Central pancreatectomy for benign or low-grade malignant pancreatic tumors in the neck and body of the pancreas.

BACKGROUND: For tumors in the neck and body of the pancreas, distal pancreatectomy (DP) has been the standard surgical procedure for the last few decades and central pancreatectomy (CP) is an alternative surgical option. Whether CP better preserves remnant pancreatic endocrine and exocrine functions after surgery remains a subject of debate. AIM: To evaluate the safety and efficacy of CP compared with DP for benign or low-grade malignant pancreatic tumors in the neck and body of the pancreas. METHODS: This retrospective study enrolled 296 patients who underwent CP or DP for benign and low-malignant neoplasms at the same hospital between January 2016 and March 2020. Perioperative outcomes and long-term morbidity of endocrine/exocrine function were prospectively evaluated. RESULTS: No significant difference was observed in overall morbidity or clinically relevant postoperative pancreatic fistula between the two groups (P = 0.055). Delayed gastric emptying occurred more frequently in the CP group than in the DP group (29.4% vs 15.3%; P < 0.005). None of the patients in the CP group had new-onset or aggravated distal metastasis, whereas 40 patients in the DP group had endocrine function deficiency after surgery (P < 0.05). There was no significant difference in the incidence of diarrhea immediately after surgery, but at postoperative 12 mo, a significantly higher number of patients had diarrhea in the DP group than in the CP group (0% vs 9.5%; P < 0.05). CONCLUSION: CP is a generally safe procedure and is better than DP in preserving long-term pancreatic endocrine and exocrine functions. Therefore, CP might be a better option for treating benign or low-grade malignant neoplasms in suitable patients.

Prediction of postoperative pancreatic fistula using a nomogram based on the updated definition.

PURPOSE: The International Study Group on Pancreatic Fistula's definition of postoperative pancreatic fistula (POPF) has recently been updated. This study aimed to identify risk factors for POPF in patients having pancreaticoduodenectomy (PD) and to generate a nomogram to predict POPF. METHODS: Data on 298 patients who underwent PD from March 2012 to October 2017 was retrospectively reviewed and POPF statuses were redefined. A nomogram was constructed using data from 220 patients and validated using the remaining 78 patients. Independent risk factors for POPF were identified using univariate and multivariate analyses. A predictive nomogram was established based on the independent risk factors and was compared with existing models. RESULTS: Texture of the pancreas, size of the main pancreatic duct, portal vein invasion, and definitive pathology were the identified risk factors. The nomogram had a C-index of 0.793 and was internally validated. The nomogram performed better (C-index of 0.816) than the other most cited models (C-indexes of 0.728 and 0.735) in the validation cohort. In addition, the nomogram can assign patients into low- (less than 10%), intermediate- (10% to 30%), and high-risk (equal or higher than 30%) groups to facilitate personalized management. CONCLUSION: The nomogram accurately predicted POPF in patients having PD.

Development of a Novel Multiparametric MRI Radiomic Nomogram for Preoperative Evaluation of Early Recurrence in Resectable Pancreatic Cancer.

BACKGROUND: In pancreatic cancer, methods to predict early recurrence (ER) and identify patients at increased risk of relapse are urgently required. PURPOSE: To develop a radiomic nomogram based on MR radiomics to stratify patients preoperatively and potentially improve clinical practice. STUDY TYPE: Retrospective. POPULATION: We enrolled 303 patients from two medical centers. Patients with a disease-free survival ≤12 months were assigned as the ER group (n = 130). Patients from the first medical center were divided into a training cohort (n = 123) and an internal validation cohort (n = 54). Patients from the second medical center were used as the external independent validation cohort (n = 126). FIELD STRENGTH/SEQUENCE: 3.0T axial T1 -weighted (T1 -w), T2 -weighted (T2 -w), contrast-enhanced T1 -weighted (CET1 -w). ASSESSMENT: ER was confirmed via imaging studies as MRI or CT. Risk factors, including clinical stage, CA19-9, and radiomic-related features of ER were assessed. In addition, to determine the intra- and interobserver reproducibility of radiomic features extraction, the intra- and interclass correlation coefficients (ICC) were calculated. STATISTICAL TESTS: The area under the receiver-operator characteristic (ROC) curve (AUC) was used to evaluate the predictive accuracy of the radiomic signature in both the training and test groups. The results of decision curve analysis (DCA) indicated that the radiomic nomogram achieved the most net benefit. RESULTS: The AUC values of ER evaluation for the radiomics signature were 0.80 (training cohort), 0.81 (internal validation cohort), and 0.78 (external validation cohort). Multivariate logistic analysis identified the radiomic signature, CA19-9 level, and clinical stage as independent parameters of ER. A radiomic nomogram was then developed incorporating the CA19-9 level and clinical stage. The AUC values for ER risk evaluation using the radiomic nomogram were 0.87 (training cohort), 0.88 (internal validation cohort), and 0.85 (external validation cohort). DATA CONCLUSION: The radiomic nomogram can effectively evaluate ER risks in patients with resectable pancreatic cancer preoperatively, which could potentially improve treatment strategies and facilitate personalized therapy in pancreatic cancer. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2020;52:231-245.

The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer.

OBJECTIVES: FOLFIRINOX (FFX) or abraxane plus gemcitabine (AG)-based chemotherapy is used widely as firstline treatment for patients with pancreatic cancer. However, their use in the elderly is discouraged because of adverse events. More clinical data about the therapeutic response and tolerability to FFX or AG in elderly patents (over 70 years old) are required. METHODS: Patients with advanced pancreatic cancer (n = 203; 131 metastatic pancreatic cancer patients (MPC) and 72 locally advanced pancreatic cancer patients (LAPC)) were treated using modified-FFX (mFFX) or AG and mFFX sequentially. The patients were grouped according to their age, patients below 70 years old and patients above 70 years old. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and adverse events were compared between the groups. RESULTS: The ORRs in the elderly and in patients below 70 were similar (30.0% versus 32.3%). The median OS and PFS were also similar between the groups (mOS 13.3 m vs 12.7 m, p = 0.729, HR 0.874 (95% CI 0.5310 to 1.438); mPFS mPFS 10.6 m vs 10.3 m, p = 0.363, HR 0.800 (95% CI 0.4954 to 1.293)). However, the elderly patients suffered a higher incidence of severe adverse events (50% vs. 28.3%). CONCLUSIONS: These data could provide guidance for chemotherapy use in elderly patients with advanced pancreatic cancer. Age did not affect treatment outcome; however, supportive treatment is very important for elderly patients receiving chemotherapy.

Combination of transarterial chemoembolization and sorafenib improves outcomes of unresectable hepatocellular carcinoma: an updated systematic review and meta-analysis.

BACKGROUND: The effectiveness of combination therapy of transarterial chemoembolization and sorafenib for unresectable hepatocellular carcinoma are controversial in some studies. This meta-analysis aims to compare efficacy and safety, as well as regional disparities, between transarterial chemoembolization plus sorafenib and transarterial chemotherapy alone for hepatocellular carcinoma. METHODS: We systematically searched multiple databases to select eligible studies. Studies comparing transarterial chemoembolization plus sorafenib and transarterial chemoembolization alone for unresectable hepatocellular carcinoma were included. RESULTS: Thirteen studies including five randomized clinical trials with 2538 patients (1121 in combination therapy group and 1417 in monotherapy group) were selected. The combination therapy significantly improved time to progression (hazard ratio 0.66; 95% confidence interval 0.48-0.89; P = 0.006) and overall survival (hazard ratio 0.57; 95% confidence interval 0.45-0.72; P < 0.001) in Asian region but not in non-Asian countries (overall survival: hazard ratio 0.96, 95% confidence interval 0.73-1.20; time to progression: hazard ratio 1.08, 95% confidence interval 0.73-1.60). Additionally, disease control rate also favored combination therapy (hazard ratio 1.30; 95% confidence interval 1.00-1.69; P = 0.05), which simultaneously caused higher incidences of adverse events, including hand-foot skin reaction (relative ratio 7.03; 95% confidence interval 4.77-10.37), hematological events (relative ratio 3.14; 95% confidence interval 0.99-10.01), diarrhea (relative ratio 2.75; 95% confidence interval 1.74-4.35), hypertension (relative ratio 2.58; 95% confidence interval 1.33-4.99), rash (relative ratio 2.87; 95% confidence interval 1.86-4.43) and alopecia (relative ratio 4.88; 95% confidence interval 1.67-14.13). CONCLUSIONS: The combination of transarterial chemoembolizaiton and sorafenib significantly improves outcomes of unresectable hepatocellular carcinoma compared with transarterial chemoembolization monotherapy, especially in Asian region.

A preoperative nomogram predicts prognosis of up front resectable patients with pancreatic head cancer and suspected venous invasion.

BACKGROUND: Pancreatic head adenocarcinoma is commonly diagnosed at an advanced stage when adjacent vascular invasion is present. This study aimed to establish a preoperative prognostic nomogram for patients who underwent attempted curative resectional surgery for pancreatic head cancer with suspected peripancreatic venous invasion. METHODS: Data on all consecutive patients were retrospectively collected from 2012 to 2016 at four academic institutions. The demographic and radiological parameters were analyzed using univariate and multivariate Cox regression analyses. The final nomogram was established using the concordance Harrell's C-indices and calibration curves from data obtained in three institutions and validated in the cohort of patients coming from the fourth institution. RESULTS: The nomogram was constructed using data from 178 patients while the validation cohort consisted of 61 patients. Age, length of tumor contact, peripancreatic venous abnormalities and lymph node staging were independent factors of overall survival. The nomogram showed good probabilities of survival on calibration curves. The C-index of the model in predicting overall survival (OS) was 0.824 for the validation cohort. CONCLUSIONS: The nomogram accurately predicted OS in patients with pancreatic head cancer with suspected peripancreatic venous invasion after attempted curative pancreatic resectional surgery.

Modified-FOLFIRINOX in metastatic pancreatic cancer: A prospective study in Chinese population.

FOLFIRINOX chemotherapy has shown remarkable responses in patients with metastatic pancreatic cancer (MPC), and has significantly improved prognosis. However, FOLFIRINOX is currently not frequently applied in China because of its high incidence of adverse events, and there is no recognized optimization for this therapy in Chinese population. Modification of FOLFIRINOX may be better for its acceptance in China. In this study, we evaluated the efficacy and safety of modified-FOLFIRINOX in patients with MPC. A total of 62 MPC patients were treated with modified-FOLFIRINOX (no Fluorouracil bolus, 85% Oxaliplatin and 75% Irinotecan) between April 2014 and April 2017 in our institute. 40 of them were evaluated, with a response rate of 32.5% (13/40). The frequent grade 3/4 adverse events are neutropenia (29%) and alanine aminotransferase elevation (14.5%). No treatment-related death was observed. The median overall survival and median progression-free survival are 10.3 months and 7.0 months, respectively. In conclusion, modified-FOLFIRINOX had significantly improved tolerance with similar efficacy to FOLFIRINOX. These findings may provide evidence for the use of FOLFIRINOX in Chinese patients with MPC.

Increasing the immune activity of exosomes: the effect of miRNA-depleted exosome proteins on activating dendritic cell/cytokine-induced killer cells against pancreatic cancer.

BACKGROUND: Tumor-derived exosomes were considered to be potential candidates for tumor vaccines because they are abundant in immune-regulating proteins, whereas tumor exosomal miRNAs may induce immune tolerance, thereby having an opposite immune function. OBJECTIVE: This study was designed to separate exosomal protein and depleted exosomal microRNAs (miRNAs), increasing the immune activity of exosomes for activating dendritic cell/cytokine-induced killer cells (DC/CIKs) against pancreatic cancer (PC). METHODS: PC-derived exosomes (PEs) were extracted from cultured PANC-1 cell supernatants and then ruptured; this was followed by ultrafiltered exosome lysates (UELs). DCs were stimulated with lipopolysaccharide (LPS), PE, and UEL, followed by co-culture with CIKs. The anti-tumor effects of DC/CIKs against PC were evaluated by proliferation and killing rates, tumor necrosis factor-α (TNF-α) and perforin secretion. Exosomal miRNAs were depleted after lysis and ultrafiltration, while 128 proteins were retained, including several immune-activating proteins. RESULTS: UEL-stimulated DC/CIKs showed a higher killing rate than LPS- and PE-stimulated DC/CIKs. CONCLUSIONS: miRNA-depleted exosome proteins may be promising agonists for specifically activating DC/CIKs against PC.

Management of retroperitoneal liposarcoma: A case report and review of the literature.

Retroperitoneal liposarcoma is a rare tumor with an incidence of 2.5 per million individuals. Early diagnosis is difficult as there is an absence of specific clinical presentations. The present case study reports a patient diagnosed with retroperitoneal liposarcoma who was treated by complete surgical resection and relapsed 3 months following the surgery. In addition, the clinical data of 14 patients with retroperitoneal liposarcoma were reviewed and analyzed. The mean age of the 14 patients at presentation was 54.1 (range, 36-73 years) and 5/14 patients experienced recurrence, ranging between 1 and 10 times. Of the 12 cases that reported histological subtypes, 7 were well-differentiated liposarcoma, 2 were dedifferentiated liposarcoma, 2 were myxoid liposarcoma and 1 was mixed subtype. All the patients underwent complete resection and 5 received combined multiple organs resection (3 nephrectomy, 1 sigmoid colon and 1 multiple visceral organs). However, no patients received chemotherapy or radiotherapy. In conclusion, retroperitoneal liposarcoma is a rare disease with a high rate of recurrence. Complete resection is the predominant treatment and combined resection of adjacent organs is occasionally necessary.

Management of differentiated thyroid carcinoma with bone metastasis: a case report and review of the Chinese literature.

Differentiated thyroid carcinoma (DTC) is a common malignancy. The general treatments are thyroidectomy of the affected lobe along with lymphadenectomy. However, bone metastasis is rare in DTC compared with other malignancies and the management of metastasis foci is still controversial. Here we present a case of follicular thyroid carcinoma with the 6th cervical vertebra body metastasis successfully treated by total thyroidectomy, cervical corpectomy, and internal fixation, followed by hormone replacement therapy and radioiodine therapy. Eleven additional patients diagnosed as thyroid carcinoma with bone metastasis collected from Chinese literature between January 1996 and December 2013 were also reviewed. The mean age of the 12 patients at presentation was (53.9±9.2) years (rang, 42-72 years) and the male to female ratio was 1:2. Nine cases received total/near-total thyroidectomy or lobectomy while the other three patients refused for personal reasons. The interventions for bone metastasis were one-stage operation (9/12), I(131) adjuvant therapy (3/12), chemotherapy (1/12), and no intervention (1/12). During the follow-up, two patients died of metastatic carcinoma recurrence, one died of multiple organ metastasis, and one with an unknown reason. We conclude that the management of thyroid carcinoma with bone metastasis needs multidisciplinary cooperation. Surgical resection is still the first choice for cure, while the combined one-stage operation on the primary and metastatic sites followed by hormone replacement therapy and radioiodine therapy is an applicable treatment.

Colonic interposition between the liver and left diaphragm - management of Chilaiditi syndrome: A case report and literature review.

Chilaiditi syndrome refers to a medical condition that is indicated by the presence of Chilaiditi sign, the radiological observation of a colonic interposition between the liver and the diaphragm, and is associated with other clinical symptoms. Chilaiditi syndrome is a rare entity and therefore, is often misdiagnosed in clinical practice, however, it may be accompanied by a series of severe complications, such as bowel obstruction and perforation. The current study describes a 47-year-old male who presented with repeated abdominal pain and acute intestinal obstruction. The patient was diagnosed with Chilaiditi syndrome via radiological observation and was cured by conservative treatment. The clinical data of seven additional patients with Chilaiditi syndrome, which was reported in the Chinese literature between January 1990 and January 2013, were also collected. The pathogenesis, clinical manifestation, diagnosis and treatment of this syndrome have been reviewed and analyzed. The current study may be useful to familiarize clinical practitioners with Chilaiditi syndrome, in order to avoid a misdiagnosis during clinical treatment.

Saline conducted electric coagulation (SCEC): original experience in experimental hepatectomy.

OBJECTIVE: To evaluate the feasibility and superiority of a new coagulating and hemostatic method named "saline conducted electric coagulation (SCEC)". METHODS: The Peng's multifunction operative dissector (PMOD) was modified to enable saline to effuse persistently out of its nib at a constant speed. In a group of six New Zealand rabbits, two hepatic lobes of each rabbits were resected respectively by SCEC and conventional electric coagulation (EC). The features of SCEC were recorded by photo and compared with conventional EC. After 7 d, the coagulating depth was measured in each residual hepatic lobe. Hepatic tissue was dyed by hematoxylin and eosin (HE) and studied under a microscope. RESULTS: The coagulating depth increased with the continuation of SCEC time. Hepatectomies were performed successfully, no rabbit died in the perioperative period. The incisal surface of SCEC was gray-white with no red bleeding point. There was a thick solidified layer at the margin and a thin red-white intermittent layer between the solidified layer and normal hepatic tissue at the vertical section of SCEC. The mean coagulating depth of SCEC was 1.8 cm vs. 0.3 cm of conventional EC. Pathological examination showed a mild inflammatory reaction by SCEC. CONCLUSIONS: SCEC is a feasible and safe method for surgical hemostasis. As a new technique for liver resection, SCEC shows better coagulating effect and milder inflammatory reaction than conventional EC. Our study shows bloodless liver resection can also be performed by SCEC, especially for liver malignant tumor.

Assessment of ¹88Re marked anti MHC class II antibody by peripheral blood mononuclear cells stimulated by donor alloantigen.

BACKGROUND: Previous studies showed that anti MHC-II monoclone antibody (MAb) only had partial inhibiting effect of alloreactive mixed lymphocyte reaction (MLR) in vitro and it was unsteady and non-persistent. The aim of this research was to determine whether radioactive isotope (188)Re marked MHC-II antibody could benefit the allograft acceptance in transplantation as compared to normal MHC-II antibody. METHODS: 188Re was incorporated to 2E9/13F (ab')(2) which is against swine MHC class II antigen (MAb-(188)Re). Porcine peripheral blood mononuclear (PBMC) cells were examined for proliferation and cytokine mRNA expression after stimulation with MHC-II MAb or MAb-(188)Re. RESULTS: The proliferative response of recipient PBMCs in mixed lymphocyte reaction (MLR) to donor alloantigen showed that the stimulation index of MAb-(188)Re group was significantly lower than the MHC-II MAb group and control (P < 0.05). mRNA expression of interleukin 2, interferon Υ and tumor necrosis factor α (type 1 cytokines) was lower in MAb-(188)Re group than the MHC-II MAb group, while interleukin 10 (type 2 cytokines) was higher in MAb-(188)Re group in the first 24 hours. CONCLUSION: MAb-(188)Re could help the graft acceptance by inhibiting T cell proliferation, lowering the expression of type 1 cytokines and elevating the type 2 cytokines produced by PBMC.

Influence of CO2 pneumoperitoneum on intracellular pH and signal transduction in cancer cells.

OBJECT: The authors studied the influence of CO(2) pneumoperitoneum on intracellular pH and signal transduction arising from cancer cell multiplication in laparoscopic tumor operation. METHOD: They set up a simulation of pneumoperitoneum under different CO(2) pressure, and then measured the variation of intracellular pH (pHi) at different time and the activity of protein kinase C (PKC) and protein phosphatase 2a (PP2a) at the end of the pneumoperitoneum. After 1 week, the concentration of cancer cells in the culture medium was calculated. RESULT: When the pressure of CO(2) pneumoperitoneum was 0, 10, 20, 30 mmHg respectively, the average pHi was 7.273, 7.075, 6.783, 6.693 at the end of the pneumoperitoneum; PKC activity was 159.4, 168.5, 178.0, 181.6 nmol/(g.min) and PP2a was 4158.3, 4066.9, 3984.0, 3878.5 nmol/(g.min) respectively. After 1 week, the cancer cells concentration was 2.15 x 10(5), 2.03 x 10(5), 2.20 x 10(5), 2.18 x 10(5) L(-1). CONCLUSION: CO(2) pneumoperitoneum could promote acidosis in cancer cells, inducing the activation of protein kinase C and deactivation of protein phosphatase 2a, but it could not accelerate the mitosis rate of the cancer cells.