Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK,AKT and NF-kappa B pathways in murine RAW264.7 cells

The bone protective effects of the hydrogen molecule (H₂) have been demonstrated in several osteoporosis models while the underlying molecular mechanism has remained unclear. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. In this work, we evaluated the effects of incubation with H₂ on receptor activator of NFκB ligand (RANKL)-induced osteoclast differentiation. We found that treatment with H₂ prevented RANKL-induced osteoclast differentiation in RAW264.7 cells and BMMs. Treatment with H₂ inhibits the ability to form resorption pits of BMMs stimulated by RANKL. Treatment with H₂ reduced mRNA levels of osteoclast-specific markers including tartrate resistant acid phosphatase, calcitonin receptor, cathepsin K, metalloproteinase-9, carbonic anhydrase typeII, and vacuolar-type H⁺-ATPase. Treatment with H₂ decreased intracellular reactive oxygen species (ROS) formation, suppressed NADPH oxidase activity, down-regulated Rac1 activity and Nox1 expression, reduced mitochondrial ROS formation, and enhanced nuclear factor E2-related factor 2 nuclear translocation and heme oxygenase-1 activity. In addition, treatment with H₂ suppressed RANKL-induced expression of nuclear factor of activated T cells c1 and c-Fos. Furthermore, treatment with H₂ suppressed NF-κB activation and reduced phosphorylation of p38, extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and protein kinases B (AKT) stimulated with RANKL. In conclusion, hydrogen molecules prevented RANKL-induced osteoclast differentiation associated with inhibition of reactive oxygen species formation and inactivation of NF-κB, mitogen-activated protein kinase and AKT pathways.     

Mechanisms of graft versus host disease produced by small bowel transplantation

Mechanisms of graft versus host disease have been studied in Lew x BN animals transplanted with a Lew small bowel. Grafted mesenteric lymph nodes but not host mesenteric lymph nodes or host spleen, in small bowel transplanted rats undergoing lethal GVHD, provide a source of CTL with specific anti-recipient cytotoxic activity. Host MLN and host spleen display anti-recipient CTL activity only when GVHD is provoked by intraperitoneal lymphocyte injection. These data demonstrate that lethal GVHD after SBTx may occur in the absence of detectable cytotoxic activity in host lymphoid tissues, suggesting that other mechanisms are involved in the pathogenesis of GVHD after SBTx. GVHD after SBTx or lymphocyte transfer is associated with the appearance of TNF in the serum. The intensity and reversibility of this phenomenon correlate with both the clinical severity and the lethality of GVHD. Taken together these data highly suggest that TNF is directly involved in the pathogenesis of GVHD after SBTx.     

Predictors that Influence Contralateral Prophylactic Mastectomy Election Among Women with Ductal Carcinoma In Situ Who Were Evaluated for BRCA Genetic Testing

Background

Patients with ductal carcinoma in situ (DCIS) are at increased risk for developing contralateral breast cancer (CBC). Consequently, more women with DCIS are electing to undergo contralateral prophylactic mastectomy (CPM). We evaluated factors associated with CPM in patients with DCIS who underwent genetic counseling for BRCA testing.

Methods

This retrospective study involved 165 women with DCIS referred for genetic counseling between 2003 and 2011. Patient characteristics were age, marital and educational status, tumor markers, nuclear grade, family history of breast cancer (BC) and ovarian cancer (OC), race, Ashkenazi Jewish ancestry, and BRCA results. Univariate and multivariate logistic regression analyses were used to determine predictive factors associated with CPM election.

Results

Of 165 patients, 44 (27 %) underwent CPM. Patients <45 years of age were more likely to elect CPM (p = 0.0098). A BRCA+ mutation was found in 17 patients (10.3 %), and BRCA+ women were more likely to elect CPM than BRCA or untested women (p = 0.0001). Patients who had a family history of OC (57.7 %) were more likely to choose CPM than those with no family history (p = 0.0004). Younger age, BRCA+, and an OC family history remained significant in the multivariate model (p < 0.008).

Conclusion

The CPM rate among patients with DCIS who undergo genetic counseling is high. Factors associated with increased likelihood of CPM among this group were age, BRCA+, and a family history of OC. Further studies are needed to evaluate patients’ perceptions of CBC risk and their role in the likelihood of CPM choice.     

Dynamic regulation and dysregulation of the water channel aquaporin-2: a common cause of and promising therapeutic target for water balance disorders

The human body is two-thirds water. The ability of ensuring the proper amount of water inside the body is essential for the survival of mammals. The key event for maintenance of body water balance is water reabsorption in the kidney collecting ducts, which is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and never allows permeation of ions or other small molecules. Under normal conditions, AQP2 is restricted within the cytoplasm of the collecting duct cells. However, when the body is dehydrated and needs to retain water, AQP2 relocates to the apical membrane, allowing water reabsorption from the urinary tubule into the cell. Its impairments result in various water balance disorders including diabetes insipidus, which is a disease characterized by a massive loss of water through the kidney, leading to severe dehydration in the body. Dysregulation of AQP2 is also a common cause of water retention and hyponatremia that exacerbate the prognosis of congestive heart failure and hepatic cirrhosis. Many studies have uncovered the regulation mechanisms of AQP2 at the single-molecule level, the whole-body level, and the clinical level. In clinical practice, urinary AQP2 is a useful marker for body water balance (hydration status). Moreover, AQP2 is now attracting considerable attention as a potential therapeutic target for water balance disorders which commonly occur in many diseases.     

A case of hypertrophic obstructive cardiomyopathy and acquired von Willebrand syndrome: response to medical therapy

Heyde’s syndrome is the combined occurrence of acquired von Willebrand disease caused by aortic valve stenosis and gastrointestinal bleeding that occurs particularly in elderly patients. The bleeding may be linked to the intravascular shear-induced proteolysis of high-molecular-weight multimers (HMWMs) of von Willebrand factor (vWF). Hypertrophic obstructive cardiomyopathy (HOCM) in the left ventricular outflow tract generates a high shear stress condition that can induce such proteolysis. We report the case of a 70-year-old woman with HOCM who had severe anemia and loss of HMWMs. After reduction of the outflow gradient by medical treatment, vWF normalized, and her anemia alleviated.     

Role of the VEGF 936 gene polymorphism and VEGF-A levels in the late-term arteriovenous fistula thrombosis in patients undergoing hemodialysis

Purpose

Vascular access is vital for hemodialysis patients. A major factor that facilitates arteriovenous (AV) fistula failure is stenosis and thrombosis due to intimal hyperplasia developing in the venous segment of AV fistula. It has been reported that VEGF accelerated re-endothelialization, reduction in intimal thickening, and/or mural thrombus formed in the injured vascular structures. In this study, we aimed to identify the effect of the VEGF 936 gene polymorphism and vascular endothelial growth factor-A (VEGF-A) levels in the late period of AV fistula loss in hemodialysis patients.

Methods

The study was carried out with a patient group of 42 individuals who experienced two or more fistula thrombosis in the late period after the AV fistula operation and also a control group of 38 patients who have not had any AV fistula thrombosis history for 3 years or more. All participants were assessed for VEGF-936C/T gene polymorphism and VEGF-A levels.

Results

VEGF-936C/T genotypes were determined in the large proportion in the control group (31.6 %), while VEGF-936C/C genotypes were determined in a large proportion in the patient group (90.5 %). Individuals carrying the VEGF-936C/C genotype had an increased risk of 5.54 for getting AV fistula thrombosis. The VEGF-A levels of patient group (27.3 ± 43.5 pg/ml) were significantly lower than those of the control group (70.7 ± 53.1 pg/ml).

Conclusion

There is an increased risk of AV fistula thrombosis in individuals carrying the VEGF-936C/C genotype. The other renal replacement modalities should be considered in patients with this genotype. As a result, it will be possible to prevent the morbidity and mortality due to fistula failure.     

Pulmonary oedema in two parturients with hypertrophic obstructive cardiomyopathy (HOCM)

Two patients with hypertrophic obstructive cardiomyopathy (HOCM) presented for delivery. The first had a repeat Caesarean section with general anaesthesia and the second gave birth vaginally with epidural analgesia. Both patients developed pulmonary oedema in the peripartum period. These cases highlight the delicate fluid requirements of the pregnant patient with HOCM. The fluid management of the parturient is discussed with particular emphasis on the pathophysiology of HOCM. The indications for invasive monitoring are presented.     

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.     

Renin inhibition ameliorates renal damage through prominent suppression of both angiotensin I and II in human renin angiotensinogen transgenic mice with high salt loading

Background

The renin–angiotensin–aldosterone system (RAAS) plays pivotal roles in the pathogenesis of chronic kidney disease (CKD) progression. Aliskiren, a direct renin inhibitor, inhibits the rate-limiting step of the RAAS without any alternative pathway. It is proven to reduce albuminuria in CKD patients treated with angiotensin blockade. However, there are few reports which evaluate the advantage of aliskiren as the first-line drug against CKD progression in RAAS-activated hypertensive patients.

Methods

Tsukuba hypertensive mice (THM), double transgenic mice carrying both the human renin and human angiotensinogen genes, were fed a high-salt diet and treated with hydraladine, ramipril and aliskiren for 10 weeks. Blood pressure and urinary albumin excretion were measured every 2 weeks during the experimental period. We evaluated renal histological changes and gene expression. Plasma angiotensin concentration was measured to evaluate the RAAS inhibitory effect.

Results

High-salt-loaded THM showed severe hypertension and renal injury. All antihypertensive drugs suppressed blood pressure and prevented renal disease progression. RAAS blockade showed a higher renoprotective effect than hydraladine despite an equivalent blood pressure lowering effect. Aliskiren exhibited even stronger renoprotection than ramipril. Plasma angiotensin concentration was increased in THM fed both normal salt and high salt. Hydraladine did not alter the plasma angiotensin concentration. Ramipril significantly decreased angiotensin II concentration. Aliskiren treatment almost completely suppressed angiotensin I and resulted in lower angiotensin II concentration than ramipril treatment.

Conclusion

Aliskiren prevents renal disease progression by suppressing both angiotensin I and II in RAAS-activated pathology. Our data suggest the application of a renin inhibitor for preventing kidney disease progression in CKD patients.     

Clinical manifestations of autosomal recessive polycystic kidney disease (ARPKD): kidney-related and non-kidney-related phenotypes

Autosomal recessive polycystic kidney disease (ARPKD), although less frequent than the dominant form, is a common, inherited ciliopathy of childhood that is caused by mutations in the PKHD1-gene on chromosome 6. The characteristic dilatation of the renal collecting ducts starts in utero and can present at any stage from infancy to adulthood. Renal insufficiency may already begin in utero and may lead to early abortion or oligohydramnios and lung hypoplasia in the newborn. However, there are also affected children who have no evidence of renal dysfunction in utero and who are born with normal renal function. Up to 30 % of patients die in the perinatal period, and those surviving the neonatal period reach end stage renal disease (ESRD) in infancy, early childhood or adolescence. In contrast, some affected patients have been diagnosed as adults with renal function ranging from normal to moderate renal insufficiency to ESRD. The clinical spectrum of ARPKD is broader than previously recognized. While bilateral renal enlargement with microcystic dilatation is the predominant clinical feature, arterial hypertension, intrahepatic biliary dysgenesis remain important manifestations that affect approximately 45 % of infants. All patients with ARPKD develop clinical findings of congenital hepatic fibrosis (CHF); however, non-obstructive dilation of the intrahepatic bile ducts in the liver (Caroli’s disease) is seen at the histological level in only a subset of patients. Cholangitis and variceal bleeding, sequelae of portal hypertension, are life-threatening complications that may occur more often in advanced cases of liver disease. In this review we focus on common and uncommon kidney-related and non-kidney-related phenotypes. Clinical management of ARPKD patients should include consideration of potential problems related to these manifestations.     

Toll-like receptors,immunoproteasome and regulatory T cells in children with Henoch–Schönlein purpura and primary IgA nephropathy

Background

Henoch–Schönlein purpura (HSP) nephritis and primary IgA nephropathy (pIgAN) present with glomerular IgA deposits, but differ with regard to clinical features. The suspected involvement of different immune system pathways is largely unknown.

Methods

This study was aimed at investigating some of the immunological features including Toll-like receptors (TLR), proteasome (PS)/immunoproteasome (iPS) switch, and the regulatory T cell system (Treg/Th17 cells) in 63 children with HSP with/without renal involvement and in 25 with pIgAN. Real-time PRC (Taqman) was used to quantify mRNA levels in peripheral blood mononuclear cells (PBMC).

Results

The expression of mRNAs encoding for TLR4 in both HSP and pIgAN was higher than in controls (HC) and in both diseases FoxP3mRNA and TGF-β1mRNA expression was significantly lower than in HC. A switch from PS to iPS (LMP2/β1) was detected only in PBMC of HSP and it correlated with the level of TLR2mRNA, which was selectively increased only in children with HSP.

Conclusion

Children with HSP and pIgAN present with similar signs of engagement of the innate immunity and regulatory T cell depression. The increased immunoproteasome switch, which correlated with TLR2 activation, may suggest an innate immunity pathway peculiar to HSP vasculitic presentation. This research area also deserves further investigation for possible therapeutic applications.     

Transcystic or Transductal Stone Extraction during Single-Stage Treatment of Choledochocystolithiasis: A Systematic Review

Background

Choledochocystolithiasis can be managed by endoscopic retrograde cholangiopancreaticography (ERCP) or laparoscopically by transcystic (TC) or transductal (TD) stone extraction.

Objective

The aim of this study was to systematically review safety and effectiveness of combined endoscopic/laparoscopic management versus total laparoscopic management for choledochocystolithiasis with specific emphasis on TC versus TD stone extraction.

Methods

MEDLINE/PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched systematically to identify trials on combined endoscopic/laparoscopic and total laparoscopic management for choledochocystolithiasis. Laparoscopic common bile duct (CBD) exploration was divided into TD and TC approach. Primary outcomes were successful stone clearance from CBD, postoperative/procedural morbidity, and mortality.

Results

Eight randomized trials with 965 patients were included. Successful bile duct clearance varied between 52.6 and 97 % in the ERCP groups, 80.4 and 100 % in the TC groups, and 58.3 and 100 % in the TD groups. There were more bile leaks after TD stone extraction (11 %) than after ERCP (1 %) and TC stone extraction (1.7 %). Total morbidity varied between 9.1 and 38.3 % in the ERCP groups, 7 and 10.5 % in the TC groups, and 18.4 and 26.7 % in the TD groups. Methodological and statistical heterogeneity among the trials precluded a meaningful meta-analysis.

Conclusion

Stone clearance rates are comparable between the three modalities, but TD stone extraction is associated with a higher risk of bile leaks and should only be performed by highly experienced surgeons. TC stone extraction seems a more accessible technique with lower complication rates. If unsuccessful, per- or postoperative endoscopic stone extraction is a viable option.     

Collagen type III alpha 1 polymorphism (rs1800255, COL3A1 2209 G>A) assessed with high-resolution melting analysis is not associated with pelvic organ prolapse in the Dutch population

Introduction and hypothesis

The rs1800255, COL3A1 2209 G>A polymorphism in the alpha 1 chain of collagen type III has been associated with an increased risk of pelvic organ prolapse (POP). In one of our previous studies however, polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) misdiagnosed rs1800255, COL3A1 2209 G>A in 6 % of cases. The high-resolution melting (HRM) analysis on the contrary obtained a 100 % accordance for this specific polymorphism and was used in the present study to validate this risk factor for POP.

Methods

In this case–control study, women with and without symptoms of POP were included and compared. DNA was extracted from blood samples. HRM analysis was used to assess for the presence of the homozygous rs1800255. Groups were compared using the Pearson chi-square, Mann–Whitney, and t tests. The discrepancy between HRM and PCR-RFLP results was investigated using PCR-RFLP results available from our previous study.

Results

The study included 354 women: 272 patients with POP and 82 controls; 18 (7 %) cases versus 3 (4 %) controls had a homozygous rs1800255, COL3A1 2209 G>A polymorphism (odds ratio 1.9, 95 % confidence interval 0.5–6.9, compared to the wild type), and thus no association between POP and the homozygous polymorphism could be demonstrated. A discrepancy between HRM and PCR-RFLP results was found in 8 % of the samples.

Conclusions

The previously found statistically significant association between the rs1800255, COL3A1 2209 G>A polymorphism as measured with PCR-RFLP and POP could no longer be demonstrated. This raises concerns regarding the results of other association studies using PCR-RFLP.     

Progressive renal decline as the major feature of diabetic nephropathy in type 1 diabetes

Despite almost universal implementation of renoprotective therapies over the past 25 years, the risk of end-stage renal disease (ESRD) in type 1 diabetes (T1D) is not decreasing, and ESRD remains the major cause of excess morbidity and premature mortality [1]. Such a state of affairs prompts a call to action. In this review we re-evaluated the proteinuria-centric model of diabetic nephropathy and showed its deficiencies. On the basis of extensive studies that we have been conducting on the patients attending the Joslin Clinic, we propose that progressive renal decline, not abnormalities in urinary albumin excretion, should be considered as the major feature of disease processes leading to ESRD in T1D. The etiology of diabetic nephropathy should be reconsidered in light of our new findings so our perspective can be broadened regarding new therapeutic targets available for interrupting the progressive renal decline in T1D. Reduction in the loss of glomerular filtration rate, not reduction of albumin excretion rate, should become the measure for evaluating the effectiveness of new therapeutic interventions. We need new accurate methods for early diagnosis of patients at risk of progressive renal decline or, better still, for detecting in advance which patients will have rapid, moderate or minimal rate of progression to ESRD.     

Z-plasty a rational and effective technique for pilonidal sinus

Background

Pilonidal disease is a commonly encountered problem with multiple surgical options. With Z-plasty, primary closure ensures faster healing while the alteration of local anatomy reduces recurrence.

Methods

Twenty patients underwent Z-plasty for sacrococcygeal pilonidal sinus between 2007 and 2010. Prospective data of these patients were analyzed.

Results

The mean duration of symptoms was 24 months and, in the main, included pus discharging sinus and pain. Wound healing after the procedure averaged 12 days. No recurrences were recorded at a follow-up of six to 24 months.

Conclusion

The Z-plasty technique, based on a rational approach, is an effective procedure for treating pilonidal disease in terms of both faster healing and lower recurrence rates.     

Locoregional Recurrence and Survival Outcomes by Type of Local Therapy and Trastuzumab Use Among Women with Node-Negative,HER2-Positive Breast Cancer

Background

While human epidermal growth factor receptor 2 (HER2) overexpression is an adverse breast cancer prognostic factor, it is unclear whether there are differences in outcomes between types of local treatment in this population. This retrospective study examined locoregional recurrence and survival in women with node-negative, HER2+ breast cancer treated with breast-conserving therapy (BCT) versus mastectomy.

Methods

Subjects were 748 patients with pT1–2, N0, M0 HER2+ breast cancer, treated with BCT (n = 422) or mastectomy (n = 326). Trastuzumab was used in 54 % of subjects. The 5-year Kaplan–Meier locoregional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), and overall survival (OS) were compared between cohorts treated with BCT versus mastectomy. Subgroup analyses of LRR and survival were performed separately among patients treated with BCT or mastectomy to examine the effect of trastuzumab on outcomes in each group.

Results

Median follow-up was 4.4 years. Patients treated with mastectomy had higher proportions of grade 3 histology (69 vs 60 %, p = 0.004) and lower rates of hormone therapy (51 vs 64 %, p < 0.001) and trastuzumab therapy (50 vs 57 %, p = 0.04). The 5-year outcomes in women treated with BCT compared with mastectomy were: LRRFS 98.0 versus 98.3 % (p = 0.88), BCSS 97.2 versus 96.1 % (p = 0.70), and OS 95.5 versus 93.4 % (p = 0.19). Trastuzumab was associated with similar LRRFS and improved OS in both local treatment groups.

Conclusions

BCT is safe in the population of women with pT1–2, N0, HER2+ breast cancer, providing high rates of locoregional control and survival equivalent to mastectomy. Trastuzumab was associated with improved survival in both groups.     

Resistance exercise: a strategy to attenuate inflammation and protein-energy wasting in hemodialysis patients?

Purpose

Patients undergoing hemodialysis (HD) present persistent inflammation and protein-energy wasting (PEW), which contributes to high rates of mortality. This study aimed to assess the effects of a resistance exercise training program (RETP) on inflammation and PEW in HD patients.

Methods

Thirty-seven patients (56.7 % men, 45.9 ± 14.1 years, 23.5 ± 3.9 kg/m²) performed 6 months of intradialytic RETP. Plasma adhesion molecules levels (ICAM-1 and VCAM-1) were measured using the enzyme immunometric assay, and interleukin-6 (IL-6), C-reactive protein, and tumor necrosis factor-alpha by ELISA. Anthropometric, physical capacity, and PEW (simultaneously presence of: BMI <23 kg/m², serum albumin <3.8 g/dL, and reduced arm muscle area) were analyzed.

Results

There was a reduction of ICAM-1 [(1,934.1 pg/mL (1,031.8–2,875.0) vs. 1,571.1 pg/mL (447.1–2,985.5), p < 0.05], VCAM-1 [5,259.51 pg/mL (3,967.4–6,682.4) vs. 3,062.11 pg/mL (2,034.0–5,034.4), p < 0.05], and CRP levels (2.3 ± 0.9 to 1.6 ± 0.6 pg/mL, p < 0.001) after 6 months of RETP. Body composition improved, albumin increased (3.7 ± 0.3 to 3.9 ± 0.2, p < 0.05), and the number of patients presenting PEW was decreased (p = 0.005).

Conclusions

Resistance exercise program for 6 months seems to be effective in reducing inflammation and PEW of HD patients. The universal trial number of this study is U1111-1139-1326.     

Osteoarthritis after cold injuries

Frostbite is a thermal injury resulting in localised tissue damage due to inadequate circulation when the ambient temperature is below freezing. Osteoarthritis (OA) can develop after cold injuries. A 30-year old rock-climber presented with clinical and radiological signs of OA in his right middle and ring finger distal interphalangeal joints (DIPJ). He denied any hand trauma but had suffered frostbite to his fingers at the age of 19 during a trip in the Himalayas. Arthrodesis was performed in a functional position for his activities. The exact pathophysiology is unknown, but it is believed that both freezing and rapid rewarming are contributing factors. We postulate that osteoarthritis after frostbite in young adults is more likely to occur as the growth plate is nearing maturity. Initially, the ischaemic insult is partially remedied during reperfusion, but further cartilage damage may continue during the remodelling phase as the young adult continues to be active and the joints are subjected to constant load transmission. This may explain the variability in the timing of clinical presentation with osteoarthritis. Arthrodesis is indicated for symptomatic cases and facilitates continued interest in active sports. Hobbies should be considered in the history, including exposure to extreme weather conditions when young active patients present with OA. Level of Evidence: Level V, diagnostic study.     

The role of ERCP in the era of EUS-FNA for preoperative cytological confirmation of resectable pancreatic ductal adenocarcinoma

Purpose

In patients with pancreatic ductal carcinoma (PDAC), EUS-FNA carries a risk of cancer seeding. To avoid this risk, we attempted to obtain preoperative cytological confirmation of adenocarcinoma by ERCP. The aim of this study was to assess the validity of our diagnostic strategy.

Methods

The medical records of 124 consecutive patients who were investigated for potentially resectable PDAC were retrospectively reviewed, and the ability to detect adenocarcinoma by ERCP was evaluated.

Results

ERCP was performed in 115 patients, 69 of whom had positive cytology results. Thirty-four patients underwent EUS-FNA, 29 of whom had positive cytology results. A total of 98 patients (79 %), therefore, had preoperative cytological confirmation of adenocarcinoma, which was more frequent in patients with lesions of the head of the pancreas than in those with lesions of the body or tail of the pancreas. The postoperative pathological diagnosis demonstrated malignant pancreatic neoplasms in 122 patients (98 %), including 111 with PDAC. EUS-FNA did not affect the rate of postoperative peritoneal dissemination.

Conclusions

Our strategy using ERCP as the initial diagnostic modality for obtaining cytological confirmation of potentially resectable PDAC seems to be adequate, yielding a high rate of positive cytology, especially in cases with tumors of the head of the pancreas.