High ligation with posterior wall repair for inguinal hernia repair in young adults: a nationwide cohort study.

Purpose: This study evaluated the difference in the recurrence of inguinal hernia in young adult patients who underwent either high ligation alone or high ligation with posterior wall repair using nationwide data. Methods: This retrospective study included young adult patients (aged 16-30 years) who underwent surgery for inguinal hernia between June 1, 2013 and December 31, 2020. Data from the National Health Information Database from the Korea Health Insurance Service were used for this study. Patients were divided into 2 groups (high ligation alone and posterior wall repair). The primary outcome was the difference in recurrent inguinal hernia surgeries between the 2 groups. Results: Among the 10,803 patients included in the study, 947 underwent high ligation alone, and 9,856 underwent high ligation with posterior wall repair. Recurrence was observed in 18 patients (1.9%) in the high ligation only group and 84 (0.85%) in the high ligation with posterior wall repair group. Log-rank test findings revealed that recurrence was less frequent in the high ligation with posterior wall repair group than in the high ligation only group (P = 0.003). In the multivariate analysis of factors influencing recurrence, posterior wall repair (hazard ratio, 0.241; P = 0.001) was shown to significantly lower the recurrence. Conclusion: Posterior wall repair might be necessary for inguinal hernia repair in young adults.

Comprehensive RNA-sequencing analysis of colorectal cancer in a Korean cohort.

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers.

Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. Various CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, they have not been validated for Korean patients owing to the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles for 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array; the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5' untranslated, and first exon regions. However, hypomethylated positions were enriched in the open-sea regions considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon. The results showed a higher prevalence of microsatellite instability status and MLH1 methylation in tumors with high CMP signatures than in those with low or non-CIMP signatures. Therefore, our methylome analysis and dataset provide insights into applying CRC-associated methylation markers for Korean patients regarding cancer diagnosis and prognosis. [BMB Reports 2024; 57(3): 161-166].

The effect of circular stapler size on anastomotic stricture formation in colorectal surgery: A propensity score matched study.

BACKGROUND: Small circular staplers possess the advantage of being relatively easy to use when compared to larger circular staplers. However, there is some contention as to whether the use of small circular staples in colorectal surgery increases the incidence of anastomotic strictures. This study aimed to determine whether the frequency of anastomosis site stricture formation differs depending on stapler size when performing anastomosis in colorectal surgery. METHODS: Patients who underwent surgery for colon or rectal disease between June 1, 2009, and December 31, 2021, and who had circular staplers used for the formation of intestinal anastomoses post colectomy were included in our study. Propensity score matching with a 1:1 ratio using logistic regression was performed. The primary outcome was the anastomotic stricture rate, and the secondary outcome was total anastomotic complications. RESULTS: A total of 875 patients who were operated on by surgeons using 28/29-mm and 25-mm circular staplers were included. After propensity score matching, 106 patients were assigned to each group. Anastomotic strictures occurred in two cases (1.9%) from the 25-mm group and in four cases (3.8%) from the 28/29-mm group. There were no statistically significant differences between the two groups (p = 0.683). Anastomotic complications were observed in two cases (1.9%) from the 25-mm group and in six cases (5.7%) from the 28/29-mm group; no statistically significant differences were found (p = 0.280). CONCLUSION: Circular stapler size does not influence anastomotic stricture formation in colorectal surgery.

Personalised circulating tumour DNA assay with large-scale mutation coverage for sensitive minimal residual disease detection in colorectal cancer.

BACKGROUND: Postoperative minimal residual disease (MRD) detection using circulating-tumour DNA (ctDNA) requires a highly sensitive analysis platform. We have developed a tumour-informed, hybrid-capture ctDNA sequencing MRD assay. METHODS: Personalised target-capture panels for ctDNA detection were designed using individual variants identified in tumour whole-exome sequencing of each patient. MRD status was determined using ultra-high-depth sequencing data of plasma cell-free DNA. The MRD positivity and its association with clinical outcome were analysed in Stage II or III colorectal cancer (CRC). RESULTS: In 98 CRC patients, personalised panels for ctDNA sequencing were built from tumour data, including a median of 185 variants per patient. In silico simulation showed that increasing the number of target variants increases MRD detection sensitivity in low fractions (<0.01%). At postoperative 3-week, 21.4% of patients were positive for MRD by ctDNA. Postoperative positive MRD was strongly associated with poor disease-free survival (DFS) (adjusted hazard ratio 8.40, 95% confidence interval 3.49-20.2). Patients with a negative conversion of MRD after adjuvant therapy showed significantly better DFS (P < 0.001). CONCLUSION: Tumour-informed, hybrid-capture-based ctDNA assay monitoring a large number of patient-specific mutations is a sensitive strategy for MRD detection to predict recurrence in CRC.

Postoperative effects of laparoscopic Hartmann reversal: A multicenter propensity score matched study.

BACKGROUND: Although the advantages of laparoscopic Hartmann reversal (LHR) compared to open Hartmann reversal (OHR) have been reported in the literature, the number of multicenter studies with good matching investigating this topic is rare. In the present study, we aimed to confirm the advantages of LHR in terms of short-term outcomes through propensity score matching of LHR and OHR groups, using data collected from multiple institutions. METHODS: Patients who underwent Hartmann reversal at six institutions under the Catholic Medical Center of the Catholic University of Korea between January 1, 2005, and December 31, 2021, were included. The patients were divided into the LHR and OHR groups based on the technique used. The two groups were matched using propensity score matching (1:1 ratio, logistic regression with the nearest-neighbor method). The primary outcome was postoperative ileus (POI) frequency, and secondary outcomes were time to solid diet (days) and length of stay (days). RESULTS: Among 337 patients, propensity score matching was performed on 322, after excluding 15 who had undergone open conversion. Of these, 63 patients were assigned to each group through propensity score matching. There was no difference in the frequency of adhesiolysis (77.8% vs. 82.5%, p = 0.503) or the operation time. (210 (IQR 159-290) vs. 233 (IQR 160-280), p = 0.718) between the two groups. As the primary outcome, the LHR group showed significantly lower POI frequency than the OHR group. (4.8% vs. 22.2%, p = 0.0041) Regarding the secondary outcomes, the LHR group showed a shorter period to solid diet than the OHR group. The length of hospital stay was also significantly shorter in the LHR group (4 vs. 6, p < 0.0001; 9 vs. 12, p<0.0001). CONCLUSION: LHR is an effective method to ensure faster recovery of patients after surgery compared to OHR.

Advantages of using a polymeric clip versus an endoloop during laparoscopic appendectomy in uncomplicated appendicitis: a randomized controlled study.

BACKGROUND: Polymeric clips are easy to apply, but whether they present more advantages than endoloops is unclear. This single-center, open-label, randomized controlled trial study was conducted to compare the advantages of using a polymeric clip versus an endoloop in terms of the surgical time. METHODS: Adult patients who were diagnosed with acute appendicitis without perforation on preoperative abdominal computed tomography and underwent laparoscopic appendectomy between August 6, 2019, and December 26, 2022, were included. Single-blinded randomization was performed in a 1:1 ratio between the endoloop and polymeric clip groups. The primary endpoint was the difference in surgery time between the polymeric clip and endoloop groups. The secondary endpoints were the difference in the application time of each instrument, difference in operation and anesthesia fees, as well as the frequency of complications. RESULTS: The completed trial included 104 and 103 patients in the polymeric clip and endoloop groups, respectively. The median surgery time with a polymeric clip was shorter than that with an endoloop; however, the difference was not significant (18 min 56 s vs 19 min 49 s, p = 0.426). Interestingly, the median time from applying the instrument to appendiceal cutting in the polymeric clip group was significantly shorter than that in the endoloop group (49.0 s vs 84.5 s, p < 0.001). No significant difference was observed between the two groups in terms of surgical (p = 0.120) and anesthetic (p = 0.719) costs, as well as the total number of postoperative complications (p > 0.999). CONCLUSION: A polymeric clip is a safe instrument that can reduce the time from applying the instrument to appendiceal cutting, although it does not affect the overall surgical time and operation fee when performing laparoscopic appendectomy for uncomplicated appendicitis. TRIAL REGISTRATION: KCT0004154.

Mesh size may not affect recurrence in laparoscopic totally extraperitoneal repair of inguinal hernias.

A mesh is usually employed to cover defects when performing laparoscopic totally extraperitoneal repair (TEP) of inguinal hernias. However, there is insufficient evidence for an appropriate mesh size. Therefore, we aimed to compare the recurrence rate between large- and medium-mesh laparoscopic TEP. Patients who underwent laparoscopic TEP for primary inguinal hernias from January 2012 to March 2020 were included. We retrospectively reviewed electric medical records. The primary outcome was the difference in recurrence rate between the large and medium meshes. The large mesh was 10.3 × 15.7 cm, and the medium mesh was 7.9 × 13.4 cm or 9 × 13 cm. In total, 446 patients were included in the study. Of these patients, 177 were in the large-mesh group, and 269 were in the medium-mesh group. The average ages of the large- and medium-mesh groups were 58.4 and 56.9 years, respectively (P = .361). In both groups (large vs medium), males were dominant (93.2% vs 93.6%, P = .850), and indirect hernias (87.0% vs 88.1%, P = .740) were dominant. There was no difference in body mass index (P = .883) or hernia side (P = .770). Peritoneal tearing as an intraoperative complication occurred frequently in the large-mesh group (13.6% vs 3.3%, P < .001). During the mean follow-up period of 28 months, recurrence occurred in 3 (1.7%) and 13 (4.8%) patients in the large- and medium-mesh groups, respectively. However, there was no statistical significance (P = .262). Mesh size may not affect recurrence after laparoscopic TEP of primary inguinal hernias.

Short-Term Impact of Temporary Shutdown of a University-Affiliated Hospital on Patients With Colorectal Cancer During the Coronavirus Disease 2019 Pandemic.

Owing to in-hospital transmission of coronavirus disease 2019 (COVID-19), Uijeongbu St. Mary's Hospital, a university-affiliated hospital in South Korea, was temporarily closed for disinfection in March 2020. This study aimed to investigate the impact of both the hospital shutdown and the prolonged COVID-19 pandemic on short-term outcomes of colorectal cancer (CRC) patients. We retrospectively reviewed the clinicopathologic data of 607 patients who were surgically treated for CRC from May 2018 to September 2021. Nodal upstaging, higher lymphatic invasion and abdominoperineal resection rates for 3 months after the hospital resumed surgery following the shutdown in the first wave of the COVID-19 pandemic were detected, without worse short-term morbidity or mortality. The incidence of adverse pathologic features of CRC such as lymphatic, venous, and perineural invasion was higher throughout the COVID-19 pandemic era. Further follow-up of CRC patients treated in the pandemic era for long-term oncologic outcomes is needed.

Simultaneous Integrated Boost Volumetric Modulated Arc Therapy for Rectal Cancer: Long-Term Results after Protocol-Based Treatment.

Background: Volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) is an advanced form of radiotherapy (RT) technology. The purpose of this study was to report long-term treatment outcomes in patients with locally advanced rectal cancer undergoing VMAT-SIB based concurrent chemoradiotherapy (CRT). Methods: Between January 2016 and January 2018, a total of 22 patients with operable stage II-III rectal adenocarcinoma were recruited for the pre-designed VMAT-SIB RT protocol. All patients underwent standard diagnostic and staging work-up. The RT target volumes included the following areas: PTV1 = mesorectum that contained gross tumors and enlarged lymph node regions and PTV2 = mesorectum and regional lymphatics from L4-5/S1 to 3-4 cm below the tumor or levator ani muscle, excluding PTV1. The VMAT-SIB dose prescription was as follows: PTV1 = 52.5 Gy/daily 2.1 Gy/25 fractions, PTV2 = 45 Gy/daily 1.8 Gy/25 fractions. Results: The mean age of the study population was 64 (range, 18-84) years, and 15 (68.2%) patients were male. Radical operation (total mesorectal excision) was performed by either low anterior resection, ultralow anterior resection, or abdominal perineal resection. All five (22.7%) of the patients with confirmed increasing serum carcinoembryonic antigen (CEA) level at diagnosis showed normalization of serum CEA level after the planned treatment. Among 20 patients who underwent preoperative CRT and surgery, tumor down staging in T- and N-stages was achieved in 10 patients (50%) and 13 patients (65%), respectively, with 20% of ypT0/Tis. With a median follow-up of 54.2 (range, 22.6-61.1) months, the 5-year disease-free survival, overall survival, and local control rates were 64.6%, 81.8%, and 84.4%, respectively. Five patients developed distant metastasis and one developed local recurrence as a first event. Two cases with anastomosis site leakage, three with adhesive ileus, and two with abscess formation were observed during postoperative periods. Conclusions: The current VMAT-SIB-based CRT protocol provided acceptable treatment and toxicity outcomes.

Use of gentamicin-collagen sponge (Collatamp® G) in minimally invasive colorectal cancer surgery: A propensity score-matched study.

BACKGROUND: Minimally invasive surgery is commonly used to treat patients with colorectal cancer, although it can cause surgical site infections (SSIs) that can affect the oncologic outcome. Use of a gentamicin-collagen sponge may help reduce the occurrence of SSIs. We aimed to determine the effectiveness of a gentamicin-collagen sponge in reducing SSIs in minimally invasive surgery for colorectal cancer. METHODS: We retrospectively reviewed the records of 310 patients who were diagnosed with colorectal cancer at our hospital and underwent minimally invasive surgery between December 1, 2018, and February 28, 2021. Propensity score matching was conducted with a 1:1 ratio using logistic regression. The primary outcome was the incidence of SSIs in the mini-laparotomy wound. The secondary endpoints were factors affecting the incidence of SSIs. RESULTS: After propensity score matching, 130 patients were assigned to each group. There were no differences in clinical characteristics between the two groups. SSIs occurred in 2 (1.5%) and 3 (2.3%) patients in the gentamicin-collagen sponge and control groups, respectively (p<0.999). The following factors showed a statistically significant association with SSIs: body mass index >25 kg/m2 (odds ratio, 39.0; 95% confidence interval, 1.90-802.21; p = 0.018), liver disease (odds ratio, 254.8; 95% confidence interval, 10.43-6222.61; p = 0.001), and right hemicolectomy (odds ratio, 36.22; 95% confidence interval, 2.37-554.63; p = 0.010). CONCLUSION: Applying a gentamicin-collagen sponge to the mini-laparotomy wound did not reduce the frequency of SSIs. Further studies should be conducted on whether the selective use of gentamicin-collagen sponges may help reduce SSIs in high-risk patients.

Routine antibiotics may not be needed to treat uncomplicated right diverticulitis: A retrospective cohort study.

We aimed to investigate whether antibiotic administration is necessary for patients with uncomplicated right colonic diverticulitis. Data from patients diagnosed with uncomplicated right colonic diverticulitis, who received inpatient treatment at a single center between January 2019 and January 2021, were retrospectively examined. The patients were divided into two groups according to whether antibiotics were administered. The patients were matched between groups using propensity score matching in a 1:1 ratio using logistic regression with the nearest-neighbor method. The primary study outcome was the length of hospital stay, and the secondary outcomes were time to the introduction of sips of water and a soft diet. The study included 138 patients who received antibiotics and 59 who did not. After propensity score matching, 55 patients were assigned to each treatment group. There was no significant difference between the two groups in terms of age (p = 0.772), sex (p>0.999), body mass index (p = 0.121), prehospital symptom duration (p = 0.727), initial body temperature (p = 0.661), white blood cell count (p = 0.688), or C-reactive protein level (p = 0.337). There was also no statistically significant difference in the length of hospital stay between the no antibiotic and antibiotic groups (3.1±0.7 days vs. 3.0±1.0 days, p = 0.584). Additionally, no significant difference was observed between the no antibiotic and antibiotic groups with respect to time to sips of water (2.1±0.7 days vs. 1.8±0.9 days, p = 0.100) and time to the introduction of a soft diet (2.4±0.8 days vs. 2.1±0.9 days, p = 0.125). The findings suggest that routine antibiotics may be not required for treating patients with uncomplicated right colonic diverticulitis.

The development and validation of a predictive model for recurrence in rectal cancer based on radiological and clinicopathological data.

OBJECTIVE: To develop a prediction model for recurrence by incorporating radiological and clinicopathological prognostic factors in rectal cancer patients. METHODS: All radiologic and clinicopathologic data of 489 patients with rectal cancer, retrospectively collected from a single institution between 2009 and 2013, were used to develop a predictive model for recurrence using the Cox regression. The model performance was validated on an independent cohort between 2015 and 2017 (N = 168). RESULTS: Out of 489 derivative patients, 103 showed recurrence after surgery. The prediction model was constructed with the following four significant predictors: distance from anal verge, MR-based extramural venous invasion, pathologic nodal stage, and perineural invasion (HR: 1.69, 2.09, 2.59, 2.29, respectively). Each factor was assigned a risk score corresponding to HR. The derivation and validation cohort were classified by sum of risk scores into 3 groups: low, intermediate, and high risk. Each of these groups showed significantly different recurrence rates (derivation cohort: 13.4%, 35.3%, 61.5 %; validation cohort: 6.2%, 23.7%, 64.7%). Our new model showed better performance in risk stratification, compared to recurrence rates of tumor node metastasis (TNM) staging in the validation cohort (stage I: 3.6%, II: 12%, III: 30.2%). The area under the receiver operating characteristic curve of the new prediction model was higher than TNM staging at 3-year recurrence in the validation cohort (0.853 vs. 0.731; p = .009). CONCLUSIONS: The new risk prediction model was strongly correlated with a recurrence rate after rectal cancer surgery and excellent for selection of high-risk group, who needs more active surveillance. KEY POINTS: • Multivariate analysis revealed four significant risk factors to be MR-based extramural venous invasion, perineural invasion, nodal metastasis, and the short distance from anal verge among the radiologic and clinicopathologic data. • Our new recurrence prediction model including radiologic data as well as clinicopathologic data showed high predictive performance of disease recurrence. • This model can be used as a comprehensive approach to evaluate individual prognosis and helpful for the selection of highly recurrent group who needs more active surveillance.

Routine colonoscopy may be needed for uncomplicated acute right colonic diverticulitis.

BACKGROUND: Routine colonoscopy is recommended to determine the coexistence of colon cancer after medical treatment for colon diverticulitis. However, in the case of uncomplicated diverticulitis diagnosed by computed tomography, the clinical relevance of routine follow-up colonoscopy has recently been debated. Yet, the role of follow-up colonoscopy for right colon diverticulitis, which tends to develop at a younger age than left colon diverticulitis, has not been specifically evaluated. Therefore, we aimed to evaluate the incidence of right colon cancer or colonic adenomatous polyps, detected by routine colonoscopy, after conservative management of acute uncomplicated right colon diverticulitis. METHODS: Patients with uncomplicated right colon diverticulitis (modified Hinchey stage Ia) diagnosed by computed tomography imaging, between 2011 and 2017, and who underwent follow-up colonoscopy surveillance after treatment were included. The primary outcome was the incidence of colon cancer, with the detection rate of adenoma being the secondary outcome. Information for analysis was retrieved retrospectively from patients' medical records. RESULTS: The study group included 330 consecutive patients, with a mean age of 41.9 years, and 51.9% being men. For the primary outcome, the rate of colon cancer on follow-up colonoscopy was 0.3% (1/330 cases). The rate of adenoma detection was 20.9% (69/330 cases) and advanced adenoma (> 10 mm in diameter; or exhibiting a > 25% villous component or severe dysplasia), including colon cancer, was observed in 9 patients (2.7%). CONCLUSIONS: In patients with acute uncomplicated right colonic diverticulitis, routine colonoscopy after conservative treatment may be necessary because although the colon cancer detection rate is low, it is possible to detect advanced colon adenoma.

Which prognostic factors are important for long-term outcomes in symptomatic obstructive colon cancer? A multi-institutional retrospective cohort study.

Purpose: The prognostic factors in obstructive colon cancer have not been clearly identified. We aimed to identify the prognostic factor to establish optimal treatment strategy in obstructive colon cancer. Methods: Patients who underwent surgery for primary colon cancer in stages II and III with symptomatic obstruction from 2004 to 2010 in six hospitals were retrospectively collected. Clinicopathological and surgical outcomes were compared between stent insertion and emergent surgery group. Multiple regression analysis and survival curve analysis were used to identify the prognostic factors in symptomatic obstructive colon cancer. Results: Among 210 patients, 168 patients (80.0%) underwent stent insertion followed by surgery and 42 patients (20.0%) underwent emergent surgery. Laparoscopic approach (55.4% vs. 23.8%, p < 0.001) and adequate lymph node (LN) harvest (≥12) (93.5% vs. 69.0%, p < 0.001) were significantly higher in stent insertion group. In multiple regression analysis, emergent surgery (hazard ratio [HR], 2.153; 95% confidence interval [CI], 1.031-4.495), vascular invasion (HR, 6.257; 95% CI, 2.784-14.061), and omitting adjuvant chemotherapy (HR, 3.107; 95% CI, 1.394-6.925) were independent poor prognostic factors in 5-year overall survival, and N stage (N1 HR, 3.095; 95% CI, 1.316-7.284; N2 HR, 4.156; 95% CI, 1.671-10.333) was the only poor prognostic factor in 5-year disease-free survival. Conclusion: In symptomatic obstructive colon cancer, emergent surgery, N stage, vascular invasion, and omission of adjuvant chemotherapy were independent poor prognostic factors. Stent insertion is suggested as the initial treatment for symptomatic obstructive colon cancer, and adjuvant chemotherapy is recommended, especially when vascular invasion or LN metastasis is confirmed.

Clinical effect of multimodal perioperative pain management protocol for minimally invasive colorectal cancer surgery: Propensity score matching study.

BACKGROUND: Reducing postoperative pain with less opioid is critical in postoperative care. Author developed our multimodal perioperative pain management protocol and it consists of preoperative medication, intraoperative ultrasound-guided laparoscopic transverse abdominis plane (LTAP) block and postoperative medication. This study aimed to evaluate the clinical effect of the multimodal perioperative pain management protocol for minimally invasive colorectal cancer surgery. METHODS: Of 596 colorectal surgery cases for colorectal cancer, 133 patients managed with multimodal perioperative pain protocol (group 1) and 463 patients managed without multimodal perioperative pain protocol (group 2) were enrolled in this study. To adjust for baseline differences and selection bias, operative outcomes and complications were compared after propensity score matching (PSM). RESULTS: After 1:1 propensity score matching, well-matched 133 patients in each group were evaluated. The median VAS scores on post-operative day 1 (2.1 ± 1.1 vs. 3.9 ± 1.8, p < 0.001) and day 2 (2.0 ± 1.2 vs. 3.8 ± 1.7, p < 0.001) was significantly reduced in group 1. The length of postoperative hospital stays was also significantly shorter in Group 1 (4.4 ± 3.0 vs. 5.8 ± 5.6; p = 0.014). CONCLUSION: Implementing multimodal perioperative pain protocols reduced postoperative pain and hospital stay of minimally invasive colorectal surgery.

Phorbol 12-Myristate 13-Acetate Induced Toxicity Study and the Role of Tangeretin in Abrogating HIF-1α-NF-κB Crosstalk In Vitro and In Vivo.

Phorbol 12-myristate 13-acetate (PMA) is a potent tumor promoter and highly inflammatory in nature. Here, we investigated the toxic effects of PMA on different model system. PMA (10 µg) caused chromosomal aberrations on the Allium cepa root tip and induced mitotic dysfunction. Similarly, PMA caused embryonic and larval deformities and a plummeted survivability rate on zebrafish embryo in a dose-dependent manner. Persistently, PMA treatment on immortalized human keratinocyte human keratinocyte (HaCaT) cells caused massive inflammatory rush at 4 h and a drop in cell survivability at 24 h. Concomitantly, we replicated a cutaneous inflammation similar to human psoriasis induced by PMA. Herein, we used tangeretin (TAN), as an antagonist to counteract the inflammatory response. Results from an in vivo experiment indicated that TAN (10 and 30 mg/kg) significantly inhibited PMA stimulated epidermal hyperplasia and intra-epidermal neutrophilic abscesses. In addition, its treatment effectively neutralized PMA induced elevated reactive oxygen species (ROS) generation on in vitro and in vivo systems, promoting antioxidant response. The association of hypoxia-inducible factor 1-alpha (HIF-1α)-nuclear factor kappa-light-chain-enhancer of activated b cells (NF-κB) crosstalk triggered by PMA enhanced PKCα-ERK1/2-NF-κB pathway; its activation was also significantly counteracted after TAN treatment. Conclusively, we demonstrated TAN inhibited the nuclear translocation of HIF-1α and NF-κB p65. Collectively, TAN treatment ameliorated PMA incited malignant inflammatory response by remodeling the cutaneous microenvironment.