Impact of hepatic artery variation on surgical and oncological outcomes in robotic pancreaticoduodenectomy.

BACKGROUND: In patients with hepatic artery variation (HAV), feasibility and justification of robotic pancreatoduodenectomy (RPD) for periampullary lesions have been not been well established. METHODS: A total of 600 patients with periampullary lesions receiving RPD or open pancreaticoduodenectomy (OPD) were identified from our prospectively collected computer database. Surgical outcomes, oncological radicality, and survival outcomes after RPD in HAV ( +) and (-) patients were compared. RESULTS: The incidence of HAV was 16%, including 12.7% in patients with RPD and 23.0% in those with OPD. In the HAV ( +) group, vascular injury rate had no statistical difference between the RPD (3.7%) and OPD (9.1%) patients, P = 0.404. Among the RPD patients, those with HAV ( +) had longer operation time (8.5 ± 2.5 vs. 7.7 ± 2.0 h, P = 0.013) and higher vascular injury (3.8% vs. 0.6%, P = 0.024) when compared with the HAV (-) patients. There was no significant difference between the HAV ( +) and (-) patients with RPD regarding blood loss, open conversion, vascular resection, and surgical mortality and morbidity. There was no survival difference between the HAV ( +) and (-) patients with pancreatic head adenocarcinoma after RPD. There was no survival difference between RPD and OPD in the HAV ( +) group. CONCLUSIONS: When compared with OPD, RPD is feasible and justifiable without increasing vascular injury rate for patients with HAV ( +). Hepatic artery variation has no negative impact on surgical, oncological, and survival outcomes following an RPD, if it is accurately identified pre-operatively and appropriately managed intraoperatively.

[Morphological predictors of water-electrolyte disorders in patients with preventive ileostomy after rectal resection for cancer]. / Issledovanie morfologicheskikh prediktorov vodno-elektrolitnykh narushenii u patsientov so sformirovannoi preventivnoi ileostomoi pri rezektsii pryamoi kishki po povodu raka.

OBJECTIVE: To analyze morphological changes in wall of functioning and non-functioning small intestine in patients with preventive ileostomy and to determine histological predictors of water-electrolyte disorders. MATERIAL AND METHODS: We prospectively analyzed 57 patients >18 years old who underwent rectal resection with preventive ileostomy between January 2022 and November 2023. Anthropometric data included gender, age, body mass index, ECOG and ASA classes. Complications associated with large losses through ileostomy were water-electrolyte disorders, dehydration and acute renal failure with repeated hospitalization. Morphological analysis implied intraoperative full-layer biopsy of small intestine on anterior abdominal wall (ileostomy). Intraoperative biopsy of efferent and afferent loops was also carried out. Tissue samples were examined by light microscopy. We analyzed mean height of mucous membrane villi and depth of crypts, as well as their ratio. Fibrosis and swelling of submucosa were evaluated too. The results were analyzed in the SPSS Statistics 20 software. RESULTS: Mean height of intestinal villi <465 microns (p=0.028), ratio of their height to crypt depth <4.38 (p=0.034) and submucosal fibrosis (p=0.031) significantly affected malabsorption and readmission of patients. The risk of readmission was 11.5 and 5.5 times higher in univariate analysis. Multivariate analysis revealed in-hospital dehydration with resumption of infusion therapy as a predictor of readmission (p=0.046). CONCLUSION: Ileostomy is a certain stress for the patient's body. Not every patient is able for adaptation. One of the adaptation mechanisms is hypertrophy of mucous membrane villi involved in digestion. This mechanism is less pronounced in patients with repeated hospitalizations. Preoperative morphological examination of ileum mucosa may be an additional objective predictor of possible complications of preventive ileostomy.

Propensity score-matched comparison of the oncological feasibility and survival outcomes for pancreatic adenocarcinoma with robotic and open pancreatoduodenectomy.

BACKGROUND: This study is to clarify the feasibility of and justification for robotic pancreaticoduodenectomy (RPD) in patients with pancreatic adenocarcinoma. METHODS: A 1-to-1 propensity score-matched comparison of RPD and open pancreaticoduodenectomy (OPD) was performed based on six covariates commonly used to predict the survival outcome for pancreatic adenocarcinoma. RESULTS: A total of 130 patients were enrolled, with 65 in each study group after propensity score matching. The median operating time was longer for RPD (8.3 h vs. 7.0 h, P = 0.002). However, RPD was associated with less blood loss, lower overall surgical complication rate, and lower incidence of delayed gastric emptying. The resection radicality was oncologically similar between these two groups, but the median lymph node yield was higher for RPD (18 vs. 16, P = 0.038). Before propensity score matching, the 5-year survival was better in RPD (27.0% vs. 17.6%, P = 0.006). After matching, there was still a trend towards improved overall survival in the RPD group; however, the difference in 5-year survival between RPD and OPD was not significant (24.5% vs. 19.7%, P = 0.088). CONCLUSION: RPD is not only technically feasible with no increase in surgical risk but also oncologically justifiable without compromising survival outcome. However, unlike randomized control trials, the limitations in this propensity score-matched analysis only accounted for 6 observed covariates commonly used to predict the survival outcome in patients with pancreatic adenocarcinoma, and confounders not included in this study could also affect our results.

Surgical, survival, and oncological outcomes after vascular resection in robotic and open pancreaticoduodenectomy.

BACKGROUND: To evaluate the surgical, oncological, and survival outcomes after pancreaticoduodenectomy (PD) with superior mesenteric vein (SMV)/portal vein (PV) resection by either robotic PD (RPD) or open PD (OPD). METHODS: Data of patients with periampullary lesions undergoing PD were retrieved from a prospectively collected computer database. Surgical risks as well as oncological and survival outcomes were compared between patients with (vein resection group) and without SMV/PV resection (without vein resection group). RESULTS: A total of 391 patients undergoing pancreaticoduodenectomy were enrolled, including 43 (11.0%) and 384 (89.0%) patients with and without vein resection, respectively. Eleven (25.6%) of PDs with vein resection were performed using the robotic approach. Operation time in the vein resection group was significantly longer (median of 8 vs. 7 h). Blood loss, curative resection (R0) rate, and harvested lymph node number were similar between these two groups. Surgical outcomes including postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), chyle leakage, wound infection, and hospital stay were not significantly different between the two groups. There was no survival difference between these groups, with 1- and 3-year survival rates of 92.6% and 26.5%, respectively, for vein resection group, vs. 70.3% and 37.2%, respectively, for the without vein resection group. CONCLUSIONS: PD with vein resection is technically feasible by OPD and RPD in selected patients. Additional SMV/PV would not increase the surgical risks of PD and could achieve similar survival outcomes for pancreatic head adenocarcinoma when compared to PD without vein resection.

Continuous Transversus Abdominis Plane Block for Primary Open Inguinal Hernia Repair: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Patients undergoing open inguinal hernia repair may experience moderate to severe postoperative pain. We assessed opioid consumption in subjects who received a continuous transversus abdominis plane block in addition to standard multimodal analgesia. DESIGN: Randomized, double-blind, placebo-controlled. SETTING: Tertiary academic medical center. SUBJECTS: Adult patients undergoing open inguinal hernia repair at Virginia Mason Medical Center. A total of 90 patients were enrolled. METHODS: Subjects presenting for surgery were randomized to receive either a continuous transversus abdominis plane block or a subcutaneous sham block. The primary outcome was opioid consumption within the first 48 hours after surgery. Secondary outcomes included pain scores, activities assessment scores, and opioid-related adverse events. Multimodal analgesia utilized in both groups included acetaminophen, nonsteroidal anti-inflammatory drugs, and surgical local anesthetic infiltration. RESULTS: Eighty-two subjects, 42 from the block group and 40 from the sham group, completed the study, per protocol. The intention-to-treat analysis demonstrated no difference in 48-hour postoperative oxycodone equivalent consumption between the block and sham groups (27.8 mg ± 26.8 vs 32 mg ± 39.2, difference -4.4 mg, P = 0.55). There was a statistically significant reduction in pain scores at 24 hours in the block group. There were no other differences in secondary outcomes. CONCLUSIONS: Continuous transversus abdominis plane blocks provide modest improvements in pain after open inguinal hernia repair but fail to significantly reduce opioid consumption or improve functional activity levels in the setting of multimodal analgesia use.

Comparison of a 1064-nm neodymium-doped yttrium aluminum garnet picosecond laser using a diffractive optical element vs. a nonablative 1550-nm erbium-glass laser for the treatment of facial acne scarring in Asian patients: a 17-week prospective, randomized, split-face, controlled trial.

BACKGROUND: Novel picosecond lasers using a diffractive optical element (P-DOE) have been available for skin resurfacing with distinct mechanisms. However, there are limited data directly comparing P-DOE and conventional fractional lasers for the treatment of atrophic acne scarring. OBJECTIVES: We sought to compare the efficacy and safety of a 1064-nm neodymium-doped yttrium aluminium garnet P-DOE and a non-ablative fractional laser (NAFL) in the treatment of acne scarring. METHODS: A prospective, randomized, split-face, controlled trial was performed. One randomly assigned half-side of each patient's face (n = 25) was treated with four consecutive sessions of P-DOE at 3-week intervals and the other side with NAFL, with subsequent follow-up for 8 weeks after the final sessions. The efficacy and safety of the two lasers were determined by the Echelle d'Evaluation Clinique des Cicatrices d'acné (Scale of Clinical Evaluation of Acne Scars; ECCA) grading scale, Investigator's Global Assessment (IGA) score and patients' reports at the final visit. Histologic analysis was also performed. RESULTS: The P-DOE-treated side achieved a significantly better improvement in acne appearance (ECCA per cent reduction: 55% vs. 42%) with less severe pain (4.3 vs. 5.6) (P < 0.05). The IGA score and subjective satisfaction were consistent with ECCA score results. Occurrences of treatment-related side-effects were also lower in the group treated with P-DOE (P < 0.05). Histologic analysis revealed elongation and increased density of neocollagen fibres, elastic fibres and mucin throughout the dermis from both sides. CONCLUSIONS: Compared with NAFL, P-DOE afforded better clinical outcomes and fewer side-effects in the treatment of acne scarring in Asian patients.

[Ways of limbs salvage in postoperative period of treatment of complications of diabetic foot syndrome]. / Puti sokhraneniia konechnosti v posleoperatsionnom periode lecheniia oslozhnenii sindroma diabeticheskoi stopy.

The article deals with the use of a genetically engineered drug for stimulation of angiogenesis as a component of combined treatment of complications of ischaemic form of diabetic foot syndrome, showing comparative results of using therapeutic angiogenesis in patients in whom it was impossible to perform operative revascularization of the affected extremity, also providing a detailed description of the methodology of combined treatment of pyonecrotic complications of diabetic foot syndrome. The study included a total of 62 patients with pyonecrotic complications of Wagner grade III-IV diabetic foot syndrome. The patients were divided into two groups. Group One patients after minor amputation on the foot were assigned to receive conventional basic therapy and topical treatment of the foot wound with antiseptics and modern dressings. Group Two patients, besides basic therapy, additionally received combined treatment which was carried out in two stages and included urokinase, sulodexide, and a venotonic agent. Local treatment of the foot wound was performed with the help of two-stage vacuum therapy. Both groups were further subdivided into subgroups A and B. The patients in subgroups B of both groups in order to prevent progression of limb ischaemia were additionally given Neovasculgen, a genetically engineered drug for stimulation of angiogenesis. The patients of subgroups A of both groups did not receive this drug. The immediate results were assessed on the 1st, 7th and 14th days of treatment by the dynamics of changes in subjective symptoms, cytograms of the wound surface, level of partial pressure of oxygen in capillary blood of foot tissues, and the necessity to perform repeated necrectomy. The remote results were evaluated by the dynamics of changes in the pain-free walking distance, maximum distance walked, ankle-brachial index, linear velocity of blood flow through tibial arteries and partial pressure of oxygen in capillary blood of the affected limb at the 6th, 12th and 36th months after the performed treatment, as well as by the limb salvage and patients' survival during 3 years.

Hyperprogressive disease during PD-1/PD-L1 blockade in patients with non-small-cell lung cancer.

BACKGROUND: Immune checkpoint blockade with Programmed cell death 1 (PD-1)/PD-L1 inhibitors has been effective in various malignancies and is considered as a standard treatment modality for patients with non-small-cell lung cancer (NSCLC). However, emerging evidence show that PD-1/PD-L1 blockade can lead to hyperprogressive disease (HPD), a flair-up of tumor growth linked to dismal prognosis. This study aimed to evaluate the incidence of HPD and identify the determinants associated with HPD in patients with NSCLC treated with PD-1/PD-L1 blockade. PATIENTS AND METHODS: We enrolled patients with recurrent and/or metastatic NSCLC treated with PD-1/PD-L1 inhibitors between April 2014 and November 2018. Clinicopathologic variables, dynamics of tumor growth, and treatment outcomes were analyzed in patients with NSCLC who received PD-1/PD-L1 blockade. HPD was defined according to tumor growth kinetics (TGK), tumor growth rate (TGR), and time to treatment failure (TTF). Immunophenotyping of peripheral blood CD8+ T lymphocytes was conducted to explore the potential predictive biomarkers of HPD. RESULTS: A total of 263 patients were analyzed. HPD was observed in 55 (20.9%), 54 (20.5%), and 98 (37.3%) patients according to the TGK, TGR, and TTF. HPD meeting both TGK and TGR criteria was associated with worse progression-free survival [hazard ratio (HR) 4.619; 95% confidence interval (CI) 2.868-7.440] and overall survival (HR, 5.079; 95% CI, 3.136-8.226) than progressive disease without HPD. There were no clinicopathologic variables specific for HPD. In the exploratory biomarker analysis with peripheral blood CD8+ T lymphocytes, a lower frequency of effector/memory subsets (CCR7-CD45RA- T cells among the total CD8+ T cells) and a higher frequency of severely exhausted populations (TIGIT+ T cells among PD-1+CD8+ T cells) were associated with HPD and inferior survival rate. CONCLUSION: HPD is common in NSCLC patients treated with PD-1/PD-L1 inhibitors. Biomarkers derived from rationally designed analysis may successfully predict HPD and worse outcomes, meriting further investigation of HPD.

Astrocytic water channel aquaporin-4 modulates brain plasticity in both mice and humans: a potential gliogenetic mechanism underlying language-associated learning.

The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n=60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n=650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n=45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.

Diagnostic utility of skin autofluorescence when patch test results are doubtful.

BACKGROUND: The standard diagnostic test for allergic contact dermatitis is the patch test, which can also be used to identify irritant contact dermatitis. Doubtful reactions (?+) can be often clinically relevant to individuals and can require additional tests. OBJECTIVES: The purpose of this study was to examine whether autofluorescence (AF) measurements in patients with doubtful reactions are helpful in diagnosing contact dermatitis. METHODS: Patients with a history of contact dermatitis were patch tested on the upper back for 48-hours of occlusion using aqueous solutions of 5% sodium lauryl sulfate. Reaction intensity was scored, and AF was measured on reactive lesions and non-lesions. Three dermatologists classified the results as positive or negative using the fluorescence photographs of patients with a doubtful reaction. RESULTS: Among doubtful reactions, the R/G% values were significantly higher in the AF- based positive group than in the negative group (P = .0086). On the other hand, the heterogeneity values of R, G, and B (HR, HG, HB) were significantly lower in the AF-based positive group (P = .0026, .0046, .0004 respectively). CONCLUSIONS: Measuring AF along with the clinical readings can help confirm doubtful patch test reactions.

Neopepsee: accurate genome-level prediction of neoantigens by harnessing sequence and amino acid immunogenicity information.

Background: Tumor-specific mutations form novel immunogenic peptides called neoantigens. Neoantigens can be used as a biomarker predicting patient response to cancer immunotherapy. Although a predicted binding affinity (IC50) between peptide and major histocompatibility complex class I is currently used for neoantigen prediction, large number of false-positives exist. Materials and methods: We developed Neopepsee, a machine-learning-based neoantigen prediction program for next-generation sequencing data. With raw RNA-seq data and a list of somatic mutations, Neopepsee automatically extracts mutated peptide sequences and gene expression levels. We tested 14 immunogenicity features to construct a machine-learning classifier and compared with the conventional methods based on IC50 regarding sensitivity and specificity. We tested Neopepsee on independent datasets from melanoma, leukemia, and stomach cancer. Results: Nine of the 14 immunogenicity features that are informative and inter-independent were used to construct the machine-learning classifiers. Neopepsee provides a rich annotation of candidate peptides with 87 immunogenicity-related values, including IC50, expression levels of neopeptides and immune regulatory genes (e.g. PD1, PD-L1), matched epitope sequences, and a three-level (high, medium, and low) call for neoantigen probability. Compared with the conventional methods, the performance was improved in sensitivity and especially two- to threefold in the specificity. Tests with validated datasets and independently proven neoantigens confirmed the improved performance in melanoma and chronic lymphocytic leukemia. Additionally, we found sequence similarity in proteins to known pathogenic epitopes to be a novel feature in classification. Application of Neopepsee to 224 public stomach adenocarcinoma datasets predicted ∼7 neoantigens per patient, the burden of which was correlated with patient prognosis. Conclusions: Neopepsee can detect neoantigen candidates with less false positives and be used to determine the prognosis of the patient. We expect that retrieval of neoantigen sequences with Neopepsee will help advance research on next-generation cancer immunotherapies, predictive biomarkers, and personalized cancer vaccines.

Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice.

BACKGROUND/OBJECTIVES: We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of peroxisome proliferator-activated receptor gamma, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice. METHODS: Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1 mg kg-1 daily) was injected intraperitoneally for 20 weeks. RESULTS: Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity and preserved pancreatic beta cells. Both whole body and subcutaneous AT weight increased in the lobeglitazone-treated group. However, lobeglitazone induced an increase in the number of small adipocyte in both epididymal and subcutaneous AT, with a significant weight decrease in the epididymal AT of db/db mice. Using flow cytometry, the CD11c-positive M1 macrophages and CD206-positive M2 macrophages in the epididymal AT were observed to exhibit a decreased M1-to-M2 ratio in lobeglitazone-treated db/db mice. Furthermore, in the lobeglitazone-treated group, interscapular brown AT was clearly visualized by 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) and its mass was significantly greater than that of the vehicle-treated group. In the lobeglitazone-treated group, beige-specific gene expression and the number of mitochondria in white AT were upregulated. Lobeglitazone, with upregulating interferon regulatory factor-4 (a key transcriptional regulator of thermogenesis), promoted the development of brown adipocytes and the differentiation of white adipocytes into beige adipocytes. CONCLUSIONS: Long-term lobeglitazone treatment has a beneficial role in remodeling and ameliorating inflammation in white AT and in glycemic control, in relation to insulin sensitivity in obese db/db mice. Moreover, lobeglitazone induced the differentiation of brown and beige adipocytes. Collectively, our data suggest that lobeglitazone treatment provides promising effects on white and brown AT as well as great improvement in glycemic control, as a potent insulin sensitizer.

Phylogeography of the Asian lesser white-toothed shrew, Crocidura shantungensis, in East Asia: role of the Korean Peninsula as refugium for small mammals.

Many peninsulas in the temperate zone played an important role as refugia of various flora and fauna, and the southern Korean Peninsula also served as a refugium for many small mammals in East Asia during the Pleistocene. The Asian lesser white-toothed shrew, Crocidura shantungensis, is a widely distributed species in East Asia, and is an appropriate model organism for exploring the role of the Korean Peninsula as a refugium of small mammals. Here, we investigated phylogenetic relationships and genetic diversity based on the entire sequence of the mitochondrial cytochrome b gene (1140 bp). A Bayesian tree for 98 haplotypes detected in 228 C. shantungensis specimens from East Asia revealed the presence of three major groups with at least 5 subgroups. Most haplotypes were distributed according to their geographic proximity. Pairwise FST's and analysis of molecular variance (AMOVA) revealed a high degree of genetic differentiation and variance among regions as well as among populations within region, implying little gene flow among local populations. Genetic evidence from South Korean islands, Jeju-do Island of South Korea, and Taiwan leads us to reject the hypothesis of recent population expansion. We observed unique island-type genetic characteristics consistent with geographic isolation and resultant genetic drift. Phylogeographic inference, together with estimates of genetic differentiation and diversity, suggest that the southern most part the Korean Peninsula, including offshore islands, played an important role as a refugium for C. shantungensis during the Pleistocene. However, the presence of several refugia on the mainland of northeast Asia is also proposed.

MicroRNA-Dependent Regulation of IGF1R Gene Expression in Hormone-Sensitive and Hormone-Resistant Prostate Cancer Cells.

Using multiple parallel sequencing on Illumina platform, we identified eight microRNAs that showed significant opposite changes of gene expression in cells of the hormone-sensitive LNCaP prostate cancer cell line and in cells of the hormone-resistant DU-145 cell line, in comparison to the microRNA expression in the normal prostate tissue cells. We found that the insulin-like growth factor 1 receptor (IGF1R) gene is a target of five microRNAs whose expression is increased in LNCaP cells and reduced in DU-145 cells.

Metastatic polyp of the gallbladder from renal cell carcinoma.

BACKGROUND: Gallbladder metastasis from renal cell carcinoma (RCC) is extremely rare. The purpose of this study is to clarify the characteristics of metastatic RCC to gallbladder. METHODS: The pooled data for analysis were collected from the case of metastatic RCC to gallbladder encountered by our institution along with sporadic cases reported in literature from 1991 to 2015. RESULTS: A total of 50 cases of metastatic RCC to gallbladder were recruited for study. Fifty-seven percentage of the primary RCC was from the right kidney and 43% from the left. The median interval between diagnoses of primary and metastatic RCC to gallbladder was 36 months, with the longest duration up to 324 months. Most (70%) were asymptomatic. The size of metastatic RCC to gallbladder ranged from 0.8 cm to 9 cm, with median of 2.6 cm. Majority (91%) of the metastatic RCCs presented as a polypoid mass with narrow stalk, and 82% were hypervascular lesion. The overall 1 year, 3 year and 5 year survival rate was 91.5%, 76.2% and 59.3% respectively, with a median of 26.5 months. Number of the metastatic site, timing of gallbladder metastasis, symptom, tumor size and operation type of cholecystectomy seemed to have no impact on survival. CONCLUSIONS: Metastatic RCC to the gallbladder should be taken into account for a gallbladder polypoid mass with narrow hypervascular stalk during the diagnosis and/or follow-up of primary RCC. Gallbladder metastasis from RCC is not necessarily to be an advanced stage with poor outcome, and cholecystectomy is recommended whenever possible.

Polypoid lesions of the gallbladder: analysis of 1204 patients with long-term follow-up.

BACKGROUND: Polypoid lesions of the gallbladder (PLG) are common, and most are benign. Few lesions are found to be malignant, but are not preoperatively distinguished as such using common imaging modalities. Therefore, we compared characteristics of benign and malignant PLGs in depth. METHODS: We enrolled 1204 consecutive patients diagnosed with PLG at Taipei Veterans General Hospital between January 2004 and December 2013. Patients underwent either surgery or regular follow-up with various imaging modalities for at least 24 months. The mean follow-up duration was 72 ± 32 months. RESULTS: Of 1204 patients, 194 underwent surgical treatment and 1010, regular follow-up. In addition, 73 % patients were asymptomatic. The mean PLG size was 6.9 ± 7.7 (range 0.8-129) mm; the PLGs of 337 patients (28 %) grew during their follow-up periods. The majority of PLGs (90.4 %) were single lesions, and 10.5 % of patients had associated gallstones. The PLGs of 20.1 % of surgical patients were malignant. Malignant PLGs were found in 32.4 % of patients ≥50 years old and in 4.7 % of those <50 years old (p < 0.001). Right quadrant abdominal pain, epigastric pain, and body weight loss were the three most common symptoms associated with malignancy. Malignant PLGs were significantly larger than benign lesions (means: 27.5 ± 18.4 mm vs. 12.3 ± 12.3 mm, respectively, p < 0.001). Notably, the size of 5 % of malignant PLGs was 3-5 mm, and that of 8 % was 5-10 mm. The negative predictive value for gallbladder malignancy was 92.8 % based on a size ≥10 mm and 100 % based on a size ≥3 mm. CONCLUSIONS: Our study reassesses the PLG size that warrants more aggressive intervention. Cholecystectomy remains mandatory for PLGs > 10 mm, but should also be considered a definitive diagnostic and treatment modality for PLGs with diameters of 3-10 mm.

Comparative analysis of the effects of CO2 fractional laser and sonophoresis on human skin penetration with 5-aminolevulinic acid.

Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy (PDT). The effective method to increase drug penetration within short incubation time overcoming skin barrier have been investigated. This study was performed to analyze and compare the effectiveness of ablative fractional laser (FXL) pretreatment and/or sonophoresis for enhancing the penetration of 5-aminolevulinic acid (ALA) into human skin in vivo. Twenty-four identical 1 × 1 cm2 treatment areas were mapped on the backs of ten healthy male subjects. Each area received FXL pretreatment and/or sonophoresis with different energy settings and ALA incubation times. After treatments, porphyrin fluorescence reflecting the ALA penetration were measured. Application of ablative CO2 FXL pretreatment resulted to higher fluorescence intensities than the non-treatment group. Incubation times were positively correlated with the increments of ALA penetration. However, increasing pulse energy or combining with sonophoresis did not show additional positive effects on ALA penetration. Ablative CO2 FXL pretreatment effectively facilitated ALA penetration in human skin in vivo. Ablative CO2 FXL alone without sonophoresis setting pulse energy of 10 and 20 mJ with more than 60 min of ALA incubation time could be an ideal setting for ALA penetration.

Autologous adipose tissue-derived stem cells for the treatment of complex perianal fistulas not associated with Crohn's disease: a phase II clinical trial for safety and efficacy.

PURPOSE: Injection of adipose tissue-derived stem cells (ASCs) is a novel method for the treatment of complex perianal fistulas. We aimed to evaluate the safety and efficacy of ASCs in the treatment of complex anal fistulas not associated with Crohn's disease. METHODS: A phase II clinical trial was performed comparing two different doses of ASCs (group 1: 1 × 107 cells/mL and group 2: 2 × 107 cells/mL). Eligible patients were administered an amount of ASCs proportional to the length of the fistula by injection into the submucosal layer surrounding the internal opening and inside of the fistula tract. ASCs at twice the initial concentration were administered if complete closure was not achieved within 8 weeks. The efficacy endpoint was the complete closure of fistulas 8 weeks after injection. Patients demonstrating complete closure at week 8 were subjected to follow-up for 6 months. RESULTS: Fifteen patients were injected with ASCs; thirteen completed the study. Complete closure was observed in 69.2% (9/13) of patients at 8 weeks. Three of five patients in group 1, and six of eight in group 2 displayed complete closure; no significant differences were observed between the groups. Six of nine patients who showed complete closure participated in additional follow-up; five (83.3%) showed persistent response at 6 months. No grade 3 or 4 adverse events (AEs) were observed; observed AEs were not related to ASC treatment. CONCLUSION: ASCs might be a good option for the treatment of complex perianal fistulas are not healed by conventional operative procedures.