Proposal for splenectomy-omitting radical distal pancreatectomy in well-selected left-sided pancreatic cancer: multicenter survey study

Background

When distal pancreatectomy is carried out for left-sided pancreatic cancer, splenectomy is usually performed not only for margin-negative resection but also for effective clearance of the splenic hilar lymph nodes (LNs). However, the incidence of splenic hilar LN metastasis in these patients has not been definitively determined.

Methods

From April 2010 to June 2011, in a pilot study, we analyzed the medical records of twelve patients who had undergone radical antegrade modular pancreatosplenectomy. Potential remnant soft tissue around the splenic hilum, which would be left following an extended Warshaw’s procedure, was dissected and sent to a pathologist. Three Japanese medical centers conducted a retrospective survey of splenic hilar lymph node metastasis in left-sided pancreatic cancer to support our study.

Results

In the pilot study, all twelve patients had adenocarcinoma with a median tumor size of 2 cm. Six patients had LN metastasis and a median number of 4 splenic hilar LNs were evaluated; however, no splenic hilar LN metastasis was noted. In the Japanese multicenter survey (n = 85), only four patients had splenic LN metastasis. Small (<3 cm) and proximal (neck/body) left-sided pancreatic cancer might not be associated with splenic hilar LN metastasis (P < 0.05).

Conclusions

In well-selected left-sided pancreatic cancer, the incidence of splenic hilar LN metastasis is low enough that splenectomy-omitting radical distal pancreatectomy would be feasible. The rationale for routine splenectomy should be re-evaluated, and the oncologic effects of the preserved spleen need to be investigated further.     

Comparison of phased-array 3.0-T and endorectal 1.5-T magnetic resonance imaging in the evaluation of local staging accuracy for prostate cancer

OBJECTIVE: To retrospectively evaluate local staging accuracy for prostate cancer at 3.0-T magnetic resonance imaging (MRI) by comparing with that at 1.5-T MRI. METHODS: Two groups, each consisting of 54 patients, were included by matching for age, prostate specific antigen, and Gleason score. Before radical prostatectomy, 1 group underwent 3.0-T MRI using a phased-array coil, and the other 1.5-T MRI using an endorectal coil. T2-weighted MR images at 3.0 and 1.5 T were analyzed in consensus by 2 radiologists, and their staging accuracy was compared with histology. Artifact and overall image quality were compared at both 3.0 and 1.5 T. RESULTS: Accuracy for T3 stage at 3.0 and 1.5 T were 72% (39/54) and 70% (38/54), respectively (P > 0.05). The 3.0-T MRI had a lower incidence of MR artifacts than the 1.5-T MRI (P < 0.05). However, overall imaging quality at both 3.0 and 1.5 T had no significant difference (P > 0.05). CONCLUSIONS: The 3.0-T phased-array MRI is equivalent to the 1.5-T endorectal MRI in evaluating local staging accuracy for prostate cancer without significant loss of imaging quality.     

H2O2 enhances Ca2+ release from osteoblast internal stores

The physiological activity of osteoblasts is known to be closely related to increased intracellular Ca2+ activity ([Ca2+]i) in osteoblasts. The cellular regulation of [Ca2+]i in osteoblasts is mediated by Ca2+ movements associated with Ca2+ release from intracellular Ca2+ stores, and transmembrane Ca2+ influx via Na+-Ca2+ exchanger, and Ca2+ ATPase. Reactive oxygen species, such as H2O2, play an important role in the regulation of cellular functions, and act as signaling molecules or toxins in cells. In this study, we investigated the effects of H2O2 on cellular Ca2+ regulation in osteoblasts by measuring intracellular Ca2+ activities using cellular calcium imaging techniques. Osteoblasts were isolated from the femurs and tibias of neonatal rats, and cultured for 7 days. The cultured osteoblasts were loaded with a Ca2+-sensitive fluorescent dye, Fura-2, and fluorescence images were monitored using a cooled CCD camera, and subsequently analyzed using image analyzing software. The results obtained are as follows: (1) The osteoblasts with lower basal Ca2+ activities yielded a transient Ca2+ increase, a Ca2+ spike, while osteoblasts with higher basal Ca2+ activities showed a continuous increase in [Ca2+]i leading to cell death. (2) Ca2+ spikes, generated after removing Na+ from superfusing solutions, were blocked by H2O2 and this was followed by a sustained increase in Ca2+ activity. (3) ATP- induced Ca2+ spikes were inhibited by pretreating with H2O2 and this was followed by a continuous increase of [Ca2+]i. When cells were pretreated with the exogenous nitric oxide (NO) donor S-Nitroso-N-acetylpenicilance (SNAP, 50 microM), treatments of ATP (1 mM) induced a Ca2+ spike-like increase, but [Ca2+]i did not return to the basal level. (4) The expression of inositol- 1,4,5-triphosphate receptor (IP3R) was enhanced by H2O2. Our results suggest that H2O2 modulates intracellular Ca2+ activity in osteoblasts by increasing Ca2+ release from the intracellular Ca2+ stores.     

Effects of vagus nerve preservation and vagotomy on peptide YY and body weight after subtotal gastrectomy

AIM: To investigate the relationship between the function of vagus nerve and peptide YY_3-36 and ghrelin levels after subtotal gastrectomy.METHODS: We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer. All surgeries were performed by a single skilled surgeon. We measured peptide YY_3-36, ghrelin, leptin, insulin, growth hormone levels, and body weight immediately before and one month after surgery.RESULTS: Vagus nerve preservation group showed less body weight loss and less increase of peptide YY_3-36 compared with vagotomy group (-5.56 ± 2.24 kg vs -7.85 ± 1.57 kg, P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL, P = 0.021, respectively). Moreover, patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY_3-36 level, typically less than 20% [6 (66.7%) vs 0 (0.0%), P = 0.011, odd ratio = 3.333, 95% confidence interval (1.293, 8.591)].CONCLUSION: Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy, and this phenomenon may be related to the suppressed activity of peptide YY_3-36.     

Comparison of Cancer Detection Rates Between TRUS-Guided Biopsy and MRI-Targeted Biopsy According to PSA Level in Biopsy-Naive Patients: A Propensity Score Matching Analysis

Background

The purpose of the study was to compare cancer detection rates between 12-core transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and multiparametric magnetic resonance imaging (mpMRI)-guided target prostate biopsy (MRI-TBx) according to prostate-specific antigen (PSA) level in biopsy-naive patients.

Altered expression of K+ -Cl- cotransporters affects fast paired-pulse inhibition during GABA receptor activation in the gerbil hippocampus

K+ -Cl- cotransporter (KCC) plays an important role in maintaining neuronal activity. However, the effect of seizure activity or pharmacological manipulation of GABAergic transmission on KCC expression remains to be clarified. Therefore, the present study was performed to investigate whether seizure activity or GABA receptor agonist treatment changes KCC expression in the gerbil hippocampus. Furthermore, the effect of blockade of KCC on inhibitory transmission in the dentate gyrus was identified following applications of GABA receptor agonists. The distribution of KCC immunoreactivity in the hippocampus was similarly detected between seizure-resistant (SR) and seizure-sensitive (SS) gerbils. Baclofen (a GABAB receptor agonist) treatment markedly increased KCC expression in the gerbil hippocampus. Baclofen treatment significantly reduced paired-pulse inhibition in the dentate gyrus. Furosemide (a KCC inhibitor) treatment amplified the effect of baclofen on paired-pulse responses. In contrast, muscimol (a GABAA receptor agonist) treatment reduced KCC expression. Enhanced paired-pulse inhibition by muscimol treatment was not affected by furosemide treatment. These findings suggest that seizure activity in the gerbil may not affect KCC expression in the hippocampus. In addition, altered KCC immunoreactivity induced by baclofen or muscimol may play an important role in maintaining or regulating inhibitory transmission during GABA receptor activation.     

Is Endoscopic Papillectomy Safe for Ampullary Adenomas with High-Grade Dysplasia?

Objectives  This study was designed to provide safe management guidelines for ampullary adenoma by analysis of clinicopathological features. Background  The treatment of ampullary cancer has been established; however, the indications for treatment of ampullary adenoma remain controversial. Methods  Between July 1997 and July 2008, a total of 33 patients were diagnosed with ampullary adenoma prior to procedures: 20 endoscopic papillectomies (ESP), 5 transduodenal resections (TDR), and 8 pancreatoduodenectomies (PD). Results  The false-negative rate of biopsy for cancer was 27.5% (8/29). Coexistence of cancer in patients with pre-high-grade dysplasia (HGD) was 50.0% (5/10), whereas it was 15.7% in pre-low-grade dysplasia (LGD). In addition, the rate of recurrence was 80% (8/10) in patients with pre-HGD. The size of tumor by final pathology was 1.27 ± 0.89 cm in LGD, 1.81 ± 0.99 cm in HGD, and 1.98 ± 1.08 cm in cancer group. There was a significant correlation between size of tumor and final pathology (P = 0.036). According to receiver operating characteristic (ROC) curve, criterion to predict HGD/cancer was tumor size larger than 1.5 cm; sensitivity and specificity were 55.6% and 80.0%, respectively, and likelihood ratio was 2.778. However, size of tumor was not associated with preprocedural pathology. Conclusions  Ampullary adenoma with preprocedural HGD was highly associated with coexistence of cancer and recurrence. Moreover, most of large tumors were treated by surgical procedures and proved to be cancer. Therefore, we suggest that ampullary adenoma with preprocedural HGD or more than 1.5 cm should not be managed with endoscopic papillectomy due to high associated rates of recurrence.     

Prognostic impact of the pretreatment aspartate transaminase/alanine transaminase ratio in patients treated with first‐line systemic tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma

Objectives

To examine the prognostic role of the pretreatment aspartate transaminase/alanine transaminase or De Ritis ratio in patients with metastatic renal cell carcinoma receiving first‐line systemic tyrosine kinase inhibitor therapy.

Methods

We retrospectively searched the medical records of 579 patients with metastatic renal cell carcinoma who visited Samsung Medical Center, Seoul, Korea, from January 2001 through August 2016. After excluding 210 patients, we analyzed 360 patients who received first‐line tyrosine kinase inhibitor therapy. Cancer‐specific survival and overall survival were defined as the primary and secondary end‐points, respectively. A multivariate Cox proportional hazards regression model was used to identify independent prognosticators of survival outcomes.

Results

The overall population was divided into two groups according to the pretreatment De Ritis ratio as an optimal cut‐off value of 1.2, which was determined by a time‐dependent receiver operating characteristic curve analysis. Patients with a higher pretreatment De Ritis ratio (≥1.2) had worse cancer‐specific survival and overall survival outcomes, compared with those with a lower De Ritis ratio (<1.2). Notably, a higher De Ritis ratio (≥1.2) was found to be an independent predictor of both cancer‐specific survival (hazard ratio 1.61, 95% confidence interval 1.13–2.30) and overall survival outcomes (hazard ratio 1.69, 95% confidence interval 1.19–2.39), along with male sex, multiple metastasis (≥2), non‐clear cell histology, advanced pT stage (≥3), previous metastasectomy and the Memorial Sloan Kettering Cancer Center risk classification.

Conclusion

Our findings show that the pretreatment De Ritis ratio can provide valuable information about the survival outcomes of metastatic renal cell carcinoma patients receiving first‐line tyrosine kinase inhibitor therapy.

     

Effects of sulodexide on hemostatic factors, lipid profile, and inflammation in chronic peritoneal dialysis patients.

Sulodexide, a standardized extractive glycosaminoglycan containing 80% "fast moving" heparin and 20% dermatan sulfate, decreased plasma D-dimer, a marker of intravascular coagulation, and fibrinogen levels in chronic peritoneal dialysis patients. Blood levels of von Willebrand factor, lipid, and high-sensitivity C-reactive protein were not significantly changed. No bleeding episodes were reported. These results suggest that sulodexide was effective in partially reversing the thrombogenic coagulation profile without increasing the risk of bleeding.