Validation of a scoring system to predict bladder dysfunction after laparoscopic rectal cancer surgery.

PURPOSE: A recent trend in  urinary catheter management in patients who underwent laparoscopic rectal cancer surgery is early removal. However, some patients develop bladder dysfunction and require urinary re-catheterization. In 2016, a scoring system to predict bladder dysfunction after laparoscopic rectal cancer surgery was developed in our institution. The aim of this study was to demonstrate the validity of this scoring system and to determine the suitability of patients for early removal of urinary catheter. METHODS: A single-center, retrospective study from a prospective database was conducted on 234 patients who underwent elective laparoscopic rectal cancer surgery between January 2016 and December 2019. According to bladder dysfunction predictive score, the urinary catheter was removed on the first postoperative day (low-risk group) and fifth postoperative day (high-risk group). After catheter removal, all patients were managed using in-house protocols. RESULTS: Of 234 patients, 130 (55.6%) were classified as a low-risk group. The overall incidence of bladder dysfunction was 8.5% (11/130) in the low-risk group and 13.5% (14/104) in the high-risk group. CONCLUSION: The scoring system developed to predict bladder dysfunction showed good overall performance for discriminating between patients suitable or not for early removal of urinary catheter after laparoscopic rectal cancer surgery.

Clinical outcomes of single-incision robotic cholecystectomy versus conventional 3-port laparoscopic cholecystectomy

Background: Few studies have compared the surgical results of single-incision robotic cholecystectomy (SIRC) with those of conventional laparoscopic cholecystectomy (CLC). The purpose of this study was to evaluate the relative clinical efficacy of SIRC by comparing the number of postoperative days, pain level and complications between the 2 surgical methods. Methods: We retrospectively collected demographic, perioperative and postoperative data for all patients who underwent SIRC or CLC performed by a single surgeon from June 2016 to May 2017. Operative time was recorded, divided into anesthesia time, docking time, console time and total operation time. Postoperative pain was measured with the Numerical Pain Rating Scale. Results: A total of 121 patients underwent cholecystectomy during the study period, of whom 61 had SIRC and 60 had CLC. The mean total operation time of SIRC and CLC was 93.52 (SD 20.27) minutes and 37.67 (SD 19.73) minutes, respectively (p < 0.001). The total operation time excluding console time of SIRC was significantly longer than that of CLC (82.77 [SD 18.27] min v. 37.67 [SD 19.73] min) (p < 0.001). The mean Numerical Pain Rating Scale score was 4.73 (SD 1.23) (SIRC: 4.75 [SD 1.24]; CLC: 4.70 [SD 1.22]) (p = 0.8) within 1 hour after the operation; scores after 6 hours and 1 day decreased in a similar manner in the 2 groups (p = 0.1). Conclusion: Postoperative pain, use of an additional port, complication rates, operation time and cost of SIRC were similar to or greater than those of CLC. Large randomized controlled trials are needed to examine the true benefits of SIRC.

Contexte: Peu d'études ont comparé les résultats chirurgicaux de la cholécystectomie robotique par incision unique (CRIU) à ceux de la cholécystectomie laparoscopique classique (CLC). Le but de la présente étude était d'évaluer l'efficacité clinique relative de la CRIU en comparant le nombre de jours postopératoires, l'intensité de la douleur et les complications avec les 2 méthodes chirurgicales. Méthodes: Nous avons recueilli de manière rétrospective les données démographiques, périopératoires et postopératoires de tous les patients soumis à une CRIU ou à une CLC effectuée par un seul chirurgien entre juin 2016 et mai 2017. Le temps opératoire a été enregistré, subdivisé entre anesthésie, temps d'installation, temps à la console et durée totale de l'intervention. La douleur postopératoire a été mesurée au moyen d'une échelle numérique d'évaluation de la douleur. Résultats: En tout, 121 patients ont subi une cholécystectomie durant la période de l'étude, dont 61, une CRIU et 60, une CLC. La durée opératoire totale moyenne des CRIU et des CLC a été de 93,52 (É.-T. 20,27) minutes et de 37,67 (É.-T. 19,73) minutes, respectivement (p < 0,001). La durée opératoire totale excluant le temps à la console a été significativement plus longue avec la CRIU qu'avec la CLC (82,77 [É.-T. 18,27] minutes c. 37,67 [É.-T. 19,73] minutes) (p < 0,001). Le score moyen à l'échelle numérique d'évaluation de la douleur a été de 4,73 (É.-T. 1,23) (CRIU : 4,75 [É.-T. 1,24]; CLC : 4,70 [É.-T. 1,22]) (p = 0,8) 1 heure suivant l'intervention; après 6 heures et après 1 jour, les scores avaient diminué de façon similaire dans les 2 groupes (p = 0,1). Conclusion: La douleur postopératoire, l'utilisation d'un port additionnel, les taux de complication, le temps opératoire et le coût de la CRIU ont été similaires ou supérieurs à ceux de la CLC. Il faudra réaliser de plus grands essais randomisés et contrôlés pour analyser les bénéfices réels de la CRIU.

Prospective analysis of delayed colorectal post-polypectomy bleeding.

BACKGROUNDS/AIMS: Although post-polypectomy bleeding is the most frequent complication after colonoscopic polypectomy, only few studies have investigated the incidence of bleeding prospectively. The aim of this study was to investigate the incidence of delayed post-polypectomy bleeding and its associated risk factors prospectively. METHODS: Patients who underwent colonoscopic polypectomy at Kangbuk Samsung Hospital from January 2013 to December 2014 were prospectively enrolled in this study. Trained nurses contacted patients via telephone 7 and 30 days after polypectomy and completed a standardized questionnaire regarding the development of bleeding. Delayed post-polypectomy bleeding was categorized as minor or major and early or late bleeding. Major delayed bleeding was defined as a > 2-g/dL drop in the hemoglobin level, requiring hospitalization for control of bleeding or blood transfusion; late delayed bleeding was defined as bleeding occurring later than 24 h after polypectomy. RESULTS: A total of 8175 colonoscopic polypectomies were performed in 3887 patients. Overall, 133 (3.4%) patients developed delayed post-polypectomy bleeding. Among them, 90 (2.3%) and 43 (1.1%) patients developed minor and major delayed bleeding, respectively, and 39 (1.0%) patients developed late delayed bleeding. In the polyp-based multivariate analysis, young age (< 50 years; odds ratio [OR] 2.10; 95% confidence interval [CI] 1.18-3.68), aspirin use (OR 2.78; 95% CI 1.23-6.31), and polyp size of > 10 mm (OR 2.45; 95% CI 1.38-4.36) were significant risk factors for major delayed bleeding, while young age (< 50 years; OR 2.6; 95% CI 1.35-5.12) and immediate bleeding (OR 3.3; 95% CI 1.49-7.30) were significant risk factors for late delayed bleeding. CONCLUSIONS: Young age, aspirin use, polyp size, and immediate bleeding were found to be independent risk factors for delayed post-polypectomy bleeding.

Prospective Analysis of Minor Adverse Events After Colon Polypectomy.

BACKGROUND: The risks of minor adverse events (MAEs) such as abdominal pain and bloating after colon polypectomy (CP) are less clearly documented than major adverse events. However, these complications may cause significant discomfort during the performance of normal activities. We aimed to estimate the incidence of MAE, associated risk factors, and healthcare resource utilization after CP. METHODS: Patients who underwent CP were prospectively enrolled in this study. Trained nurses contacted patients by telephone at 7 and 30 days after the CP and administered a standardized questionnaire to obtain information regarding the development of complications. MAEs were defined as any discomfort the patient experienced after CP excluding major bleeding, perforation, and post-polypectomy coagulation syndrome. RESULTS: Among a total of 2716 patients, 2253 patients completed the interview at 7 and 30 days. MAEs occurred in 263 patients (11.7%) before day 7, among which the most common were abdominal pain (4.5%), rectal bleeding (2.8%), and bloating (2.6%). Cumulative incidence of MAEs was in 267 patients (11.9%) at 30 days. On multivariate analysis, female sex (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.58-3.18) and use of meperidine (OR 1.54, 95% CI 1.04-2.27) were risk factors for the occurrence of MAEs. Two patients (0.7%) required hospital admission, 117 patients (43.8%) were treated medically in the outpatient clinic, and the majority at 148 patients (55.4%) experienced resolution of symptoms after observation. CONCLUSIONS: The post-CP MAE rate was as low as 11.8%. The MAEs occurred mainly in the first seven postoperative days and resulted in little use of healthcare resources.

Scoring Systems Used to Predict Bladder Dysfunction After Laparoscopic Rectal Cancer Surgery.

BACKGROUND: Postoperative bladder dysfunction often occurs after rectal cancer surgery, necessitating long-term urinary catheter drainage. The aim of this study was to evaluate the feasibility of early catheter removal and to propose scoring systems that may predict urinary dysfunction after laparoscopic rectal cancer surgery. METHODS: A total of 110 patients who underwent elective laparoscopic rectal cancer surgery were included in this prospective observational study. The urinary catheter was removed on the first postoperative day. RESULTS: The overall incidence of bladder dysfunction was 29.1 % (32/110). The incidence of bladder dysfunction was significantly higher in patients with an age of 65 years or older, male gender, and anastomosis levels from the anal verge of 6 cm or below (P = 0.03, 0.002, and 0.03, respectively). By setting a cut-off of two of the risk factors, this simple scoring system can predict postoperative bladder dysfunction with sensitivity of 96.9 %, specificity of 50.0 %, and accuracy of 63.6 %. A scoring system based on regression coefficients was also conducted according to the following formula: bladder dysfunction predicting score = 18 (1 for male or 0 for female) +0.5 (age, years) -2 (anastomosis level, cm). With this method, a cut-off value of 35+ points predicts postoperative bladder dysfunction with a sensitivity of 81.3 %, specificity of 71.8 %, and accuracy of 74.5 %. CONCLUSIONS: Bladder dysfunction after laparoscopic rectal cancer surgery following early catheter removal occurred in 29.1 % of patients. Two scoring systems using three risk factors (age, male gender, and anastomosis level) may predict postoperative bladder dysfunction.

Prognostic significance of quantitative carcinoembryonic antigen and cytokeratin 20 mRNA detection in peritoneal washes of gastric cancer patients.

BACKGROUND/AIMS: Peritoneal carcinomatosis is the most common recurrence type in gastric cancer. Disseminated tumor cells derived from serosal invasion may be indicators of early peritoneal seeding and subsequent peritoneal dissemination. Reverse-transcriptase polymerase chain reaction (RT-PCR) techniques have been introduced to aid in detection of disseminated tumor cells in peritoneal washes, however, use of a single molecular marker lacks adequate sensitivity. We sought to improve both sensitivity and specificity in detecting disseminated tumor cells in peritoneal washes by using two markers; carcinoembryonic antigen (CEA) and cytokeratin 20 mRNA (CK20 mRNA). METHODOLOGY: Between July 2007 and June 2010, peritoneal washing samples were collected from 131 patients who underwent surgery for histologically proven gastric cancer. CEA and CK20 mRNA levels were quantified using a Light Cycler. RESULTS: Analysis using of the two markers had higher sensitivity (93.9%) and specificity (87.7%) than single marker detection (p<0.01, p<0.001 respectively). These analyses also correlated with various clinicopathological factors, and aided in predicting survival and peritoneal recurrence. CONCLUSIONS: Two-marker analysis has a significant correlation of survival or peritoneal recurrence in gastric cancer, and this analysis may be more useful as a prognostic predictor of peritoneal recurrence compared with RT-PCR mediated detection of CEA or CK20 alone.

Prognostic factors associated with long-term survival and recurrence in pancreatic adenocarcinoma.

BACKGROUND/AIMS: It is very important to determine the prognostic factors for pancreatic adenocarcinoma when choosing surgical and conservative management strategies. In this study, we identified prognostic factors for survival and recurrence in patients with histologically proven pancreatic adenocarcinoma. METHODOLOGY: Between January 2003 and December 2009, 82 patients with histologically proven pancreatic adenocarcinoma were considered for this study. Follow-up consisted of personal contact with patients or review of electronic medical records at this center and was terminated on December 31, 2011 or upon the patient's death. RESULTS: Overall survival rates of all patients at 1, 3, and 5 years were 51.9, 21.6 and 16.0%. Preoperative jaundice was the only independent prognostic factor for total pancreatic cancer patients, while N stage and perineural invasion in pathological findings was identified as an independent prognostic factor for survival of patients with surgical resection. Chemotherapy was the only independent prognostic factor for survival of patients who underwent palliative surgical bypass. CONCLUSIONS: Preoperative jaundice in any patients, lymph node metastasis, perineural invasion in patients with surgical resection, and chemotherapy in patients undergoing palliative surgical bypass are important prognostic factors for survival of pancreatic cancer.

Unveiling the profound advantages of total neoadjuvant therapy in rectal cancer: a trailblazing exploration.

The standard treatments for locally advanced rectal cancer typically involved neoadjuvant therapy with either short-course radiation or long-course chemoradiation, followed by radical surgery and adjuvant chemotherapy. While the advancement of surgical techniques and the adoption of multimodal therapy have greatly contributed to reducing local failure, there has been limited improvement in overall survival, primarily due to the stagnation in systemic failure. In response to this challenge, a new strategy known as total neoadjuvant therapy (TNT) has emerged, involving the administration of both full-dose chemotherapy and radiation before surgery. It has shown promise in reducing systemic failure, enhancing tumor regression, and improving treatment adherence, ushering in a new era in the standard treatment of locally advanced rectal cancer. This review aims to summarize the evolution of multimodal treatments for locally advanced rectal cancer, ultimately converging into the current TNT strategy, and provides an assessment of the benefits and limitations of TNT based on available evidence, serving as a foundation for selecting the best treatment option.

Short- and long-term outcomes of subtotal/total colectomy in the management of obstructive left colon cancer.

PURPOSE: Surgical management of obstructive left colon cancer (OLCC) is still a matter of debate. The classic Hartmann procedure (HP) has a disadvantage that requires a second major operation. Subtotal colectomy/total abdominal colectomy (STC/TC) with ileosigmoid or ileorectal anastomosis is proposed as an alternative procedure to avoid stoma and anastomotic leakage. However, doubts about morbidity and functional outcome and lack of long-term outcomes have made surgeons hesitate to perform this procedure. Therefore, this trial was designed to provide data for morbidity, functional outcomes, and long-term outcomes of STC/TC. METHODS: This study retrospectively analyzed consecutive cases of OLCC that were treated by STC/TC between January 2000 and November 2020 at a single tertiary referral center. Perioperative outcomes and long-term outcomes of STC/TC were analyzed. RESULTS: Twenty-five descending colon cancer (45.5%) and 30 sigmoid colon cancer cases (54.5%) were enrolled in this study. Postoperative complications occurred in 12 patients. The majority complication was postoperative ileus (10 of 12). Anastomotic leakage and perioperative mortality were not observed. At 6 to 12 weeks after the surgery, the median frequency of defecation was twice per day (interquartile range, 1-3 times per day). Eight patients (14.5%) required medication during this period, but only 3 of 8 patients required medication after 1 year. The 3-year disease-free survival was 72.7% and 3-year overall survival was 86.7%. CONCLUSION: The risk of anastomotic leakage is low after STC/TC. Functional and long-term outcomes are also acceptable. Therefore, STC/TC for OLCC is a safe, 1-stage procedure that does not require diverting stoma.

Clinical outcomes and prognostic factors of cone-beam CT-guided radiofrequency ablation for pulmonary metastases in colorectal cancer patients.

AIM: Radiofrequency ablation (RFA) has been increasingly used for the treatment of pulmonary metastases in various malignancies. METHODS: A retrospective analysis was performed to establish the safety and efficacy of cone-beam computed tomography (CBCT)-guided RFA in patients with metastatic colorectal cancer between 2016 and 2019, and the prognostic factors of local tumor control were assessed. RESULTS: A total of 31 patients with colorectal cancer underwent 48 sessions of lung RFA. The mean diameter of metastases targeted for RFA was 11 mm (range: 4-32), and the RFA was technically successful in 43 sessions (90%). There were 14 complications (29%), the majority of which required no intervention, with no cases of mortality. The median follow-up duration from RFA in the surviving 29 patients was 18.0 months. Only two patients (6%) died of disease progression, and the 3-year overall survival rate was 91% (95% CI: 83-99). Local tumor progression (LTP) of the RFA site was observed in 27%, and the LTP-free survival rates at 1 and 2 years were 81% (95% CI: 70-82) and 64% (95% CI: 50-77), respectively. Multivariate analysis showed that the progression of extra-RFA sites and the presence of extrapulmonary metastasis were independent prognostic factors significantly associated with LTP at RFA site. CONCLUSION: Lung RFA using CBCT guidance is a comparatively safe and effective option for the treatment of lung metastases from colorectal cancer. However, the control of extrapulmonary metastases should be accompanied by combined or sequential systemic treatment and local treatment.

RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous Adenoma.

Colorectal cancers (CRC) are classified into consensus molecular subtypes (CMS) based on gene expression profiles. The revised classification system iCMS was proposed by considering intrinsic epithelial status, microsatellite instability (MSI), and fibrosis. This study aimed to provide molecular evidence for the adenoma-carcinoma sequence concept by examining CRC and synchronous adenomas using iCMS. Epithelial CMS cell proportion was estimated using CiberSortx, an in silico cell fractionation method that included CMS cell types among the reference cell types. A random forest (RF) model estimated the posterior probabilities of CMS classes, which were compared with the CiberSortx results. Gene expression profiles of the published iCMS signature panel were retrieved from our dataset and subjected to heatmap clustering for classification. Bulk RNA sequencing data were collected from 29 adenocarcinomas and 11 adenoma samples. CiberSortx showed all CRC contained either CMS2 or CMS3 as the major epithelial cancer cell type. The RF model classified approximately half of the CRC as CMS4, whereas CMS4 was hardly detected by CiberSortx. Because they were enriched with myofibroblasts as per the CiberSortx classification, we tentatively designated them as iCMS2-F/iCMS3-F. iCMS coupled with the application of an in silico cell fractionation method can provide the molecular dissection of CRC and adenoma.

Prognostic significance of the metastatic lymph node ratio in patients with gastric cancer.

BACKGROUND: In gastric cancer, the classification of lymph node status is still a controversial prognostic factor. Recent studies have proposed a new prognostic factor (metastatic lymph node ratio: MLR) for gastric cancer patients who undergo curative resection. The present study tested the hypothesis that MLR was better than the current pN staging system by analyzing the correlation between MLR and the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system, by analyzing the correlation between MLR and 5-year overall survival (OS), by comparing area under the curve (AUC), and by performing univariate and multivariate analyses for OS. METHODS: Of 409 patients who were diagnosed with gastric adenocarcinoma between January 2003 and December 2006, 370 patients underwent curative resection and were included in this study. The prognostic significance of the number of metastatic lymph nodes and the metastatic lymph node ratio were compared in AUC and univariate and multivariate Cox regression analyses. RESULTS: MLR was significantly correlated with the depth of invasion and the number of lymph node metastases (p < 0.001). Increasing MLR also was statistically correlated with a lower 5-year OS rate (p < 0.001). The AUC of MLR and the number of lymph node metastases were not significantly different (p = 0.825). MLR was an independent prognostic factor on multivariate analysis, but the number of metastatic lymph nodes was not. CONCLUSIONS: MLR can be a prognostic factor in patients who undergo radical resection for gastric cancer and can overcome the limitations of existing prognostic factors.

Targeting cytokines and signaling molecules related to immune pathways in atopic dermatitis: therapeutic implications and challenges.

Although atopic dermatitis (AD) is primarily a Th2-driven disease, it shows high heterogeneity with additional variable contributions of the Th22, Th17, and Th1 pathways, depending on the subtype of the disease. Expanding knowledge and understanding of AD pathogenesis has promoted the development of numerous novel therapeutics that target cytokines and their signaling molecules, representatively, Janus kinases, involved in the underlying immune pathways, resulting in therapeutic success and failure. The first FDA approval was for the targeted biologic dupilumab. Although this proved the therapeutic relevance of targeting Th2 cytokines in moderate-to-severe forms of AD, it did not treat all patients, necessitating additional targeted therapeutics that modulate other cytokine pathways to resolve AD in all subtypes. Three more recently FDA-approved targeted therapeutics and several others that have been developed represent different targeted approaches directed to the Th2, Th22, Th17, or Th1 pathways. This review summarizes the main features and clinical outcomes of various approaches targeting cytokines and signaling molecules in these different pathways in view of both successful and failed cases, with a discussion of their therapeutic implications. In future, AD should be treated with more specific treatments reflecting the disease heterogeneity, but the current development of targeted therapeutics has faced some challenges in this context, which is also discussed.

Epidemiology, Risk Factors, and Prevention of Colorectal Cancer-An English Version.

Colorectal cancer (CRC) is the fourth most common malignancy in Korea and has been ranked as the third leading cause of cancer deaths in 2020. Although the incidence and mortality rates of CRC have decreased in recent years in Korea, it is still a significant public health burden. From the early 1990s until the mid-2000s, the 5-year relative survival of patients with CRC in Korea continuously increased. This finding appears to be a consequence of the successful introduction of a government-led screening program; the development of improved surgical techniques, anticancer drugs, and adjuvant treatment; and the advancement of medical resources and infrastructure along with economic growth. However, the improvement in survival has stagnated since the late 2000s. The recent coronavirus disease 2019 outbreak led to a reduction in hospital visits and screenings, which is expected to cause a stage shift to advanced disease stages and a worse prognosis for patients with CRC. Exploring modifiable environmental risk factors and appropriate screening test methods in Korea is necessary to overcome these challenges. Primary prevention through risk factor mediation and secondary prevention using suitable screening programs can help reduce the incidence and mortality rates of CRC.

Risk factors for hemorrhoidal disease among healthy young and middle-aged Korean adults.

Hemorrhoidal disease is a highly prevalent anorectal condition causing substantial discomfort, disability, and decreased quality of life. Evidence on preventable risk factors for hemorrhoidal disease is limited. We conducted a cross-sectional study of 194,620 healthy men and women who completed a health screening exam including colonoscopy in 2011-2017. We evaluated potential risk factors of hemorrhoidal disease, including lifestyle factors, medical history, birth history, gastrointestinal symptoms, and anthropometric measurements. The prevalence of hemorrhoidal disease was 16.6%, and it was higher in females than in males (17.2 vs. 16.3%; P < 0.001). Compared to men, the prevalence of hemorrhoidal disease was higher in parous women (adjusted odds ratio [OR] 1.06; 95% confidence interval [CI] 1.02-1.10), and lower in nulliparous women (adjusted OR 0.92; 95% CI 0.86-0.98). In the adjusted analyses, older age, female sex, smoking, overweight, and being hypertensive were independently associated with the presence of hemorrhoidal disease. The prevalence of hemorrhoidal disease was positively associated with body mass index and waist circumference in parous women. The prevalence of hemorrhoidal disease was higher in older age, females, ever-smokers, and hypertensive participants. The association of excess adiposity with the prevalence of hemorrhoidal disease differed by sex and parity.

Comparison of blowhole colostomy and loop ostomy for palliation of acute malignant colonic obstruction.

PURPOSE: Surgery to create a stoma for decompression might be required for unresectable stage IV cancer patients with complete colonic obstruction. The aim of this study was to compare the results of blowhole colostomy with those of loop ostomy. METHODS: Palliative ileostomy or colostomy procedures performed at a single center between January 2011 and October 2020, were analyzed retrospectively. Fifty-nine patients were identified during this period. The demographic characteristics and outcomes between the blowhole colostomy group (n=24) and the loop ostomy group (n=35) were compared. RESULTS: The median operative time tended to be shorter in the blowhole colostomy group (52.5 minutes; interquartile range [IQR], 43-65) than in the loop ostomy group (60 minutes; IQR, 40-107), but the difference did not reach statistical significance (P=0.162). The median length of hospital stay was significantly shorter with blowhole colostomy (blowhole, 13 days [IQR, 9-23]; loop, 21 days [IQR, 14-37]; P=0.013). Mean cecum diameter was significantly larger in the blowhole group than in the loop group (8.83±1.91 cm vs. 6.78±2.36 cm, P=0.001), and the emergency operation rate was higher in the blowhole group than in the loop group (22 of 24 [91.7%] vs. 23 of 35 [65.7%], P=0.021). CONCLUSION: In surgical emergencies, diverting a blowhole colostomy can be safe and effective for palliative management of colonic obstruction in patients with end-stage cancer and might reduce the operative time in emergent situations.

Safety of appendectomy during pregnancy in the totally laparoscopic age.

Purpose: Acute appendicitis is the most common nonobstetric indication for surgical intervention during pregnancy. In the argument of the optimal surgical approach to acute appendicitis in pregnancy, laparoscopy seems to be won with a similar complication rate and shorter postoperative recovery than open. We aimed to compare perioperative outcomes of appendectomy in pregnant and nonpregnant women in the totally laparoscopic age. Methods: We retrospectively analyzed 556 nonincidental appendectomies performed in women (aged 18-45 years) between January 2014 and December 2018. To reduce the confounding effects, we used propensity score considering the variables age, American Society of Anesthesiologists physical status classification, and the operative finding; whether the appendicitis was simple or complicated. After propensity score matching, the outcomes of 15 pregnant women were compared with those of the 30 nonpregnant women. Results: All the operations were performed with laparoscopy. Most of the pregnant cases were in their first and second trimester. The postoperative morbidity rate was significantly higher in the pregnant group before propensity score matching; however, the significance disappeared after matching. Operative outcomes and the parameters related to the postoperative recovery were not different between the two groups. Two patients in their first trimester decided to terminate the pregnancy after appendectomy. One patient in her second trimester experienced preterm labor which was resolved spontaneously. There was no other obstetric adverse outcome. Conclusion: In the laparoscopy age, appendectomy during pregnancy is safe and not associated with a significantly increased risk of postoperative complication.

An Unusual Case of Colon Perforation With Multiple Transmural Ulcers After Use of Polmacoxib and Everolimus in a Metastatic Breast Cancer Patient.

Everolimus (Afinitor) is an inhibitor of mammalian target of rapamycin. Polmacoxib (Acelex) is a nonsteroidal anti-inflammatory drug that belongs to the cyclooxygenase-2 (COX-2) inhibitor family and is mainly used for treatment of arthritis. Intestinal perforation has not been reported previously as a complication of everolimus, and perforation of the lower intestinal tract caused by a selective COX-2 inhibitor is extremely rare. We present here a case of colon perforation that occurred after use of polmacoxib in a metastatic breast cancer patient who had been treated with everolimus for the preceding six months.

Clinicopathological characteristics and outcomes of gastrointestinal stromal tumors with high progranulin expression.

BACKGROUND & AIMS: Progranulin (PGRN) is known to promote tumorigenesis and proliferation of several types of cancer cells. However, little is known about the clinicopathological features of patients with gastrointestinal stromal tumors (GISTs) with regard to PGRN expression. METHODS: A retrospective analysis was performed on patients with GISTs who underwent curative surgical resection between 2007 and 2017. PGRN expression was evaluated by immunohistochemical (IHC) analysis and semi-quantitatively categorized (no expression, 0; weak, 1+; moderate, 2+; strong, 3+). Tumors with a staining intensity of 2+ or 3+ were considered high PGRN expression. RESULTS: Fifty-four patients were analyzed; 31 patients (57%) were male. The median age at surgery was 60 years (range, 33-79), and the most common primary site was the stomach (67%). Thirty-five patients (65%) had spindle histology; 42 patients (78%) were separated as a high-risk group according to the modified National Institutes of Health (NIH) classification. High PGRN-expressing tumors were observed in 27 patients (50%), had more epithelioid/mixed histology (68% vs. 32%; p = 0.046), and KIT exon 11 mutations (76% vs. 24%; p = 0.037). Patients with high PGRN-expressing tumors had a worse recurrence-free survival (RFS) (36% of 5-year RFS) compared to those with low PGRN-expressing tumors (96%; p<0.001). Multivariate analysis showed that high PGRN expression and old age (>60 years) were independent prognostic factors for poor RFS. CONCLUSIONS: High PGRN-expressing GISTs showed more epithelioid/mixed histology and KIT exon 11 mutations. PGRN overexpression was significantly associated with poor RFS in patients with GISTs who underwent curative resection.

Development of JAK inhibitors for the treatment of immune-mediated diseases: kinase-targeted inhibitors and pseudokinase-targeted inhibitors.

JAKs are a family of intracellular tyrosine kinases consisting of four members, JAK1, JAK2, JAK3, and TYK2. They are key components of the JAK-STAT pathway that transmit signals of many cytokines involved in the pathogenesis of numerous immune-mediated diseases and have been major molecular targets in developing new drugs for the treatment of such diseases. Some small-molecule inhibitors of JAKs have been approved by the FDA for rheumatoid arthritis, psoriatic arthritis, and inflammatory bowel disease. Now, newer JAK inhibitors with isoform-selectivity among the four different JAKs are being developed, with the aim of improving clinical outcomes compared with earlier developed drugs with pan-JAK inhibition. Most of these selective inhibitors target the kinase domains of JAKs, functioning through the traditional inhibition mode of kinases; but recently those that target their pseudokinase domains, allosterically inhibiting the enzymes, have been under development. In this review, key characteristics, efficacy, and safety of FDA-approved and representative drugs in late stages of development are briefly described in order to provide clinical implications with respect to JAK inhibitor selectivity and future development perspectives. The recent development of pseudokinase-targeted inhibitors of JAKs is also included.