiro ano e 36,3% em cinco anos. CONCLUSÕES: O transplante hepático é uma modalidade de tratamento com bons resultados de sobrevida global e sobrevida livre de doença, em pacientes selecionados com metástases hepáticas irressecáveis de tumores neuroendócrinos. No entanto, a seleção rigorosa dos pacientes é necessária para obter melhores resultados e o momento ideal para a indicação do transplante ainda é um tema controverso na literatura.