MRI-defined T3, clear mesorectal fascia mid-low rectal cancer: is neoadjuvant treatment necessary?

AIM: Neoadjuvant treatments (nCRT) are becoming the standard treatment for patients with stage II or III mid-low rectal cancer. Recently, some studies have shown that surgery alone may be sufficient for patients with T3 rectal cancer. This raises the question of whether nCRT is necessary for all patients with T3 rectal cancer. Therefore, this study compared the clinical outcomes of patients with MRI-defined T3, clear MRF mid-low rectal cancer treated with surgery alone (TME group) or nCRT followed by surgery (nCRT + TME group). METHODS: A total of 1509 patients were enrolled in this study. After a 1:1 propensity score matching analysis, 480 patients were included in each group. The primary endpoint was 3-year disease-free survival (DFS). The secondary endpoints included the perioperative outcomes, histopathologic outcomes, and other follow-up outcomes. RESULTS: nCRT had advantages in rates of sphincter-preserving surgery and tumor downstaging, but it was accompanied by a higher rate of enterostomies. At 3 years after surgery, local recurrence occurred in 3.3% of patients in the TME group and in 3.5% of patients in the nCRT + TME group (P = 0.914), the DFS rates were 78.3% in the TME group and 75.3% in the nCRT + TME group (P = 0.188), and the overall survival rates were 90.3% in the TME group and 89.9% in the nCRT + TME group (P = 0.776). CONCLUSIONS: Surgery alone versus nCRT followed by surgery may provide similar long-term oncological outcomes for patients with MRI-defined T3, clear MRF, and mid-low rectal cancer. nCRT may cause overtreatment in some patients.

Morbidity, Mortality, and Pathologic Outcomes of Transanal Versus Laparoscopic Total Mesorectal Excision for Rectal Cancer Short-term Outcomes From a Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine the morbidity, mortality, and pathologic outcomes of transanal total mesorectal resection (taTME) versus laparoscopic total mesorectal excision (laTME) among patients with rectal cancer with clinical stage I to III rectal cancer below the peritoneal reflection. BACKGROUND: Studies with sufficient numbers of patients allowing clinical acceptance of taTME for rectal cancer are lacking. Thus, we launched a randomized clinical trial to compare the safety and efficacy of taTME versus laTME. METHODS: A randomized, open-label, phase 3, noninferiority trial was performed at 16 different hospitals in 10 Chinese provinces. The primary endpoints were 3-year disease-free survival and 5-year overall survival. The morbidity and mortality within 30 days after surgery, and pathologic outcomes were compared based on a modified intention-to-treat principle; this analysis was preplanned. RESULTS: Between April 13, 2016, and June 1, 2021, 1115 patients were randomized 1:1 to receive taTME or laTME. After exclusion of 26 cases, modified intention-to-treat set of taTME versus laTME groups included 544 versus 545 patients. There were no significant differences between taTME and laTME groups in intraoperative complications [26 (4.8%) vs 33 (6.1%); difference, -1.3%; 95% confidence interval (CI), -4.2% to 1.7%; P =0.42], postoperative morbidity [73 (13.4%) vs 66 (12.1%); difference, 1.2%; 95% CI, -2.8% to 5.2%; P =0.53), or mortality [1 (0.2%) vs 1 (0.2%)]. Successful resection occurred in 538 (98.9%) versus 538 (98.7%) patients in taTME versus laTME groups (difference, 0.2%; 95% CI, -1.9% to 2.2%; P >0.99). CONCLUSIONS: Experienced surgeons can safely perform taTME in selected patients with rectal cancer.

Interaction analysis of high-risk pathological features on adjuvant chemotherapy survival benefit in stage II colon cancer patients: a multi-center, retrospective study.

BACKGROUND: We aimed to analyze the benefit of adjuvant chemotherapy in high-risk stage II colon cancer patients and the impact of high-risk factors on the prognostic effect of adjuvant chemotherapy. METHODS: This study is a multi-center, retrospective study, A total of 931 patients with stage II colon cancer who underwent curative surgery in 8 tertiary hospitals in China between 2016 and 2017 were enrolled in the study. Cox proportional hazard model was used to assess the risk factors of disease-free survival (DFS) and overall survival (OS) and to test the multiplicative interaction of pathological factors and adjuvant chemotherapy (ACT). The additive interaction was presented using the relative excess risk due to interaction (RERI). The Subpopulation Treatment Effect Pattern Plot (STEPP) was utilized to assess the interaction of continuous variables on the ACT effect. RESULTS: A total of 931 stage II colon cancer patients were enrolled in this study, the median age was 63 years old (interquartile range: 54-72 years) and 565 (60.7%) patients were male. Younger patients (median age, 58 years vs 65 years; P < 0.001) and patients with the following high-risk features, such as T4 tumors (30.8% vs 7.8%; P < 0.001), grade 3 lesions (36.0% vs 22.7%; P < 0.001), lymphovascular invasion (22.1% vs 6.8%; P < 0.001) and perineural invasion (19.4% vs 13.6%; P = 0.031) were more likely to receive ACT. Patients with perineural invasion showed a worse OS and marginally worse DFS (hazardous ratio [HR] 2.166, 95% confidence interval [CI] 1.282-3.660, P = 0.004; HR 1.583, 95% CI 0.985-2.545, P = 0.058, respectively). Computing the interaction on a multiplicative and additive scale revealed that there was a significant interaction between PNI and ACT in terms of DFS (HR for multiplicative interaction 0.196, p = 0.038; RERI, -1.996; 95%CI, -3.600 to -0.392) and OS (HR for multiplicative interaction 0.112, p = 0.042; RERI, -2.842; 95%CI, -4.959 to -0.725). CONCLUSIONS: Perineural invasion had prognostic value, and it could also influence the effect of ACT after curative surgery. However, other high-risk features showed no implication of efficacy for ACT in our study. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, NCT03794193 (04/01/2019).

Survival after curative resection for stage I colorectal mucinous adenocarcinoma.

PURPOSE: The prognostic value of the mucinous adenocarcinoma histotype on the early stages especially for stage I colorectal cancer (CRC) is still unclear. This study determined the clinicopathologic characteristics and long-term outcome of stage I colorectal mucinous adenocarcinomas (MAC). METHODS: Among the total of 530 patients with stage I CRC (58 having MAC and 472 having non-MAC) who underwent radical resection, the correlation between clinicopathological factors and MAC was analyzed. Multivariate analysis was performed to determine whether mucinous histotype itself was an independent prognostic impact in stage I patients. RESULTS: MACs were observed more frequently located in the colon than rectum (p = 0.049), more frequently displayed the deficient mismatch repair (dMMR) phenotype (p = 0.001) and had a greater frequency of T2 stage (p = 0.002). The rate of recurrence was 15.3% and the mortality was 9.2% among all stage I CRC patients. There was no difference in disease-free survival and overall survival between MACs and non-MACs. On multivariate analysis, older age (p = 0.009, hazard ratio: 2.22), rectal cancer (p = 0.008, hazard ratio: 3.21), lymphovascular invasion (LVI) (p < 0.001, hazard ratio: 6.28), and deficient mismatch repair (dMMR) phenotypes (p = 0.044, hazard ratio: 2.62) were independently associated to poor survival of stage I CRC. A high carcinoembryonic antigen level (p = 0.034, hazard ratio: 1.86), rectal cancer (p = 0.035, hazard ratio: 1.81), LVI (p = 0.002, hazard ratio: 3.59) and dMMR phenotypes (p = 0.009, hazard ratio: 2.85) were independently related to short disease-free survival of stage I CRC. CONCLUSIONS: Compared with non-MAC, MAC patients had more T2 patients and more dMMR phenotypes in stage I CRC at presentation, but the mucinous histology is not a significant predictor of recurrence and prognosis in stage I CRC.

Three-year outcomes of transanal total mesorectal excision versus standard laparoscopic total mesorectal excision for mid and low rectal cancer.

INTRODUCTION: Since transanal total mesorectal excision (taTME) was introduced, it has become an important topic in rectal cancer treatment. Many previous studies reported positive relevant short-term results, histopathological results, and associated complications. Recently, concerns regarding the oncological safety of taTME have been raised due to reports showing high local recurrences (LR) rates. Therefore, this study aimed to compare the 3-year outcomes between taTME and laparoscopic total mesorectal excision (laTME) for mid-low rectal cancer. METHODS: A total of 104 patients who underwent taTME were matched with 208 patients treated by laTME. The primary endpoint was 3-year LR rate; secondary endpoints in this matched-cohort study included the perioperative outcomes and histopathological outcomes. RESULTS: taTME was associated with lower permanent ostomy rate (1% vs 13.5%) and lower conversion rate (0% vs 3.4%) compared to laTME. A similar quality of resected specimens was detected for each group. In both groups, the local recurrence rate was 3.8%. Within 3 years after surgery, the disease-free survival (DFS) rates were 78.8% in the taTME group and 76.9% in the laTME group (P = 0.640), while the overall survival (OS) rates were 93.3% in the taTME group and 89.9% in the laTME group (P = 0.327). CONCLUSION: No significant differences regarding 3-year local recurrence rate (3.8%) were observed in the taTME group compared to laTME group.

Modified FOLFOXIRI With or Without Cetuximab as Conversion Therapy in Patients with RAS/BRAF Wild-Type Unresectable Liver Metastases Colorectal Cancer: The FOCULM Multicenter Phase II Trial.

PURPOSE: This trial evaluated the addition of cetuximab to a modified FOLFOXIRI (mFOLFOXIRI: 5-fluorouracil/folinic acid, oxaliplatin, irinotecan) as conversion therapy in a two-group, nonrandomized, multicenter, phase II trial in patients with initially technically unresectable colorectal liver-limited metastases (CLM) and BRAF/RAS wild-type. PATIENTS AND METHODS: Patients were enrolled to receive cetuximab (500 mg/m2 ) plus mFOLFOXIRI (oxaliplatin 85 mg/m2 , irinotecan 165 mg/m2 , folinic acid 400 mg/m2 , 5-fluorouracil 2,800 mg/m2 46-hour infusion, every 2 weeks) (the cetuximab group) or the same regimen of mFOLFOXIRI alone (the control group), in a 2:1 ratio allocation. The primary endpoint was the rate of no evidence of disease (NED) achieved. Secondary endpoints included resection rate, objective response rate (ORR), survival, and safety. RESULTS: Between February 2014 and July 2019, 117 patients were registered for screening at six centers in China, and 101 of these were enrolled (67 cetuximab group, 34 control group). The rate of NED achieved was 70.1% in the cetuximab group and 41.2% in the control group (difference 29.0%; 95% confidence interval [CI], 9.1%-48.8%; p = .005). Patients in the cetuximab group had improved ORR (95.5% vs. 76.5%; difference 19.1%; 95% CI, 17.4%-36.4%; p = .010) compared with those in control group. Progression-free survival and overall survival showed the trend to favor the cetuximab group. The incidence of grade 3 and 4 adverse events was similar in the two groups. CONCLUSION: Addition of cetuximab to mFOLFOXIRI improved the rate of NED achieved. This combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable CLM. IMPLICATIONS FOR PRACTICE: This trial evaluated the addition of cetuximab to a modified FOLFOXIRI as conversion therapy in a phase II trial in patients with initially technically unresectable colorectal liver-limited metastases and BRAF/RAS wild-type. The rate of no evidence of disease achieved was 70.1% in the cetuximab plus modified FOLFOXIRI group and 41.2% in the modified FOLFOXIRI group. Objective response rates, overall survival, and progression-free survival were improved in the cetuximab group when compared with the modified FOLFOXIRI group. Addition of cetuximab to modified FOLFOXIRI increased the rate of no evidence of disease achieved, and this combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable colorectal liver-limited metastasis.

Transanal Total Mesorectal Excision in Mid-Low Rectal Cancer: Evaluation of the Learning Curve and Comparison of Short-term Results With Standard Laparoscopic Total Mesorectal Excision.

BACKGROUND: Ever since transanal total mesorectal excision was introduced by Sylla and Lacy in 2010, it has become more popular among colorectal surgeons. However, some surgeons hesitate to use it, because this novel approach differs greatly from laparoscopic total mesorectal excision and requires a long learning curve. OBJECTIVE: This study analyzed the learning curve of transanal total mesorectal excision procedure and compared the different phases of transanal total mesorectal excision with laparoscopic total mesorectal excision. DESIGN: This is retrospective case-control study. SETTINGS: We used data from the approved colorectal cancer database of the Sixth Affiliated Hospital of Sun Yat-sen University. PATIENTS: The patients involved in this study underwent transanal total mesorectal excision performed by a single surgeon (L.K.) or underwent laparoscopic transanal total mesorectal excision performed by experienced surgeons. INTERVENTIONS: Transanal or laparoscopic resection of mid-low rectal cancer was conducted. MAIN OUTCOMES MEASURES: Perioperative complication and resection margin were measured. RESULTS: A total of 342 patients were included in both groups. The learning curve of transanal total mesorectal excision was divided into 3 phases. Data show that demographics and tumor characteristics were not significantly different between the matched groups. Indeed, during phase 1, only operative time was longer than in the laparoscopic group, whereas, during phase 2, results from the transanal group were comparable with the laparoscopic group. Results show that, during phase 3, operative time, intraoperative blood loss, and postoperative hospital stay were all lower than in the laparoscopic group. Local recurrence occurred in 3 patients during phase 1 and in 1 patient during phase 2. LIMITATIONS: This study was a small retrospective study and focused on just 1 surgeon performing transanal total mesorectal excision. CONCLUSIONS: Short-term and histopathologic outcomes are similar compared between a transanal group and matched laparoscopic group. Transanal total mesorectal excision also provided good oncologic outcomes. See Video Abstract at http://links.lww.com/DCR/B450. ESCISIN MESORRECTAL TOTAL TRANSANAL EN EL CNCER DE RECTO MEDIOBAJO EVALUACIN DE LA CURVA DE APRENDIZAJE Y COMPARACIN DE RESULTADOS A CORTO PLAZO CON TME LAPAROSCPICA ESTNDAR: ANTECEDENTES:Desde que Sylla y Lacy introdujeron la escisión mesorrectal total transanal en 2010, se ha vuelto más popular entre los cirujanos colorrectales. Sin embargo, algunos cirujanos dudan en utilizarlo, porque este nuevo método difiere mucho de la escisión mesorrectal total laparoscópica y requiere una larga curva de aprendizaje.OBJETIVO:Este estudio analizó la curva de aprendizaje del procedimiento de escisión mesorrectal total transanal y comparó las diferentes fases de la escisión mesorrectal total transanal con la escisión mesorrectal total laparoscópica.DISEÑO:Este es un estudio retrospectivo de casos y controles.ENTORNO CLINICO:Utilizamos base de datos de cáncer colorrectal aprobada del Sexto Hospital Afiliado de la Universidad Sun Yat-sen (Guangzhou, China).PACIENTES:Los pacientes involucrados en este estudio fueron sometidos a escisión mesorrectal total transanal realizada por un solo cirujano (LK) o se sometieron a escisión mesorrectal total transanal laparoscópica realizada por cirujanos experimentados.INTERVENCIONES:Resección transanal o laparoscópica de cáncer de recto medio-bajo.PRINCIPALES MEDIDAS DE VOLARCION:complicación perioperatoria y margen de resección.RESULTADOS:Se incluyó un total de 342 pacientes en ambos grupos. La curva de aprendizaje de la escisión mesorrectal total transanal se dividió en tres fases. Los datos muestran que las características demográficas y tumorales no fueron significativamente diferentes entre los grupos emparejados. De hecho, durante la fase 1, solo el tiempo operatorio fue más largo que en el grupo laparoscópico. Mientras que durante la fase 2, los resultados del grupo transanal fueron comparables a los del grupo laparoscópico. Los resultados muestran que durante la fase 3, el tiempo operatorio, la pérdida de sangre intraoperatoria y la estancia hospitalaria postoperatoria fueron menores que en el grupo laparoscópico. La recurrencia local ocurrió en 3 pacientes durante la fase 1 y en 1 paciente durante la fase 2.LIMITACIONES:Este estudio fue un estudio retrospectivo pequeño y se centró en un solo cirujano que realizaba la escisión mesorrectal total transanal.CONCLUSIÓN:Los resultados a corto plazo e histopatológicos son similares en comparación entre el grupo transanal y el grupo laparoscópico emparejado. La escisión mesorrectal total transanal también proporcionó buenos resultados oncológicos. Consulte Video Resumen en http://links.lww.com/DCR/B450.

Transanal and transabdominal combined endoscopic resection of rectal stenosis and anal reconstruction based on transanal endoscopic technique.

OBJECTIVE: To propose a method for the resection of the rectal anastomotic stenosis and anal reconstruction based on the transanal endoscopic technique through a transanal and transabdominal combined endoscopic resection, and to verify its clinical effectiveness. METHODS: Thirty-eight patients with anastomotic stenosis were admitted to the Sixth Affiliated Hospital, Sun Yat-sen University, China, from January 2016 to September 2019. Patients were divided into an experimental group (17 patients) and a control group (21 patients) subjected to the removal of the intestinal stenosis followed by anal reconstruction, they underwent transanal and transabdominal endoscopic surgery and traditional transabdominal surgery, respectively. Data on intraoperative blood loss, operation time, postoperative recovery, and prognosis were collected. RESULTS: (1) The median intraoperative blood loss was approximately 100 ml, without conversion to laparotomy during the surgery and intraoperative complications. The safety of the surgical operation was improved. (2) The operation time was shortened compared to previous reports, and the median operative time was 193 min. The average time of transanal endoscopic dissociation to the retroperitoneal fold was 76 min. (3) Laparoscopic assistance was carried out on 14 of the17 patients, and the incision was reduced. (4) The short-term curative effect was quite satisfactory, without permanent stoma. The average time to recover food intake after the surgery was 1.5 days. The average ambulation time was 3 days. Within 30 days after the surgery, one case suffered anastomotic leakage and then underwent refunctioning stoma through a second surgery. One patient suffered from intestinal obstruction, and the condition was improved through a conservative treatment. One case experienced delayed abdominal wound healing. CONCLUSION: The transanal and transabdominal endoscopic resection of the rectal anastomotic stenosis and anal reconstruction reduced the difficulty of the surgery, improved its safety, shortened the operation time, decreased the operative complications, and enabled patients to recover well after surgery.

Comparison of pathological outcomes after transanal versus laparoscopic total mesorectal excision: a prospective study using data from randomized control trial.

INTRODUCTION: Total mesorectal excision (TME) is the standard procedure for middle lower rectal cancer, and transanal total mesorectal excision (taTME) was founded as a valid alternative to the open and laparoscopic TME. The quality of the procedure performed is important for prognosis of patients. This study was designed to compare the pathological results of taTME with those of laparoscopic TME (laTME), based on the data from a randomized control trial (RCT: NCT02966483). METHODS: Between April 2016 and November 2018, all rectal cancer patients who underwent taTME or laTME in the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) and enrolled in the RCT were included in this study. The data from all participants were prospectively input in a standardized database. RESULTS: In total 128 patients were included in the taTME group and 133 patients were included in the laTME group. The demographics and tumor characteristics were not significantly different between the two group. T3 or N0 lesions were most common in both groups. The mesorectum specimen was complete or nearly complete in all patients. The positive distal resection margin (DRM) was detected in 2 (1.5%) cases in the laTME group versus no cases in the taTME group (P = 0.498), and the distance between the tumor and DRM in the taTME group (1.4 ± 1.1) may have the longer tendency than that in the laTME group (1.3 ± 0.9) (P = 0.745). The positive circumferential resection margin was detected in 2 cases in each group (P = 0.674). The median number of resected lymph nodes was 15.0 in taTME group versus 16.0 in the laTME group (P = 0.069). CONCLUSION: The pathological outcomes between transanal and laparoscopic total mesorectal excision are similar. The rate of positive resection margin could not be significant decreased, nonetheless the decrease trend could be shown.

Transanal total mesorectal excision for rectal cancer: a preliminary report.

BACKGROUND: Currently, the majority cases of the novel down-to-up transanal total mesorectal excision (TaTME) were performed in a hybrid approach with conventional laparoscopic assistance because of less operative difficulty. However, although cases are limited, the successes of TaTME in a pure approach (without laparoscopic assistance) indicate that the costly and less mini-invasive hybrid TaTME could be potentially avoided. METHODS: In the present single institutional, prospective study, we attempted to demonstrate the safety and feasibility of this approach in rectal cancer by evaluating the short-term results of our first 20 TaTME cases. For the majority of cases, we adopted a strategy that laparoscopic assistance was not introduced unless it was required during the planned pure TaTME procedure. RESULTS: A total of 20 patients (12 males and 8 females) were analyzed in this study, including 11 cases (55 %) of pure TaTME and 9 cases (45 %) of hybrid TaTME. Overall, the median operative time was 200 min (range 70-420), along with a median estimated blood loss of 50 ml (range 20-800). Morbidity rate was 20 % (one urethral injury, two urinary retentions, one anastomotic hemorrhage and one mild anastomotic leak). The median number of harvested lymph nodes was 12 (range 1-20). All specimens were intact in mesorectum without positive distal and circumferential resection margins. Among the 15 patients who were preoperatively scheduled to undertake pure TaTME, four patients (26.7 %) required converting to laparoscopic assistance. Moreover, among these 15 patients, the results of the comparative analysis between female and male subgroups favor the former, suggesting easier operation in them. CONCLUSION: This preliminary study demonstrates that TaTME in rectal cancer is safe and feasible. The strategy of not introducing laparoscopic assistance unless it is required while performing the planned pTaTME should be cautiously explored. Further studies with larger sample size and longer follow-up are warranted.

The predicting value of postoperative body temperature on long-term survival in patients with rectal cancer.

This study aimed to assess the association between postoperative body temperature and prognosis in patients with rectal cancer. Five hundred and seven patients with stage I to III rectal cancers were enrolled in the current study. Basal body temperature (BBT, measured at 6 am) and maximal body temperature (MBT) on each day after surgery were analyzed retrospectively. Patients were divided into two equal groups according to the median of BBT and MBT at each day. The primary end points were disease-free survival (DFS) and overall survival (OS). The univariate and multivariate analyses showed that patients with low D0-MBT (<37.4 °C) had lower 3-year DFS [adjusted hazard ratio (HR) 1.56 (95 % CI 1.08-2.24, P = 0.017)] as well as OS [adjusted HR 1.72 (95 % CI 1.05-2.82, P = 0.032)] rate as compared to those with high D0-MBT (>37.4 °C). In the subset of 318 patients with T3 stage tumor and the subgroup of 458 patients without blood transfusion as well, low D0-MBT continues to be an independent predictor of DFS/OS with an adjusted HR equal to 1.48 (95 % CI 1.02-2.24, P = 0.046)/1.68 (95 % CI 1.04-2.99, P = 0.048) and 1.45 (95 % CI 1.02-2.13, P = 0.048)/1.59 (95 % CI 1.01-2.74, P = 0.049), respectively. In addition, we found that patients have higher risk of 1-year recurrence if those were exhibiting low preoperative BBT (<36.6 °C) (17 vs. 10 %, P = 0.034). Low body temperature (D0-MBT < 37.4 °C) after surgery was an independent predictor of poor survival outcomes in patients with rectal cancer.

Effects and mechanism of dehydroepiandrosterone on epithelial-mesenchymal transition in bronchial epithelial cells.

BACKGROUND: Chronic persistent asthma is characterized by airway remodeling, in which epithelial-mesenchymal transition (EMT) may play a significant role. Dehydroepiandrosterone (DHEA), a steroid hormone and testosterone analog, is considered as an important immunomodulating hormone. However, its role in EMT remains unclear. We sought to investigate whether transforming growth factor-ß1 (TGF-ß1) stimulates human bronchial epithelial cells (16HBE-14o) to undergo EMT, and whether this transition can be abrogated by DHEA. METHODS: The 16HBE-14o cells were stimulated with 5 ng/ml TGF-ß1 for 3 days to induce EMT, with or without DHEA pretreatment, and assayed for epithelial or mesenchymal markers using Western Blot. The involvement of phosphoinositide 3-kinase (PI3K) -mediated signaling pathway was also evaluated, the epithelial cells were also incubated with pharmacological approaches (agonists and antagonists of Akt, LY294002 or IGF-1) or flutamide, the antagonist of androgen receptor. Results were analyzed using nonparametric statistical tests. RESULTS: Our data demonstrate that treatment of 16HBE-14o cells with TGF-ß1 for 3 days induced EMT as reflected by conversion to the spindle-like morphology, loss of E-cadherin, and acquisition of a-smooth muscle actin (a-SMA). Pretreatment of 16HBE-14o cells with DHEA preserved the epithelial-like morphology, restored the expression of E-cadherin, and abolished the activation of a-SMA, and this effect is a PI3K-dependent mechanism. CONCLUSION: Our results indicate that TGF-ß1 induces EMT in a PI3K-dependent manner in 16HBE-14o cells. DHEA inhibits the bronchial epithelial to mesenchymal transition via the inhibition of PI3K/Akt-dependent signal pathway stimulated by TGF-ß1. Therefore, DHEA may be a useful therapy for asthma.

LDCNet: Lightweight dynamic convolution network for laparoscopic procedures image segmentation.

Medical image segmentation is fundamental for modern healthcare systems, especially for reducing the risk of surgery and treatment planning. Transanal total mesorectal excision (TaTME) has emerged as a recent focal point in laparoscopic research, representing a pivotal modality in the therapeutic arsenal for the treatment of colon & rectum cancers. Real-time instance segmentation of surgical imagery during TaTME procedures can serve as an invaluable tool in assisting surgeons, ultimately reducing surgical risks. The dynamic variations in size and shape of anatomical structures within intraoperative images pose a formidable challenge, rendering the precise instance segmentation of TaTME images a task of considerable complexity. Deep learning has exhibited its efficacy in Medical image segmentation. However, existing models have encountered challenges in concurrently achieving a satisfactory level of accuracy while maintaining manageable computational complexity in the context of TaTME data. To address this conundrum, we propose a lightweight dynamic convolution Network (LDCNet) that has the same superior segmentation performance as the state-of-the-art (SOTA) medical image segmentation network while running at the speed of the lightweight convolutional neural network. Experimental results demonstrate the promising performance of LDCNet, which consistently exceeds previous SOTA approaches. Codes are available at github.com/yinyiyang416/LDCNet.

The clinical relevance of adjuvant chemotherapy in locally advanced rectal cancer patients achieving near pathological complete response following neoadjuvant chemoradiotherapy: Insights from ypT stage.

BACKGROUND: Near-pathological complete response (Near-pCR) patients constitute a distinct subgroup with limited research attention. The clinical relevance of adjuvant chemotherapy (ACT) in this patient cohort remains uncertain. METHODS: We conducted a retrospective analysis of 245 patients with locally advanced rectal cancer (LARC) who achieved near-pCR following neoadjuvant chemoradiotherapy (NCRT) between 2011 and 2018. Based on their receipt of ACT or not (non-ACT), patients were divided into two groups. We examined their characteristics, treatment modalities, and survival outcomes, particularly focusing on 5-year disease-free survival (DFS) and 5-year overall survival (OS). RESULTS: Among the 245 near-pCR patients, 191 (77.96%) received ACT, and 42 (17.14%) experienced disease recurrence. All 54 (22.04%) Patients in the non-ACT group exhibited a lower 5-year DFS rate (72.2% vs. 85.9%, P = 0.014) and a similar 5-year OS rate (87.0% vs. 91.1%, P = 0.351). Interestingly, those with ypT3-T4 stage tumors demonstrated a worse DFS (76.8% vs. 89.9%, P = 0.010) and OS (87.5% vs. 97.0%, P = 0.004) compared to their counterparts with ypT1-T2 stage tumors. Patients with Non-Downstage tumors showed inferior DFS (76.9% vs. 88.3%, P = 0.025) and OS (87.2% vs. 93.0%, P = 0.166) in comparison to patients with Downstage tumors. The ACT subgroup in patients with Downstage demonstrated statistically better 5-year DFS (93.0% vs. 71.4%, P = 0.001) but analogous survival rates for 5-year OS (OS: 94.0% vs. 89.3%, P = 0.402). Pathological T stage 3-4, perineural invasion (PNI) (positive) and ACT were independent factors influencing 5-year DFS in multivariate analysis. Both univariate and multivariate analysis demonstrated a link between serum carcinoembryonic antigen (CEA) before treatment ≥5 ng/ml and shorter 5-year OS. Notably, near-pCR patients with positive lymph nodes experienced notably diminished 5-year DFS in the absence of ACT post-surgery (61.1% vs. 93.2%, P < 0.001). CONCLUSIONS: ACT demonstrated a significant positive impact on the prognosis of select near-pCR patients, particularly those with ypT1-T2 stage tumors and positive lymph nodes. ypT staging may emerge as a valuable criterion for precise post-surgical ACT guidance in near-pCR patients.

Long-term oncological outcomes of transanal versus laparoscopic total mesorectal excision for mid-low rectal cancer: a retrospective analysis of 2502 patients.

BACKGROUND: Transanal total mesorectal resection (taTME) has recently emerged as a promising surgical approach for the treatment of mid-low rectal cancer. However, there is limited evidence on the long-term survival outcomes associated with taTME. This retrospective study aimed to compare the overall survival (OS), disease-free survival (DFS), and cancer-specific survival of taTME and laparoscopic TME (laTME) in patients with mid-low rectal cancer. MATERIALS AND METHODS: From July 2014 to June 2022, a total of 3627 patients were identified from two prospective cohorts: the laparoscopic rectal surgery cohort and the CNTAES cohort. To balance the baseline characteristics between the taTME and laTME groups, propensity score matching (PSM) was performed. RESULTS: A total of 2502 patients were included in the study. Prior to PSM, the laTME group comprised 1853 patients, while the taTME group comprised 649 patients. The 5-year OS (82.9% vs. 80.4%, P =0.202) and 5-year DFS (74.4% vs. 72.5%, P =0.167) were comparable between the taTME and laTME groups. After PSM, the taTME group showed no statistically significant difference in the 5-year OS (83.1% vs. 79.2%, P =0.101) and 5-year DFS (74.8% vs. 72.1%, P =0.135) compared to the laTME group. Subgroup analysis further suggested that taTME may potentially reduce the risk of death [hazard ratio 0.652; (95% CI, 0.452-0.939)] and disease recurrence [hazard ratio 0.736; (95% CI, 0.562-0.965)] specifically in patients with low rectal cancer. CONCLUSION: In this study, taTME demonstrated comparable oncologic safety to laTME in patients with mid-low rectal cancer. Moreover, the results indicate that taTME may confer potential survival benefits for patients with low rectal cancer.

Inflammatory stress response after transanal vs laparoscopic total mesorectal excision: a cohort study based on the TaLaR trial.

BACKGROUND: Transanal total mesorectal excision (taTME) is a novel approach to radical surgery for low rectal cancer; however, it is not clear whether taTME causes a more severe inflammatory stress response than laparoscopic total mesorectal excision (laTME). Therefore, the authors conducted this study to address this question, with the secondary objective of analyzing the predictive effect of inflammatory indexes on postoperative infective complications between laTME and taTME. METHODS: A total of 545 cases of laTME and 544 cases of taTME from the TaLaR randomized controlled trial were included. Inflammatory stress response was assessed via C-reactive protein (CRP), white blood cell count, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, and prognostic nutritional index. Inflammatory indexes were measured and calculated preoperatively (t1) and on postoperative days one (t2) and seven (t3). The accuracy of inflammatory indexes as predictor of infective complications was evaluated by areas under the receiver operating characteristic curve. RESULTS: Preoperative blood parameters were comparable between the two surgical methods. There were no significant differences in CRP, white blood cell count, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, or prognostic nutritional index between the two surgical methods at any time point ( P >0.05). Among the inflammatory indexes at three time points, CRP on the first postoperative day was the most accurate predictor of infective complications, which is suitable for two surgical methods. The AUC was 0.7671 ( P <0.0001) with a cutoff of 39.84 mg/l, yielding 94% sensitivity and 47% specificity. CONCLUSIONS: Compared with laTME, taTME surgery has no obvious disadvantage with respect to the postoperative inflammatory stress response. In addition, inflammatory indexes were favorable in predicting infective complications, with the best results for CRP on the first postoperative day. Defining the specific predictors for laTME and taTME is unnecessary.

CD24-Targeted NIR-II Fluorescence Imaging Enables Early Detection of Colorectal Neoplasia.

Colorectal cancer (CRC) continues to be a major health issue even though screening methods have facilitated early detection. Despite the high sensitivity of white-light colonoscopy, it frequently overlooks invasive flat or depressed lesions, which can lead to the development of larger, advanced tumors. Fluorescence molecular imaging (FMI) offers a promising approach for early tumor detection by targeting specific molecular characteristics of lesions. CD24 is upregulated during the adenoma-to-CRC transition, providing a potential target for FMI. Here, we developed a second near-infrared window (NIR-II) fluorescent probe with a high affinity for CD24 and evaluated its efficacy and targeting ability in cellular models, murine models, and clinical samples of CRC. CD24 expression was elevated in 76% of adenomas and 80% of CRCs. In a colitis-associated cancer mouse model, NIR-II imaging with the CD24-targeted probe achieved a significantly higher tumor-to-background ratio compared to conventional NIR-I imaging. The probe demonstrated exceptional sensitivity (92%) and specificity (92%) for detecting CRC, including small lesions less than 1 mm in size. This led to the identification of precancerous lesions missed by white-light detection and lesions missed by NIR-I imaging. Moreover, ex vivo human tissue incubation with the probe supported the potential for intraprocedural lesion identification via topical probe application during colonoscopy. In conclusion, this study successfully demonstrates the potential of CD24-targeted NIR-II imaging for identifying colorectal neoplasia, highlighting its significance for early CRC detection in the gastrointestinal tract.

Effects of tumour budding on adjuvant chemotherapy in colorectal cancer.

BACKGROUND: High tumour budding has been indicated as a risk factor of poor survival in colorectal cancer. This study aimed to investigate the impact of tumour budding grades and the use of adjuvant chemotherapy on prognosis in patients with colorectal cancer. METHODS: This study included consecutive colorectal cancer patients who underwent radical surgery for primary colorectal adenocarcinoma at The Sixth Hospital of Sun Yat-sen University between 2009 and 2019. Tumour budding was assessed based on the recommendations of the International Tumor Budding Consensus Conference using haematoxylin and eosin (H&E)-stained slides with tumour samples. The primary outcome of interest was to correlate tumour budding with disease-free survival and overall survival; the secondary outcome was investigation of the impact of adjuvant therapy on different tumour budding grades. In addition, a subgroup analysis was performed for the effects of lymphocytic infiltration on adjuvant chemotherapy in patients with Bd3. RESULTS: Of 709 eligible patients, 412 with colorectal cancer were included. According to the International Tumor Budding Consensus Conference, 210 (50.9 per cent), 127 (30.8 per cent) and 75 (18.2 per cent) were classified as low budding (Bd1), intermediate budding (Bd2) and high budding (Bd3) respectively. Patients with Bd1, Bd2 and Bd3 had 5-year disease-free survival rates of 82.9 per cent, 70.1 per cent and 49.3 per cent respectively, and 5-year overall survival rates of 90 per cent, 79.5 per cent and 62.7 per cent respectively (P <0.001). Adjuvant chemotherapy yielded a significant survival benefit in patients with Bd3 (5-year disease-free survival, 65 per cent versus 31.4 per cent, P <0.001; 5-year overall survival, 84.4 per cent versus 63.1 per cent, P <0.001), but not in those with Bd1 or Bd2. In patients with Bd3, the benefit of adjuvant chemotherapy was maintained in those with low, but not high lymphocytic infiltration. CONCLUSION: High grade of tumour budding was strongly correlated with poorer survival outcomes in colorectal cancer. Patients with Bd3 benefited from adjuvant chemotherapy, with the exclusion of patients with high lymphocytic infiltration.

Clinical significance of positive resection margin for patients with rectal neuroendocrine tumors within 20 mm following initial endoscopic resection: A multi-center study.

BACKGROUND: The incidence of rectal neuroendocrine tumors (RNETs) has witnessed a significant surge, with a notable proportion being amenable to endoscopic removal. However, the clinical significance of positive resection margin for RNETs patients following endoscopic resection remain unknown, resulting in a lack of consensus regarding the appropriateness of implementing salvage treatment. METHODS: In this large, multicenter, retrospective cohort study, we analyzed the medical records of individuals who underwent endoscopic resection for RNETs and classified them into two groups: the positive resection margin and the negative resection margin group. The overall survival (OS) and disease-free survival (DFS) were compared among two group. The independent variables were identified using univariate and multivariate logistic regression analyses to predict positive resection margin. Then, the model was established to predict the patients with positive resection margin using multivariate logistic regression. RESULTS: 181 RNETs patients (34.3 %) represented positive margin after endoscopic resection. Following a median follow-up period of 72 months, tumor recurrence manifested in 12 out of 527 patients (2.2 %) and the presence of positive resection margin was associated with worse DFS. Independent factors correlating with positive resection margin included endoscopic resection method choice, RNETs located in the low rectum, NLR >4.44 and tumor size exceeding 14.89 mm. A prediction model was therefore established with high predictive accuracy and excellent clinical applicability determined by calibration curves and DCA curve. Among RNETs patients with positive margin following endoscopic resection, implementing salvage treatment was beneficial for improving DFS and salvage endoscopic resection offer equal efficiency compared with salvage radical resection. CONCLUSIONS: Positive resection margin following endoscopic resection may indicate negative prognosis. Salvage treatment can improve the prognosis of RNETs patients with positive resection margin. Notably, salvage local resection exhibited similar efficacy compared with radical surgery in term of survival benefit.

Photoacidolysis-Mediated Iridium(III) Complex for Photoactive Antibacterial Therapy.

Photoactive antibacterial therapy is one of the novel therapeutic methods that has great application potential and prospects for curbing bacterial infections. In this work, a photoactivated iridium complex (Ir-Cl) is synthesized for photoactive antibacterial research. Ir-Cl exhibits photoacidolysis, which can generate H+ and be converted into a photolysis product Ir-OH under blue light irradiation. At the meantime, this process is accompanied by 1O2 generation. Notably, Ir-Cl can selectively permeate S. aureus and exhibit excellent photoactive antibacterial activity. Mechanism studies show that Ir-Cl can ablate bacterial membranes and biofilms under light irradiation. Metabolomics analysis proves that Ir-Cl with light exposure mainly disturbs some amino acids' degradation (e.g., valine, leucine, isoleucine, arginine) and pyrimidine metabolism, which indirectly causes the ablation of biofilms and ultimately produces irreversible damage to S. aureus. This work provides guidance for metal complexes in antibacterial application.