Shou-Wang Cai

Prognostic significance of mast cell count following curative resection for pancreatic ductal adenocarcinoma

BACKGROUND Recently, there is evidence that the number of mast cells in various solid cancers increases with tumor progression. The role of mast cells in promoting tumor progression, however, has not been well studied in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the prognostic value of mast cell counts in different zones of the neoplasm in patients with PDAC after curative resection. METHODS Numbers of mast cells and microvessels were assessed by immunohistochemistry in tissues from 103 patients with PDAC and 10 patients with normal pancreas. All patients with PDAC underwent partial pancreatic resection. The investigators paid particular attention to the distribution of mast cells in each specimen. RESULTS High mast cell counts in the intratumoral border zone correlated with the presence of lymphatic and microvascular invasion, lymph node metastasis, and TNM stage, and were an independent prognostic factor for overall survival (P < .001). In contrast, neither in the intratumoral center zone nor in the peritumoral zones was mast cell count associated with OS. Mast cell counts in the intratumoral border zone, but not in the peritumoral or in the intratumoral center zone, were correlated with microvessel counts. CONCLUSION The present study shows a zone-specific distribution of mast cells in PDAC and highlights the importance of invasive front in the prognosis of patients with PDAC after curative resection. Zone-specific evaluation of mast cell and microvessel counts may be helpful for prognostic assessment and therapeutic decision making in PDAC.

Risk scoring system and predictor for clinically relevant pancreatic fistula after pancreaticoduodenectomy.

AIM To establish a scoring system to predict clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). METHODS The clinical records of 921 consecutive patients who underwent PD between 2008 and 2013 were reviewed retrospectively. Postoperative pancreatic fistula (POPF) was defined and classified by the international study group of pancreatic fistula (ISGPF). We used a logistic regression model to determine the independent risk factors of CR-POPF and developed a scoring system based on the regression coefficient of the logistic regression model. The optimal cut-off value to divide the risk strata was determined by the Youden index. The patients were divided into two groups (low risk and high risk). The independent sample t test was used to detect differences in the means of drain amylase on postoperative day (POD) 1, 2 and 3. The optimal cut-off level of the drain amylase to distinguish CR-POPF from non-clinical POPF in the two risk strata groups was determined using the receiver operating characteristic (ROC) curves. RESULTS Grade A POPF occurred in 106 (11.5%) patients, grade B occurred in 57 (6.2%) patients, and grade C occurred in 32 (3.5%) patients. A predictive scoring system for CR-POPF (0-6 points) was constructed using the following four factors: 1 point for each body mass index ≥ 28 [odds ratio (OR) = 3.86; 95% confidence interval (CI): 1.92-7.75, P = 0.00], soft gland texture (OR = 4.50; 95%CI, 2.53-7.98, P = 0.00), and the difference between the blood loss and transfusion in operation ≥ 800 mL (OR = 3.45; 95%CI, 1.92-7.75, P = 0.00); and from 0 points for a 5 mm or greater duct diameter to 3 points for a less than 2 mm duct (OR = 8.97; 95%CI: 3.70-21.77, P = 0.00). The ROC curve showed that the area under the curve of this score was 0.812. A score of 3 points was suggested to be the best cut-off value (Youden index = 0.485). In the low risk group, a drain amylase level ≥ 3600 U/L on POD3 could distinguish CR-POPF from non-clinical POPF (the sensitivity and specificity were 75% and 85%, respectively). In the high risk group, the best cut-off was a drain amylase level of 1600 (the sensitivity and specificity were 77 and 63%, respectively). CONCLUSION A 6-point scoring system accurately predicted the occurrence of CR-POPF. In addition, a drain amylase level on POD3 might be a predictor of this complication.

Post-pancreaticoduodenectomy hemorrhage risk factors, managements and outcomes

BACKGROUND Post-pancreaticoduodenectomy (PD) hemorrhage (PPH) is an uncommon but serious complication. This retrospective study analyzed the risk factors, managements and outcomes of the patients with PPH. METHODS A total of 840 patients with PD between 2000 and 2010 were retrospectively analyzed. Among them, 73 patients had PPH: 19 patients had early PPH and 54 had late PPH. The assessment included the preoperative history of disease, pancreatic status and surgical techniques. Other postoperative complications were also evaluated. RESULTS The incidence of PPH was 8.7% (73/840). There were no independent risk factors for early PPH. Male gender (OR=4.40, P=0.02), diameter of pancreatic duct (OR=0.64, P=0.01), end-to-side invagination pancreaticojejunostomy (OR=5.65, P=0.01), pancreatic fistula (OR=2.33, P=0.04) and intra-abdominal abscess (OR=12.19, P<0.01) were the independent risk factors for late PPH. Four patients with early PPH received conservative treatment and 12 were treated surgically. As for patients with late PPH, the success rate of medical therapy was 27.8% (15/54). Initial endoscopy was operated in 12 patients (22.2%), initial angiography in 19 (35.2%), and relaparotomy in 15 (27.8%). Eventually, PPH resulted in 19 deaths. The main causes of death were multiple organ failure, hemorrhagic shock, sepsis and uncontrolled rebleeding. CONCLUSIONS Careful and ongoing observation of hemorrhagic signs, especially within the first 24 hours after PD or within the course of pancreatic fistula or intra-abdominal abscess, is recommended for patients with PD and a prompt management is necessary. Although endoscopy and angiography are the standard procedures for the management of PPH, surgical approach is still irreplaceable. Aggressive prevention of hemorrhagic shock and re-hemorrhage is the key to treat PPH.

Effects of intensive insulin therapy combined with low molecular weight heparin anticoagulant therapy on severe pancreatitis.

The current study explored the effects of intensive insulin therapy (IIT) combined with low molecular weight heparin (LMWH) anticoagulant therapy on severe acute pancreatitis (SAP). A total of 134 patients with SAP that received treatment between June 2008 and June 2012 were divided randomly into groups A (control; n=33), B (IIT; n=33), C (LMWH; n=34) and D (IIT + LMWH; n=34). Group A were treated routinely. Group B received continuous pumped insulin, as well as the routine treatment, to maintain the blood sugar level between 4.4 and 6.1 mmol/l. Group C received a subcutaneous injection of LMWH every 12 h in addition to the routine treatment. Group D received IIT + LMWH and the routine treatment. The white blood cell count, hemodiastase, serum albumin, arterial partial pressure of oxygen and prothrombin time were recorded prior to treatment and 1, 3, 5, 7 and 14 days after the initiation of treatment. The intestinal function recovery time, incidence rate of multiple organ failure (MOF), length of hospitalization and fatality rates were observed. IIT + LMWH noticeably increased the white blood cell count, hemodiastase level, serum albumin level and the arterial partial pressure of oxygen in the patients with SAP (P<0.05). It markedly shortened the intestinal recovery time and the length of stay and reduced the incidence rate of MOF, the surgery rate and the fatality rate (P<0.05). It did not aggravate the hemorrhagic tendency of SAP (P>0.05). IIT + LMWH had a noticeably improved clinical curative effect on SAP compared with that of the other treatments.

Expression of scFv‐Mel‐Gal4 triple fusion protein as a targeted DNA‐carrier in Escherichia Coli

Liver‐directed gene therapy has become a promising treatment for many liver diseases. In this study, we constructed a multi‐functional targeting molecule, which maintains targeting, endosome‐escaping, and DNA‐binding abilities for gene delivery. Two single oligonucleotide chains of Melittin (M) were synthesized. The full‐length cDNA encoding anti‐hepatic asialoglycoprotein receptor scFv C1 (C1) was purified from C1/pIT2. The GAL4 (G) gene was amplified from pSW50‐Gal4 by polymerase chain reaction. M, C1 and G were inserted into plasmid pGC4C26H to product the recombinant plasmid pGC‐C1MG. The fused gene C1MG was subsequently subcloned into plasmid pET32c to product the recombinant plasmid C1MG/pET32c and expressed in Escherichia coli BL21. The scFv‐Mel‐Gal4 triple fusion protein (C1MG) was purified with a Ni2+ chelating HiTrap HP column. The fusion protein C1MG of roughly 64 kD was expressed in inclusion bodies; 4.5 mg/ml C1MG was prepared with Ni2+ column purification. Western blot and immunohistochemistry showed the antigen‐binding ability of C1MG to the cell surface of the liver‐derived cell line and liver tissue slices. Hemolysis testing showed that C1MG maintained membrane‐disrupting activity. DNA‐binding capacity was substantiated by luciferase assay, suggesting that C1MG could deliver the DNA into cells efficiently on the basis of C1MG. Successful expression of C1MG was achieved in E. coli, and C1MG recombinant protein confers targeting, endosome‐escaping and DNA‐binding capacity, which makes it probable to further study its liver‐specific DNA delivery efficacy in vivo. Copyright

Ultrasound-guided radiofrequency ablation of the segmental Glissonian pedicle: A new technique for anatomic liver resection.

BACKGROUND Anatomic liver resection is widely accepted as the optimal surgical treatment for hepatocellular carcinoma (HCC); however, the complexity of conventional operative methods limits their use. To explore the possibility of using modern techniques to achieve a simpler approach, we have evaluated ultrasound-guided segmental radiofrequency ablation (RFA) of the Glissonian pedicle before liver resection in a porcine model and in HCC patients. METHODS This study had 2 stages. First, we piloted anatomic liver resection using ultrasound-guided RFA of the segmental Glissonian pedicle in 6 Bama miniature pigs. Having found this technique safe and effective, we selected 21 HCC patients to treat with the same approach. RESULTS The pigs had no postoperative mortality or morbidity. Demarcation areas were apparent in all targeted segments. The mean length of segmental portal, arterial, and biliary tract branches ablated was 1.7, 1.4, and 1.6 cm, respectively. Human HCC operations consisted of 8 subsegmentectomies, 8 segmentectomies, and 5 multisegmentectomies. The procedure was feasible in all patients, with no mortality, morbidity, or need for blood transfusions. A demarcation area was apparent in all patients within 157 seconds of RF application for each target feeding vessel. The mean number of target feeding vessels was 2 (range, 1-7). CONCLUSION Our study demonstrates that ultrasound-guided RFA ablation of the segmental Glissonian pedicle is expedient, safe, and effective, and is suitable for resection of any hepatic segments or subsegments, from segments 2 to 8.

A New Segmental Hepatectomy Approach Using Ultrasound-Guided Portal Branch Infusion of a Thermosensitive Gel in Pigs

ABSTRACT Background: The aim of this study was to evaluate the safety, feasibility, and efficacy of a new segmental hepatectomy (SH) approach using intraoperative ultrasound (IOUS) guided infusion of a reversible thermosensitive gel into the portal vein branch in pigs; Materials and Methods: Poloxamer 407 aqueous solution (20%, W/V) was mixed with indocyanine green (P407-ICG) in this study to make it green, and it remained liquid at room temperature and turned into a firm gel upon reaching body temperature. In experiment I, six pigs were used to detect the outcome of infusing the mixture into the biliary tract, liver parenchyma, and hepatic vein for a safety study. In experiment II, another 12 pigs were randomly segmented into two groups [SH group and partial hepatectomy (PH) group] to investigate the feasibility and efficacy of the new approach using IOUS-guided infusion of the mixture into the portal branch; Results: No thermosensitive gel-induced abnormal changes were observed in the safety study. In the SH group, IOUS-guided infusion of the P407-ICG solution was effective in occluding the portal blood temporarily and demarcating the target liver segment to achieve precise SH. The blood loss in the SH group was significantly less than that of the PH group; Conclusions: SH assisted by IOUS-guided infusion of the reversible thermosensitive gel into the feeding portal vein branches is feasible, safe, simple, and effective.

Usefulness of three-dimensional visualization technology in minimally invasive treatment for infected necrotizing pancreatitis

AIM To explore the value of three-dimensional (3D) visualization technology in the minimally invasive treatment for infected necrotizing pancreatitis (INP). METHODS Clinical data of 18 patients with INP, who were admitted to the PLA General Hospital in 2017, were retrospectively analyzed. Two-dimensional images of computed tomography were converted into 3D images based on 3D visualization technology. The size, number, shape and position of lesions and their relationship with major abdominal vasculature were well displayed. Also, percutaneous catheter drainage (PCD) number and puncture paths were designed through virtual surgery (percutaneous nephroscopic necrosectomy) based on the principle of maximum removal of infected necrosis conveniently. RESULTS Abdominal 3D visualization images of all the patients were well reconstructed, and the optimal PCD puncture paths were well designed. Infected necrosis was conveniently removed in abundance using a nephroscope during the following surgery, and the median operation time was 102 (102 ± 20.7) min. Only 1 patient underwent endoscopic necrosectomy because of residual necrosis. CONCLUSION The 3D visualization technology could optimize the PCD puncture paths, improving the drainage effect in patients with INP. Moreover, it significantly increased the efficiency of necrosectomy through the rigid nephroscope. As a result, it decreased operation times and improved the prognosis.