Comparison of Single-Incision Plus One Additional Port Laparoscopy-assisted Anterior Resection with Conventional Laparoscopy-assisted Anterior Resection for Rectal Cancer

Background

Reduced-port laparoscopic surgery is the latest innovation in minimally invasive surgery. We performed single-incision plus one additional port laparoscopy-assisted anterior resection (SILS + 1-AR) starting in August 2010. This study aimed at evaluating the feasibility of SILS + 1-AR and comparing it with that of conventional laparoscopy-assisted anterior resection (C-AR).

Methods

Patients with preoperative clinical stage 0 to stage III rectal cancer were included. Demographic, intraoperative, and pathological examination data, as well as short-term outcome data, of 20 patients who underwent SILS + 1-AR were retrospectively compared with that of 20 patients who underwent C-AR. Invasiveness of the two procedures was also evaluated through a vital signs diary and hematological examination on postoperative days (POD) 1, 3, and 7.

Results

Operating time, mean estimated blood loss, the number of lymph nodes dissected, the number of lymph node metastases, and the mean distal resection margin length were not significantly different. However, postoperative neutrophil counts in the SILS + 1-AR group were lower than those in the C-AR group (P = 0.085). A significant difference in body temperature was observed in the SILS + 1-AR group on POD 1 (P = 0.028). No significant differences were observed in perioperative and overall morbidity between the two groups. Conversion to open surgery was required in 2 (10 %) of the 20 patients in the SILS + 1-AR group. The mean postoperative length of stay and recurrence rates were similar in the two groups.

Conclusion

SILS + 1-AR for rectal cancer is similar to C-AR in safety, feasibility, and provision of oncological radicality.     

Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephropathy

Background

The primary abnormal manifestation in immunoglobulin A nephropathy (IgAN) is recurring bouts of hematuria with or without proteinuria. Although immunohistochemical analysis of renal biopsy tissue remains the gold standard not only for diagnosis but also for evaluating the activity of IgAN, new sensitive and reasonably specific noninvasive tests are emerging to guide therapeutic strategy applicable to all stages of IgAN. The present study examined serum levels of galactose-deficient IgA1 (Gd-IgA1) and its immune complex (IgA/IgG-IC) as noninvasive markers for the disease activity.

Methods

We enrolled 50 IgAN patients (male 40 %, median age 37 years) showing complete or partial clinical remission after steroid pulse therapy with tonsillectomy (TSP) whose clinical data and serum could be followed up for 3–5 years.

Results

Cross-sectional analysis revealed that the degree of hematuria and proteinuria were significantly associated with levels of Gd-IgA1 and levels of IgA/IgG-IC. Longitudinal analysis further showed that from the group of 44 patients with heavy hematuria before TSP, 31 patients showed complete disappearance of hematuria (group A), but the remaining patients did not (group B). Although the levels of Gd-IgA1 and IgA/IgG-IC in the two groups before TSP were similar, percentage decrease of Gd-IgA1 and IgA/IgG-IC levels in group A was significantly higher than in group B.

Conclusion

Disease activity of IgAN assessed by hematuria and proteinuria correlated with serum levels and changes of Gd-IgA1 and IgA/IgG-IC. These new noninvasive disease activity markers can be useful for future activity scoring system and guiding therapeutic approaches.     

Correlation study of chronic nonbacterial prostatitis with the levels of COX-2 and PGE2 in prostatic secretion

Objective

The prostatitis syndrome is a multifactorial condition of largely unknown etiology. This study is to analyze the relationship between cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) with the chronic nonbacterial prostatitis (CNBP).

Methods

A total of 172 CNBP patients and 151 healthy males were recruited as CNBP and control group, respectively. The prostatic fluid was collected and tested by pre- and post-massage test. White blood cell (WBC) number was counted, and the contents of COX-2 and PGE2 were determined by double antibody-based sandwich enzyme-linked immuno-sorbent assay. The pain and discomfort of each patient were scored according to the National Institutes of Health chronic prostatitis symptom index.

Results

Compared with the control group, CNBP group displayed significantly higher WBC count, COX-2 level, and PGE2 level. Contents of COX-2 and PGE2 in prostatic secretion of CNBP group were positively correlated with pain scores (r = 0.855 and 0.675, respectively, P < 0.01) and total symptom scores (r = 0.674 and 0.566, respectively, P < 0.01). A significantly positive correlation between COX-2 and PGE2 levels was also discovered (r = 0.493, P < 0.05). The WBC number was not obviously correlated with the accumulations of COX-2 and PGE2 or the clinic symptoms of CNBP.

Conclusion

Increase in PGE2 concentration caused by activated COX-2 pathway may contribute to the pain or discomfort symptom of the CNBP patients. Our results indicate that selective COX-2 inhibitors have application prospect in CNBP treatment.     

Characterization and Treatment of Local Recurrence Following Breast Conservation for Ductal Carcinoma In Situ

Purpose

The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences.

Methods

We conducted a retrospective cohort study using two data sources of patients who experienced a recurrence (DCIS or invasive cancer) following breast-conserving surgery (BCS) for index DCIS: patients with an index DCIS diagnosed from 1997 to 2008 at the academic institutions of the National Comprehensive Cancer Network (NCCN; N = 88) and patients with an index DCIS diagnosed from 1990 to 2001 at community-based integrated healthcare delivery sites of the Health Maintenance Organization Cancer Research Network (CRN) (N = 182).

Results

Just under half of local recurrences in both cohorts were invasive cancer. While 40 % of patients in both cohorts underwent mastectomy alone at recurrence, treatment of the remaining patients varied. In the earlier CRN cohort, most other patients underwent repeat BCS (39 %) with only 18 % receiving mastectomy with reconstruction, whereas only 16 % had repeat BCS and 44 % had mastectomy with reconstruction in the NCCN cohort. Compared with patients not treated with radiation, those who received radiation for index DCIS were less likely to undergo repeat BCS (NCCN: 6.6 vs. 37 %, p = 0.001; CRN: 20 vs. 48 %, p = 0.0004) and more likely to experience surgical complications after treatment of recurrence (NCCN: 15 vs. 4 %, p = 0.17; CRN: 40 vs. 25 %, p = 0.09).

Conclusion

We found that treatment of recurrences after BCS and subsequent complications may be affected by the use of radiotherapy for the index DCIS. Initial treatment of DCIS may have long-term implications that should be considered.     

Neurocognition in children with autosomal recessive polycystic kidney disease in the CKiD cohort study

Background

Autosomal recessive polycystic kidney disease (ARPKD) is an inherited disorder characterized by enlarged, cystic kidneys with progressive chronic kidney disease (CKD), systemic hypertension, and congenital hepatic fibrosis. Children with ARPKD can have early onset CKD and severe hypertension, both of which are known to have adverse neurocognitive effects. The objectives of this study were (1) to determine whether ARPKD patients have greater neurocognitive deficits compared to that of children with other causes of CKD, and (2) to examine the relative prevalence of hypertension in ARPKD, a known risk factor for neurocognitive dysfunction.

Methods

We performed a cross-sectional, control-matched analysis of 22 ARPKD patients with mild-to-moderate CKD in the Chronic Kidney Disease in Children (CKiD) cohort study, compared with a control group of 44 children with other causes of CKD, matched based on glomerular filtration rate, age at study entry, and age at diagnosis.

Results

Children with ARPKD in this cohort had neurocognitive functioning comparable to children with other causes of CKD in domains of intellectual functioning, academic achievement, attention regulation, executive functioning, and behavior. Blood pressure parameters were similar between the two groups; however, ARPKD patients required a significantly greater number of antihypertensive medications to achieve similar BP levels.

Conclusions

ARPKD patients are potentially at risk for neurocognitive dysfunction due to early onset CKD and more severe hypertension. However, this study of children with mild-to-moderate CKD in the CKiD cohort did not demonstrate increased risk in children with ARPKD compared to children with other causes of CKD. Further studies are needed to determine if these findings are applicable to children with more severe manifestations of ARPKD.     

Comparison of Nodal Metastasis Between BRCA Mutation Carriers and Non-BRCA Mutation Carriers with Breast Cancer

Objective

This study evaluates whether nodal status differs between breast cancer patients with BRCA mutations and those confirmed not to harbor mutations.

Methods

A prospective database identified patients with breast cancer who underwent genetic testing and axillary staging. Comparative variables included age, as well as tumor characteristics such as size, grade, lymphovascular invasion (LVI), estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2-neu), and nodal status.

Results

Overall, 235 patients with breast cancer underwent genetic testing for BRCA mutations from June 2000 to May 2012. Of these patients, 74 (31.4 %) were found to express BRCA 1 and/or 2 mutations, and 161 (68.5 %) patients were verified to have no detectable BRCA mutation. Among the entire 235 patients tested, 92 (39.1 %) were found to have nodal disease. In univariable analysis, only LVI and tumor size correlated with presence of nodal metastasis. Of the 74 BRCA mutation carriers, 34 (45.9 %) had nodal metastasis compared with 58 of the 161 (36 %; p = 0.15) patients without a BRCA mutation. BRCA mutation carriers with nodal disease were more likely to have poorly differentiated tumors than those without mutations who had nodal disease (24/33 [72.7 %] vs. 27/57 [47.4 %]; p = 0.027).

Conclusion

BRCA mutations are not themselves predictive of nodal metastasis. Patients with BRCA mutations did not have a statistically significant higher prevalence of nodal metastasis than those without mutations.     

Expression and regulation of toll-like receptors (TLRs) in human intervertebral disc cells

Purpose

Although inflammatory processes play an essential role in painful intervertebral disc (IVD) degeneration, the underlying regulatory mechanisms are not well understood. This study was designed to investigate the expression, regulation and importance of specific toll-like receptors (TLRs)—which have been shown to play an essential role e.g. in osteoarthritis—during degenerative disc disease.

Methods

The expression of TLRs in human IVDs was measured in isolated cells as well as in normal or degenerated IVD tissue. The role of IL-1β or TNF-α in regulating TLRs (expression/activation) as well as in regulating activity of down-stream pathways (NF-κB) and expression of inflammation-related genes (IL-6, IL-8, HSP60, HSP70, HMGB1) was analyzed.

Results

Expression of TLR1/2/3/4/5/6/9/10 was detected in isolated human IVD cells, with TLR1/2/4/6 being dependent on the degree of IVD degeneration. Stimulation with IL-1β or TNF-α moderately increased TLR1/TLR4 mRNA expression (TNF-α only), and strongly increased TLR2 mRNA expression (IL-1β/TNF-α), with the latter being confirmed on the protein level. Stimulation with IL-1β, TNF-α or Pam3CSK4 (a TLR2-ligand) stimulated IL-6 and IL-8, which was inhibited by a TLR2 neutralizing antibody for Pam3CSK4; IL-1β and TNF-α caused NF-κB activation. HSP60, HSP70 and HMGB1 did not increase IL-6 or IL-8 and were not regulated by IL-1β/TNF-α.

Conclusion

We provide evidence that several TLRs are expressed in human IVD cells, with TLR2 possibly playing the most crucial role. As TLRs mediate catabolic and inflammatory processes, increased levels of TLRs may lead to aggravated disc degeneration, chronic inflammation and pain development. Especially with the identification of more endogenous TLR ligands, targeting these receptors may hold therapeutic promise.     

Association between non-alcoholic fatty liver disease and chronic kidney disease in population with prediabetes or diabetes

Purpose

The relationship between chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in population with diabetes remains controversial. Our current study aimed to explore the association between NAFLD and CKD in population with prediabetes or diabetes.

Methods

A cross-sectional study was conducted in Zhuhai city from June to October 2012. A total of 190 out of 334 participants with prediabetes or diabetes were enrolled in this study. CKD was defined as estimated GFR <60 ml/min per 1.73 m² and/or albumin-to-creatinine ratio ≥30 mg/g. NAFLD was diagnosed on the basis of ultrasonographic and excluded fatty liver disease caused by other reasons such as drinking. The association between NAFLD and CKD was then analyzed using SPSS (version 19.0).

Results

Subjects with NAFLD were more likely with a higher urinary albumin-to-creatinine ratio (P < 0.001). CKD were common among patients with NAFLD than those without NAFLD (P < 0.05). NAFLD was significantly associated with CKD (P < 0.05) in the unadjusted analyses as well as after adjustment for potential confounders. The unadjusted odd ratio and adjusted odd ratio for CKD were 2.25 (95 % CI 1.07–4.77, P = 0.034) and 2.68 (95 % CI 1.12–6.01, P = 0.016). When further adjusted for hypertension, serum high-density lipoprotein and serum fasting glucose, the association of NAFLD with CKD was still significant (OR 2.78, 95 % CI 1.03–7.52, P = 0.044).

Conclusions

Our current study suggests that ultrasound-diagnosed NAFLD is associated with CKD among population with prediabetes or diabetes.     

Postsurgical coagulopathy in a hemophilia A patient with inhibitors: efficacy of recombinant factor VIIa

Perioperative hemostatic management in patients with hemophilia A who develop the coagulation factor VIII (FVIII) inhibitor is challenging, because exogenous FVIII is neutralized, which boosts the inhibitor to provoke postoperative coagulopathy. Recombinant activated factor VII (rFVIIa) has become available for this type of patient, although FVIII is sometimes required. We treated a 56-year-old male patient with hemophilia A with FVIII inhibitor scheduled for total hip arthroplasty (THA) and total knee arthroplasty (TKA). We used rFVIIa for THA; however, the amount of bleeding was 2,500 ml and blood transfusion was required, which boosted FVIII inhibitor after surgery. The TKA was then scheduled for 19 months later, after the level of the inhibitor had reduced to the preoperative level. Unfortunately, rFVIIa failed to improve PT/APTT, and thus we used recombinant factor VIII (rFVIII). The amount of bleeding during TKA was 1,340 ml, while the level of the inhibitor increased to a greater level than that after THA, provoking uncontrollable bleeding. For anesthetic management in hemophilia A patients with FVIII inhibitor, anesthesiologists must pay attention to postoperative coagulopathy, and every effort should be used to minimize exposure to FVIII. Furthermore, when rFVIIa is ineffective, postponement of surgery until rFVIIa regains its efficacy may be beneficial as compared to an operation with FVIII.     

The effect of noggin interference in a rabbit posterolateral spinal fusion model

Study design

Noggin protein levels and spinal fusion rates were compared in a rabbit model after application of siRNA against BMP antagonist noggin in paraspinal muscle.

Objective

To test whether endogenous BMPs are sufficient to form bone in the absence of their antagonists, using noggin siRNA to interrupt the negative feedback loop on endogenous BMP within the paraspinal muscles in rabbits.

Summary of background data

Unused Posterolateral lumbar fusion is a standard surgical treatment for many spinal disorders, yet even under ideal conditions the rate of non-fusion approaches 25 %. BMPs are effective in promoting bone formation, and are inhibited by antagonists such as noggin. We have previously shown that in this model, endogenous BMPs are present and endogenous BMP antagonist noggin is strongly increased during spinal fusion. Previous studies have found that noggin siRNA enhanced spinal fusion in combination with supra-physiological amounts of exogenous BMP; however, the effect of the siRNA alone remains unknown.

Methods

A posterolateral intertransverse rabbit lumbar fusion was utilized, as established by Boden et al. SiRNA against noggin was electroporated into paraspinal muscle to determine its effect on fusion. Outcome measures included noggin protein expression, and assessment of spinal fusion at 6 weeks.

Results

SiRNAs were effective in reducing overexpressed noggin in vitro. Noggin protein was successfully knocked down in vivo for the initial 7 days in our rabbit model and returned to detectable levels by 4 weeks and to normal levels by 6 weeks. The overall fusion rate was not significantly enhanced compared to established controls from our earlier work (Tang et al.).

Conclusions

Early noggin suppression does not appear to enhance the BMP activity sufficiently to significantly affect final fusion rates in our model.     

Melatonin improves functional outcome via inhibition of matrix metalloproteinases-9 after photothrombotic spinal cord injury in rats

Background

Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 play an important role in secondary inflammatory reaction and blood–central nervous system (CNS) barrier disruption after spinal cord injury (SCI). Theoretically, it is expected that early blockade of activation of MMPs can provide neuro-protective effects from secondary tissue damage and improve functional neurological outcomes. The aim of this study was to investigate the expression and the activity of MMP-2 and MMP-9, and to determine the regulatory effect of melatonin on MMP expression and activity after photochemically induced SCI in rats.

Methods

Female Sprague–Dawley rats weighing between 250 and 300 g (age 8 weeks) received focal ischemia by photothrombosis using Rose Bengal (RB). The injured animals were divided into two groups; one group received 50 mg/kg of melatonin intraperitoneally, starting 1 h after injury and at 12 h intervals for 7 days, while animals in the control group received weight-adjusted doses of a saline vehicle. In each group, the expressions and activities of MMP-2 and MMP-9 were assessed by Western blot and gelatin zymography at various times from 6 h to 3 days. The locomotor function was assessed using the Basso-Beattie-Bresnahan (BBB) scale at 3 days after SCI and then once per week for 4 weeks. The animals were killed at 28 days after the injury, and the histopathology of the lesions was assessed.

Findings

The expressions and activities of MMP-9 were increased at 6, 24, 48, and 72 h after SCI in the control group. In the melatonin-treated group, the expression of MMP-9 was significantly decreased at 24, 48, and 72 h after SCI compared with the control group, and the activity of MMP-9 was significantly reduced at 72 h after SCI. In contrast, there were no significant changes in the MMP-2 level in both groups during the experimental period. Melatonin treatment following photochemically induced SCI in rats significantly ameliorated the functional deficits. On histopathologic examination, the lesion size in the spinal cord after photothrombotic insult was significantly reduced by melatonin administration.

Conclusions

This study showed that the up-regulation of MMP-9 correlated with the secondary damage after SCI in rats. The results of this study suggest that the ability of melatonin to reduce secondary tissue damage is intimately related to the reduction of MMP-9 expression, resulting in functional improvement.     

CCR2 Elimination in Mice Results in Larger and Stronger Tibial Bones but Bone Loss is not Attenuated Following Ovariectomy or Muscle Denervation

Bone loss due to age and disuse contributes to osteoporosis and increases fracture risk. It has been hypothesized that such bone loss can be attenuated by modulation of the C–C chemokine receptor 2 (CCR2) and/or its ligands. The objectives of this study were to examine the effects of genetic elimination of CCR2 on cortical and trabecular bones in the mouse tibia and how bone loss was impacted following disuse and estrogen loss. Female CCR2 knockout (CCR2^?/?) and wildtype mice underwent ovariectomy (OVX) or denervation of musculature adjacent to the tibia (DEN) to induce bone loss. Cortical and trabecular structural properties as well as mechanical properties (i.e., strength) of tibial bones were measured. Compared to wildtype mice, CCR2^?/? mice had tibiae that were up to 9 % larger and stronger; these differences could be explained mainly by the 17 % greater body mass (P < 0.001) of CCR2^?/? mice. The majority of the tibia’s structural and functional responses to OVX and DEN were similar regardless of the lack or presence of CCR2, indicating that CCR2 is not protective against bone loss per se. These findings indicate that while CCR2^?/? mice do have larger and stronger bones than do wildtype mice, there is minimal evidence that CCR2 elimination provides protection against bone loss during disuse and estrogen loss.     

Surgical Resection Is Better than Transarterial Chemoembolization for Hepatocellular Carcinoma Beyond Milan Criteria Independent of Performance Status

Background and Aims

Performance status is tightly linked with survival in patients with hepatocellular carcinoma (HCC). We investigated the impact of performance status on HCC patients beyond the Milan criteria receiving surgical resection (SR) or transarterial chemoembolization (TACE).

Methods

A total of 909 patients with HCC beyond the Milan criteria were retrospectively analyzed by using propensity score analysis.

Results

The baseline characteristics were similar between the SR and TACE group for patients with performance status 0 in the propensity model. More patients in the TACE group with performance status ≥1 had Child-Turcotte-Pugh class A compared to the SR group (p?=?0.044) in the propensity model. SR provided significantly better long-term overall survival than TACE in patients selected in the propensity model regardless of performance status (both p?TACE was associated with 2.279-fold and 3.066-fold increased risk of mortality in performance status 0 and performance status ≥1 in the propensity model (95 % confidence interval, 1.476–3.591 and 1.570–5.989), respectively.

Conclusions

For either performance status 0 or ≥1 HCC patients beyond the Milan criteria, SR provides significantly better long-term survival than TACE. SR should be considered a priority treatment in these patients independent of performance status.     

The incidence of a first major osteoporotic fracture in Iceland and implications for FRAX

Summary

Based on an extensive cohort study over 25 years, the present study supports the assumption that major osteoporotic fractures can be reasonably predicted from hip fracture rates.

Introduction

The construct for FRAX models depends on algorithms to adjust for double counting of fracture outcomes in some models and in others, to estimate the incidence of a major fracture from hip fracture rates. The aim of the present study was to test the validity of these algorithms in a large prospective cohort.

Methods

The incidence of hip, clinical spine, distal forearm, and humerus fracture was determined in the prospective and ongoing population-based Reykjavik Study with follow up of 257,001 person-years. The incidence of a first major fracture was compared with the correction factors used in FRAX to adjust the incidence of several fracture outcomes for double counting. In addition, the incidence of a major osteoporotic fracture estimated from the Icelandic hip fracture rates was compared with the Malmo ratios used in FRAX.

Results

The adjustments necessary to account for multiple fracture outcomes were similar to those previously derived from Sweden. Additionally, incidence of a first major osteoporotic fracture was similar to that derived for FRAX models.

Conclusion

The findings of the present study support the algorithms used in FRAX to estimate the incidence of a first major fracture and the predictive value of hip fracture for other major fractures.     

Immediate and long-term high levels of plasma homocysteine after extracorporeal shock wave lithotripsy in patients with renal stone disease

Background

Plasma homocysteine levels increase in patients with chronic renal failure. Numerous studies have demonstrated that kidney function is one of the most important determinants of plasma total homocysteine (tHcy) concentration. In this study we aimed to evaluate the relationship between tHcy levels and extracorporeal shock wave lithotripsy (ESWL) for patients with renal stones and to see if the change in homocysteine levels continued if renal dysfunction improved.

Materials and methods

The study consisted of 20 patients who underwent first-time ESWL for renal stones. Every patient gave 3 blood samples at 24 h before surgery and at 2 days and at 3 months after ESWL for measurement of plasma levels of tHcy, creatinine, vitamin B₆, and vitamin B₁₂.

Results

The 20 patients (12 male, 8 female) had a mean age of 42.8 ± 11.7 years. tHcy levels showed a statistically significant increase from 9.4 ± 1.4 to 18 ± 4.8 and 11.2 ± 2.1 at 2 days and at 3 months, respectively. Serum creatinine also showed a statistically significant increase compared to baseline at 2 days and at 3 months after ESWL.

Conclusion

After first-time ESWL, the increase in serum levels of creatinine and tHcy due to renal injury, such as ischemia/reperfusion injury, may be severe and continue for a long period, such as 3 months. According to baseline levels, the increase in homocysteine levels as an indicator of oxidant stress was more severe than the creatinine levels after ESWL for renal stones. Our patients were first-time ESWL patients; however, in patients who undergo EWSL more than once long-term high tHcy levels should also be considered as renal.     

Effects of laser irradiation at different wavelengths (660, 810, 980, and 1,064 nm) on mucositis in an animal model of wound healing

The aim of the present study was to compare the effectiveness of four different laser wavelengths (660, 810, 980, and 1,064 nm) used for low-level laser therapy (LLLT) on the healing of mucositis in an animal model of wound healing by investigating the expression of platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-β), and blood-derived fibroblast growth factor (bFGF). Thirty-five male Wistar albino rats with a weight of 250–300 g body mass and 5 months old were used in the study. All animals were intraperitoneally injected with 100 mg/kg of 5-fluorouracil (5-FU) on the first day and 65 mg/kg of 5-FU on the third day. The tip of an 18-gauge needle was used in order to develop a superficial scratching on the left cheek pouch mucosa by dragging twice in a linear movement on third and fifth days. After ulcerative mucositis were clinically detected on the animals' left cheek pouch mucosa, the laser therapy was started. Four different laser wavelengths (660 nm, HELBO, Bredent; 810 nm, Fotona XD, Fotona; 980 nm, ARC Fox; and 1,064 nm, Fidelis Plus 3, Fotona) used for LLLT at ED 8 J/cm² daily from the first to the fourth days. Oval excisional biopsy was taken from the site of the wound, and the expression of PDGF, TGF-β, and bFGF was evaluated. The obtained data were analyzed by one2-way ANOVA, and then Tukey HSD tests were used for pairwise comparisons among groups (α?=?0.05). The one-way ANOVA test indicated that expression values of the growth factors, PDGF and bFGF, were significantly affected by irradiation of different wavelengths of lasers (p?TGF-β was not affected by irradiation of different wavelengths of lasers (p?>?0.05). The highest PDGF expression was detected in neodymium-doped yttrium aluminum garnet (Nd:YAG) laser group (p?p?>?0.05). The highest bFGF expression was detected in 980-nm diode and Nd:YAG laser groups (p?p?>?0.05). These findings suggest that low-level Nd:YAG and 980-nm diode laser therapy accelerate the wound healing process by changing the expression of PDGF and bFGF genes responsible for the stimulation of the cell proliferation and fibroblast growth.     

Protective effects of adiponectin on uncoupling of glomerular VEGF–NO axis in early streptozotocin-induced type 2 diabetic rats

Purpose

To determine whether adiponectin could reduce microalbuminuria and provide renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular vascular endothelial growth factor (VEGF)–nitric oxide (NO) axis in streptozotocin-induced type 2 diabetic rats.

Methods

Wistar rats were randomly divided into normal control group, diabetic nephropathy (DN) group induced by high-fat feeding and streptozotocin, diabetic rats injected with adenovirus-expressed adiponectin (AD-AdipoQ), and diabetic rats injected with AD-IRES-EGFP as control. Blood and urine samples were collected. Endothelium-dependent vasodilatation (EDV) of the aorta was measured. Renal tissues were collected for CD34 immunohistochemistry. Glomerular NO and VEGF levels were measured by the Griess reaction and Western blot testing, respectively.

Results

Injections of AD-AdipoQ significantly increased serum adiponectin levels and reduced the urinary albumin-to-creatinine ratio in diabetic rats (P < 0.05). The levels of plasma glucose, serum insulin, high-sensitivity C-reactive protein, and malondialdehyde were significantly reduced in diabetic rats after injections of AD-AdipoQ (P < 0.05). Severe EDV impairment was observed in the DN group, which was improved by AD-AdipoQ. CD34 expression in the glomeruli was also higher in diabetic rats, indicating increased proliferation of glomerular endothelial cells. However, AD-AdipoQ improved the increased proliferation of endothelial cells in the glomeruli. Diabetic rats showed increased glomerular VEGF levels and reduced NO levels. This uncoupling of the VEGF–NO axis was partially improved by AD-AdipoQ.

Conclusion

Adiponectin reduces the degree of microalbuminuria and has renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular VEGF–NO axis in early diabetic nephropathy.     

Isoflurane anaesthesia for a patient with long Q-T syndrome

A case report of a patient known to have long Q-T syndrome (LQTS) undergoing elective oral surgery is presented. While nitrous oxide-narcotic, nitrous oxide-enflurane, or nitrous oxide-halothane techniques for anaesthetic management of LQTS have been previously reported, we report the use of nitrous oxide-isoflurane for the maintenance of anaesthesia. The authors feel that isoflurane is a safe anaesthetic agent for use in LQTS.     

Genomic Profiling of Intrahepatic Cholangiocarcinoma: Refining Prognosis and Identifying Therapeutic Targets

Background

The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection.

Methods

Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined.

Results

The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis.

Conclusions

Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.     

Painful micturition in a small child: an unusual clinical picture of paroxysmal extreme pain disorder

Background

Paroxysmal extreme pain disorder (PEPD) is a rare autosomal dominant pain disorder linked to a mutation in the SCN9A gene, which encodes voltage-gated sodium channel Nav1.7. Abnormal pain sensitivity occurs because of changes in the properties of voltage-gated sodium channels. Different mutations in SCN9A and a spectrum of clinical expressions have been described.

Case-Diagnosis/Treatment

Here we describe a 3-year-old child with a rare clinical picture of PEPD. Extremely painful voiding had been present since the child’s birth. The diagnosis was confirmed by the detection of a heterozygous pathogenic mutation in the SCN9A gene, c.554G>A (p.Arg185His) inherited paternally. The same mutation was also found in the girl’s father, who has occasionally had some pain in his jaw while yawning since childhood. Significant reduction of the pain was achieved with carbamazepine.

Conclusions

The case is interesting because the same mutation as that found in the girl and her father has been found in patients with small fiber sensory neuropathy. These data do not correlate with the clinical picture of our case and her father, but intra- and interfamily phenotypic diversity in symptoms associated with a gain-of-function variant of Na(V)1.7 are also described and may explain our case.