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1.
Int J Surg ; 110(4): 2034-2043, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38668657

BACKGROUND: The territory of D3-D4 lymphadenectomy for upper rectal and sigmoid colon cancer varies, and its oncological efficacy is unclear. This prospective study aimed to standardize the surgical technique of robotic D3-D4 lymphadenectomy and clarify its oncologic significance. METHODS: Patients with upper rectal or sigmoid colon cancer with clinically suspected more than N2 lymph node metastasis were prospectively recruited to undergo standardized robotic D3-D4 lymphadenectomy. Immediately postsurgery, the retrieved lymph nodes were mapped to five N3-N4 nodal stations: the inferior mesenteric artery, para-aorta, inferior vena cava, infra-renal vein, and common iliac vessels. Patients were stratified according to their nodal metastasis status to compare their clinicopathological data and overall survival. Univariate and multivariate analyses were performed to determine the relative prognostic significance of the five specific nodal stations. Surgical outcomes and functional recovery of the patients were assessed using the appropriate variables. RESULTS: A total of 104 patients who successfully completed the treatment protocol were assessed. The standardized D3-D4 lymph node dissection harvested sufficient lymph nodes (34.4±7.2) for a precise pathologic staging. Based on histopathological analysis, 28 patients were included in the N3-N4 nodal metastasis-negative group and 33, 34, and nine patients in the single-station, double-station, and triple-station nodal metastasis-positive groups, respectively. Survival analysis indicated no significant difference between the single-station nodal metastasis-positive and N3-N4 nodal metastasis-negative groups in the estimated 5-year survival rate [53.6% (95% CI: 0.3353-0.7000) vs. 71.18% (95% CI: 0.4863-0.8518), P=0.563], whereas patients with double-station or triple-station nodal metastatic disease had poor 5-year survival rates (24.76 and 22.22%), which were comparable to those of AJCC/UICC stage IV disease than those with single-station metastasis-positive disease. Univariate analysis showed that the metastatic status of the five nodal stations was comparable in predicting the overall survival; in contrast, multivariate analysis indicated that common iliac vessels and infra-renal vein were the only two statistically significant predictors (P<0.05) for overall survival. CONCLUSIONS: Using a robotic approach, D3-D4 lymph node dissection could be safely performed in a standardized manner to remove the relevant N3-N4 lymphatic basin en bloc, thereby providing significant survival benefits and precise pathological staging for patients. This study encourages further international prospective clinical trials to provide more solid evidence that would facilitate the optimization of surgery and revision of the current treatment guidelines for such a clinical conundrum.


Lymph Node Excision , Lymphatic Metastasis , Robotic Surgical Procedures , Sigmoid Neoplasms , Humans , Lymph Node Excision/standards , Lymph Node Excision/methods , Female , Male , Middle Aged , Robotic Surgical Procedures/standards , Robotic Surgical Procedures/methods , Aged , Prospective Studies , Sigmoid Neoplasms/surgery , Sigmoid Neoplasms/pathology , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Lymph Nodes/pathology , Lymph Nodes/surgery , Adult
2.
J Vis Exp ; (205)2024 Mar 15.
Article En | MEDLINE | ID: mdl-38557663

Extracellular matrix (ECM) plays a critical role in cell behavior and development. Organoids generated from human induced pluripotent stem cells (hiPSCs) are in the spotlight of many research areas. However, the lack of physiological cues in classical cell culture materials hinders efficient iPSC differentiation. Incorporating commercially available ECM into stem cell culture provides physical and chemical cues beneficial for cell maintenance. Animal-derived commercially available basement membrane products are composed of ECM proteins and growth factors that support cell maintenance. Since the ECM holds tissue-specific properties that can modulate cell fate, xeno-free matrices are used to stream up translation to clinical studies. While commercially available matrices are widely used in hiPSC and organoid work, the equivalency of these matrices has not been evaluated yet. Here, a comparative study of hiPSC maintenance and human intestinal organoids (hIO) generation in four different matrices: Matrigel (Matrix 1-AB), Geltrex (Matrix 2-AB), Cultrex (Matrix 3-AB), and VitroGel (Matrix 4-XF) was conducted. Although the colonies lacked a perfectly round shape, there was minimal spontaneous differentiation, with over 85% of the cells expressing the stem cell marker SSEA-4. Matrix 4-XF led to the formation of 3D round clumps. Also, increasing the concentration of supplement and growth factors in the media used to make the Matrix 4-XF hydrogel solution improved hiPSC expression of SSEA-4 by 1.3-fold. Differentiation of Matrix 2-AB -maintained hiPSC led to fewer spheroid releases during the mid-/hindgut stage compared to the other animal-derived basement membranes. Compared to others, the xeno-free organoid matrix (Matrix 4-O3) leads to larger and more mature hIO, suggesting that the physical properties of xeno-free hydrogels can be harnessed to optimize organoid generation. Altogether, the results suggest that variations in the composition of different matrices affect stages of IO differentiation. This study raises awareness about the differences in commercially available matrices and provides a guide for matrix optimization during iPSC and IO work.


Induced Pluripotent Stem Cells , Animals , Humans , Basement Membrane , Extracellular Matrix/chemistry , Organoids/metabolism , Cell Differentiation , Hydrogels/metabolism
3.
Int J Surg ; 110(3): 1577-1585, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38051917

INTRODUCTION: This study aimed to investigate whether the incidence, patterns, and surgical outcomes of small bowel obstruction (SBO) have changed in the era of minimally invasive surgery (MIS) for primary colorectal cancer (CRC). METHODS: Consecutive patients who underwent laparotomy for SBO were divided into MIS and traditional open surgery (TOS) groups based on the previous colorectal cancer operation technique used. The MIS group was selected from 1544 consecutive patients who underwent MIS as a treatment for primary CRCs between 2014 and 2022, while the TOS group was selected from 1604 consecutive patients who underwent TOS as a treatment for primary CRCs between 2004 and 2013. The demographics, clinicopathological features, and surgical outcomes were compared between the two groups. RESULTS: The SBO incidence in patients who underwent MIS for primary CRC was significantly lower than that in patients who underwent TOS (4.4%, n =68/1544 vs. 9.7%, n =156/1604, P <0.0001). Compared with the TOS group, the MIS group had significantly different ( P <0.0001) SBO patterns: adhesion (48.5 vs. 91.7%), internal herniation (23.5 vs. 2.6%), external herniation (11.8 vs. 1.9%), twisted bowel limbs (4.4 vs. 0.6%), ileal volvulus with pelvic floor adhesion (5.9 vs. 1.9%), and nonspecific external compression (5.9 vs. 1.3%). A subset analysis of patients with adhesive SBO (ASBO) showed that the MIS group tended to ( P <0.0001) have bands or simple adhesions (75.8%), whereas the TOS group predominantly had matted-type adhesions (59.4%). Furthermore, SBO in the MIS group had an acute (<3 months) or early (3-12 months) onset (64.7%), while that in the TOS group ( P <0.0001) had an intermediate or a late onset. When the surgical outcomes of SBO were evaluated, the TOS group had significantly more ( P <0.0001) blood loss and longer operation time; however, no significant difference was observed in the surgical morbidity/mortality (Clavien-Dindo classification ≧3, 11.8 vs. 14.1%, P =0.6367), hospitalization, and readmission rates between the two groups. Postoperative follow-up showed that the estimated 3-year (11.37 vs. 18.8%) and 6-year (25.54 vs. 67.4%) recurrence rates of SBO were significantly lower ( P =0.016) in the MIS group than in the TOS group. CONCLUSIONS: The wide adoption of MIS to treat primary CRC has led to a lower incidence, altered patterns, and reduced recurrence rates of SBO. Awareness of this new trend will help develop surgical techniques to prevent incomplete restoration of anatomical defects and bowel malalignments specifically associated with MIS for CRC, as well as facilitate timely and appropriate management of SBO complications whenever they occur.


Colorectal Neoplasms , Intestinal Obstruction , Humans , Retrospective Studies , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Intestinal Obstruction/epidemiology , Tissue Adhesions/surgery , Tissue Adhesions/complications , Minimally Invasive Surgical Procedures/adverse effects , Treatment Outcome , Colorectal Neoplasms/surgery , Colorectal Neoplasms/complications , Postoperative Complications/epidemiology , Postoperative Complications/etiology
4.
Asian J Surg ; 47(2): 923-932, 2024 Feb.
Article En | MEDLINE | ID: mdl-38042659

BACKGROUND: The effect of positron emission tomography (PET) on the surgical treatment of locoregionally recurrent colorectal cancer (LRRCRC) remains unclear and warrants further investigation. MATERIAL AND METHODS: A total of 193 patients with LRRCRC were identified from a prospectively maintained institutional database, of whom 134 LRRCRCs were deemed resectable and underwent resection with curative intent, whereas the remaining 59 LRRCRCs were unresectable. Patients with resectable LRRCRC were further classified according to whether recurrence was detected solely by PET (n = 35, PET-only group) or by a combination of computed tomography (CT)/magnetic resonance imaging (MRI) and PET (n = 99, CT/MRI/PET group). Clinicopathologic features, operative morbidity/mortality, and overall survival were compared between the patient groups based on long-term follow-up for at least 5 years. RESULTS: Patients in the PET-only group tended to have less extensive organ resection (p = 0.0074), less blood loss (p < 0.0001), and shorter operation time and hospitalization (p < 0.0001), but surgical complication and readmission rates were not significantly different (p > 0.05) compared with the CT/MRI/PET group. Although the PET-only group had significantly higher R0 resection rate (80 % vs. 54.55 %, p = 0.0079), they also had a higher risk (17.14 % vs. 2.02 %, p = 0.0011) of sham operation. The estimated 5-year and 10-year survival rates significantly decreased in order (p < 0.0001) from PET-only (85.71 % and 57.98 %) and CT/MRI/PET (41.41 % and 15.93 %) to unresectable group of patients (16.95 % and 1.88 %). Subset analysis of the CT/MRI/PET group indicated that PET improved surgical decision-making because 24 (24.2 %) LRRCRCs that manifested on CT/MRI as equivocal lesions were later confirmed by PET as resectable recurrences, while 18 (19.4 %) LRRCRCs that manifested on CT/MRI as resectable lesions were later diagnosed by PET as more disseminated unresectable recurrences and precluded futile surgery. CONCLUSION: PET alone can identify a subset (20.9 %) of LRRCRCs with less tumor burden for timely surgery; PET in combination with CT/MRI can better define the resectability of LRRCRCs. The positive impacts of PET can translate into better surgical outcomes, with enhanced safety and patient survival.


Colorectal Neoplasms , Neoplasm Recurrence, Local , Humans , Positron-Emission Tomography , Tomography, X-Ray Computed , Magnetic Resonance Imaging , Colorectal Neoplasms/pathology , Positron Emission Tomography Computed Tomography
5.
World J Surg ; 47(12): 3149-3158, 2023 Dec.
Article En | MEDLINE | ID: mdl-37851067

BACKGROUND: Acute appendicitis is one of the most common abdominal emergencies, with management approaches that vary depending on the available resources and setting. However, there is a lack of studies on the differences of surgical outcomes and quality of care between tertiary care hospitals and regional hospitals. METHODS: This multicenter retrospective study included 2158 consecutive adult patients between January 2014 and June 2018 at three hospitals. The patient cohort was divided into regional hospital group (N = 1223) and tertiary care hospital group (N = 935). Baseline characteristics and perioperative outcomes were compared, and factors associated with surgical delay and postoperative complication were investigated. RESULTS: Patients in tertiary care hospital group had longer surgical waiting time (17.3 vs. 12.0 h, p < 0.001), higher risks of surgical delay exceeding 24 h (OR = 2.94, 95% CI 2.17-4.01, p < 0.001), longer operation time (64 vs. 50 min, p < 0.001), more appendix perforation (22.4 vs. 13.3%, p < 0.001), and higher hospital cost compared with regional hospital group. In multivariate analysis, factors associated with surgical delay were tertiary care hospital (OR = 2.94, 95% CI 2.18-4.01, p < 0.001) and delay diagnosis (OR = 18.7, 95% CI 11.7-30.1, p < 0.001), while those associated with postoperative complications were older age (OR = 1.02, 95% CI 1.00-1.04, p = 0.013), male sex (OR = 2.38, 95% CI 1.11-5.52, p = 0.031), surgical delay (OR = 2.99, 95% CI 1.30-6.47, p = 0.007), and appendix perforation (OR = 5.61, 95% CI 2.72-11.85, p < 0.001). CONCLUSIONS: Patients at tertiary care hospitals had longer waiting time, more surgical delays, and appendix perforations, and these were risk factors of postoperative complications. Establishing an effective referral system to redirect appendicitis patients with less complex medical histories from tertiary care hospitals to regional hospitals may enhance the quality of patient care and outcomes, while also reducing medical costs.


Appendicitis , Humans , Adult , Male , Appendicitis/diagnosis , Appendicitis/surgery , Appendicitis/etiology , Retrospective Studies , Tertiary Care Centers , Appendectomy/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Treatment Outcome
6.
Altern Lab Anim ; 51(4): 263-288, 2023 Jul.
Article En | MEDLINE | ID: mdl-37282515

Animal experimentation has been integral to drug discovery and development and safety assessment for many years, since it provides insights into the mechanisms of drug efficacy and toxicity (e.g. pharmacology, pharmacokinetics and pharmacodynamics). However, due to species differences in physiology, metabolism and sensitivity to drugs, the animal models can often fail to replicate the effects of drugs and chemicals in human patients, workers and consumers. Researchers across the globe are increasingly applying the Three Rs principles by employing innovative methods in research and testing. The Three Rs concept focuses on: the replacement of animal models (e.g. with in vitro and in silico models or human studies), on the reduction of the number of animals required to achieve research objectives, and on the refinement of existing experimental practices (e.g. eliminating distress and enhancing animal wellbeing). For the last two years, Oncoseek Bio-Acasta Health, a 3-D cell culture-based cutting-edge translational biotechnology company, has organised an annual International Conference on 3Rs Research and Progress. This series of global conferences aims to bring together researchers with diverse expertise and interests, and provides a platform where they can share and discuss their research to promote practices according to the Three Rs principles. In November 2022, the 3rd international conference, Advances in Animal Models and Cutting-Edge Research in Alternatives, took place at the GITAM University in Vishakhapatnam (AP, India) in a hybrid format (i.e. online and in-person). These conference proceedings provide details of the presentations, which were categorised under five different topic sessions. It also describes a special interactive session on in silico strategies for preclinical research in oncology, which was held at the end of the first day.


Animal Experimentation , Animals , Humans , Models, Animal , Drug Discovery , India , Animal Testing Alternatives
7.
Mol Oncol ; 17(1): 119-133, 2023 01.
Article En | MEDLINE | ID: mdl-36409270

GalNAc-type O-glycosylation and its initiating GalNAc transferases (GALNTs) play crucial roles in a wide range of cellular behaviors. Among 20 GALNT members, GALNT2 is consistently associated with poor survival of patients with colorectal cancer in public databases. However, its clinicopathological significance in colorectal cancer remains unclear. In this study, immunohistochemistry showed that GALNT2 was overexpressed in colorectal tumors compared with the adjacent nontumor tissues. GALNT2 overexpression was associated with poor survival of colorectal cancer patients. Forced expression of GALNT2 promoted migration and invasion as well as peritoneal metastasis of colorectal cancer cells. In contrast, GALNT2 knockdown with siRNAs or knockout with CRISPR/Cas9 system suppressed these malignant properties. Interestingly, we found that GALNT2 modified O-glycans on AXL and determined AXL levels via the proteasome-dependent pathway. In addition, the GALNT2-promoted invasiveness was significantly reversed by AXL siRNAs. These findings suggest that GALNT2 promotes colorectal cancer invasion at least partly through AXL.


Colorectal Neoplasms , N-Acetylgalactosaminyltransferases , Humans , Cell Line, Tumor , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Glycosylation , Neoplasm Invasiveness , N-Acetylgalactosaminyltransferases/genetics , Polypeptide N-acetylgalactosaminyltransferase
8.
Biomater Adv ; 142: 213165, 2022 Nov.
Article En | MEDLINE | ID: mdl-36341744

We previously demonstrated that transplantation of menstrual blood-derived stromal cells (MenSCs) is a safe and effective therapy for treating intrauterine adhesions (IUA). However, improving the colonization and therapeutic efficiency of MenSCs is still needed before full clinical application. Here, we established an amniotic membrane extract (AME)-enriched RGD hydrogel, and evaluated the therapeutic effect of this adjuvant combined with MenSCs transplantation in an IUA rat model. Our results indicated that AME promoted the proliferation and secretion of MenSCs in vitro, up-regulated the expression of apoptosis-suppressing gene BCL2 and down-regulated the expression of apoptosis-related genes Caspase-3 and Caspase-8. The AME-enriched hydrogel was biocompatible, and improved the survival of MenSCs in vitro and in vivo. It also promoted the retention of MenSCs in IUA uterus and augmented the effects of MenSCs on improving uterus morphology, endometrial proliferation, endometrial receptivity and fibrosis suppression. In addition, co-transplantation of MenSCs with AME-enriched hydrogel markedly down-regulated the expressions of inflammation-related genes IL10 and TGFß while up-regulated the IL4/IFN-γ ratio in the IUA endometrium, and improved the expressions of cell proliferation-related antigen, gland-regeneration-related marker leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), angiogenesis-related marker platelet and endothelial cell adhesion molecule 1 (PECAM1), endometrial receptivity related genes ITGα5 and ITGß3. Our study suggested that AME and MenSCs had a synergistic effect. Co-transplantation of MenSCs with AME-enriched hydrogel provided a promising approach for stem cell-based IUA treatment.


Amnion , Uterine Diseases , Animals , Female , Humans , Rats , Hydrogels/metabolism , Stromal Cells , Tissue Adhesions/drug therapy , Uterine Diseases/metabolism
9.
Cancer Control ; 29: 10732748221130164, 2022.
Article En | MEDLINE | ID: mdl-36165718

INTRODUCTION: Clinical trials, although academically accepted as the most effective treatment available for cancer patients, poor accrual to clinical trials remains a significant problem. A clinical trials navigator (CTN) program was piloted where patients and/or their healthcare professionals could request a search and provide a list of potential cancer clinical trials in which a patient may be eligible based on their current status and disease. OBJECTIVES: This study examined the outcomes of a pilot program to try to improve clinical trials accrual with a focus on patients at medium to small sized cancer programs. Outcomes examined included patient disposition (referral to and accrual to interventional trials), patient survival, sites of referral to the CTN program. METHODS: One 0.5 FTE navigator was retained. Stakeholders referred to the CTN through the Canadian Cancer Clinical Trials Network. Demographic and outcomes data were recorded. RESULTS: Between March 2019 and February 2020, 118 patients from across Canada used the program. Seven per cent of patients referred were enrolled onto treatment clinical trials. No available trial excluded 39% patients, and 28% had a decline in their health and died before they could be referred or enrolled onto a clinical trial. The median time from referral to death was 109 days in those that passed. CONCLUSION: This novel navigator pilot has the potential to increase patient accrual to clinical trials. The CTN program services the gap in the clinical trials system, helping patients in medium and small sized cancer centres identify potential clinical trials at larger centres.


Neoplasms , Humans , Canada , Clinical Trials as Topic , Cross-Sectional Studies , Diterpenes , Neoplasms/therapy , Patient Selection , Research Design
10.
Tech Coloproctol ; 26(11): 905-914, 2022 11.
Article En | MEDLINE | ID: mdl-35987827

BACKGROUND: The aim of this study was to determine if robotic surgery can reproduce the technical advantages and oncologic outcomes of laparoscopic surgery for the treatment of locally advanced colorectal cancer invading the urinary bladder. METHODS: We retrospectively reviewed the prospectively maintained data of patients with locally advanced colorectal cancer invading the urinary bladder undergoing robotic or laparoscopic surgery between June 2006 and November 2020. Clinicopathologic features, surgical outcomes, and oncologic efficacy were compared between patient groups of robotic or laparoscopic surgery. All patients underwent surgery with the intent of R0 resection for the primary tumor. Major surgical complications were defined as Clavien-Dindo grade ≥ III. Multivariate regression analysis was performed to identify risk factors. RESULTS: A total of 41 patients (M:F = 32:9; median age: 63 [42-88] years) were analysed; 32 underwent laparoscopic surgery and 9 underwent robotic surgery. There was no statistically significant difference between the two groups in baseline demographic and clinicopathologic features. There were no significant differences in terms of mean operative time (353.24 vs. 387.33 min), mean blood loss (315.00 vs. 171.11 mL), mean number of lymph nodes harvested (27.16 vs. 23.50), R0 resection (89.7 vs. 66.7%), conversion (12.5 vs. 11.1%), major complication rate (9.4 vs. 22.2%), mean time to flatus passage (4.8 vs. 4.1 days), mean postoperative length of hospital stay (18.9 vs. 19.8 days), 5-year disease-free survival rate (64.6 vs. 62.5%) and overall survival rate (75.3 vs. 83.3%). Multivariate analysis showed that R1 resection was the only independent prognostic factor for reduced disease-free survival (hazard ratio 21.386; 95% confidence interval 1.991-229.723; p = 0.0115). CONCLUSIONS: Robotic surgery can reproduce the technical advantages and oncologic outcomes of laparoscopic surgery for the treatment of locally advanced colorectal cancer invading the urinary bladder. However, larger studies are mandatory to clarify the role of robotic surgery in such a scenario.


Colorectal Neoplasms , Laparoscopy , Robotic Surgical Procedures , Urinary Bladder , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Feasibility Studies , Humans , Laparoscopy/adverse effects , Length of Stay , Middle Aged , Postoperative Complications/etiology , Retrospective Studies , Robotic Surgical Procedures/adverse effects , Treatment Outcome , Urinary Bladder/pathology , Urinary Bladder/surgery
11.
J Formos Med Assoc ; 121(10): 2057-2064, 2022 Oct.
Article En | MEDLINE | ID: mdl-35288017

BACKGROUND: Ramucirumab is indicated for salvage treatment after failure of first-line treatment for metastatic colorectal cancer (mCRC). However, the application of ramucirumab at later-line treatment in real-world practice has not received much discussion. METHODS: In this retrospective study, we enrolled 70 patients with mCRC who received ramucirumab plus chemotherapy at National Taiwan University Hospital between 2018 and 2019. RESULTS: Compared with those who received third- or later-line ramucirumab treatment, patients who received second-line ramucirumab treatment had significantly longer median time to treatment discontinuation (mTTD; 6.7 vs 3.6 months, P = .004) and median overall survival (mOS; not reached vs 7.6 months, P = .009). Multivariate analyses revealed that second-line ramucirumab and triplet chemotherapy backbone were the only independent predictive factors for long mTTD and mOS. Patients who received ramucirumab with triplet chemotherapy had a significantly longer mOS than did patients who received ramucirumab with doublet chemotherapy (not reached vs 5.6 months, P = .002). Among those receiving second-line ramucirumab treatment, combination with triplet chemotherapy led to a longer mTTD than did combination with doublet chemotherapy, but the difference was non-significant (not reached vs 4.4 months, P = .108). By contrast, in patients receiving fourth- or later-line ramucirumab, combination with triplet chemotherapy led to significantly longer mTTD than did combination with doublet chemotherapy (8.0 vs 2.9 months, P = .032). CONCLUSION: Ramucirumab plus triplet chemotherapy may be an alternative regimen in patients with mCRC, particularly as a later-line treatment modality.


Colonic Neoplasms , Colorectal Neoplasms , Rectal Neoplasms , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms/etiology , Fluorouracil , Humans , Retrospective Studies , Salvage Therapy , Ramucirumab
12.
World J Emerg Surg ; 17(1): 16, 2022 03 17.
Article En | MEDLINE | ID: mdl-35300711

BACKGROUND: This study aimed to evaluate the necessity of abdominal drainage after laparoscopic appendectomy in patients with complicated appendicitis. METHODS: Patients with acute appendicitis undergoing laparoscopic appendectomy at two hospitals between January 2014 and December 2018 were retrospectively included. Complicated appendicitis was defined as the American Association for the Surgery of Trauma (AAST) grade ≥ II. The patients were classified according to the AAST grade and the indwelling of abdominal drainage. The postoperative surgical outcomes and recovery were compared among patient groups to evaluate the impact of abdominal drainage for patients with complicated appendicitis undergoing laparoscopic appendectomy. RESULTS: A total of 1241 patients was retrospectively included. Among them, there were 820 patients with simple appendicitis (AAST grade I) and 421 patients with complicated appendicitis (AAST grade ≥ II). For complicated appendicitis, the drainage group (N = 192) tended to harbor more overall complications, intra-abdominal abscess formation, time to resume a soft diet, and the postoperative length of hospitalization (P = 0.0000 for all). Multivariate logistic regression confirmed that abdominal drainage increased the risk of overall complications [Odds ratio (OR) 2.439; 95% confidence interval (CI) 1.597-3.726; P ≤ 0.0001] and failed to decrease the risk of intra-abdominal abscess formation (OR 1.655; 95% CI 0.487-5.616; P = 0.4193). Multivariate linear regression analysis also showed that the drainage group harbored longer postoperative length of hospitalization (Coefficients: 20.697; 95% CI 15.251-26.143; P < 0.0001) and time to resume a soft diet (Coefficients: 45.899; 95% CI 34.502-57.297; P < 0.0001). CONCLUSIONS: Abdominal drainage did not prevent overall complications in patients with complicated appendicitis; paradoxically, it delayed the convalescence. Our results discourage the routine use of abdominal drainage and suggest that abdominal drainage should be performed sparingly.


Abdominal Abscess , Appendicitis , Laparoscopy , Abdominal Abscess/etiology , Abdominal Abscess/surgery , Appendectomy/adverse effects , Appendectomy/methods , Appendicitis/complications , Appendicitis/surgery , Drainage/methods , Humans , Laparoscopy/methods , Length of Stay , Postoperative Complications/etiology , Retrospective Studies
13.
Child Obes ; 18(2): 143-146, 2022 03.
Article En | MEDLINE | ID: mdl-34619035

Pandemic mitigation measures may lead to excess weight gain in children. Our objective was to assess weight gain during the COVID-19 pandemic in children of ages 4-12 years with overweight and obesity in San Francisco, CA. Children with BMI ≥85th percentile measured at a clinic visit from January to March 2020 were recruited. Follow-up BMI measurements were obtained between October 2020 and March 2021 from the electronic medical record or through a video study visit. Pre- and post-BMI measurements were obtained on n = 91 participants. The majority were Latino (85%) and publicly insured (91%). Mean monthly weight gain was 0.73 kg [standard deviation (SD) 0.47], equivalent to yearly weight gain of 8.8 kg. Mean monthly change in BMI z-score was 0.02 (SD 0.04) equivalent to yearly increase in BMI-z of 0.24. Weight gain among children in San Francisco with overweight and obesity during the COVID-19 pandemic far exceeded healthy weight gain for this age group.


COVID-19 , Pediatric Obesity , Body Mass Index , COVID-19/epidemiology , Child , Child, Preschool , Humans , Overweight/epidemiology , Pandemics , Pediatric Obesity/epidemiology , SARS-CoV-2 , San Francisco/epidemiology , Weight Gain
14.
Stem Cell Reports ; 16(10): 2548-2564, 2021 10 12.
Article En | MEDLINE | ID: mdl-34506726

The specification of inhibitory neurons has been described for the mouse and human brain, and many studies have shown that pluripotent stem cells (PSCs) can be used to create interneurons in vitro. It is unclear whether in vitro methods to produce human interneurons generate all the subtypes found in brain, and how similar in vitro and in vivo interneurons are. We applied single-nuclei and single-cell transcriptomics to model interneuron development from human cortex and interneurons derived from PSCs. We provide a direct comparison of various in vitro interneuron derivation methods to determine the homogeneity achieved. We find that PSC-derived interneurons capture stages of development prior to mid-gestation, and represent a minority of potential subtypes found in brain. Comparison with those found in fetal or adult brain highlighted decreased expression of synapse-related genes. These analyses highlight the potential to tailor the method of generation to drive formation of particular subtypes.


Interneurons/metabolism , Neural Stem Cells/metabolism , Pluripotent Stem Cells/metabolism , Transcriptome , Cell Differentiation , Cellular Reprogramming Techniques/methods , Humans , Single-Cell Analysis , Transcription Factors/metabolism
15.
J Clin Med ; 10(16)2021 Aug 20.
Article En | MEDLINE | ID: mdl-34442007

The outcome of radiofrequency ablation (RFA) for liver metastases from colorectal cancer (CRLM) has been thought to be inferior to metastasectomy. However, the recent development of multielectrode RFA (multi-RFA) systems has made the ablation zone larger and more complete. Thus, we assessed the survival benefits of this modality in cases of metachronous CRLM. This retrospective study assessed patients diagnosed with resectable metachronous CRLM between 2013 and 2016; 132 patients were categorized by treatment for liver metastases: multi-RFA (n = 68), hepatectomy (n = 34), or systemic treatment only (n = 30). Therapeutic effectiveness, outcomes, and intervention-related complications were compared between groups. Median overall survival (OS), recurrence-free survival (RFS), and intrahepatic recurrence-free survival (IHRFS) were 69.8, 85.2, and 59.7 months for the hepatectomy group; 53.4, 41.3, and 32.3 months for the multi-RFA group; and 19.1, 7.1, and 7.1 months for the systemic treatment group. No significant differences were observed between the multi-RFA and hepatectomy groups after a median follow-up of 59.8 months. This study demonstrated that multi-RFA and hepatectomy provide similar survival benefits for patients with resectable CRLM. Multi-RFA may represent a reliable treatment option for the management of resectable liver metastases.

16.
Acad Pediatr ; 21(8): 1434-1440, 2021.
Article En | MEDLINE | ID: mdl-34023488

OBJECTIVE: To understand the impact of the coronavirus disease 2019 (COVID-19) pandemic on parental perceptions of health behaviors and food insecurity among children with overweight and obesity living in San Francisco and to assess the relationship between food insecurity and dietary intake during the pandemic. METHODS: Parents of children ages 4 to 12 in San Francisco with body mass index ≥85th percentile measured at a clinic visit at a Federally Qualified Health Center or academic practice from January 1st to March 15th, 2020 were eligible to participate. Parents completed a survey reporting on child health behaviors and household food insecurity prior to and since the start of the pandemic. Survey items were abstracted from validated surveys with adaptations. Regression models evaluated associations between food insecurity and dietary intake variables. RESULTS: Most participants (n = 145) were publicly insured (90%), Latino (77%), and spoke Spanish at home (70%). Parents perceived that child mean daily nonacademic screen time was higher during the pandemic compared to before (3.8 hours vs 1.6 hours). Mean daily physical activity was reported to be lower compared to prior to the pandemic (1 hour vs 1.8 hours). On average, reported bedtime shifted 1.6 hours later. Food insecurity increased significantly but was not associated with intake of fruits, vegetables, sugar-sweetened beverages, or foods with added sugar during the pandemic. CONCLUSIONS: Parents of children with overweight or obesity in San Francisco perceive increased child screen time, decreased physical activity and later bedtimes during the COVID-19 pandemic. Findings suggest a need for policies that support healthy lifestyle behaviors among low-income children during the pandemic.


COVID-19 , Pandemics , Child , Child, Preschool , Health Behavior , Humans , Obesity/epidemiology , Overweight/epidemiology , Parents , Perception , SARS-CoV-2
18.
Sci Rep ; 11(1): 372, 2021 01 11.
Article En | MEDLINE | ID: mdl-33431915

A series of stable and ready-to-use bioinks have been developed based on the xeno-free and tunable hydrogel (VitroGel) system. Cell laden scaffold fabrication with optimized polysaccharide-based inks demonstrated that Ink H4 and RGD modified Ink H4-RGD had excellent rheological properties. Both bioinks were printable with 25-40 kPa extrusion pressure, showed 90% cell viability, shear-thinning and rapid shear recovery properties making them feasible for extrusion bioprinting without UV curing or temperature adjustment. Ink H4-RGD showed printability between 20 and 37 °C and the scaffolds remained stable for 15 days at temperature of 37 °C. 3D printed non-small-cell lung cancer (NSCLC) patient derived xenograft cells (PDCs) showed rapid spheroid growth of size around 500 µm in diameter and tumor microenvironment formation within 7 days. IC50 values demonstrated higher resistance of 3D spheroids to docetaxel (DTX), doxorubicin (DOX) and erlotinib compared to 2D monolayers of NSCLC-PDX, wild type triple negative breast cancer (MDA-MB-231 WT) and lung adenocarcinoma (HCC-827) cells. Results of flow property, shape fidelity, scaffold stability and biocompatibility of H4-RGD suggest that this hydrogel could be considered for 3D cell bioprinting and also for in-vitro tumor microenvironment development for high throughput screening of various anti-cancer drugs.


Bioprinting/methods , Drug Screening Assays, Antitumor , Hydrogels/chemistry , Neoplasms/pathology , Tissue Scaffolds/chemistry , A549 Cells , Animals , Carcinoma, Non-Small-Cell Lung/pathology , Cells, Cultured , Drug Screening Assays, Antitumor/instrumentation , Drug Screening Assays, Antitumor/methods , Humans , Ink , Lung Neoplasms/pathology , Materials Testing , Mice , Mice, Inbred NOD , Mice, Transgenic , Models, Biological , Polysaccharides/chemistry , Printing, Three-Dimensional , Tissue Engineering/methods , Tumor Microenvironment/physiology
19.
Int J Colorectal Dis ; 36(3): 509-516, 2021 Mar.
Article En | MEDLINE | ID: mdl-33128083

PURPOSE: Current guidelines suggest that adjuvant chemotherapy (AC) be administered to all locally advanced (clinically T3-4 or N-positivity) rectal cancer patients undergoing neoadjuvant chemoradiotherapy (nCRT) and radical surgical resection regardless of the final pathological staging (yp staging). This study aimed to evaluate the necessity of AC for ypT0-2N0 rectal cancer. METHODS: Patients with ypT0-2N0 rectal cancer, who received nCRT and radical surgical resection, were recruited retrospectively at a university hospital. The main outcome was to evaluate the 5-year overall survival (OS) and disease-free survival (DFS) between ypT0-2N0 rectal cancer patients with AC and those without AC. We also identified potential independent prognostic factors associated with poor outcomes. RESULTS: One hundred and ten ypT0-2N0 rectal cancer patients (ypT0: n = 6; ypT1: n = 44; ypT2: n = 60) were followed up for a median of 60 months. No significant difference was observed in DFS and 5-year OS between patients with AC and those without AC. The risk of recurrence was associated with the postoperative pathological staging (0% with ypT0, 2.4% with ypT1, and 10% with ypT2). In the multivariate analysis, retrieval of < 12 lymph nodes was an independent favorable prognostic factor, which correlated with a higher OS (HR: 2.263; 95% CI: 1.093-4.687, P = 0.028). Intra-tumor lymphovascular and perineural invasion were poor prognostic markers for shorter DFS (HR: 5.940; 95% CI: 1.150-30.696, P = 0.033). CONCLUSION: Postoperative AC is not required for patients with ypT0-2N0 rectal cancer downstaged by nCRT, especially in those without poor prognostic factors.


Neoadjuvant Therapy , Rectal Neoplasms , Chemoradiotherapy , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Disease-Free Survival , Humans , Neoplasm Recurrence, Local , Neoplasm Staging , Rectal Neoplasms/pathology , Retrospective Studies
20.
Psychol Trauma ; 12(8): 897-903, 2020 Nov.
Article En | MEDLINE | ID: mdl-33346680

OBJECTIVE: This study examined the use of Healing Touch (HT), a biofield therapy, as an intervention in treating posttraumatic stress disorder (PTSD). It exemplifies the upswing of biofield (energy field) therapies that have been taking place recently for a number of clinical conditions, including cancer, pain, arthritis, movement restriction, and energy psychology. Theoretically, the human body is the physical aspect of an individualized field of energy (biofield) in which electrical activity functions as a complex, organized whole or system. Hypothetically, this system plays a critical role in the effective treatment of PTSD. Trauma-induced congested energy in vital areas of the human body, particularly the chakras and the funnel-shaped crown-to-transpersonal channel, impedes the natural release of unwanted energy of emotions, thereby becoming a major obstacle to treatment. This qualitative and quantitative study examined the use of HT as an effective intervention to break up and clear away congested energy, promote a strong energy flow, and allow the natural release of unwanted energy of emotions to normalize. The test group would average a mean reduction of symptom severity of at least 18 points after 10 treatments, as measured by the psychometrically sound self report measure of PTSD symptom severity for military use. METHOD: In a 2-armed randomized crossover waitlist controlled trial, combat veterans experienced the impact of HT techniques complementing standard care on the severity of their PTSD symptoms. RESULTS: The test group's mean reduction of symptom severity was a clinically significant 18.11 points, along with a reliable change of 5.57 points for the control group. Overall, subjects reported a range of positive physical and psychological effects. CONCLUSION: Although continued research using larger samples is needed, it may be concluded that HT is a low-risk, low-cost intervention for PTSD that should be implemented as a treatment option, especially in combination with "gold-standard" therapies. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Stress Disorders, Post-Traumatic/therapy , Therapeutic Touch/methods , Veterans/psychology , Cross-Over Studies , Female , Humans , Male , Middle Aged , Treatment Outcome , Veterans/statistics & numerical data
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