A comprehensive validation of the novel 8th edition of American Joint Committee on Cancer staging manual for the long-term survivals of patients with non-functional pancreatic neuroendocrine neoplasms.

Histologically, the World Health Organization has classified pancreatic neuroendocrine neoplasms (p-NENs) into well-differentiated pancreatic neuroendocrine tumors (G1/G2 p-NETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (G3 p-NECs) based on tumor mitotic counts and Ki-67 index. Recently, the 8th edition of American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging manual has incorporated some major changes in 2017 that the TNM staging system for p-NENs should only be applied to well-differentiated G1/G2 p-NETs, while poorly-differentiated G3 p-NECs be classified according to the new system for pancreatic exocrine adenocarcinomas. However, this new manual for p-NENs has seldom been evaluated.Data of patients with both G1/G2 and G3 non-functional p-NENs (NF-p-NENs) from our institution was retrospectively collected and analyzed using 2 new AJCC 8th staging systems. We also made survival comparisons between the 8th and 7th edition system separately for different subgroups.For G1/G2 NF-p-NETs, there were 52 patients classified in AJCC 8th edition stage I, 40 in stage II, 41 in stage III and 19 in stage IV. As for G3 NF-p-NECs, 17, 19, 24, and 18 patients were respectively defined from AJCC 8th edition stage I to stage IV. In terms of the AJCC 7th staging system, the 230 patients with NF-p-NENs were totally distributed from stage I to stage IV (94, 63, 36, 37, respectively). For the survival analysis of both G1/G2 NF-p-NETs and G3 NF-p-NECs, the AJCC 7th edition system failed to discriminate the survival differences when compared stage III with stage II or stage IV (P > .05), while the 8th edition ones could perfectly allocate patients into 4 statistically different groups (P < .05). The HCIs of AJCC 8th stage for G1/G2 NF-p-NETs [HCI=0.658, 95% confidence interval (CI)=0.602-0.741] and stage for G3 NF-p-NECs (HCI=0.704, 95% CI=0.595-0.813) was both statistically larger than those of AJCC 7th stage for different grading NF-p-NENs [(HCI=0.578, 95% CI=0.557-0.649; P=.031), (HCI=0.546, 95% CI=0.531-0.636; P = .019); respectively], indicating a more accurate predictive ability for the survivals of NF-p-NENs.Our data suggested the 2 new AJCC 8th staging systems were superior to its 7th edition for patients with both G1/G2 NF-p-NETs and G3 NF-p-NECs.

Clinical Features and Long-Term Survival of Metastatic Hepatic Neuroendocrine Neoplasms Secondary to Gastroenteropancreatic Site: An Analysis by Applying the Grading Classification.

METHOD: Data of patients who were surgically treated and clinicopathologically diagnosed as (MH)-NENs secondary to (GEP)-NENs at West China Hospital of Sichuan University from January 2006 to December 2018 were retrospectively collected and analyzed by the grading classification for (GEP)-NENs. RESULTS: We identified 150 patients with (MH)-NENs secondary to (GEP)-NENs, including 10 patients with G1 NETs, 26 with G2 NETs, 33 with G3 NETs, and 81 with G3 NECs. There were significant differences between patients with G1/G2/G3 NETs and those with G3 NECs, such as age at diagnosis (P=0.041), synchronous liver lesion (P=0.032), incidental diagnosis (P=0.014), tumor largest diameter (P=0.047), vascular invasion (P=0.017), and extrahepatic metastatic disease (P=0.029). The estimated 3-year overall survival for patients with G1 NETs, G2 NETs, G3 NETs, and G3 NECs was 100%, 79.4%, 49.5%, and 20.7%, respectively (P < 0.001). The survival of G1 NETs or G2 NETs was significantly better than that of G3 NETs (P=0.013, P=0.037, respectively) and G3 NECs (P=0.001, P < 0.001; respectively). Patients with G3 NECs present notably worse survival than those with G3 NETs (P=0.012), while survival comparison between G1 NETs and G2 NETs was not statistically different (P=0.131). The grading classification for (GEP)-NENs was an effective independent predictor of survival for (MH)-NENs secondary to (GEP)-NENs (hazard ratio: 4.234; 95% confidence intervals: 1.984-6.763; P=0.003). CONCLUSION: Our demonstration revealed that the grading classification for (GEP)-NENs could well stratify (MH)-NENs secondary to (GEP)-NENs into prognostic groups and supported its wide use in clinical practice.

World Health Organization grading classification for pancreatic neuroendocrine neoplasms: a comprehensive analysis from a large Chinese institution.

BACKGROUND: Pancreatic neuroendocrine neoplasms (p-NENs) are a group of highly heterogeneous tumors with distinct clinicopathological features and long-term prognosis. In 2017, in order to better stratify patients into prognostic groups and predicting their outcomes, World Health Organization (WHO) officially updated its grading system for p-NENs which distinguished these neoplasms among Grading 1 (G1) pancreatic neuroendocrine tumors (p-NETs), G2 p-NETs, G3 p-NETs and G3 pancreatic neuroendocrine carcinomas (p-NECs). However, this new grading classification for p-NENs has not yet been rigorously validated. METHODS: Data of patients who were surgically treated and histopathologically diagnosed as p-NENs at West China Hospital of Sichuan University from January 2002 to December 2018 were retrospectively collected and analyzed according the novel WHO 2017 grading classification. RESULTS: We eventually enrolled 480 eligible patients with p-NENs in our present study, in which 150 patients with WHO 2017 G1 p-NETs, 158 with G2 p-NETs, 64 with G3 p-NETs and 108 with G3 p-NECs were identified. The estimated 5-year overall survival for patients with G1 p-NETs, G2 p-NETs, G3 p-NETs and G3 p-NECs was 75.8, 58.4, 35.1 and 11.1%, with a median survival time of 85.3mons, 67.4mons, 51.3mons and 26.8mons, respectively. Patients with G2 p-NETs present notably worse survival than those with G1 p-NETs (P = 0.03). Survival of G3 p-NETs were significantly worse than that of G1 p-NETs or G2 p-NETs (P < 0.001, P = 0.023, respectively), as well as that when comparing G3 p-NECs with G1 p-NETs or G2 p-NETs (P < 0.001, P < 0.001, respectively). Patients with G3 p-NECs showed statistically shorter survival than those with G3 p-NETs (P < 0.001). Both WHO 2017 and 2010 grading criteria could be independent predictor for the OS of p-NENs (P = 0.016, P = 0.022; respectively). The 95% confidence intervals of WHO 2017 grading classification (0.983-9.454) was slightly smaller than that of WHO 2010 criteria (0.201-13.374), indicating a relatively more accurate predicting ability for the prognosis of p-NENs. CONCLUSION: The WHO 2017 grading classification for p-NENs could successfully allocate patients into four groups with distinct clinical features and significant survival differences, which might be superior to the WHO 2010 criteria for its better prognostic stratification and more accurate predicting ability.

Enhancement of Antitumor Efficacy of Paclitaxel-Loaded PEGylated Liposomes by N,N-Dimethyl Tertiary Amino Moiety in Pancreatic Cancer.

INTRODUCTION: Pancreatic cancer, or pancreatic duct adenocarcinoma (PDAC), remains one of the most lethal cancers and features insidious onset, highly aggressive behavior and early distant metastasis. The dense fibrotic stroma surrounding tumor cells is thought to be a shield to resist the permeation of chemotherapy drugs in the treatment of PDAC. Thus, we synthesized a pancreas-targeting paclitaxel-loaded PEGylated liposome and investigated its antitumor efficacy in the patient-derived orthotopic xenograft (PDOX) nude mouse models of PDAC. METHODS: The PTX-loaded PEGylated liposomes were prepared by film dispersion-ultrasonic method and modified by an N,N-dimethyl tertiary amino residue. Morphology characteristics of the PTX-loaded liposomes were observed by transmission electron microscope (TEM). The PDOX models of PDAC were established by orthotopic implantation and imaged by a micro positron emission tomography/computed tomography (PET/CT) imaging system. The in vivo distribution and antitumor study were then carried out to observe the pancreas-targeting accumulation and the antitumor efficacy of the proposed PTX liposomes. RESULTS: PTX loaded well into both modified (PTX-Lip2N) and unmodified (PTX-Lip) PEGylated liposomes with spherical shapes and suitable parameters for the endocytosis process. The PDOX nude mouse models were successfully created in which high 18F-FDG intaking regions were observed by micro-PET/CT. In addition to higher cellular uptakes of PTX-Lip2N by the BxPC-3 cells, the proposed nanoparticle had a notable penetrating ability towards PDAC tumor tissues, and consequently, the antitumor ability of PTX-Lip2N was significantly superior to the unmodified PTX-Lip in vivo PDOX models and even more effective than nab-PTX in restraining tumor growth. CONCLUSION: The modified pancreas-targeting PTX-loaded PEGylated liposomes provide a promising platform for the treatment of pancreatic cancer.

Survivals of patients with pancreatic neuroendocrine carcinomas: An in-depth analysis by the American Joint Committee on Cancer 8th tumor-node-metastasis staging manual.

Recently, the American Joint Committee on Cancer (AJCC) 8th staging manual stipulated the World Health Organization (WHO) G3 pancreatic neuroendocrine carcinomas (p-NECs) should all be classified by the system for pancreatic exocrine adenocarcinomas, which had ignored the heterogeneity of G3 p-NECs. We focused on demonstrating whether the heterogeneous subgroups of G3 p-NECs would influence the accurate application of AJCC 8th staging systems.G3 p-NECs were divided into well-differentiated and poorly-differentiated subgroups, whose clinical features and overall survival (OS) were compared. Survival analysis by applying 2 new AJCC 8th staging systems to well-differentiated G3 p-NECs were performed to validate whether these subgroup patients should also be staged by the system proposed for all G3 p-NECs.We enrolled 172 patients who were histopathologically diagnosed as G3 p-NECs, including 64 well-differentiated G3 p-NECs and 108 poorly-differentiated ones, whose patient demographics and tumor characteristics present no notably differences (P > .05), except their Ki-67 index and mitotic rate (P = .031, P = .025; respectively). The estimated OS of well-differentiated G3 p-NECs was significantly better than those of poorly-differentiated tumors (P < .001). When applying the new AJCC system for all G3 p-NECs to well-differentiated G3 tumors, 18, 22, 12, and 12 patients were respectively distributed in the new AJCC Stage I, Stage II, Stage III, and Stage IV. Using the AJCC 8th staging system for WHO G1/G2 pancreatic neuroendocrine tumors (p-NETs) to well-differentiated G3 p-NECs, there were 5, 25, 22, and 12 patients classified from the new AJCC Stage I to Stage IV, respectively. The system for G1/G2 p-NETs could significantly differentiate the survival differences between each new stage of well-differentiated G3 p-NECs (P < .05), while comparisons of survivals between Stage II with Stage III or Stage III with Stage IV by the system for G3 p-NECs were not statistically different (P = .334, P = .073; respectively).G3 p-NECs were heterogeneous with well-differentiated and poorly-differentiated subgroups. Both AJCC 8th staging systems proposed for all G3 p-NECs and G1/G2 p-NETs were practical for well-differentiated G3 p-NECs, while the one originally applied to G1/G2 p-NETs appeared to be superior in performance due to its better prognostic stratification and more accurate predicting ability.

Prognostic Validity of the American Joint Committee on Cancer Eighth Edition TNM Staging System for Surgically Treated and Well-Differentiated Pancreatic Neuroendocrine Tumors: A Comprehensive Analysis of 254 Consecutive Patients From a Large Chinese Institution.

OBJECTIVES: We aimed to validate the novel American Joint Committee on Cancer (AJCC) eighth edition staging manual for well-differentiated (G1/G2) pancreatic neuroendocrine tumors (pNETs). METHODS: Data of eligible patients were retrospectively collected, grouped, and analyzed by applying the new AJCC system. RESULTS: According to the AJCC eighth staging manual for pNETs, 93, 66, 53, and 42 patients had stage I, II, III, and IV disease, respectively, with estimated 5-year overall survival (OS) rates of 96.9%, 92.8%, 48.4%, and 16.8% (P < 0.005), respectively. A total of 57, 28, 20, and 17 patients with G1 pNETs and 36, 38, 33, and 25 ones with G2 tumors were defined by the new AJCC system as having stage I, II, III, and IV disease, respectively. The estimated 5-year OS for stage I, II, III and IV disease was 100.0%, 97.1%, 52.5%, and 18.2%, respectively, for G1 pNETs (P < 0.005) and 94.2%, 90.3%, 38.7%, and 12.7%, respectively, for G2 tumors (P < 0.005). The novel AJCC classification, tumor grading, and radical resection were all prognostic predictors for OS in patients with pNETs. CONCLUSIONS: The new AJCC eighth staging system for well-differentiated pNETs was prognostic and might be adopted in clinical practice.

A novel gemcitabine derivative-loaded liposome with great pancreas-targeting ability.

Gemcitabine (Gem) is a standard first-line treatment for pancreatic cancer (PC). However, its chemotherapeutic efficacy is hampered by various limitations such as short half-life, metabolic inactivation, and lack of tumor localizing. We previously synthesized a lipophilic Gem derivative (Gem formyl hexadecyl ester, GemC16) that exhibited improved antitumor activity in vitro. In this study, a target ligand N,N-dimethyl-1,3-propanediamine was conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol-2000)] (DSPE-PEG-NHS) to form DSPE-PEG-2N. Then, pancreas-targeting liposomes (2N-LPs) were prepared using the film dispersion-ultrasonic method. GemC16-loaded 2N-LPs displayed near-spherical shapes with an average size distribution of 157.2 nm (polydispersity index (PDI) = 0.201). The encapsulation efficiency of GemC16 was up to 97.3% with a loading capacity of 8.9%. In human PC cell line (BxPC-3) and rat pancreatic acinar cell line (AR42J), cellular uptake of 2N-LPs was significantly enhanced compared with that of unmodified PEG-LPs. 2N-LPs exhibited more potent in vitro cytotoxicity against BxPC-3 and AR42J cell lines than PEG-LPs. After systemic administration in mice, 2N-LPs remarkably increased drug distribution in the pancreas. In an orthotopic tumor mouse model of PC, GemC16-bearing liposomes were more effective in preventing tumor growth than free GemC16. Among these treatments, 2N-LPs showed the best curative effect. Together, 2N-LPs represent a promising nanocarrier to achieve pancreas-targeting drug delivery, and this work would provide new ideas for the chemotherapy of PC.

Survivals of patients with surgically treated and High-grade pancreatic neuroendocrine carcinomas: A comparative study between two American Joint Committee on Cancer 8th tumor-node-metastasis staging systems.

BACKGROUND AND OBJECTIVE: We aimed to compare the two new defined tumor-node-metastasis (TNM) systems in the American Joint Committee on Cancer (AJCC) 8th staging manual for overall survival (OS) analysis of G3 pancreatic neuroendocrine carcinomas (p-NECs) that are currently proposed for pancreatic exocrine adenocarcinomas (p-EACs) and G1/G2 pancreatic neuroendocrine tumors (p-NETs), respectively. METHODS: The data of patients who were surgically treated and histopathologically diagnosed with G3 p-NECs at West China Hospital of Sichuan University from January 2002 to June 2017 were retrospectively analyzed and compared using the two new AJCC staging systems. RESULTS: Applying the p-EAC AJCC 8th TNM staging system to G3 p-NECs, the estimated 3-year OSs for each stage were 86.7%, 76.0%, 44.5% and 20.7%, respectively (P < 0.001). According to the G1/G2 p-NETs staging system, the estimated OSs at 3 years for each new AJCC stage were 100.0%, 83.6%, 47.1% and 20.7%, respectively (P < 0.001). The system for p-EACs significantly discriminated the survival difference of G3 p-NECs between Stage I and Stage II (P = 0.019), while the other one for G1/G2 p-NETs could not (P = 0.108). The consistent results of Akaike information criteria with Harrell's concordance index indicated that the AJCC 8th staging system for p-EACs was superior when applied to G3 p-NECs for its better prognostic stratification and more accurate prediction ability for OS. CONCLUSIONS: Our analysis demonstrated that both TNM systems in the AJCC 8th staging manual were prognostic for patients with G3 p-NECs; however, the classification originally applied to p-EACs was superior and supported its use in clinical practice.

Pancreatic panniculitis and solid pseudopapillary tumor of the pancreas: A case report.

Solid pseudopapillary tumor of the pancreas (SPTP), also known as solid and papillary epithelial neoplasm of the pancreas, is a rare pancreatic exocrine tumor that is difficult to diagnose before surgery. Pancreatic panniculitis is a rare type that occurs in less than 3% of all patients with pancreatic diseases. We here report a 19-year-old woman who presented with persistent left upper quadrant pain without obvious cause for 1 d. The patient also developed subcutaneous nodules involving lower abdomen bilaterally and lower limbs, and subcutaneous nodules were pathologically diagnosed as pancreatic panniculitis. Plain abdominal computed tomography revealed a soft-tissue mass in the body and tail of the pancreas, which was closely associated with the gastric wall. Contrast-enhanced ultrasound showed inhomogeneous echogenicity in the anterior pancreatic body, which had blurred parenchymal demarcation of the body and tail of the pancreas. Contrast-enhanced abdominal computed tomography revealed a mixed density mass with solid and cystic components in the body and tail of the pancreas, and the solid component was markedly enhanced. The lesion was pathologically diagnosed as SPTP after laparoscopic resection. Clinicians should be aware of the clinical manifestation, diagnosis, and treatment of pancreatic panniculitis and SPTP.

Prognostic validation of the updated 8th edition Tumor-Node-Metastasis classification by the Union for International Cancer Control: Survival analyses of 307 patients with surgically treated gallbladder carcinoma.

In December 2016, the Union for International Cancer Control (UICC) published the 8th edition of the Tumor-Node-Metastasis (TNM) classification of malignant tumors, including a number of vital changes in the definitions of the T2 category, the N category and the stages of gallbladder cancer (GBC). The clinical value of this newly updated classification in patients with surgically treated GBC has not been rigorously validated. The present study aimed to analyze the prognosis of patients with GBC in a high-volume surgical unit, and to validate the prognostic value of the new UICC TNM classification, particularly the main changes in the stages of GBC. Data from 307 patients who were surgically treated and histopathologically diagnosed with GBC between January 2011 and July 2016 in The West China Hospital (Chengdu, Sichuan, China) were retrospectively collected and analyzed. The new UICC criteria distributed 32, 60, 99 and 116 eligible patients in stages I, II, III and IV, respectively. The differences in overall survival time between each stage (I-IV) demonstrated statistical significance (P<0.05). As a result of the main change of this classification, the novel definitions of T2a and T2b effectively stratified the prognosis of patients with T2 GBC (P<0.001). Furthermore, patients with stage IIa tumors also obtained significantly improved overall survival time compared with patients with stage IIb tumors (P=0.04), whereas the comparison between patients with stage IIb and IIIa tumors did not present any notable difference (P=0.20). Additionally, the new N category stratified the survival of the patients effectively (P<0.001). Together with curative resection, this latest classification was indicated to be an independent predictor of survival via multivariate analysis (hazard ratio, 6.25; 95% confidence interval, 3.81-10.26; P<0.001). In conclusion, the newly updated UICC TNM classification could effectively reflect the clinical outcome of patients with surgically treated GBC. Furthermore, tumor location could predict the survival of surgically treated T2 GBC. The novel classification of the N category by the number of lymph nodes involved was also demonstrated to be valid.

Use of Clavien-Dindo classification in evaluating complications following pancreaticoduodenectomy in 1,056 cases: A retrospective analysis from one single institution.

The Clavien-Dindo (C-D) classification is a simple and feasible grading system of postoperative complications. The aim of the present study was to apply this system to retrospectively classify all types of post-pancreaticoduodenectomy (PD) complications (PPCs) and to systematically identify associated risk factors. Between January 2009 and December 2014, the C-D classification was applied to retrospectively classify PPCs for 1,056 patients who had undergone PD at the West China Hospital. Univariate and multivariate analyses were performed to link perioperative parameters and mortality with the severity of PPCs, which were subdivided into overall PPCs (Grade I-V), severe PPCs (Grade III-V) and mortality (Grade V). The number of patients with Clavien-Dindo grade I, II, IIIa, IIIb, IVa, IVb and V complications was 185 (17.5%), 128 (12.1%), 50 (4.7%), 25 (2.4%), 35 (3.3%), 19 (1.8%) and 33 (3.1%), respectively. A total of 475 (45.0%) patients experienced overall PPCs; 168 (15.9%) patients experienced severe PPCs; and 33 patients succumbed to mortality following PD. The following risk factors were identified following PD: Preoperative hypoproteinemia was correlated with all three subdivisions; obstructive jaundice was associated with severe PPCs and mortality; and older age was revealed to be an independent risk factor of mortality. A large retrospective study was performed in the present study and PD was correlated with a high occurrence of PPCs. The Clavien-Dindo system represents a broad applicable and feasible approach to evaluating PPCs in patients following PD. The independent risk factors of PPCs that were identified in the present study require further validation using the Clavien-Dindo classification in additional prospective studies.

Incidence of and Risk Factors and Reinterventions for Post-Pancreatoduodenectomy Hemorrhage: Retrospective Analysis.

AIMS: To analyze the incidence of and risk factors for post-pancreatoduodenectomy (PD) hemorrhage (PPH) and to evaluate the outcomes of reinterventions for PPH. METHODS: All PDs between January 2009 and December 2014 were retrospectively evaluated. PPH was evaluated according to the criteria of the International Study Group of Pancreatic Surgery. Both univariate and multivariate analyses of risk factors for PPH and mortality were performed. Reinterventions were also evaluated. RESULTS: Of the 1,056 PDs during the study period, 78 (7.4%) developed PPH, including 36 with grade B and 42 with grade C. Of these 78 patients, 24 (30.8%) died of PPH-related causes. Multivariate analysis showed that older age, higher total bilirubin concentration, and postoperative pancreatic fistula (POPF) were independent risk factors for PPH. Patients who died of PPH were significantly older and had lower preoperative hemoglobin and albumin concentrations than patients who did not die of PPH. Of the 78 patients with PPH, 58 underwent reintervention, including 27 who underwent angiography, 24 who underwent endoscopy, 24 who underwent re-laparotomy, and 15 who underwent more than one reintervention. CONCLUSIONS: Older age, total bilirubin, and POPF are independent risk factors for PPH. Higher mortality are associated with advanced PPH and poor nutritional conditions.

Functional and non-functional pancreatic neuroendocrine tumours: ENETS or AJCC TNM staging system?

BACKGROUND: There are currently 2 Tumour-Node-Metastasis (TNM) staging systems for pancreatic neuroendocrine tumours (p-NETs) - European Neuroendocrine Tumour Society (ENETS) and American Joint Committee on Cancer (AJCC). P-NETs being heterogeneous, we investigated the prognostic value of the 2 systems in p-NETs, as a whole, and more interestingly in functional and non-functional sub-groups separately, with a view to ascertaining any potential clinical benefits of using one system over the other. METHODS: Data from patients with surgically resected p-NETs were retrospectively reviewed. Kaplan-Meier method and Cox Regression proportional hazards model were used to analyse overall survival (OS) and prognostic predictors respectively. RESULTS: In the whole group of 165 patients, both TNM systems successfully discriminated OS differences when comparing stages I and II with stages III and IV (P<0.05); ENETS stage III patients had a significantly better OS than those in stage IV (P=0.003). Patients with functional p-NETs in ENETS stage II showed a statistically better OS than those in stages III and IV (P<0.05). For non-functional tumours, the AJCC staging system could effectively discriminate between the OS differences of patients in stage I with stages III and IV, or stage II with III and IV (P<0.05). Along with surgical intent and World Health Organisation (WHO) 2010 grade, both ENETS and AJCC staging systems were effective predictors of OS for different function-status p-NETs. CONCLUSIONS: The ENETS system might have potential advantages when applied to all p-NETs and to the functional sub-group, while the AJCC system might be clinically more practical for non-functional p-NETs.

Risk factors for pain after Frey's procedure in chronic pancreatitis.

Pancreatic pain is the most frequent symptom of chronic pancreatitis (CP) and is difficult to treat. This retrospective study aimed to determine the risk factors for pain in CP.From January 2009 and March 2014, 75 consecutive patients with CP who underwent Frey's procedure were reviewed for this study. According to Izbicki pain scores, these patients were divided into 2 groups: (1) pain (Izbicki pain score of >10 after a decrease of >50%) and (2) pain-free (Izbicki pain score of ≤10). Demographic data, medical history, postoperative variables, and follow-up evaluations of the patients were documented.The postoperative pain score (11.8) was significantly lower than the preoperative score (51.8) after a median follow-up of 4.2 years. Alcoholism (odds ratio [OR] 7.767, P = .002) and preoperative analgesic medication use (OR 4.113, P = .030) were independent risk factors for pain.Frey's procedure is an effective operation for pain relief in patients with CP. Alcoholism and preoperative analgesic medication use were 2 factors for failure to achieve complete pain relief.

Transjugular intrahepatic portosystemic shunt versus open splenectomy and esophagogastric devascularization for portal hypertension with recurrent variceal bleeding.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) and open splenectomy and esophagogastric devascularization (OSED) are widely used to treat patients with portal hypertension and recurrent variceal bleeding (PHRVB). This study aimed to compare the effectiveness between TIPS and OSED for the treatment of PHRVB. METHODS: The data were retrospectively retrieved from 479 cirrhotic patients (Child-Pugh A or B class) with PHRVB, who had undergone TIPS (TIPS group) or OSED (OSED group) between January 1, 2010 and October 31, 2014. RESULTS: A total of 196 patients received TIPS, whereas 283 underwent OSED. Within one month after TIPS and OSED, the rebleeding rates were 6.1% and 3.2%, respectively (P=0.122). Significantly lower incidence of pleural effusion, splenic vein thrombosis, and pulmonary infection, as well as higher hepatic encephalopathy rate, shorter postoperative length of hospital stay, and higher hospital costs were observed in the TIPS group than those in the OSED group. During the follow-up periods (29 months), significantly higher incidences of rebleeding (15.3% vs 4.6%, P=0.001) and hepatic encephalopathy (17.3% vs 3.9%, P=0.001) were observed in the TIPS group than in the OSED group. The incidence of in-stent stenosis was 18.9%. The survival rates were 91.3% in the TIPS group and 95.1% in the OSED group. The long-term liver function did not worsen after either TIPS or OSED. CONCLUSION: For the patients with liver function in the Child-Pugh A or B class, TIPS is not superior over OSED in terms of PHRVB treatment and rebleeding prevention.

Pheochromocytoma of the pancreas: A report of three cases and a literature review.

Pheochromocytoma is primarily derived from the adrenal medulla. The majority of extra-adrenal pheochromocytoma cases occur in the superior para-aortic region and para-adrenal area. However, pheochromocytoma originating from the pancreas is rare. The present study reports the cases of three patients who had no history of hypertension but were post-operatively diagnosed with pheochromocytoma located in the pancreas. Of the three patients, two were admitted to hospital due to abdominal pain, and imaging examinations revealed a soft-tissue lesion in the head of pancreas. Local resection of the pancreatic tumor was successfully performed and a diagnosis of pheochromocytoma derived from the pancreas was subsequently made by pathologists. The third patient was admitted to hospital for surgical treatment due to the identification of a continuously growing lesion in the tail of pancreas during physical examinations. Distal resection of the pancreas was stopped during surgery when the patient's blood pressure and heart rate suddenly increased to 180/110 mmHg and 140 beats/min, respectively. Due to a marked rise in noradrenaline and adrenaline levels in the blood subsequent to surgery, the patient was diagnosed with pancreatic pheochromocytoma. The present study additionally reviewed the associated literature concerning pheochromocytoma in order to improve the understanding of this rare clinical phenomenon. The aim of the present study is to highlight to surgeons that although patients may not present with typical clinical manifestations due to the non-functional status of the tumor, undiagnosed pheochromocytoma of the pancreas should be considered when surgeons observe an unexpected hypertensive crisis during pancreatic tumor surgery.

Applications of a novel tumor-grading-metastasis staging system for pancreatic neuroendocrine tumors: An analysis of surgical patients from a Chinese institution.

The ability to stratify patients with pancreatic neuroendocrine tumors (p-NETs) into prognostic groups has been hindered by the absence of a commonly accepted staging system. Both the 7th tumor-node-metastasis (TNM) staging guidelines by the American Joint Committee on Cancer (AJCC) and the 2010 grading classifications by the World Health Organization (WHO) were validated to be unsatisfactory.We aim to evaluate the feasibility of combining the latest AJCC and WHO criteria to devise a novel tumor-grading-metastasis (TGM) staging system. We also sought to examine the stage-specific survival rates and the prognostic value of this new TGM system for p-NETs.Data of 120 patients with surgical resection and histopathological diagnosis of p-NETs from January 2004 to February 2014 in our institution were retrospectively collected and analyzed. Based on the AJCC and WHO criteria, we replaced the stage N0 and N1 with stage Ga (NET G1 and NET G2) and Gb (NET G3 and MANEC) respectively, without changes of the definition of T or M stage. The present novel TGM staging system was grouped as follows: stage I was defined as T1-2, Ga, M0; stage II as T3, Ga, M0 or as T1-3, Gb, M0; stage III as T4, Ga-b, M0 and stage IV as any T, M1.The new TGM staging system successfully distributed 55, 42, 12, and 11 eligible patients in stage I to IV, respectively. Differences of survival compared stage I with III and IV for patients with p-NETs were both statistically significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001). Patients in stage I showed better a survival than those in stage II, whereas difference between stages III and IV was not notable (P = 0.001, P = 0.286, respectively). In multivariate models, when the TGM staging system was evaluated in place of the individual T, G, and M variables, this new criteria were proven to be an independent predictor of survival for surgically resected p-NETs (P < 0.05).Stratifying patients well, the current proposed TGM staging system was predictive for overall survival of p-NETs and could be more widely applied in clinical practice.

Survival Analyses for Patients With Surgically Resected Pancreatic Neuroendocrine Tumors by World Health Organization 2010 Grading Classifications and American Joint Committee on Cancer 2010 Staging Systems.

In 2010, World Health Organization (WHO) reclassified pancreatic neuroendocrine tumors (p-NETs) into 4 main groups: neuroendocrine tumor G1 (NET G1), neuroendocrine tumor G2 (NET G2), neuroendocrine carcinoma G3 (NEC G3), mixed adeno and neuroendocrine carcinoma (MANEC). Clinical value of these newly updated WHO grading criteria has not been rigorously validated. The authors aimed to evaluate the clinical consistency of the new 2010 grading classifications by WHO and the 2010 tumor-node metastasis staging systems by American Joint Committee on Cancer (AJCC) on survivals for patients with surgically resected p-NETs. Moreover, the authors would validate the prognostic value of both criteria for p-NETs.The authors retrospectively collected the clinicopathologic data of 120 eligible patients who were all surgically treated and histopathologically diagnosed as p-NETs from January 2004 to February 2014 in our single institution. The new WHO criteria were assigned to 4 stratified groups with a respective distribution of 62, 35, 17, and 6 patients. Patients with NET G1 or NET G2 obtained a statistically better survival compared with those with NEC G3 or MANEC (P < 0.001). Survivals of NET G1 was also better than those of NET G2 (P = 0.023), whereas difference of survivals between NEC G3 and MANEC present no obvious significance (P = 0.071). The AJCC 2010 staging systems were respectively defined in 61, 36, 12, and 11 patients for each stage. Differences of survivals of stage I with stage III and IV were significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001); whereas comparisons of stage I with stage II and stage III with IV were not statistically significant (P = 0.129, P = 0.286; respectively). Together with radical resection, these 2 systems were both significant in univariate and multivariate analysis (P < 0.05).The newly updated WHO 2010 grading classifications and the AJCC 2010 staging systems could consistently reflect the clinical outcome of patients with surgically resected p-NETs. Meanwhile, both criteria could be independent predictors for survival analysis of p-NETs.

[Effect of CD86 Gene Modified Recipient Dendritic Cell on Mix Cultured Donor-derived Islet with Recipient-derived Lymphocyte in vitro].

OBJECTIVE: To investigate the effect of CD86 gene modified recipient dendritic cell (DC) on mix cultured donor-derived islet with recipient-derived lymphocyte in vitro. METHODS: DCs were separated from bone marrow of BALB/c mice and identified by flow cytometry. Chemically synthesized CD86 siRNA was transferred into DC. Donor islets were separated from the pancreas of SD rats. Acridine orange (AO)/Propidium iodide (PI) staining was conducted to assess the viability of islets. Lymphocytes were collected from the spleen of SD rats and then co-cultured with CD86 gene modified recipient DCs. CD86 gene modified recipient DC, donor-derived islet (400 IEQ) and recipient-derived lymphocyte (1 x 10(6)) were mix cultured in vitro. Four groups were set: blank group (islets of SD rat only), control 1 group (islets of SD rat with splenic lymphocyte of BALB/c mice) , control 2 group (islets of SD rat, splenic lymphocyte of BALB/c mice with normal recipient DC) and experimental group (islets of rat, splenic lymphocyte of BALB/c mice with CD86 gene modified recipient DC). After 3 days culture, the cellular morphology of culture was observed with light inverted microscope. The levels of IL-2, IL-4, IL-10 and IFN-γ in the culture supernatant were tested, and islets viability was assessed by AO/PI staining. GSIS was conducted and stimulation index (SD was calculated. RESULTS: Typical DC morphology was found from the collected cells. The positive rates of CD1lc, CD80 and CD86 protein expression on DCs were 86.26% ± 9.73%, 72.64% ± 8.55% and 77.18% ± 10.23%, respectively. The positive rate of CD86 protein expression on DCs after transfection was 23.64% ± 5.25%. The viability of islets was over 95%. After 3 days culture, the level of IL-10 increased significantly and the levels of IL-2 and INF-γ decreased significantly in experimental group (vs. control 1 and control 2 groups, P < 0.05). The level of IL-4 was similar in control 1, control 2 and experimental groups, but the proliferation rate of lymphocyte in the experimental group was the lowest one, the viability of islets in the experimental group was the best and the SI was the highest. The levels of IL-2, IL-4, IL-10 and IFN-γ in the experimental group were higher than those in the blank group. CONCLUSION: CD86 gene modified recipient DC loaded with donor-derived antigen could protect the islet function in vitro to some extent.