CT-guided pretreatment biopsy diagnosis in patients with thymic epithelial tumours: diagnostic accuracy and risk of seeding.

AIM: To investigate the diagnostic performance of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) for thymic epithelial tumours (TETs) and the complication rate after PTNB including seeding after PTNB. MATERIALS AND METHODS: This retrospective study identified PTNBs for anterior mediastinal lesions between May 2007 and September 2021. The diagnostic performance for TETs and complications were investigated. The concordance of the histological grades of TETs between PTNB and surgery was evaluated. The factors associated with pleural seeding after PTNB were determined using Cox regression analysis. RESULTS: Of 387 PTNBs, 235 PTNBs from 225 patients diagnosed as TETs (124 thymomas and 101 thymic carcinomas) and 150 PTNBs from 133 patients diagnosed as other than TETs were included. The sensitivity, specificity, and accuracy for TETs were 89.4% (210/235), 100% (210/210), and 93.5% (360/385), respectively, with an immediate complication rate of 4.4% (17/385). The concordance rate of the histological grades between PTNB and surgery was 73.3% (77/105) after excluding uncategorised types of thymomas. During follow-up after PTNB (median duration, 38.8 months; range, 0.3-164.6 months), no tract seeding was observed. Pleural seeding was observed in 26 patients. Thymic carcinoma (hazard ratio [HR], 5.94; 95% confidence interval [CI], 2.07-17.08; p=0.001) and incomplete resection (HR, 3.29; 95% CI, 1.20-9.02; p=0.02) were associated with pleural seeding, while the biopsy approach type (transpleural versus parasternal) was not associated (p=0.12). CONCLUSIONS: Pretreatment biopsy for TETs was accurate and safe and may be considered for diagnosing TETs, particularly when the diagnosis is challenging and histological diagnosis is mandatory.

Laparoscopic total extra-peritoneal (TEP) inguinal hernia repair under local anesthesia by topical lidocaine injection.

PURPOSE: Laparoscopic total extra-peritoneal (TEP) inguinal hernia repair is usually performed under general anesthesia (GA) for muscle relaxation. However, TEP hernia repair may be reluctant in high-risk patients of GA. The aim of this study was to compare the outcomes of the TEP under GA and local anesthesia (LA). METHODS: We retrospectively analyzed patients with inguinal hernia who underwent TEP under GA or LA in a single center from December 2016 to May 2018. The outcomes, such as demographics, duration of surgery, length of hospital stay, visual analog scale (VAS), and postoperative complications, were compared in each group. RESULTS: Seventy-six patients with inguinal hernia underwent TEP under GA (n = 52) or LA (n = 24). Total operation time (mean ± standard deviation; GA, 111.6 ± 23.0 min; LA, 76.3 ± 18.0 min; p < 0.001) and length of hospital stay (GA, 38.3 ± 11.6 min; LA, 30.3 ± 15.6 min; p < 0.014) were shorter in LA group compared to GA group. There were no significant differences in postoperative VAS (1 h, p = 0.247; 4 h, p = 0.086; 12 h, p = 0.469; 24 h, p = 0.411), postoperative adverse effects (vomiting, p = 0.570; urinary retention, p = 0.214; headache, p = 0.494), and postoperative complications (seroma, p = 0.348; scrotal edema, p = 0.178; recurrence, p = 0.822) between LA group and GA group. CONCLUSION: Compared with GA, there were no differences in postoperative pain and complications in patients who underwent TEP hernia repair under LA. Furthermore, in LA group, total operation time and length of hospital stay were shortened.

Initial experience with a suprapubic single-port robotic right hemicolectomy in patients with colon cancer.

BACKGROUND: We developed a novel suprapubic single-port robotic right hemicolectomy (spRHC) procedure for patients with right colon cancer using a da Vinci SP Surgical System. The aim of this study was to determine the safety and feasibility of this technique. METHODS: We performed the spRHC procedure on five patients with right colon cancers between July and September 2020. All procedures including colon mobilization, D3 lymphadenectomy, and intracorporeal anastomosis were completed using the single-port robotic platform through a mini-transverse suprapubic incision and an additional assistant port. Data regarding patient characteristics, perioperative outcomes and pathologic results were analyzed. RESULTS: Four of the five patients were males. The median age was 69 years (range, 58-77 years).Two patients received preoperative chemotherapy for advanced colon cancer. The median total operative time was 160 min (range, 150-240 min). The median docking time was 4 min 40 s (range, 2 min 10 s-5 min 10 s). The median console time was 105 min (range, 100-120 min). There were no conversions to multiport or open surgeries. The median hospital stay was 7 days (range, 5-12 days). One patient experienced a wound infection. The median number of harvested lymph nodes was 41 (range, 39-50 lymph nodes). CONCLUSIONS: SpRHC is safe and feasible. However, further comparative studies are needed to assess whether this procedure can provide patients with significant benefits compared with multiport robotic surgery.

An initial experience with a novel technique of single-port robotic resection for rectal cancer.

BACKGROUND: The da Vinci single-port (SP) system is designed to facilitate single-incision robotic surgery in a narrow space. We developed a new procedure of rectal resection using this system. The aim of the present study was to evaluate the technical feasibility and safety of SP robotic rectal resection for rectal cancer patients based on our initial experience. METHODS: A study was conducted on consecutive patients with mid or low rectal cancer who had SP robotic resection at our institution between July and September 2020. The demographic characteristics, perioperative data, and pathology results of the patients were retrospectively analyzed. RESULTS: There were 5 patients (3 males, 2 females, median age 57 years (range 36-73 years). The median tumor height from the anal verge was 4 cm (range 3-5 cm). Two patients received preoperative chemoradiotherapy for advanced rectal cancer. A single docking was conducted, and the median docking time was 4 min 20 s (range 3 min 30 s to 5 min). The median total operation time was 195 min (range 155-240 min), and the median time of pelvic dissection was 45 min (range 36-62 min). All patients had circumferential and distal tumor-free resection margins. One patient experienced an anastomosis-related complication. The median duration of hospital stay was 7 days (range 7-8 days). CONCLUSIONS: Our initial experience suggests that SP robotic rectal resection is safe and feasible. Further clinical trials comparing SP and multiport robotic rectal resection should be conducted to verify the superior aspects of this new system.

FoxO1 as a Regulator of Aquaporin 5 Expression in the Salivary Gland.

Forkhead box O1 (FoxO1) is a multifunctional initiator, mediator, and repressor of autoimmune diseases in an organ- or disease-specific manner. However, the role of FoxO1 in the salivary gland has not yet been elucidated. In this study, we discovered that FoxO1 and aquaporin 5 (AQP5) are both significantly downregulated in the patients with primary Sjögren syndrome, an autoimmune disease accompanying salivary gland dysfunction. Pharmacologic or genetic perturbation of FoxO1 in the rat salivary gland acinar cell line, SMG-C6, induced a significant downregulation of AQP5 expression, as observed in clinical specimens. There was a strong correlation between FoxO1 and AQP5 expression because FoxO1 is a direct regulator of AQP5 expression in salivary gland acinar cells through its interaction with the promoter region of AQP5. Serial injection of a FoxO1 inhibitor into mice induced a reduction of AQP5 expression in submandibular glands and, consequently, hyposalivation, which is one of the major clinical symptoms of primary Sjögren syndrome. However, there was no sign of inflammation or cell damage in the submandibular glands harvested from mice treated with the FoxO1 inhibitor. In conclusion, our findings indicate that FoxO1 in salivary gland tissue acts as a direct regulator of AQP5 expression. Thus, downregulation of FoxO1 observed in primary Sjögren syndrome is a putative mechanism for hyposalivation without the involvement of previously reported soluble factors in primary Sjögren syndrome patient sera.

Long-term clinical outcomes of total mesorectal excision and selective lateral pelvic lymph node dissection for advanced low rectal cancer: a comparative study of a robotic versus laparoscopic approach.

BACKGROUND: The long-term outcomes of minimally invasive lateral pelvic lymph node dissection (LPND) are not completely known. The aim of this study was to compare long-term outcomes between robotic and laparoscopic LPND in low rectal cancer patients with suspected lymph node metastasis in the pelvic sidewall. METHODS: We retrospectively reviewed the records of all rectal cancer patients who had laparoscopic or robotic total mesorectal excision (TME) with LPND between March 2006 and June 2016. Stage IV patients were excluded. The outcomes of patients who had laparoscopic and robotic TME with LPND were compared. RESULTS: Twenty-nine patients had laparoscopic LPND and 70 had robotic LPND. No significant differences in patient characteristics were observed between the two groups. The urinary retention rate was lower in the robotic group than in the laparoscopic group (7.1% vs. 24.1%; p = 0.043). During a median follow-up of 44.3 months, the overall recurrence rates were 48.3% and 31.4% in the laparoscopic and robotic groups, respectively (p = 0.175). The 5-year disease-free survival rates were 50.4% and 67.0% in the laparoscopic and robotic groups, respectively (p = 0.227). The 5-year overall survival rates were 65.0% and 92.2% in the laparoscopic and robotic groups, respectively (p = 0.017). CONCLUSIONS: Robotic TME with LPND is safe and feasible. In particular, it is associated with lower urinary retention. Robotic TME with LPND might yield a similar local recurrence rate and 5-year disease-free survival, but favorable long-term overall survival as compared to the laparoscopic approach. However, considering the retrospective nature and both major variables of TME and LPND involved together, this should be cautiously interpreted.

Ribosomal protein S3 associates with the TFIIH complex and positively regulates nucleotide excision repair.

In mammalian cells, the bulky DNA adducts caused by ultraviolet radiation are mainly repaired via the nucleotide excision repair (NER) pathway; some defects in this pathway lead to a genetic disorder known as xeroderma pigmentosum (XP). Ribosomal protein S3 (rpS3), a constituent of the 40S ribosomal subunit, is a multi-functional protein with various extra-ribosomal functions, including a role in the cellular stress response and DNA repair-related activities. We report that rpS3 associates with transcription factor IIH (TFIIH) via an interaction with the xeroderma pigmentosum complementation group D (XPD) protein and complements its function in the NER pathway. For optimal repair of UV-induced duplex DNA lesions, the strong helicase activity of the TFIIH complex is required for unwinding damaged DNA around the lesion. Here, we show that XP-D cells overexpressing rpS3 showed markedly increased resistance to UV radiation through XPD and rpS3 interaction. Additionally, the knockdown of rpS3 caused reduced NER efficiency in HeLa cells and the overexpression of rpS3 partially restored helicase activity of the TFIIH complex of XP-D cells in vitro. We also present data suggesting that rpS3 is involved in post-excision processing in NER, assisting TFIIH in expediting the repair process by increasing its turnover rate when DNA is damaged. We propose that rpS3 is an accessory protein of the NER pathway and its recruitment to the repair machinery augments repair efficiency upon UV damage by enhancing XPD helicase function and increasing its turnover rate.

The change of bone mineral density and bone metabolism after gastrectomy for gastric cancer: a meta-analysis.

Bone mineral density (BMD) is significantly decreased after gastrectomy in patients with gastric cancer. Calcium malabsorption, secondary hyperparathyroidism, and dominant bone resorption appear to contribute to bone loss in these patients. Patients should undergo early surveillance and nutritional or pharmacologic intensive interventions for bone health. PURPOSE: Survivorship care, including bone health, has become an important issue in gastric cancer. We performed a meta-analysis of the available observational studies to determine whether and how osteoporosis risk is increased after gastrectomy in patients with gastric cancer. METHODS: A total of 1204 patients (802 men) from 19 cohort studies were included. We evaluated the prevalence of osteoporosis in postgastrectomy patients, comparing the incidence according to the type of gastrectomy and sex. Additionally, we evaluated changes in bone mineral density (BMD) and bone metabolism-related markers pre- to postoperatively and between patients who underwent gastrectomy and matched controls. Proportion meta-analysis was performed and pooled odds ratios (ORs) were calculated. RESULTS: The pooled incidence estimate was 36% [95% confidence interval (CI), 32-40]. The incidence of osteoporosis was significantly higher in women than in men (OR = 1.90, p < 0.001) but was similar between partial and total gastrectomy groups (OR = 0.983, p = 0.939). BMD was significantly decreased, and calcium, phosphorous, and parathyroid hormone levels were significantly increased in patients after gastrectomy compared to those before gastrectomy. BMD and calcium and 25OH-vitamin D levels were significantly decreased, and parathyroid hormone and 1,25OH-vitamin D levels were significantly increased in the gastrectomy group compared to that in the control group. CONCLUSION: We found that BMD is significantly decreased after gastrectomy in patients with gastric cancer. Vitamin D deficiency and secondary hyperparathyroidism are suggested to be common mechanism underlying BMD impairment. After resection, patients should undergo long-term nutritional and bone health surveillance, in addition to their oncological follow-up.

Bactericidal and cytotoxic activity of a diarylheptanoid (etlingerin) isolated from a ginger (Etlingera pubescens) endemic to Borneo.

AIMS: The aim of this study was to investigate the antimicrobial activities of Etlingera pubescens, and to isolate and identify the antimicrobial compound. METHODS AND RESULTS: The crude extracts of E. pubescens were obtained through methanol extraction, and evaluated for antimicrobial activities. From this extract, 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate (etlingerin) was isolated. When compared to curcumin (a compound with a similar chemical structure), etlingerin showed twofold lower minimum inhibitory concentration values while also being bactericidal. Through time kill assay, etlingerin showed rapid killing effects (as fast as 60 min) against the Gram-positive bacteria (Staphylococcus aureus ATCC 43300 and Bacillus subtilis ATCC 8188). Further assessment revealed that etlingerin caused leakage of intracellular materials, therefore suggesting alteration in membrane permeability as its antimicrobial mechanism. Cytotoxicity study demonstrated that etlingerin exhibited approximately 5- to 12-fold higher IC50 values against several cell lines, as compared to curcumin. CONCLUSIONS: Etlingerin isolated from E. pubescens showed better antibacterial and cytotoxic activities when compared to curcumin. Etlingerin could be safe for human use, though further cytotoxicity study using animal models is needed. SIGNIFICANCE AND IMPACT OF THE STUDY: Etlingerin has a potential to be used in treating bacterial infections due to its good antimicrobial activity, while having potentially low cytotoxicity.

Clinical usefulness of two-phase 18F-sodium-fluoride (18F-NaF) bone PET/CT for evaluating treatment response of bone metastases from breast cancer: Case report. / Utilidad clínica de la PET/TC ósea doble fase con 18F-fluoruro de sodio (18F-NaF) para valorar la respuesta terapéutica de las metástasis óseas del cáncer de mama: informe de un caso.

We report the case of a breast cancer patient in whom a two-phase 18F-sodium-fluoride (18F-NaF) bone PET/CT was useful for detecting hidden bone metastases and assessing treatment response. The patient underwent a two-phase bone PET/CT to evaluate a newly developed lesion found on bone scintigraphy following surgery. In the perfusion and bone phase PET/CT images, focally increased perfusion and bony uptake were found in the sacrum and L5 vertebra, suggesting bone metastases of breast cancer. Therefore, the patient subsequently underwent palliative treatment. In another twoPET/CT studies (each including two-phase bone images) performed after 3and 6months of follow-up, the perfusion phase images showed an improvement of the lesion uptake more clearly than in the bone phase images in the visual and semi-quantitative analyses, and thus the perfusion phase images were more useful for clarifying the treatment response earlier than the bone phase images. This is the first case showing the clinical usefulness of 18F-NaF bone PET/CT with the perfusion imaging technique for evaluating bone metastases and the therapeutic response of metastatic bone lesions.

Prognostic value of CT attenuation and FDG uptake of adipose tissue in patients with pancreatic adenocarcinoma.

AIM: To investigate the prognostic significance of computed tomography (CT) attenuation and 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) uptake in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) for predicting overall survival (OS) in patients with pancreatic adenocarcinoma. MATERIALS AND METHODS: Data were collected retrospectively from 66 patients with pancreatic adenocarcinoma who had undergone pretreatment combined FDG positron-emission tomography (PET)/CT imaging and subsequent curative or palliative treatment. Metabolic parameters of primary tumour including total lesion glycolysis (TLG) and heterogeneity factor were measured. Volume, CT attenuation (attenuation), and FDG uptake of SAT and VAT were derived from PET/CT acquisitions. Survival analysis using Cox proportional hazard modelling was performed to assess the relationship between both attenuation and FDG uptake of fat tissue and OS. RESULTS: During follow-up, 33 patients (50%) died and the median OS was 12 months. There were significant positive correlations between attenuation and mean standardised uptake values of both SAT (p<0.001, r=0.697) and VAT (p<0.001, r=0.742). Attenuation and FDG uptake of adipose tissue were significantly associated with heterogeneity factor and T stage. Patients with high FDG uptake and attenuation of SAT and VAT had significantly worse OS than those with low values. On multivariate analysis, attenuation of SAT (p=0.047) and VAT (p=0.021), and FDG uptake of VAT (p=0.005) were correlated significantly with OS after adjusting for age, sex, body mass index, TNM stage, and TLG. CONCLUSIONS: CT attenuation of SAT and VAT, and FDG uptake of VAT significantly correlated with OS in patients with pancreatic adenocarcinoma, independent of TNM staging and TLG.

Day-case holmium laser enucleation of the prostate: feasibility, safety and predictive factors.

Introduction Transurethral resection of the prostate has remained the most common operation for bladder outlet obstruction in the UK, but it is associated with potential morbidity and median two-day length of hospital stay. Holmium laser enucleation of the prostate (HoLEP) provides an alternative procedure. Provision of day-case HoLEP would improve patient care through increased efficiency. We assessed the feasibility and safety of day-case HoLEP and examined predictive factors for increased length of hospital stay. Materials and methods Patients presenting for HoLEP by a single surgeon from September 2013 to September 2016 were considered for day-case surgery. Patients were discharged following assessment by the operating surgeon and met predetermined discharge criteria. Factors contributing to day-case success were identified. Results In total, 210 patients (mean age 70.3 ± 8.5 years) underwent HoLEP, with 74 (35.3%) discharged as true day-cases and a further 84 (40.0%) discharged within 23 hours. Readmission rate was 5.5%, with all complications Clavien-Dindo grade I or II. Factors associated with successful day-case operation included low-volume prostates (≤ 40 g) (odds ratio, OR, 3.097, 95% confidence interval, CI, 1.619-5.924, P = 0.0001) and morning surgical lists (OR 6.124, 95% CI 2.526-14.845, p<0.001). Discussion and conclusion Day-case HoLEP is both feasible and safe, with low readmission rates. Two factors were significantly associated with successful day-case surgery: small volume prostate and morning theatre lists. Addressing these factors through preoperative planning can improve day-case surgery rates and improve bed throughput.

Concurrent use of capecitabine with radiation therapy and survival in breast cancer (BC) after neoadjuvant chemotherapy.

PURPOSE: Capecitabine has been studied as a radiosensitizer, and our study seeks to examine the association of concurrent capecitabine/radiation therapy (RT) on event-free- (EFS) and overall survival (OS) in women with breast cancer (BC) with residual disease after neoadjuvant chemotherapy (NAC). METHODS/PATIENTS: In a retrospective study of women with BC who received adriamycin/taxane-based NAC from 2004-2016, we identified 21 women administered concurrent capecitabine/RT. To assess differences in survival, we selected a clinical control cohort (n = 57) based on criteria used to select patients for capecitabine/RT. We also created a matched cohort (2:1), matching on tumor subtype, pathological stage and age (< 50 or 50+ years). Differences in EFS, using STEEP criteria, and OS, using all-cause mortality, between those who received capecitabine/RT and controls were assessed. RESULTS: Of the 21 women who received capecitabine/RT, median age was 52 years. The majority were pathologic stage III (n = 15) and hormone receptor-positive/HER2-negative BC (n = 20). In those receiving capecitabine/RT, there were 9 events, compared with 14 events in clinical and 10 events in matched controls. Capecitabine/RT was associated with worse OS in clinical (HR 3.83 95% CI 1.12-13.11, p = 0.03) and matched controls (HR 3.71 95% CI 1.04-13.18, p = 0.04), after adjusting for clinical size, pathological stage and lymphovascular invasion. Capecitabine/RT was also associated with a trend towards worse EFS in clinical (HR 2.41 95% CI 0.86-6.74, p = 0.09) and matched controls (HR 2.68 95% CI 0.91-7.90, p = 0.07) after adjustment. CONCLUSION: Concurrent capecitabine/RT after NAC is associated with worse survival and should be carefully considered in BC.

Emerging treatment paradigms for brain metastasis in non-small-cell lung cancer: an overview of the current landscape and challenges ahead.

Advances in the last decade in genomic profiling and the identification of druggable targets amenable to biological agents have transformed the management and survival of a subgroup of patients with brain metastasis in non-small-cell lung cancer. In parallel, clinicians have reevaluated the role of whole brain radiotherapy in selected patients with brain metastases to reduce neurocognitive toxicity. Continual progress in this understudied field is required: optimization of the sequence of schedules for therapies in patients with brain metastases of differing genomic profiles, focusing on new strategies to overcome mechanisms of biological resistance and increasing drug penetrability into the central nervous system. This review summarizes the field to date and possible treatment strategies based on current evidence.

Limited Dorsal Myeloschisis and Congenital Dermal Sinus: Comparison of Clinical and MR Imaging Features.

BACKGROUND AND PURPOSE: While limited dorsal myeloschisis is a distinctive form of spinal dysraphism, it may be confused with congenital dermal sinus. The aim of this study was to describe clinical and MR imaging findings of limited dorsal myeloschisis that can distinguish it from congenital dermal sinus. MATERIALS AND METHODS: We retrospectively reviewed the clinical and MR imaging findings of 12 patients with limited dorsal myeloschisis and 10 patients with congenital dermal sinus. Skin abnormalities, neurologic deficits, and infectious complication were evaluated on the basis of clinical information. We evaluated the following MR imaging features: visibility of the tract along the intrathecal course, attachment site of the tract, level of the conus medullaris, shape of the spinal cord, and presence of intradural lesions such as dermoid/epidermoid tumors. RESULTS: A crater covered with pale epithelium was the most common skin lesion in limited dorsal myeloschisis (10/12, 83%). Infectious complications were common in congenital dermal sinus (6/10, 60%), whereas none were found in limited dorsal myeloschisis (P = .003). The following MR imaging findings were significantly different between the 2 groups (P < .05): 1) higher visibility of the intrathecal tract in limited dorsal myeloschisis (10/12, 83%) versus in congenital dermal sinus (1/10, 10%), 2) the tract attached to the cord in limited dorsal myeloschisis (12/12, 100%) versus various tract attachments in congenital dermal sinus, 3) dorsal tenting of the cord in limited dorsal myeloschisis (10/12, 83%) versus in congenital dermal sinus (1/10, 10%), and 4) the presence of dermoid/epidermoid tumors in congenital dermal sinus (6/10, 60%) versus none in limited dorsal myeloschisis. CONCLUSIONS: Limited dorsal myeloschisis has distinct MR imaging features: a visible intrathecal tract with dorsal tenting of the cord at the tract-cord union. Limited dorsal myeloschisis was not associated with infection and dermoid/epidermoid tumors.

Academic requirements for Certificate of Completion of Training in surgical training: Consensus recommendations from the Association of Surgeons in Training/National Research Collaborative Consensus Group.

BACKGROUND: Surgical trainees are expected to demonstrate academic achievement in order to obtain their certificate of completion of training (CCT). These standards are set by the Joint Committee on Surgical Training (JCST) and specialty advisory committees (SAC). The standards are not equivalent across all surgical specialties and recognise different achievements as evidence. They do not recognise changes in models of research and focus on outcomes rather than process. The Association of Surgeons in Training (ASiT) and National Research Collaborative (NRC) set out to develop progressive, consistent and flexible evidence set for academic requirements at CCT. METHODS: A modified-Delphi approach was used. An expert group consisting of representatives from the ASiT and the NRC undertook iterative review of a document proposing changes to requirements. This was circulated amongst wider stakeholders. After ten iterations, an open meeting was held to discuss these proposals. Voting on statements was performed using a 5-point Likert Scale. Each statement was voted on twice, with ≥80% of votes in agreement meaning the statement was approved. The results of this vote were used to propose core and optional academic requirements for CCT. RESULTS: Online discussion concluded after ten rounds. At the consensus meeting, statements were voted on by 25 delegates from across surgical specialties and training-grades. The group strongly favoured acquisition of 'Good Clinical Practice' training and research methodology training as CCT requirements. The group agreed that higher degrees, publications in any author position (including collaborative authorship), recruiting patients to a study or multicentre audit and presentation at a national or international meeting could be used as evidence for the purpose of CCT. The group agreed on two essential 'core' requirements (GCP and methodology training) and two of a menu of four 'additional' requirements (publication with any authorship position, presentation, recruitment of patients to a multicentre study and completion of a higher degree), which should be completed in order to attain CCT. CONCLUSION: This approach has engaged stakeholders to produce a progressive set of academic requirements for CCT, which are applicable across surgical specialties. Flexibility in requirements whilst retaining a high standard of evidence is desirable.

Hyponatremia with Persistent Elevated Urinary Fractional Uric Acid Excretion: Evidence for Proximal Tubular Injury?

BACKGROUND/AIMS: Hyponatremia associated with high urinary fractional excretion of uric acid which persists after serum sodium is corrected is the cardinal feature of salt losing nephropathy (SLN). We hypothesize that low grade proximal tubular injury is present in SLN because the proximal tubule is the main site of uric acid and sodium transport. METHODS: Five subjects with SLN were compared to four subjects with recurrent hyponatremia and three healthy individuals. Urinary NGAL (neutrophil gelatinase associated lipocalin, a marker of tubular injury) and fasting urinary fructose levels (a marker of proximal tubular injury) were measured. RESULTS: Subjects with SLN (n=5) showed elevated fractional uric acid excretion (22 ± 6 vs 4 ± 2 percent, p<0.0001), elevated urinary NGAL levels (62 ± 37 vs 9 ± 7 ng/mg creatinine, p=0.001) and fasting urinary fructose levels compared with the 7 controls (383 ± 465 vs 60 ± 34µmole/µg creatinine, p <0.001). A strong correlation between urinary NGAL levels and urinary fructose levels was observed (r =0.87, p<0.001). CONCLUSION: High urinary fractional excretion of uric acid in SLN is associated with elevated NGAL and fasting urinary fructose levels suggesting that SLN may involve tubular injury.

Identification of high-risk amino-acid substitutions in hematopoietic cell transplantation: a challenging task.

Allogeneic hematopoietic cell transplantation (HCT) offers the potential to cure hematologic malignancies. In the absence of an HLA-matched donor, HLA mismatched unrelated donors may be used, although risks of GvHD and treatment-related mortality (TRM) are higher. Identification and avoidance of amino-acid substitution and position types (AASPT) conferring higher risks of TRM and GvHD would potentially improve the success of transplantation from single HLA mismatched unrelated donors. Using random forest and logistic regression analyses, we identified 19 AASPT associated with greater risks for at least one adverse transplant outcome: grade III-IV acute GvHD, TRM, lower disease-free survival or worse overall survival relative to HLA-matched unrelated donors and to other AASPT. When tested in an independent validation cohort of 3530 patients, none of the AASPT from the training set were validated as high risk, however. Review of the literature shows that failure to validate original observations is the rule and not the exception in immunobiology and emphasizes the importance of independent validation before clinical application. Our current data do not support avoiding any specific class I AASPT for unrelated donors. Additional studies should be performed to fully understand the role of AASPT in HCT outcomes.

Quantitative Assessment of Neovascularization after Indirect Bypass Surgery: Color-Coded Digital Subtraction Angiography in Pediatric Moyamoya Disease.

BACKGROUND AND PURPOSE: For the postoperative follow-up in pediatric patients with Moyamoya disease, it is essential to evaluate the degree of neovascularization status. Our aim was to quantitatively assess the neovascularization status after bypass surgery in pediatric Moyamoya disease by using color-coded digital subtraction angiography. MATERIALS AND METHODS: Time-attenuation intensity curves were generated at ROIs corresponding to surgical flap sites from color-coded DSA images of the common carotid artery, internal carotid artery, and external carotid artery angiograms obtained pre- and postoperatively in 32 children with Moyamoya disease. Time-to-peak and area under the curve values were obtained. Postoperative changes in adjusted time-to-peak (ΔTTP) and ratios of adjusted area under the curve changes (ΔAUC ratio) of common carotid artery, ICA, and external carotid artery angiograms were compared across clinical and angiographic outcome groups. To analyze diagnostic performance, we categorized clinical outcomes into favorable and unfavorable groups. RESULTS: The ΔTTP at the common carotid artery increased among clinical and angiographic outcomes, in that order, with significant differences (P = .003 and .005, respectively). The ΔAUC ratio at the common carotid artery and external carotid artery also increased, in that order, among clinical and angiographic outcomes with a significant difference (all, P = .000). The ΔAUC ratio of ICA showed no significant difference among clinical and angiographic outcomes (P = .418 and .424, respectively). The ΔTTP for the common carotid artery of >1.27 seconds and the ΔAUC ratio of >33.5% for the common carotid artery and 504% for the external carotid artery are revealed as optimal cutoff values between favorable and unfavorable groups. CONCLUSIONS: Postoperative changes in quantitative values obtained with color-coded DSA software showed a significant correlation with outcome scores and can be used as objective parameters for predicting the outcome in pediatric Moyamoya disease, with an additional cutoff value calculated through the receiver operating characteristic curve.

Single monosomy as a relatively better survival factor in acute myeloid leukemia patients with monosomal karyotype.

Monosomal karyotype (MK) defined by either ⩾2 autosomal monosomies or single monosomy with at least one additional structural chromosomal abnormality is associated with a dismal prognosis in patients with acute myeloid leukemia (AML). It was detected in 174 of 3041 AML patients in South Korean Registry. A total of 119 patients who had received induction therapy were finally analyzed to evaluate the predictive factors for a positive prognosis. On multivariate analysis, single monosomy, the absence of abn(17p), ⩾10% of cells with normal metaphase and the achievement of a complete remission (CR) after induction therapy were significant factors for more favorable outcomes. Especially, single monosomy remained as a significantly independent prognostic factor for superior survival in both patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR and who did not. Allo-HSCT in CR improved overall survival significantly only in patients with a single monosomy. Our results suggest that MK-AML may be biologically different according to the karyotypic subtype and that allo-HSCT in CR should be strongly recommended to patients with a single monosomy. For other patients, more prudent treatment strategies should be examined. Furthermore, the biological mechanism by which a single monosomy influences survival should be investigated.