Active surveillance in metastatic pancreatic neuroendocrine tumors: A 20-year single-institutional experience.

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are heterogeneous and indolent; systemic therapy is not essential for every patient with metastatic PanNET. The National Comprehensive Cancer Network guidelines state that delaying treatment is an option for PanNET with distant metastasis, if the patient has stable disease. However, specific factors that influence surveillance were not mentioned. In addition, data regarding the period of active surveillance in patients with metastatic PanNET are lacking. AIM: To specifically determine factors influencing active surveillance in patients with liver metastatic nonfunctioning PanNETs (NF-PanNETs). METHODS: Seventy-six patients with liver metastatic NF-PanNETs who received active surveillance from a high-volume institution were enrolled. Time to disease progression (TTP) and time to initiation of systemic therapy were determined. RESULTS: Thirty-one (40.8%) patients had recurrent liver disease after R0 resection; 45 (59.2%) were diagnosed with liver metastasis. The median follow-up period was 42 mo and 90.7% patients were observed to have disease progression. The median TTP (mTTP) was 10 mo. Multivariate analysis showed that the largest axis of the liver metastasis > 5 mm (P = 0.04), non-resection of the primary tumor (P = 0.024), and T3-4 stage (P = 0.028) were associated with a shorter TTP. The mTTP in patients with no risk factors was 24 mo, which was significantly longer than that in patients with one (10 mo) or more (6 mo) risk factors (P < 0.001). A nomogram with three risk factors showed reasonable calibration, with a C-index of 0.603 (95% confidence interval: 0.47-0.74). CONCLUSION: Active surveillance may only be safe for metastatic NF-PanNET patients with favorable risk factors, and other patients progressed rapidly without treatment. Further studies with a larger sample size and a control group are needed.

New observations on the utility of CA19-9 as a biomarker in Lewis negative patients with pancreatic cancer.

BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is the best-validated biomarker for pancreatic cancer. The National Comprehensive Cancer Network (NCCN) guideline asserts that "CA19-9 will be undetectable in Lewis antigen-negative individuals". However, reports of CA19-9 secretion and its significance in Lewis (-) patients with pancreatic cancer have been inconsistent. This study was to examine serum CA19-9 levels in patients with pancreatic cancer according to Lewis status. METHODS: Patients with pancreatic cancer (1482 cases) were retrieved from a prospectively maintained database. Patients with benign pancreatic disease (210 cases) and normal subjects (315 cases) were used as controls. Lewis genotypes were examined by fucosyltransferase 3 (FUT3) sequencing. RESULTS: In patients with pancreatic cancer, 8.4% of subjects were Lewis (-), but only 41.9% of Lewis (-) subjects had CA19-9 values ≤ 2 U/mL. CA19-9 was even elevated (>37 U/mL) in 27.4% of Lewis (-) patients. The area under the receiver operating characteristic (ROC) curve for CA19-9 as a diagnostic biomarker was 0.842 in Lewis (-) patients with pancreatic cancer, which is closing to that of CA19-9 applied in all of patients with pancreatic cancer (0.898). Lewis (-) status was an independent prognostic factor for shorter survival in a multivariable analysis (hazard ratio (HR), 1.30, 95% confidence interval (CI), 1.03-1.64; P = 0.028). CONCLUSIONS: Not all Lewis (-) patients with pancreatic cancer are non-secretors of CA19-9. Contrary to general understanding, CA19-9 can retain its utility as a biomarker in these patients in spite of Lewis (-) genotype.

Mismatch repair status as a beneficial predictor of fluorouracil-based adjuvant chemotherapy for pancreatic cancer.

BACKGROUND: Prior studies have indicated that patients with colorectal cancer with deficient mismatch repair have particular clinicopathologic features that distinguish them from patients with tumors with proficient mismatch repair. However, the effect of the mismatch repair status on outcomes after adjuvant chemotherapy for pancreatic cancer is still unknown. METHODS: Pancreatic cancer patients who underwent R0 resection between January 2013 and December 2015 at Fudan University Shanghai Cancer Center were included in this study. Mismatch repair status was determined by immunohistochemistry of mismatch repair proteins. Prognostic factors for deficient mismatch repair and proficient mismatch repair tumors were analyzed using Cox models. RESULTS: In total, 442 of 590 patients met the inclusion criteria, and their mismatch repair status was determined; the study group consisted of 75 patients with deficient mismatch repair and 367 patients with proficient mismatch repair. Among the 147 patients who underwent surgery alone, patients with deficient mismatch repair tumors had a better overall survival than patients with proficient mismatch repair tumors (hazard ratio = 0.555 [95% confidence interval 0.331-0.931]; P = .026). Compared with patients who underwent surgery, 161 patients who received gemcitabine-based adjuvant chemotherapy had improvements in both disease-free survival and overall survival, regardless of mismatch repair status. However, 5-fluorouracil-based adjuvant chemotherapy yielded a favorable disease-free survival in the proficient mismatch repair group but conferred no survival advantage in the deficient mismatch repair group (hazard ratio = 0.930 [95% confidence interval 0.497-1.743]; P = .821). CONCLUSION: Mismatch repair status in pancreatic cancer patients is not only a prognostic indicator but also a potential guiding factor for the use of 5-fluorouracil-based adjuvant chemotherapy.

The combination of HTATIP2 expression and microvessel density predicts converse survival of hepatocellular carcinoma with or without sorafenib.

Our previous studies have demonstrated that sorafenib can promote the dissemination of hepatocellular carcinoma (HCC) through downregulation of HTATIP2, a suppressor of tumor growth and metastasis that is associated with inhibition of angiogenesis. Here, we investigated the predictive values of the HTATIP2 level and microvessel density (MVD) with or without sorafenib administration for HCC. Three independent cohorts were included. Using tissue microarray, we assessed the relationship between HTATIP2 expression/MVD and overall survival. The results showed that high HTATIP2 expression and a low MVD value were independent protective prognostic factors after curative HCC resection (297 cases/cohort 1); however, both parameters were converted to independent negative prognostic indicators for patients with postsurgical sorafenib treatment (69/143 cases/cohort 2; P<0.05 for all). This same relationship was observed in patients that received sorafenib treatment for advanced HCC (83 cases/cohort 3; efficacy measures and survival analyses, P<0.05 for all). Moreover, the combination of HTATIP2 and MVD had better power to predict patient death and disease recurrence (P<0.001 for both). We conclude that the combination of HTATIP2 and MVD predicts the converse survival of HCC with or without sorafenib intervention. Our findings can assist in the selection of candidates for personalized treatment with sorafenib.

Green tea drinking and risk of pancreatic cancer: a large-scale, population-based case-control study in urban Shanghai.

BACKGROUND: Little is known about the etiology of pancreatic cancer. Epidemiological studies on tea consumption and pancreatic cancer risk have been inconclusive. The purpose of the present study was to investigate the association between green tea drinking and the risk of pancreatic cancer in urban Shanghai, China. METHODS: In this population-based case-control study conducted in urban Shanghai, 908 cases of pancreatic cancer and 1067 healthy controls were recruited. Information on tea drinking, including type of tea, amount of tea consumption, temperature of tea, and the duration of regular tea drinking, were collected via interview questionnaire. RESULTS: We examined the association of multiple tea drinking habits with the risk of pancreatic cancer. In women, regular green tea drinking was associated with 32% reduction of pancreatic cancer risk (OR 0.68, 95% CI 0.48-0.96), compared to those who did not drink tea regularly. Increased consumption and longer duration of tea drinking were both associated with reduced pancreatic cancer risk in women. Among regular tea drinkers, lower temperature of tea was associated with reduced risk of pancreatic cancer in both men and women, independent of amount or duration of tea drinking. CONCLUSIONS: Habits of green tea drinking, including regular drinking, amount of consumption, persistence of the habit, and tea temperature, may lower pancreatic cancer risk.

Magnetic functionalised carbon nanotubes as drug vehicles for cancer lymph node metastasis treatment.

Strategies using carbon-based nanomaterials as carriers for delivering chemotherapeutic drugs to cancers have been described well. Here a novel magnetic lymphatic-targeting drug-delivery system, based on functionalised carbon nanotubes (fCNTs), is presented with the aim of improving the outcome of cancer with lymph node involvement. The potential therapeutic effect of gemcitabine (GEM) loading magnetic multiwalled carbon nanotubes (mMWNTs) was compared with that of GEM loading magnetic-activated carbon particles (mACs) in vitro and in vivo. mMWNTs-GEM and mACs-GEM both had high anti-tumour activity in vitro similar to free drug. Subcutaneous administration of GEM loading magnetic nanoparticles resulted in successful regression and inhibition of lymph node metastasis under the magnetic field, with mMWNTs-GEM superior to mACs-GEM, and more effectively in the high-dose versus low-dose groups. The successful application of intra-lymphatic delivery of chemotherapeutics using mMWNTs highlights the clinical potential of fCNTs for future cancer metastasis treatment with high efficacy and minimum side-effects.

Carbon nanotubes in cancer diagnosis and therapy.

During the past years, great progress has been made in the field of nanomaterials given their great potential in biomedical applications. Carbon nanotubes (CNTs), due to their unique physicochemical properties, have become a popular tool in cancer diagnosis and therapy. They are considered one of the most promising nanomaterials with the capability of both detecting the cancerous cells and delivering drugs or small therapeutic molecules to these cells. Over the last several years, CNTs have been explored in almost every single cancer treatment modality, including drug delivery, lymphatic targeted chemotherapy, thermal therapy, photodynamic therapy, and gene therapy. In this review, we will show how they have been introduced into the diagnosis and treatment of cancer. Novel SWNT-based tumor-targeted drug delivery systems (DDS) will be highlighted. Furthermore, the in vitro and in vivo toxicity of CNTs reported in recent years will be summarized.

Effect of multiple-phase regional intra-arterial infusion chemotherapy on patients with resectable pancreatic head adenocarcinoma.

BACKGROUND: Regional intra-arterial infusion chemotherapy (RIAC) has been more valuable to improve prognosis and quality of life of patients with inoperable pancreatic adenocarcinomas, and adjuvant RIAC plays an important role in prolonging survival and reducing risk of liver metastasis after radical resection of pancreatic cancer, but the effect of preoperative or multiple-phase RIAC (preoperative combined with postoperative RIAC) for resectable pancreatic cancers has not been investigated. In this prospective study, the effect of multiple-phase RIAC for patients with resectable pancreatic head adenocarcinoma was evaluated, and its safety and validity comparing with postoperative RIAC were also assessed. METHODS: Patients with resectable pancreatic head cancer were randomly assigned to two groups. Patients in group A (n=50) were treated with new therapeutic mode of extended pancreaticoduodenectomy combined with multiple-phase RIAC, and those in group B (n=50) were treated with extended pancreaticoduodenectomy combined with postoperative RIAC in the same period. The feasibility, compliance and efficiency of the new therapeutic mode were evaluated by tumor size, serum tumor markers, clinical benefit response (CBR), surgical complications, mortality and toxicity of RIAC. The disease-free survival time, median survival time, incidence of liver metastasis, survival rate at 1, 2, 3 and 5 years were also observed. Life curves were generated by the Kaplan-Meier method. RESULTS: The pain relief rate and CBR in group A was 80% and 84% respectively. Serum tumor markers decreased obviously and tumors size decreased in 26% of patients after preoperative RIAC in group A. No more surgical complications, mortality or severe systemic side effects were observed in group A compared with group B. The incidence of liver metastasis in group A was 34% which was lower than 50% in group B. The disease-free survival time and median survival time in group A were 15.5 months and 18 months respectively. The 1-, 2-, 3- and 5-year survival rates were 54.87%, 34.94%, 24.51% and 12.25% respectively. There was no significant difference of survival time or survival rates between two groups. CONCLUSIONS: Multiple-phase RIAC is effective in combined therapy of resectable pancreatic head carcinomas by enhancing inhibition of tumor growth and reduction of liver metastasis, without negative effect on patients' safety or surgical procedure.