Safety and Efficacy of Oral Nalbuphine on Postoperative Pain in Hemorrhoidectomy Patients: A Randomized, Double-blind, Placebo-controlled, Pivotal Trial.

OBJECTIVES: Severe postoperative pain requiring opioid treatment has been reported in 20% to 40% of hemorrhoidectomy patients. Compared with morphine, nalbuphine offers better hemodynamic stability, a lower risk of respiratory depression, and a lower potential for addiction. Nalbuphine was developed from the intravenous form into an oral form (PHN131) to alleviate moderate-to-severe pain. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled, multiple-dose, parallel-design trial was conducted to evaluate the safety and efficacy of PHN131 in patients undergoing hemorrhoidectomy. Eligible patients were randomly assigned to receive either PHN131 soft capsules containing nalbuphine hydrochloride 60 mg or placebo capsules. Intramuscular diclofenac was the rescue analgesic. Pain was measured by the area under the curve of mean Visual Analog Scale pain intensity scores. RESULTS: Visual Analog Scale results in patients receiving PHN131 were significantly lower than placebo group scores through 48 hours postoperatively (149.2±75.52 vs. 179.6±65.97; P =0.0301). According to Brief Pain Inventory Short-Form scores, the impact of pain on quality of life was significantly smaller for the PHN131 group than for the placebo group. Time to the first use of diclofenac postoperatively was significantly longer in the PHN131 group than in the placebo group. The cumulative dosage of diclofenac in the PHN131 group was only around half of that in the placebo group ( P <0.0001). Drug-related adverse events were mild-to-moderate and resolved by the treatment end. No drug-related severe adverse events were observed. DISCUSSION: Our findings demonstrate that PHN131 is effective and well-tolerated in the treatment of moderate-to-severe post hemorrhoidectomy pain and may provide another option for patients to control their pain.

Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas.

BACKGROUND: Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin. METHODS: Microbiota composition was determined through 16S rRNA V3-V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as "tri-part samples") in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria. RESULTS: Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells. CONCLUSION: This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.

The Combination of Sleep Disorders and Depression Significantly Increases Cancer Risk: A Nationwide Large-Scale Population-Based Study.

Introduction: Sleep disorders, depression, and cancer have become increasingly prevalent worldwide. However, it is unknown whether coexistence of sleep disorders and depression influences the risk of cancer development. Therefore, we conducted a nationwide population-based study to examine this association among patients in Taiwan. Materials and Methods: A total of 105,071 individuals diagnosed with cancer and 420,284 age- and sex-matched patients without a diagnosis of cancer between 2000 and 2015 were identified from Taiwan's National Health Insurance Research Database. The underlying chronic diseases of patients that may developed cancer were gathered and studied as the predictor. A multivariate Cox proportional odds model was used to estimate the crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) to estimate the interaction effect between sleep disorders and depression on the risk of cancer. Results: After adjusting for age, sex, comorbidities, and other covariates, the cancer group was associated with increased exposure to sleep disorders than the non-cancer group (aOR = 1.440, 95% CI = 1.392−1.489, p < 0.001). In addition, patients with both sleep disorders and depression were at an even higher risk for cancer than the general population (aOR = 6.857, p < 0.001). Conclusions: This retrospective cohort study shows that patients with both sleep disorders and depression are at a higher risk of cancer. Clinically, a meticulous cancer risk evaluation is recommended for patients with both sleep disorders and depression.

Early botulinum toxin injection reduces pain after hemorrhoidectomy: a pilot study.

BACKGROUND: Hemorrhoidectomy is the standard procedure for treating high-grade hemorrhoids. However, postoperative pain usually causes patients to delay or refuse surgical treatment. Because maximal resting pressure in the internal anal sphincter plays a major role in post-hemorrhoidectomy pain, Botulinum toxin injections have been proposed to reduce it. However, the optimal timing of Botulinum toxin injections is still unclear. The aim of the present study was to compare the effectiveness of early and intraoperative Botulinum toxin injections for postoperative pain control. METHODS: In this pilot study, we enrolled patients who had grade III or IV hemorrhoids and underwent Ferguson hemorrhoidectomy at a single tertiary care center from October 1, 2018 to November 30, 2020. The experimental group received 50 U Botulinum toxin injections to the internal anal sphincter 1 week before the operation, and the control group received injections intraoperatively. The primary endpoint was the daily maximal and resting visual analogue scale (VAS) score recorded from postoperative days 0-6. The secondary endpoints were analgesia requirements, number of bowel movements per day, healing time, and postoperative length of stay. Power of the daily resting VAS score is at least 93%, but the power of the daily maximal VAS is a little lower (71%) (calculated by G*Power 3.1.9.2). RESULTS: Sixty-two patients (male: female = 27:35; mean age = 47.6 ± 13.1 years) were randomized to the experimental group (n = 31) or control group (n = 31). The experimental group  (n = 31) showed significantly shorter postoperative hospital stay than the controls (n = 31; p = 0.019). A generalized estimating equations model revealed that the group that received Botulinum toxin  yielded a significantly lower maximal (OR 0.4, 95% CI 0.2-1.0, p = 0.041) and resting (OR 0.4, 95% CI 0.2-0.7, p < 0.001) VAS compared to controls at all time points. The Botulinum toxin group also had significantly less resting pain from postoperative days 1-5, and lower maximal subjective pain scores on postoperative days 1 (p = 0.024) and 4 (p = 0.044). Similar trends were observed on other days. CONCLUSIONS: Early Botulinum toxin injection produced shorter hospital stays, and less reported pain after hemorrhoidectomy than intraoperative injections, especially for pain at rest. TRIAL REGISTRATION: Identifier: NCT04485780 on ClinicalTrials.gov (retrospectively registered).

Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide in 2020. Colonoscopy and the fecal immunochemical test (FIT) are commonly used as CRC screening tests, but both types of tests possess different limitations. Recently, liquid biopsy-based DNA methylation test has become a powerful tool for cancer screening, and the detection of abnormal DNA methylation in stool specimens is considered as an effective approach for CRC screening. The aim of this study was to develop a novel approach in biomarker selection based on integrating primary biomarkers from genome-wide methylation profiles and secondary biomarkers from CRC comorbidity analytics. A total of 125 differential methylated probes (DMPs) were identified as primary biomarkers from 352 genome-wide methylation profiles. Among them, 51 biomarkers, including 48 hypermethylated DMPs and 3 hypomethylated DMPs, were considered as suitable DMP candidates for CRC screening tests. After comparing with commercial kits, three genes (ADHFE1, SDC2, and PPP2R5C) were selected as candidate epigenetic biomarkers for CRC screening tests. Methylation levels of these three biomarkers were significantly higher for patients with CRC than normal subjects. The sensitivity and specificity of integrating methylated ADHFE1, SDC2, and PPP2R5C for CRC detection achieved 84.6% and 92.3%, respectively. Through an integrated approach using genome-wide DNA methylation profiles and electronic medical records, we could design a biomarker panel that allows for early and accurate noninvasive detection of CRC using stool samples.

Two-Person Colonoscopy as a Training Approach to Non-sedation Colonoscopy.

BACKGROUND: Reported learning curves of colonoscopy vary from 94 to 275 cases and focus on one-person colonoscopy. Our aim was to evaluate the learning curve of two-person non-sedation colonoscopy for trainees in a single tertiary care hospital. PATIENTS AND METHODS: We conducted a retrospective study in 1264 patients who underwent diagnostic or screening colonoscopies in a single institution from August 2012 to January 2013. Most of the patients (1174/1264) did not receive sedation during the procedure. All procedures were performed under two-person control. Two third-year residents who received previous colonoscopic training via a plastic model were the trainees. RESULTS: In comparison to the performance of 5 staff members, the colonoscopic outcomes showed no significant differences in the completion rates (77.2% vs. 79.8%, P = .382), average polyp numbers (.9 ± 1.7 vs. 1.0 ± 1.8, P = .453), polyp detection rates (43.5% vs. 46.3%, P = .434), or intubation lengths (96.4 ± 29.3 vs. 96.3 ± 26.7 cm, P = .939). The total procedure times for the 2 groups were 17.2 ± 10.6 minutes (trainees) and 12.9 ± 7.8 minutes (staff) (P < .001). CONCLUSION: Trainees achieved acceptable outcomes over an 81-97 case learning curve under a two-person non-sedation colonoscopy technique, an approach with potential as a transition to single-operator colonoscopy.

A Modified Bowel Preparation Regimen for Colonoscopy Providing the Patients' Satisfaction and Convenience.

BACKGROUND A complete cleansing of the bowel is a critical factor that impacts the diagnostic accuracy of colonoscopies. However, the common bowel preparation regimen of two 45 mL doses of sodium phosphate (2×NaP) often leads to uncomfortable symptoms and subsequently lower patient adherence. To improve patient adherence and satisfaction, we proposed a modified regimen composed of two sennoside tablets and one bottle of NaP (S+NaP) and we then evaluated bowel preparation quality and patient satisfaction. MATERIAL AND METHODS A total of 531 patients who underwent colonoscopies at the outpatient coloproctology clinic from January 2016 to December 2016 were retrospectively reviewed. Eligible patients were divided into two groups: S+NaP group (n=93) and 2×NaP group (n=60). We compared bowel preparation quality, adenoma detection rate (ADR), self-reported patient satisfaction scores, and adverse events among the two groups. RESULTS Regarding high bowel preparation quality, our results showed that there was no significant difference among the two groups (p=0.775), as well as no significant differences in ADRs (p=0.187). However, a lower proportion of nausea was found in the S+NaP group compared to the 2×NaP group (24.7% versus 41.7%, respectively, p=0.028). In addition, patients in the S+NaP group were more likely to be very satisfied with the regimen compared with patients in the 2×NaP group (odds ratio: 5.58; 95% confidence interval: 2.36-13.213, p<0.001). CONCLUSIONS Our modified bowel preparation regimen, S+NaP, yielded significantly higher patient satisfaction with less nausea while maintaining similar bowel preparation quality.

Oral tegafur-uracil as metronomic therapy following intravenous FOLFOX for stage III colon cancer.

The purpose of this study was to estimate the impact of metronomic therapy with oral tegafur-uracil (UFUR) following an intravenous FOLFOX regimen as surgical adjuvant chemotherapy on the overall survival (OS) and disease-free survival (DFS) of stage III colon cancer patients. From the retrospective database of patients who underwent a surgical resection for colorectal cancer at the Tri-Service General Hospital from October 2008 through December 2014, stage III colon carcinomas treated with radical R0 resection were reviewed. One hundred thirty two patients were treated with a FOLFOX regimen (comparison group), and 113 patients were treated with the same regimen followed by additional oral UFUR (UFUR group). The clinical characteristics and mean age of the comparison and UFUR groups were similar. Furthermore, for all study patients, DFS was not significantly different between the two groups. However, 5-year OS rates were 86.8% and 68.5% in the UFUR and comparison groups, respectively (p = 0.0107). Adding UFUR to a FOLFOX regimen was found to significantly improve the OS in patients with stage III colon cancer. UFUR as a maintenance therapy following FOLFOX regimen as an alternative therapeutic option for the treatment of stage III colon cancer patients.

Sebacoyl Dinalbuphine Ester Extended-release Injection for Long-acting Analgesia: A Multicenter, Randomized, Double-Blind, And Placebo-controlled Study in Hemorrhoidectomy Patients.

OBJECTIVES: This study was conducted to evaluate the safety and efficacy of single sebacoyl dinalbuphine ester (SDE) injection (150 mg/2 mL) when administered intramuscularly to patients who underwent hemorrhoidectomy for postoperative long-acting analgesia. METHODS: A total of 221 patients scheduled for hemorrhoidectomy from 6 centers in Taiwan were randomly divided into SDE group and placebo group, and received the treatment, vehicle or SDE, 1 day before the surgery. Visual analogue scale (VAS) was recorded up to 7 to 10 days. Pain intensity using VAS AUC through 48 hours after surgery was calculated as the primary efficacy endpoint. RESULTS: Area under the curve of VAS pain intensity scores (VAS AUC) through 48 hours after hemorrhoidectomy was significantly less in SDE group than those in placebo group (209.93 vs. 253.53). VAS AUC from the end of surgical procedure to day 7 was also significantly different between SDE and placebo group (630.79 vs. 749.94). SDE group consumed significantly less amount of other analgesics, such as PCA ketorolac and oral ketorolac. Median time from the end of surgery to the first use of pain relief medication was also shortened in the placebo group than in the SDE group. Most adverse events were assessed as mild and tolerable in both groups. DISCUSSION: SDE injection demonstrated an extended analgesia effect, with a statistically significant reduction in pain intensity through 48 hours and 7 days after hemorrhoidectomy.

Bilateral tension pneumothorax during colonoscopy in a patient with chronic obstructive pulmonary disease: a case report.

Colonoscopy is widely performed for the diagnosis and treatment of various colonic disorders and the screening and surveillance of colorectal neoplasia. According to research evidence, up to one-third of patients had at least 1 minor and transient gastrointestinal symptom after colonoscopy. Although severe complications developed uncommonly, they are potentially serious and life threatening. Here, we present the case of a 95-year-old man with chronic obstructive pulmonary disease who developed bilateral tension pneumothorax during therapeutic colonoscopy for sigmoid volvulus. In this case, air trapping resulting from the Valsalva maneuver under inadequate pain control may be the mechanism for fatal tension pneumothorax during colonoscopy.

Adjuvant chemotherapy with tegafur/uracil for more than 1 year improves disease-free survival for low-risk Stage II colon cancer.

BACKGROUND: It is uncertain whether adjuvant chemotherapy (CMT) improves survival in patients with low-risk Stage II colon cancer. We aimed to determine the disease-free survival (DFS) and 5-year overall survival (OS) of low-risk Stage II colon cancer patients treated with adjuvant tegafur/uracil (UFUR). METHODS: From January 2004 to December 2011, the follow-up status of 278 low-risk Stage II colon cancer patients who underwent surgery in a single medical center was retrospectively analyzed. These patients were divided into three groups based on whether they received adjuvant CMT with UFUR, adjuvant CMT with 5-fluorouracil, or surgery alone. DFS and 5-year OS curves were calculated using Kaplan-Meier survival analysis and Cox proportional hazards regression. RESULTS: In the study population, including 278 low-risk Stage II colon cancer patients with a mean age of 68.28 ± 13.01 years, 132 (47.5%) received adjuvant CMT with UFUR, 49 (17.6%) received adjuvant CMT with 5-fluorouracil, and 97 (34.9%) underwent radical surgery alone. At 5 years, the adjusted DFS and OS of low-risk Stage II colon cancer patients were 85.5% and 81.8%, respectively, in the surgery alone group and 97.9% and 96.2%, respectively, in the surgery plus UFUR > 12 months group (p = 0.004 and p = 0.098, respectively). In multivariate analysis, CMT with UFUR for more than 12 months increased DFS over surgery alone. There was no statistical difference in the 5-year OS. CONCLUSION: Adjuvant CMT treatment of low-risk Stage II colon cancer patients with UFUR for more than 12 months following surgery improves DFS over surgery alone.

Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression.

Development of colorectal cancer (CRC) involves sequential transformation of normal mucosal tissues into benign adenomas and then adenomas into malignant tumors. The identification of genes crucial for malignant transformation in colorectal adenomas (CRAs) has been based primarily on cross-sectional observations. In this study, we identified relevant genes using autologous samples. By performing genome-wide SNP genotyping and RNA sequencing analysis of adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissues (referred as tri-part samples) from individual patients, we identified 68 genes with differential copy number alterations and progressively dysregulated expression. Aurora A, SKA3, and DSN1 protein levels were sequentially up-regulated in the samples, and this overexpression was associated with chromosome instability (CIN). Knockdown of SKA3 in CRC cells dramatically reduced cell growth rates and increased apoptosis. Depletion of SKA3 or DSN1 induced G2/M arrest and decreased migration, invasion, and anchorage-independent growth. AURKA and DSN1 are thus critical for chromosome 20q amplification-associated malignant transformation in CRA. Moreover, SKA3 at chromosome 13q was identified as a novel gene involved in promoting malignant transformation. Evaluating the expression of these genes may help identify patients with progressive adenomas, helping to improve treatment.

Is preoperative bowel preparation necessary for gynecological oncology surgery?

OBJECTIVE: We investigated the necessity of preoperative bowel preparation for gynecological oncology surgery. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent gynecological oncology surgery with simultaneous colon or rectal resection between April 2005 and September 2014 at the Tri-Service General Hospital, Taipei, Taiwan. Patients were divided into two groups based on whether preoperative mechanical bowel preparation (MBP) was performed. Patient characteristics, including duration of antibiotic treatment, surgical procedures, and occurrence of surgical and nonsurgical complications, were compared. RESULTS: We enrolled 124 patients who underwent gynecological oncology surgery with simultaneous colon or rectal resection, of whom 76 received MBP and 48 did not receive mechanical bowel preparation. On comparison between the two groups, no significant differences were noted in the assessed patient characteristics, including mean age (p = 0.61), Federation of Gynecology and Obstetrics stage (p = 0.9), American Society of Anesthesiologists grade (p = 0.9), body mass index (p = 0.8), and residual tumor size (p = 0.86). Furthermore, duration of antibiotic treatment (p = 0.97), surgical procedures (p = 0.99), and total hospital days (p = 0.75), were not different between groups. The risk of surgical (p = 0.78) or nonsurgical (p = 1.0) complications was not significantly higher in the non-MBP group than in the MBP group. CONCLUSION: MBP provides no significant benefit during gynecological oncology surgery. Thus, preoperative MBP is not essential before gynecological oncology surgery and can be omitted.

Increased chemoresistance via Snail-Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative.

A tobacco-specific component, 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK), is a major risk factor for many cancers. Recent reports have demonstrated that NNK exposure may be associated with tumor progression and chemoresistance in certain cancers. However, the underlying NNK-induced mechanism contributing to the aggressiveness of colorectal cancer (CRC) has not been thoroughly studied. In this study, we used HT29 cells treated with NNK to simulate the long-term exposure of cigarette smoke. A comparative analysis was performed to evaluate cell proliferation, migration, and invasion as well as epithelial-mesenchymal transition (EMT) markers and drug-resistance genes expression, cancer stem cell (CSC) properties, and anti-apoptotic activity. Signaling pathways related to chemoresistance were also investigated. As a result, NNK exposure dose-dependently stimulates cell proliferation, enhance abilities of migration and invasion, induce EMT phenomenon, and attenuate apoptosis. Furthermore, NNK exposure also promotes the capabilities of sphere formation, upregulation of Snail, and overexpression of CD133, Nanog, OCT4, and the drug-resistant genes. Knockdown of Snail results in upregulation of Raf kinase inhibitor protein (RKIP), increased apoptosis, reversal of EMT phenomenon, and reducation of expression of CSC markers, all of which contribute to a decrease of chemoresistance. Our study demonstrates a number of related mechanisms that mediate the effect of NNK exposure on increasing CRC therapeutic resistance via the Snail signaling pathway. Targeting Snail may provide a feasible strategy for the treatment of CRC.

The molecular and clinical verification of therapeutic resistance via the p38 MAPK-Hsp27 axis in lung cancer.

UNLABELLED: Treatment failure followed by relapse and metastasis in patients with non-small cell lung cancer is often the result of acquired resistance to cisplatin-based chemotherapy. A cancer stem cell (CSC)-mediated anti-apoptotic phenomenon is responsible for the development of drug resistance. The underlying molecular mechanism related to cisplatin resistance is still controversial, and a new strategy is needed to counteract cisplatin resistance. We used a nonadhesive culture system to generate drug-resistant spheres (DRSPs) derived from cisplatin-resistant H23 lung cancer cells. The expressions of drug-resistance genes, properties of CSCs, and markers of anti-apoptotic proteins were compared between control cells and DRSPs. DRSPs exhibited upregulation of cisplatin resistance-related genes. Gradual morphological alterations showing epithelial-to-mesenchymal transition phenomenon and increased invasion and migration abilities were seen during induction of DRSPs. Compared with control cells, DRSPs displayed increased CSC and anti-apoptotic properties, greater resistance to cisplatin, and overexpression of p-Hsp27 via activation of p38 MAPK signaling. Knockdown of Hsp27 or p38 decreased cisplatin resistance and increased apoptosis in DRSPs. Clinical studies confirmed that the expression of p-Hsp27 was closely associated with prognosis. Overexpression of p-Hsp27 was usually detected in advanced-stage patients with lung cancer and indicated short survival. SUMMARY: DRSPs were useful for investigating drug resistance and may provide a practical model for studying the crucial role of p-Hsp27 in the p38 MAPK-Hsp27 axis in CSC-mediated cisplatin resistance. Targeting this axis using siRNA Hsp27 may provide a treatment strategy to improve prognosis and prolong survival in lung cancer patients.

Rectal cancer with complete clinical response after neoadjuvant chemoradiotherapy, surgery, or "watch and wait".

PURPOSE: The purpose of this study was to compare the outcomes of patients treated with chemoradiotherapy with a complete clinical response followed by either a "watch and wait" strategy or a total mesorectal excision. METHODS: This was an observational retrospective study from a single institute. Patients with locally advanced rectal cancer following chemoradiotherapy with a complete clinical response from January 1, 2007 to December 31, 2014 were included. RESULTS: The study population consisted of 18 patients who opted for a "watch and wait" policy and 26 patients who underwent radical surgery after achieving a complete clinical response. Patients had no documented treatment complications under the watch and wait policy, while 13 patients who underwent radical surgery experienced significant morbidity. There were two local recurrences in the watch and wait group; both were treated with salvage resection and had no associated mortality. In the radical surgery group, 1 patient showed an incomplete pathologic response (ypT0N1), and the remaining 25 patients showed complete pathologic responses; 1 had a distant recurrence, which was managed non-operatively, and 2 patients died of unrelated causes. The 5-year overall survival rate and median disease-free survival time were 100% and 69.78 months in the watch and wait group and 92.30% and 89.04 months in the radical surgery group. CONCLUSIONS: A watch and wait policy avoids the morbidity associated with radical surgery and preserves oncologic outcomes in our retrospective study from a single institute. It could be considered a therapeutic option in patients with locally advanced rectal cancer following chemoradiotherapy with a complete clinical response.

The outcome of 5-fluorouracil chemotherapy after the completion of neoadjuvant chemoradiotherapy, administered until 2 weeks before rectal cancer resection.

BACKGROUND: In most institutions, locally advanced rectal cancer is treated with neoadjuvant chemoradiotherapy followed by surgery 6-8 weeks later, allowing time for tumor response and recovery from chemoradiotherapy-related toxicities. In our hospital, we continuously administer chemotherapy after the completion of chemoradiotherapy, until 2 weeks before surgery for most patients. METHODS: This was a retrospective study. Patients received a diagnosis of adenocarcinoma of the rectum at our hospital between January 2003 and December 2008 and received neoadjuvant chemoradiotherapy and curative surgery. Chemoradiotherapy consisted of continuous infusion of 225 mg/m(2) 5-fluorouracil, 5 days per week. Radiation therapy was delivered at 1.8 Gy per day, 5 days per week for 5-6 weeks (median radiation dose, 50.4 Gy). Chemotherapy was continued until 2 weeks before surgery, and surgery was performed 6-8 weeks after completion of chemoradiotherapy. RESULTS: The study included 119 patients (median age, 61 years; range, 24-84 years). Twenty-nine patients (24.4%) had a complete response and 65 (54.6%) had a partial response. Over a median follow-up duration of 52 months, 10 patients experienced local recurrence and 18 had distant metastasis. The 5-year overall and disease-free survival rates were 80.6% and 72.9%, respectively. Grade 3-4 toxicity only occurred in 14 patients (11.8%). CONCLUSION: Continued chemotherapy with 5-fluorouracil after completing neoadjuvant chemoradiotherapy until 2 weeks before surgery for locally advanced rectal cancer results in a good pathological control rate, with low toxicity. Patients who achieved a complete pathological response had a better long-term oncological outcome than those who did not.

Removal of a Giant Rectosigmoid Phytobezoar without Laparotomy.

Bezoars are the uncommon result of ingestion of indigestible or poorly digestible substances. Phytobezoars are the most common bezoars in children. Small bowel obstruction, especially of the terminal ileum, is the most common complication. Colonic obstruction is rare. Most reviewed intestinal phytobezoars with obstruction necessitate laparotomy with enterotomy. Here, we report a rare case of giant rectosigmoid phytobezoar with near-total colonic obstruction. Successfully, removal of this bezoar by an alternative way of fragmentation with colonoscopy, not conventional enterotomy is needed. The patient recovered well and then discharged without any morbidity 2 days later.

Regulation of tumor progression via the Snail-RKIP signaling pathway by nicotine exposure in head and neck squamous cell carcinoma.

BACKGROUND: Recent studies suggest that long-term exposure of the carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK) found in tobacco smoke is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The underlying nicotine-mediated mechanism remains unclear. METHODS: An analysis of SCC-25 and Fadu cells with or without NNK exposure focusing on the evaluation of migration and invasion abilities, the expression of epithelial-mesenchymal transition, drug-resistance-related genes, properties of cancer stem cells (CSCs), and anti-apoptosis was performed. RESULTS: Long-term NNK exposure enhances migration and invasion with morphological alterations in a dose-dependently manner. Furthermore, NNK exposure also upregulates Snail, promotes sphere-forming ability, and overexpresses aldehyde dehydrogenase 1 (ALDH1), Nanog, OCT4, ABCG2, and MDR1. CONCLUSION: The current study confirmed that long-term NNK exposure plays a role in HNSCC by increasing anti-apoptosis and therapeutic resistance via the Snail-RKIP signaling pathway. Our data also suggest that α7 nicotinic acetylcholine receptor (α7-nAChR) inhibition or targeting Snail may provide a feasible rationale for preventing the progression of HNSCC.