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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.
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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.
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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.
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Ablation par cathéter , Tumeurs du côlon , Tumeurs colorectales , Tumeurs du foie , Tumeurs du poumon , Ablation par radiofréquence , Humains , Pronostic , Études rétrospectives , Ablation par cathéter/effets indésirables , Tumeurs du poumon/imagerie diagnostique , Tumeurs du poumon/chirurgie , Ablation par radiofréquence/méthodes , Tomodensitométrie à faisceau conique , Tumeurs colorectales/anatomopathologie , Résultat thérapeutique , Tumeurs du foie/chirurgieRÉSUMÉ
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.
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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.
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Eczéma atopique , Humains , Eczéma atopique/traitement médicamenteux , Eczéma atopique/anatomopathologie , Cytokines/métabolisme , Lymphocytes auxiliaires Th2 , Cellules Th17 , Janus kinasesRÉSUMÉ
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.
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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.
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Laparoscopie , Tumeurs du rectum , Humains , Études rétrospectives , Vessie urinaire/chirurgie , Complications postopératoires/diagnostic , Complications postopératoires/épidémiologie , Complications postopératoires/étiologie , Tumeurs du rectum/chirurgie , Laparoscopie/effets indésirablesRÉSUMÉ
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.
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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.
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Hémorroïdes/épidémiologie , Adiposité , Adulte , Facteurs âges , Sujet âgé , Coloscopie , Études transversales , Femelle , Hémorroïdes/diagnostic , Humains , Hypertension artérielle/diagnostic , Hypertension artérielle/épidémiologie , Mâle , Adulte d'âge moyen , Obésité/diagnostic , Obésité/épidémiologie , Parité , Valeur prédictive des tests , Grossesse , Prévalence , Appréciation des risques , Facteurs de risque , Séoul/épidémiologie , Facteurs sexuels , Fumer/effets indésirables , Fumer/épidémiologie , Facteurs temps , Jeune adulteRÉSUMÉ
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.
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Tumeurs gastro-intestinales , Tumeurs stromales gastro-intestinales , Régulation de l'expression des gènes tumoraux , Protéines tumorales/biosynthèse , Progranulines/biosynthèse , Adulte , Sujet âgé , Survie sans rechute , Femelle , Tumeurs gastro-intestinales/métabolisme , Tumeurs gastro-intestinales/mortalité , Tumeurs gastro-intestinales/anatomopathologie , Tumeurs gastro-intestinales/chirurgie , Tumeurs stromales gastro-intestinales/métabolisme , Tumeurs stromales gastro-intestinales/mortalité , Tumeurs stromales gastro-intestinales/anatomopathologie , Tumeurs stromales gastro-intestinales/chirurgie , Humains , Mâle , Adulte d'âge moyen , Études rétrospectives , Taux de survieRÉSUMÉ
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.
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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.
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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.
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Antinéoplasiques/usage thérapeutique , Développement de médicament , Maladies du système immunitaire/traitement médicamenteux , Inhibiteurs des Janus kinases/usage thérapeutique , Janus kinases/antagonistes et inhibiteurs , Animaux , Antinéoplasiques/effets indésirables , Humains , Maladies du système immunitaire/enzymologie , Maladies du système immunitaire/immunologie , Inhibiteurs des Janus kinases/effets indésirables , Janus kinases/métabolisme , Thérapie moléculaire ciblée , Transduction du signalRÉSUMÉ
PURPOSE: Choosing the appropriate antibiotic is important for treatment of complicated appendicitis. However, increasing multidrug resistant bacteria have been a serious problem for successful treatment. This study was designed to identify bacteria isolated from patients with complicated appendicitis and reveal their susceptibilities for antibiotics and their relationship with patient clinical course. METHODS: This study included patients diagnosed with complicated appendicitis and examined the bacterial cultures and antimicrobial susceptibilities of the isolates. Data were retrospectively collected from medical records of Kangbuk Samsung Hospital from January 2008 to February 2018. RESULTS: The common bacterial species cultured in complicated appendicitis were as follows: Escherichia coli (n=113, 48.9%), Streptococcus spp. (n=29, 12.6%), Pseudomonas spp. (n=23, 10.0%), Bacteriodes spp. (n=22, 9.5%), Klebsiella (n=11, 4.8%), and Enterococcus spp. (n=8, 3.5%). In antibiotics susceptibility testing, the positive rate of extended-spectrum beta lactamase (ESBL) was 9.1% (21 of 231). The resistance rate to carbapenem was 1.7% (4 of 231), while that to vancomycin was 0.4% (1 of 231). E. coli was 16.8% ESBL positive (19 of 113) and had 22.1% and 19.5% resistance rates to cefotaxime and ceftazidime, respectively. Inappropriate empirical antibiotic treatment (IEAT) occurred in 55 cases (31.8%) and was significantly related with organ/space surgical site infection (SSI) (7 of 55, P=0.005). CONCLUSION: The rate of antibiotic resistance organisms was high in community-acquired complicated appendicitis in Koreans. Additionally, IEAT in complicated appendicitis may lead to increased rates of SSI. Routine intraoperative culture in patients with complicated appendicitis may be an effective strategy for appropriate antibiotic regimen.
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PURPOSE: The low rate of recurrent appendicitis after initial nonsurgical management of complicated appendicitis supports the recently implemented strategy of omitting routine interval appendectomy. However, several reports have suggested an increased incidence rate of neoplasms in these patients. We aimed to identify the risk of neoplasms in the population undergoing interval appendectomy. METHODS: This study retrospectively analyzed consecutive cases of appendicitis that were treated surgically between January 2014 and December 2018 at a single tertiary referral center. Patients were divided into 2 groups depending on whether they underwent immediate or interval appendectomy. Demographics and perioperative clinical and pathologic parameters were analyzed. RESULTS: All 2,013 adults included in the study underwent surgical treatment because of an initial diagnosis of acute appendicitis. Of these, 5.5% (111 of 2,013) underwent interval appendectomy. Appendiceal neoplasm was identified on pathologic analysis in 36 cases (1.8%). The incidence of neoplasm in the interval group was 12.6% (14 of 111), which was significantly higher than that of the immediate group (1.2% [22 of 1,902], P < 0.001). CONCLUSION: The incidence rate of neoplasms was significantly higher in patients undergoing interval appendectomy. These findings should be considered when choosing treatment options after successful nonsurgical management of complicated appendicitis.
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Progranulin (PGRN) has been characterized as an autocrine growth and survival factor and is known to stimulate tumorigenesis and proliferation of several types of cancer cell. However, little is known about the prognostic role of PGRN in colorectal cancer (CRC). A retrospective analysis was performed for patients with colorectal cancer who underwent curative resection between May 2013 and June 2015. PGRN expression in tumor cells was semi-quantitatively categorized (no expression, 0; weak/focal, 1+; moderate/focal or diffuse, 2+; strong/diffuse, 3+), and high expression was considered for tumors graded ≥2+ staining intensity. A total of 109 patients (28 stage I, 32 stage II, and 49 stage III) were analyzed. Thirty-eight patients (35%) had tumors with high PGRN expression, and there was a trend of elevated pre-operative CEA and CA19-9 levels in patients with high PGRN-expressing tumors compared to those with low PGRN-expressing tumors (CEA, 49% vs. 21%; CA19-9, 21% vs. 7%). The 3-year recurrence-free survival (3Y-RFS) and overall survival rates were 83.7% (95% CI, 76.8-90.6) and 96.0% (95% CI, 92.3-99.7), respectively. Patients with high PGRN-expressing tumors had a worse rate of 3Y-RFS (66.8%) compared to those with low PGRN-expressing tumors (92.4%; p = 0.010). Multivariate analysis showed that high PGRN expression, age (>66 years), stage (III), and perineural invasion (+) were independent prognostic factors associated with poor RFS after adjusting for confounding factors including sex, MSI, tumor location, KRAS, and lympho-vascular invasion. PGRN overexpression was significantly associated with poor RFS in patients with CRC who have undergone curative resection.
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Marqueurs biologiques tumoraux/analyse , Tumeurs colorectales/anatomopathologie , Progranulines/biosynthèse , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Tumeurs colorectales/mortalité , Tumeurs colorectales/chirurgie , Procédures de chirurgie digestive , Survie sans rechute , Femelle , Humains , Mâle , Adulte d'âge moyen , Pronostic , Études rétrospectivesRÉSUMÉ
INTRODUCTION: Colonoscopy is a safe and effective procedure, but it is also an inevitably invasive one. Laparoscopic repair of colonoscopic perforations has been reported to be a safe and effective treatment. AIM: We present our surgical technique and outcomes of laparoscopic repairs using an endoscopic linear stapler for iatrogenic colonic perforation during screening colonoscopy. MATERIAL AND METHODS: Laparoscopic repair using an endoscopic linear stapler for iatrogenic colonic perforation during screening colonoscopy was performed by two experienced laparoscopic surgeons on 14 consecutive patients between April 2010 and December 2017 at our hospital. Using prospectively collected data, an observational study was performed on a per protocol basis. RESULTS: The mean age of the 14 patients who underwent laparoscopic repair was 56.6 ±9.1 years. The most common perforation site was the sigmoid colon in 10 (71.4%) patients, followed by the rectosigmoid junction in 3 (21.4%) patients and the splenic flexure in 1 (7.1%) patient. The median perforation size was 10 (range: 5-30) mm. The mean operation time was 73.9 ±28.2 min. Postoperative complications occurred in 1 (7.1%) patient. There was no postoperative mortality or reoperation within 30 days after surgery. The median time to tolerance of a regular diet was 5 (range: 3-6) days. The median postoperative hospital stay was 8.5 (range: 5-15) days. CONCLUSIONS: Laparoscopic repair using an endoscopic linear stapler is a safe, easy, and effective surgical technique to treat colonic perforation related to screening colonoscopy.
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BACKGROUND: The occurrence of pancreatic fistulae (PF) after pancreatectomy is the main cause of prolonged hospital stay, delayed chemotherapy, poor quality of life and post-operative death. The surgical drainage after pancreatectomy can induce ascending infection, early removal is recommended if the possibility of PF is low. The present study analysed the risk factors and predictors of PF, and confirmed the significance of drain fluid amylase concentration (DFA, U/L) among various factors identified. On the basis of these results, we tried to evaluate the practical clinical applicability of DFA and obtain appropriate baseline values. METHODS: From January 2014 to December 2017, 117 patients underwent major pancreatectomy with pylorus-preserving pancreatoduodenectomy, Whipple procedure, subtotal pancreatectomy or distal pancreatectomy. This study retrospectively collected and analysed demographics, pathological results and prognoses of these patients. RESULTS: Multivariate analysis indicated that the DFA obtained on day 3 after surgery (DFA 3) was the only predictor of PF with statistical significance (P < 0.001). Of all the factors tested, area under the curve was highest for DFA 3 (0.89). In addition, of all the factors tested, DFA 3 with a cut-off value of 1004 U/L had the best sensitivity (92%) and specificity (82%). CONCLUSIONS: DFA 3 of a cut-off value of 1004 U/L might be determined to be the best predictor of PF, and early removal of the surgical drain could be considered if DFA (1004 U/L) is lower than the cut-off value at 3 days after surgery.
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Amylases/analyse , Drainage/méthodes , Pancréas/enzymologie , Pancréatectomie/effets indésirables , Fistule pancréatique/diagnostic , Tumeurs du pancréas/chirurgie , Soins postopératoires/méthodes , Sujet âgé , Liquides biologiques/composition chimique , Femelle , Études de suivi , Humains , Mâle , Adulte d'âge moyen , Pancréas/chirurgie , Fistule pancréatique/enzymologie , Fistule pancréatique/étiologie , Complications postopératoires , Valeur prédictive des tests , Études rétrospectivesRÉSUMÉ
BTK is a key component of B-cell receptor signaling and functions as an important regulator of cell proliferation and survival in B-cell malignancies. The first-in-class BTK inhibitor ibrutinib is a small molecule drug that binds covalently to BTK and has been proved to be an effective treatment for various B-cell malignancies. However, it has off-target activities on non-BTK kinases that are related to side effects or might be translated into clinical limitations, with resistance to ibrutinib also reported. Much progress has been made in the development of more selective and second-generation BTK inhibitors. A recent shift in the mechanisms of action of BTK inhibitors is noteworthy, and novel inhibitors acting through noncovalent BTK inhibition are now being developed. This review describes key characteristics of ibrutinib, including current issues of its clinical use, and summarizes preclinical properties and clinical developments of second-generation BTK inhibitors for the treatment of B-cell malignancies. A review of novel noncovalent BTK inhibitors are also included.