Comparing the short-term outcomes of totally intracorporeal gastroduodenostomy with extracorporeal gastroduodenostomy after laparoscopic distal gastrectomy for gastric cancer: a single surgeon’s experience and a rapid systematic review with meta-analysis

Background

Since delta-shaped gastroduodenostomy was introduced, many surgeons have utilized laparoscopic distal gastrectomy (LDG) with totally intracorporeal Billroth I (ICBI) for gastric cancer, because it is expected to have several advantages over laparoscopic-assisted distal gastrectomy with extracorporeal Billroth I (ECBI). In this study, we compared these two reconstruction options to evaluate their outcomes.

Methods

The data of 166 gastric cancer patients who underwent LDG performed by a single surgeon between April 2009 and February 2012 were analyzed retrospectively. The subjects were divided into ECBI (n = 106) and ICBI (n = 60) groups, and then the clinical characteristics, surgical outcomes, symptoms, and change in BMI at 3 months after surgery were compared. Furthermore, a rapid systematic review and meta-analysis were conducted.

Results

The operative time was significantly shorter in the ICBI group (197.4 ± 45.5 vs. 157.1 ± 43.9 min), but blood loss was similar between the groups. Regarding surgical outcomes, there were no significant differences in the length of hospital stay, soft diet initiation, visual analogue scale, frequency of analgesics injection, and postoperative white blood cell counts and C-reactive protein levels between the groups. The surgical complication rates were 5.7 and 13.3 % in the ECBI and ICBI groups, respectively, and one case of anastomosis leakage was observed in each group. At 3 months after surgery, reflux symptoms were more frequent in the ICBI group, but other gastrointestinal symptoms and the change of BMI were similar between the groups. The meta-analysis revealed no significant differences in the operative time, time to first flatus, length of hospital stay, frequency of analgesic usages, and rates of anastomosis complications between the groups.

Conclusions

We could not demonstrate the clinical superiority of ICBI over ECBI based on our data and a rapid systematic review and meta-analysis. The anastomosis method may be selected according to patient conditions and the surgeon’s preference.     

Staging of Adenocarcinoma of the Esophagogastric Junction: Comparison of AJCC 6th and 7th Gastric and 7th Esophageal Staging Systems

Background

Adenocarcinoma of esophagogastric junction (EGJ) is currently staged by the esophageal staging criteria according to the American Joint Committee on Cancer (AJCC) staging system, 7th edition. We compared the performance of 6th gastric (G6), 7th gastric (G7), and 7th esophageal (E7) staging systems.

Methods

A total of 202 curatively resected adenocarcinomas of EGJ were analyzed. Patient outcomes were assessed according to G6, G7, and E7 staging. Tumor invasion to the subserosal or serosa layer was regarded as invasion to the adventitia for E7 staging. Performance was measured based on monotonicity (decreasing survival with increasing stage), distinctiveness (survival difference between different stages), and homogeneity (homogenous survival in the same stage).

Results

Each staging system was monotonous except for T1-2N0 lesions of E7. This was related to the introduction of histologic grade in E7 staging. Distinctiveness in each staging system was variable. As for the homogeneity, patients whose disease was staged as Ib (E7) exhibited different survival when reassessed by G6 and G7; again, this was related to histologic grading. Patients with IIIb (G7) and IIIc (E7) disease had different survival when reassessed by G6 staging, reflecting the poorer survival of patients with more than 15 lymph node metastases.

Conclusions

Staging of EGJ cancer based on the current AJCC, 7th edition, criteria of esophageal cancer staging has several limitations. We recommend considering modifications of the following in future updates of the staging system: accurate anatomical definition of tumor depth, removal of histologic grade from staging parameters, and classification of more than 15 lymph node metastases as a highly advanced stage.     

Prognostic Value of Early Postoperative Tumor Marker Response in Gastric Cancer

Background

The clinical usefulness of tumor markers as predictors of treatment outcome in patients with stomach cancer after radical gastrectomy has been poorly defined. The purpose of this study was to evaluate a comprehensive understanding of the impact of early postoperative tumor marker normalization on survival after gastrectomy.

Methods

Between January 2001 and December 2007, we enrolled 206 patients who had received radical gastrectomy as an initial treatment and had elevated carcinoembryonic antigen (CEA) (>5 ng/mL) or carbohydrate antigen (CA) 19-9 (>37 U/mL) levels. Early tumor marker response was defined as a normalization of preoperative CEA or CA19-9 values 1–2 months after gastrectomy.

Results

The mean patient age was 61 years (range 29–84 years), and 139 patients (67.5 %) were male. Early tumor marker response was identified in 150 of 206 (72.8 %) patients. Of the patients, 49 (23.8 %), 41 (19.9 %), and 116 (56.4 %) were stages I, II, and III, respectively, according to the seventh edition of the American Joint Commission on Cancer (AJCC) staging system. Both disease-free survival (DFS) and overall survival (OS) were significantly longer in patients with tumor marker response compared with nonresponse (61.5 vs. 37.6 months; P = 0.010 and 71.3 vs. 50.9 months; P = 0.008, respectively). Multivariate analyses showed that high CA19-9 level, early tumor marker response, and tumor, node, metastasis classification system stage were independent predictors of DFS and OS (P < 0.05).

Conclusions

Early CEA or CA19-9 normalization after radical gastrectomy is a strong prognostic factor for gastric cancer, especially in patients with high preoperative levels of tumor markers.     

Topiramate increases the risk of valproic acid–induced encephalopathy

Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA‐induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA‐induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA‐induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA‐induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA‐induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment.     

Surgical outcome of synchronous second primary cancer in patients with gastric cancer

PURPOSE: In order to improve the likelihood of curative and safe gastric surgery, this study investigated the clinical features and surgical outcomes of gastric cancer with a synchronous cancer. PATIENTS AND METHODS: The clinicopathological data of 10,090 gastric cancer patients at Samsung Medical Center from September 1994 to December 2006 were retrospectively analyzed. Of them, 90 patients with gastric cancer and a synchronous second primary cancer underwent simultaneous surgery for gastric cancer and second primary cancer. The clinicopathological characteristics of the patients, surgical outcome, and prognosis were examined. RESULTS: The most common synchronous second primary cancer was colorectal cancer (37 patients), followed by hepatocellular carcinoma (13 patients), renal cell carcinoma (11 patients), and pancreatic carcinoma (5 patients). The incidence of a second primary cancer in the gastric cancer patients was higher than the incidence in the general population. Stage I gastric cancer patients had more synchronous cancers than stage II patients (59 vs. 31). Postoperative complications were encountered in 7 patients. Four patients underwent reoperation. Two patients died from hepatic failure and leakage of esophagojejunal anastomosis. The 5-year survival rate of stage I and II gastric cancer was 61% and 39%, respectively. CONCLUSION: Since gastric cancer patients with a synchronous second primary cancer are not rare, the possibility of synchronous cancers in gastric cancer patients should be considered. The prognosis of early stage gastric cancer patients with a synchronous second primary cancer was influenced more by the presence of the second primary cancer than by the gastric cancer itself.     

Alterations in gene expression in vitamin D‐deficiency: Down‐regulation of liver Cyp7a1 and renal Oat3 in mice

The vitamin D‐deficient model, established in the C57BL/6 mouse after 8 weeks of feeding vitamin D‐deficient diets in the absence or presence of added calcium, was found associated with elevated levels of plasma parathyroid hormone (PTH) and plasma and liver cholesterol, and a reduction in cholesterol 7α‐hydroxylase (Cyp7a1, rate‐limiting enzyme for cholesterol metabolism) and renal Oat3 mRNA/protein expression levels. However, there was no change in plasma calcium and phosphate levels. Appraisal of the liver revealed an up‐regulation of mRNA expressions of the small heterodimer partner (Shp) and attenuation of Cyp7a1, which contributed to hypercholesterolemia in vitamin D‐deficiency. When vitamin D‐sufficient or D‐deficient mice were further rendered hypercholesterolemic with 3 weeks of feeding the respective, high fat/high cholesterol (HF/HC) diets, treatment with 1α,25‐dihydroxyvitamin D₃ [1,25(OH)₂D₃], active vitamin D receptor (VDR) ligand, or vitamin D (cholecalciferol) to HF/HC vitamin D‐deficient mice lowered the cholesterol back to baseline levels. Cholecalciferol treatment partially restored renal Oat3 mRNA/protein expression back to that of vitamin D‐sufficient mice. When the protein expression of protein kinase C (PKC), a known, negative regulator of Oat3, was examined in murine kidney, no difference in PKC expression was observed for any of the diets with/without 1,25(OH)₂D₃/cholecalciferol treatment, inferring that VDR regulation of renal Oat3 did not involve PKC in mice. As expected, plasma calcium levels were not elevated by cholecalciferol treatment of vitamin D‐deficient mice, while 1,25(OH)₂D₃ treatment led to hypercalcemia. In conclusion, vitamin D‐deficiency resulted in down‐regulation of liver Cyp7a1 and renal Oat3, conditions that are alleviated upon replenishment of cholecalciferol.     

Nephrotoxic Potential and Toxicokinetics of Melamine Combined with Cyanuric Acid in Rats

To investigate the nephrotoxic potential of melamine (MEL) and cyanuric acid (CA) in male Sprague-Dawley rats, 7-d repeated-dose studies were performed. The experimental groups of MEL100 and CA100 were orally administered with MEL and CA at 100 mg/kg/d for 7 d, respectively. In groups dosed with MEL–CA mixtures, melamine and cyanuric acid (1:1) were simultaneously administered at 4, 20, or 100 mg/kg/d for 7 d (i.e., MEL-CA4, MEL-CA20, or MEL-CA100, respectively). Body weights were not markedly affected in MEL100, CA100, and MEL-CA4 groups, but significantly reduced in MEL-CA 20 and 100 rats. Most parameters determined in sera and tissues were not markedly altered in MEL100, CA100, and MEL-CA4-treated rodents. However, BUN, creatinine, total protein, and kidney weights were significantly increased in MEL-CA20- and MEL-CA100-treated animals. Renal histopathologic findings also revealed signs of toxicity, including tubular dilatation, crystal deposition, granulomatous tubulo-interstitial inflammation, and tubular necrosis with regeneration. Data suggested that the combination of MEL and CA might be responsible for observed nephrotoxicity that was not seen following individual exposure to either MEL or CA alone. Subsequently, the concentrations of MEL and CA were determined in serum, urine, and kidney tissues by using liquid chromatography–mass spectrometry. Toxicokinetic studies indicated that MEL or CA alone might be eliminated almost completely within 24 h after dosing showing no accumulation in kidney. However, the combined MEL-CA dose produced marked accumulation of chemicals in blood and kidneys. These results suggested that combined MEL and CA might produce renal toxicity due to significant chemical accumulation in kidney accompanied by low excretion.     

The novel use of a biodegradable stent placed by percutaneous transhepatic cholangiography for the treatment of a hepaticojejunostomy biliary leak following an extended left hepatectomy and pancreaticoduodenectomy

A 61-year-old man presented with jaundice, and subsequently underwent an extended left hepatectomy and pancreaticoduodenectomy for a cholangiocarcinoma invading the head of the pancreas. The patient developed sepsis due to a biliary leak at the hepaticojejunostomy. We describe the original use of a biodegradable stent, deployed via percutaneous transhepatic cholangiography into the Roux limb, resulting in good drainage and resolution of sepsis. The chief benefit of this procedure is the lack of need for subsequent removal as well as purported reduced biofilm accumulation. We believe this to be the first reported case of this type and the literature surrounding the subject is also discussed.     

Chitosan-Based Hybrid Nanocomplex for siRNA Delivery and Its Application for Cancer Therapy

Purpose

Chitosan, a natural and biocompatible cationic polymer, is an attractive carrier for small interfering RNA (siRNA) delivery. The purpose of this study was to develop a chitosan-based hybrid nanocomplex that exhibits enhanced physical stability in the bloodstream compared with conventional chitosan complexes. Hybrid nanocomplexes composed of chitosan, protamine, lecithin, and thiamine pyrophosphate were prepared for systemic delivery of survivin (SVN) siRNA.

Methods

Physicochemical properties of the nanoparticles including mean diameters and zeta potentials were characterized, and target gene silencing and cellular uptake efficiencies of the siRNA nanocomplexes in prostate cancer cells (PC-3 cells) were measured. In vivo tumor targetability and anti-tumor efficacy by systemic administration were assessed in a PC-3 tumor xenograft mouse model by near-infrared fluorescence (NIRF) imaging and tumor growth monitoring, respectively.

Results

Mean diameters of the SVN siRNA-loaded hybrid nanocomplex (GP-L-CT) were less than 200 nm with a positive zeta potential value in water and were maintained without aggregation in culture media and 50% fetal bovine serum. SVN expression in PC-3 cells was reduced to 21.9% after treating with GP-L-CT. The tumor targetability and growth inhibitory efficacies of GP-L-CT supported the use of this novel hybrid nanocomplex as a cancer therapeutic and as a theranostic system for systemic administration.

Conclusions

A chitosan-based hybrid nanocomplex was successfully developed for the systemic delivery of SVN siRNA, which could serve as an alternative to cationic polymeric nanoparticles that are unstable in serum.