Dual-Specificity Phosphatase 4 Promotes Malignant Features in Colorectal Cancer Through Cyclic-AMP Response Element Binding Protein/Protein Kinase CAMP-Activated Catalytic Subunit Beta Activation.

INTRODUCTION: Previous studies have demonstrated that Dual-specificity phosphatase 4 (DUSP4) plays an important role in the progression of different tumor types. However, the role and mechanism of DUSP4 in colorectal cancer (CRC) remain unclear. AIMS: We investigate the role and mechanisms of DUSP4 in CRC. METHODS: Immunohistochemistry was used to investigate DUSP4 expression in CRC tissues. Cell proliferation, apoptosis and migration assays were used to validate DUSP4 function in vitro and in vivo. RNA-sequence assay was used to identify the target genes of DUSP4. Human phosphokinase array and inhibitor assays were used to explore the downstream signaling of DUSP4. RESULTS: DUSP4 expression was upregulated in CRC tissues relative to normal colorectal tissues, and DUSP4 expression showed a significant positive correlation with CRC stage. Consistently, we found that DUSP4 was highly expressed in colorectal cancer cells compared to normal cells. DUSP4 knockdown inhibits CRC cell proliferation, migration and promotes apoptosis. Furthermore, the ectopic expression of DUSP4 enhanced CRC cell proliferation, migration and diminished apoptosis in vitro and in vivo. Human phosphokinase array data showed that ectopic expression of DUSP4 promotes CREB activation. RNA-sequencing data showed that PRKACB acts as a downstream target gene of DUSP4/CREB and enhances CREB activation through PKA/cAMP signaling. In addition, xenograft model results demonstrated that DUSP4 promotes colorectal tumor progression via PRKACB/CREB activation in vivo. CONCLUSION: These findings suggest that DUSP4 promotes CRC progression. Therefore, it may be a promising therapeutic target for CRC.

Impact of tumor size on overall survival and cancer-specific survival of early-onset colon and rectal cancer: a retrospective cohort study.

PURPOSE: This study aimed to investigate the impact of tumor size on survival in early-onset colon and rectal cancer. METHODS: Early-onset colon and rectal cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Tumor size was analyzed as both continuous and categorical variables. Several statistical techniques, including restricted cubic spline (RCS), Cox proportional hazard model, subgroup analysis, propensity score matching (PSM), and Kaplan-Meier survival analysis, were employed to demonstrate the association between tumor size and overall survival (OS) and cancer-specific survival (CSS) of early-onset colon and rectal cancer. RESULTS: Seventeen thousand five hundred fifty-one (76.7%) early-onset colon and 5323 (23.3%) rectal cancer patients were included. RCS analysis confirmed a linear association between tumor size and survival. Patients with a tumor size > 5 cm had worse OS and CSS, compared to those with a tumor size ≤ 5 cm for both early-onset colon and rectal cancer. Notably, subgroup analysis showed that a smaller tumor size (≤ 50 mm) was associated with worse survival in stage II early-onset colon cancer, although not statistically significant. After PSM, Kaplan-Meier survival curves showed that the survival of patients with tumor size ≤ 50 mm was better than that of patients with tumor size > 50 mm. CONCLUSION: Patients with tumors larger than 5 cm were associated with worse survival in early-onset colon and rectal cancer. However, smaller tumor size may indicate a more biologically aggressive phenotype, correlating with poorer survival in stage II early-onset colon cancer.

Construction and validation of a nomogram for predicting overall survival of patients with stage III/IV early-onset colorectal cancer.

Purpose: This study aimed to identify prognostic factors and develop a nomogram for predicting overall survival (OS) in stage III/IV early-onset colorectal cancer (EO-CRC). Methods: Stage III/IV EO-CRC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The datasets were randomly divided (2:1) into training and validation sets. A nomogram predicting OS was developed based on the prognostic factors identified by Cox regression analysis in the training cohort. Moreover, the predictive performance of the nomogram was assessed using the receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Subsequently, the internal validation was performed using the validation cohort. Finally, a risk stratification system was established based on the constructed nomogram. Results: Of the 10,387 patients diagnosed with stage III/IV EO-CRC between 2010 and 2015 in the SEER database, 8,130 patients were included. In the training cohort (n=3,071), sex, marital status, race/ethnicity, primary site, histologic subtypes, grade, T stage, and N stage were identified as independent prognostic variables for OS. The 1-, 3-, and 5-year area under the curve (AUC) values of the nomogram were robust in both the training (0.751, 0.739, and 0.723) and validation cohorts (0.748, 0.733, and 0.720). ROC, calibration plots, and DCA indicated good predictive performance of the nomogram in both the training and validation sets. Furthermore, patients were categorized into low-, middle-, and high-risk groups based on the nomogram risk score. Kaplan-Meier curve showed significant survival differences between the three groups. Conclusion: We developed a prognostic nomogram and risk stratification system for stage III/IV EO-CRC, which may facilitate clinical decision-making and individual prognosis prediction.

Psychological status of patients with functional anorectal pain and treatment efficacy of paroxetine in alleviating the symptoms: a retrospective study.

The aim of this study was to investigate the clinical characteristics, psychological status, sleep quality, and quality of life of patients with functional anorectal pain (FAP). The study also assessed the treatment efficacy of paroxetine in alleviating FAP symptoms. A retrospective comparative study of forty-three patients with FAP who were first treated with an anal plug compound glycolate suppository versus paroxetine combined with anal plug compound glycolate suppository between November 2021 and August 2022. Pain, quality of life, depression, anxiety and sleep quality were assessed before and after treatment by the Chinese version of the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), Health-related quality of life scale (The 12-Item Short-Form Health Survey, SF-12), 17-item Hamilton Depression Rating Scale (HDRS), 14-item Hamilton Anxiety Scale (HAMA), and Pittsburgh Sleep Quality Index (PSQI). A total of 46.5% of patients with FAP were found to have anxiety symptoms (HAMA ≥ 7), 37.2% of patients with FAP were found to have depressive symptoms (HDRS ≥ 8). A total of 32.6% of patients with FAP had sleep disorders (PSQI > 10). Within 1 week after drug withdrawal, the short-term efficacy rate of oral paroxetine was 95.5%. After treatment, the symptom pain score (VAS) and sleep score were lower than those before treatment (P < 0.01). In the areas of vitality (VT), Social Functioning (SF), and Mental Health (MH), the difference between the pre-treatment and 8 weeks posttreatment scores of the study group and the control group was statistically significant (P < 0.05). FAP patients have obvious symptoms of anxiety and depression, and the incidence of sleep disturbance is prevalent. Paroxetine, a typical serotonin reuptake inhibitor (SSRI), was able to alleviate depression, anxiety, and pain symptoms in FAP, which might have clinical application prospects.

Natural course of perianal abscess in infants: a real-world study.

Natural course of perianal abscess (PA) in infancy remains obscure. This study aimed to investigate the natural course of infants with PA after conservative treatment. A retrospective cohort study was conducted in infants with PA who were treated conservatively (due to the parents' refusal of surgery), for more than 2 months between 2014 and 2020 at a single tertiary center. 153 patients (149 boys and 4 girls) were identified. The median follow-up was 5.3 years (range 3-8.2 years). Initially, 119 patients (77.8%) were completely cured by conservative treatment, and 34 (22.2%) failed. Among the 34 patients, 23 continued conservative treatment (20 cure, 3 fistula formation) and 11 underwent surgery. After conservative treatment, the rate of fistula formation, abscess recurrence, and new-onset abscess were 15.0%, 4.6%, and 6.5%, respectively. Overall, 139 patients (90.8%) were cured conservatively without surgery, and 11 (7.2%) underwent surgical management. In addition, 3 (2.0%) patients developed fistula-in-ano (under observation). PA in infants may be a time-limited and self-limited condition. Conservative management should be the first choice of treatment in most cases. Longer periods of conservative treatment may achieve better clinical outcomes in selected cases. There will be a percentage of patients (about 10%) that would require surgical treatment.

Incision and Drainage With Primary Fistulotomy of Perianal Abscess Is Safe and Effective in Neonates: A Long-Term Follow-Up Study.

Objective: Perianal abscess (PA) in neonates is poorly understood, and its management remains controversial. The aim of this study was to compare incision and drainage (ID) with or without primary fistulotomy in the management of neonatal first-time PA. Methods: A retrospective comparative study was conducted for neonates with first-time PA treated with incision and drainage with primary fistulotomy (IDF) vs. ID between 2008 and 2017. Results: In total, 138 patients (137 boys and 1 girl) were identified; 65 in the IDF group and 73 in the ID group. The median follow-up was 6.5 years (range 4-13 years). Baseline characteristics were similar between the 2 groups. The cure rate in the IDF group (98.5%, 64/65) was significantly higher than that in the ID group (80.8%, 59/73; p = 0.001). The rate of fistula formation in the IDF group (1.5%, 1/65) was significantly lower than that in the ID group (13.7%, 10/73; p = 0.01). The rate of abscess recurrence was not statistically different (p = 0.12), even though the IDF group (0%, 0/65) seemed to have a better outcome than the ID group (5.5%, 4/73). No fecal incontinence was observed in any of our patients. Conclusions: First-time PA in neonates can be treated safely and effectively by the IDF or by ID alone. The former may be advantageous over the latter in terms of the rate of cure and fistula formation.

Rupture of sigmoid colon caused by compressed air.

Compressed air has been generally used since the beginning of the 20(th) century for various applications. However, rupture of the colon caused by compressed air is uncommon. We report a case of pneumatic rupture of the sigmoid colon. The patient was admitted to the emergency room complaining of abdominal pain and distention. His colleague triggered a compressed air nozzle against his anus as a practical joke 2 h previously. On arrival, his pulse rate was 126 beats/min, respiratory rate was 42 breaths/min and blood pressure was 86/54 mmHg. Physical examination revealed peritoneal irritation and the abdomen was markedly distended. Computed tomography of the abdomen showed a large volume of air in the abdominal cavity. Peritoneocentesis was performed to relieve the tension pneumoperitoneum. Emergency laparotomy was done after controlling shock. Laparotomy revealed a 2-cm perforation in the sigmoid colon. The perforation was sutured and temporary ileostomy was performed as well as thorough drainage and irrigation of the abdominopelvic cavity. Reversal of ileostomy was performed successfully after 3 mo. Follow-up was uneventful. We also present a brief literature review.

Spontaneous perforation of pyometra presenting as acute abdomen: a rare condition with considerable mortality.

Pyometra is an uncommon and potentially lethal disease that occurs mainly in postmenopausal women. Spontaneous perforation of pyometra presenting as acute abdomen is an extremely rare complication of pyometra, and the patients are always admitted to the emergency department. An additional case is reported herein. In addition, a literature review was performed between 1949 and 2015. A correct preoperative diagnosis was made in 21.05% of all the cases. Of all cases, 25.71% were associated with malignant disease. The mortality rate of spontaneous perforation of pyometra is 31.88%. Thus, it should be considered in the differential diagnosis of acute abdomen in elderly women. Total hysterectomy along with bilateral salpingo-oophorectomy is the preferred treatment. Administration of broad-spectrum antibiotics and postoperative intensive care support are essential to reduce the high mortality.

[Accuracy of endoscopic ultrasound in the preoperative staging and the guidance of transanal endoscopic microsurgery for rectal cancer].

OBJECTIVE: To explore the accuracy of endoscopic ultrasound (EUS) in preoperative staging of rectal cancer and to guide the treatment of transanal endoscopic microsurgery (TEM) in early rectal cancer. METHODS: Clinical data of 80 patients with rectal cancer receiving EUS examination for preoperative staging in our department between June and December 2012 were retrospectively analyzed. Consistence comparison of EUS preoperative staging and pathological staging was performed to identify the accuracy of EUS preoperative staging. All the patients underwent operation within 1 week after EUS examination. According to preoperative staging, early rectal cancer(Tis or T1N0M0) patients with lesions less 20 cm to anus underwent TEM. RESULTS: The overall accuracy of EUS for preoperative T stage was 68.8%(55/80), and for T1, T2, T3, T4 was 91.3%(73/80), 83.8%(68/80), 77.5%(62/80), 85.0%(67/80), which had a good consistence with postoperative pathological T staging(Kappa=0.562). The overall accuracy of EUS for preoperative N stage was 52.7%(39/74), and for N0, N1, N2 stage was 64.9%(48/74), 55.4%(41/74), 85.1%(63/74), which had a poor consistence with postoperative pathological N staging(Kappa=0.235). Six patients underwent TEM successfully, with mean operation time 99(65 to 123) min, without intraoperative and postoperative complication, and were discharged 2-3 days after operation. Enteroscope showed good recovery 1 month later. Pathology confirmed that all the lesions were early rectal cancer. During postoperative follow-up of 14.8 (11 to 19) months, there was no local recurrence and distant metastasis. CONCLUSION: Preoperative EUS has a good accuracy with pathologic T stage, and can guide TEM in early rectal cancer.