Comparative effectiveness of primary tumor resection versus chemotherapy in patients with asymptomatic unresectable metastatic colorectal cancer: a retrospective cohort study using the target trial emulation framework.

Patients who undergo primary tumor resection (PTR) reportedly have significantly higher overall survival (OS) than those who do not undergo this procedure. However, this result is only evident in past retrospective studies, and clinical trial results did not show the same trend. Thus, it remains unclear whether primary tumor resection effectively increases survival in patients with metastatic colorectal cancer (mCRC) across different study designs. We compared the OS of patients with asymptomatic unresectable mCRC who underwent PTR with that of those who did not. This retrospective cohort study was designed to be a target trial emulation of a randomized controlled trial (RCT) that would have compared the effectiveness of PTR versus non-PTR in patients with asymptomatic unresectable mCRC from 2009 to 2017. A systematic review and meta-analysis were conducted to compare the efficacy of PTR and non-PTR in patients with mCRC, and corresponding results were compared. This cohort included 1,132 patients for a per-protocol analysis. The PTR group had non-significantly longer survival (adjusted hazard ratio: 0.70, 95% confidence interval: 0.62-1.01) than the non-PTR group in our cohort. A meta-analysis including five RCTs (1,016 patients) and our cohort found that the PTR group did not have a significantly lower mortality rate than the non-PTR group. The results of this cohort study and previous RCTs suggest that PTR is not associated with improved survival compared to systemic chemotherapy combined with targeted therapy among asymptomatic unresectable mCRC patients. Therefore, routine PTR is not recommended in these patients.

Assessing the effectiveness of targeted agents in adjuvant therapy for patients with metastatic colorectal cancer undergoing surgical resection: a retrospective cohort study.

Background: Primary tumor resection and metastasectomy may be beneficial for many patients with metastatic colorectal cancer (mCRC). Objective: To assess the differences in postoperative survival outcomes between adjuvant therapy with chemotherapy alone and chemotherapy plus targeted agents (TAs). Design: Retrospective cohort study. Methods: Patients with mCRC who underwent surgical resection for primary colorectal tumor and distant metastases and received adjuvant therapy from 1 January 2010 to 31 December 2017 were enrolled in the Taiwan Cancer Registry. We analyzed the overall survival of patients with resectable or initially unresectable mCRC who received adjuvant chemotherapy alone and chemotherapy plus TAs. Results: We enrolled 1124 and 542 patients with resectable and initially unresectable mCRC, respectively. Adjuvant chemotherapy plus TAs and chemotherapy alone resulted in similar mortality rates among patients with resectable mCRC [adjusted hazard ratio (aHR) = 1.13; 95% confidence interval (CI), 0.93-1.36]; however, it marginally reduced the mortality rate among patients with initially unresectable mCRC who underwent conversion surgery after neoadjuvant therapy (aHR = 0.81; 95% CI, 0.62-1.06). The subgroup analysis of patients who received more than nine cycles of TAs preoperatively and anti-epidermal growth factor receptor agents revealed aHRs of 0.48 (95% CI, 0.27-0.87) and 0.33 (95% CI, 0.18-0.60), respectively. Conclusion: Adjuvant chemotherapy plus TAs may improve survival in patients with initially unresectable tumors who underwent conversion surgery following neoadjuvant therapy with TAs, especially in those who respond well to the targeted therapy. Our study underscores the importance of stratifying patients with mCRC based on tumor resectability when selecting the adjuvant therapy regimen.

Comparative Effectiveness of Adjuvant Therapy on Survival in Patients With Metastatic Colorectal Cancer.

BACKGROUND/AIM: Postoperative survival outcomes are crucial in treatment decision making. This study aimed to compare the efficacy of adjuvant chemotherapy (AC)-alone with that of chemotherapy + targeted agents (CTA) in patients with metastatic colorectal cancer (mCRC) and to investigate the association between neoadjuvant therapy and survival. PATIENTS AND METHODS: Patients who underwent primary tumor excision and metastasectomy were identified in the Taiwan Cancer Registry from 2010 to 2019. The analysis assessed the influence of adjuvant therapy on survival and examined the interactions between adjuvant therapy types (AC-alone and CTA) and patient characteristics with respect to overall survival. RESULTS: Overall, 1,728 and 757 patients received AC alone and CTA, respectively. Compared to AC alone, adjuvant CTA yielded similar mortality after surgery [hazard ratio (HR)=1.03; 95% confidence interval (CI)=0.91-1.17] but resulted in marginally reduced mortality among patients treated with neoadjuvant therapy with targeted agents (HR=0.6; 95%CI=0.34-1.05) after propensity score matching. In patients with mCRC, those who received targeted agents preoperatively and postoperatively in combination with AC had the highest mortality rate (HR=1.75; 95%CI=1.33-2.32). CONCLUSION: Overall survival is comparable between adjuvant CTA and AC alone, but adjuvant CTA may be more beneficial in patients with mCRC who undergo neoadjuvant therapy with targeted agents.

Comparative Effectiveness of Cetuximab Versus Panitumumab in Patients With Metastatic Colorectal Cancer: A Nationwide Database Study.

BACKGROUND/AIM: The study aimed to determine the effectiveness of cetuximab and panitumumab on the survival of patients with metastatic colorectal cancer or those who had undergone conversion surgery and to identify their prognostic factors. PATIENTS AND METHODS: This retrospective cohort study used data from patients with metastatic colorectal cancer who received cetuximab or panitumumab as first-line targeted agent-based therapy. Overall survival and conversion surgery rates were evaluated, and the prognostic factors were determined. RESULTS: A total of 1,749 and 318 patients received cetuximab or panitumumab with chemotherapy, respectively. Overall survival and conversion surgery rates were similar between the cetuximab [hazard ratio (HR)=0.96] and panitumumab groups (HR=1.00). The prognostic factors associated with metastasectomy significantly lowered mortality among patients with metastatic colorectal cancer (HR=0.61). Older age (≥70 years), tumor stage 4B and 4C, right-sided tumors, mucinous adenocarcinoma, primary tumor resection, and the number of positive lymph nodes were associated with higher mortality and lower conversion surgery rates. CONCLUSION: Though panitumumab- and cetuximab-based therapies showed no differences, several factors, such as age over 70 years old, tumor stage 4B and 4C, undifferentiated carcinoma, mucinous carcinoma, right-sided tumor, number of positive lymph nodes, obstruction, and primary tumor resection increased the mortality risk of patients. This study underscores the importance of metastasectomy in current treatment guidelines and future clinical trials.

Mortality of patients with metastatic colorectal cancer who received elective or emergent operation after exposure to bevacizumab: A nationwide database study.

INTRODUCTION: Treatment guidelines for colorectal cancer (CRC) indicate that surgical intervention within 4 weeks or 8 weeks after bevacizumab therapy might increase the risk of postoperative complications and mortality, especially in patients who received emergent operation. Therefore, we aimed to assess the association between different surgical timings, emergent or elective surgery, and the risk of postoperative mortality. MATERIALS AND METHODS: Using the Taiwan National Health Insurance Database and Taiwan Cancer Registry, we identified patients with metastatic colorectal cancer (mCRC) who underwent surgery within 1 year of receiving bevacizumab between January 2010 and December 2017. The primary outcomes were 30-day, 60-day, and in-hospital mortality; the secondary outcomes were hospital stay, 30-day readmission rate, and surgical complications. Multivariate analysis was used to adjust for confounders. RESULTS: This study included 2,047 patients. In the multivariate analysis, patients who underwent emergent operation and had higher Charlson scores had a significantly higher mortality rate. Patients with a longer interval to surgery, more cycles of bevacizumab treatment, and distal metastectomy had the opposite result. In subgroup analysis, patients who received emergent operation within 28 days had the highest surgical mortality. CONCLUSIONS: The interval to operation among mCRC patients who receive bevacizumab treatment should exceed 4 weeks to avoid additional risk of mortality whether patients receiving elective or emergent operation. Patients who received emergent operation within 28 days of bevcizumab infusion had the highest risk of mortality.

Diving, lifting, and horizontal dissection followed by loop-clip traction (DLH+T) can facilitate mucosal flap creation during colorectal ESD.

BACKGROUND: Colorectal ESD is difficult because of the poor maneuverability and difficulty of mucosal flap creation. Diving, Lifting and Horizontal (DLH) dissection technique and loop-clip traction are two different methods to facilitate mucosal trimming and adequate mucosal flap creation. We combined the advantages of these two techniques (DLH+T) in our daily practice colorectal ESD since July 2020. OBJECTIVE: The purpose of this study was to examine the outcomes of DLH+T dissection compared with the conventional dissection. METHODS: We retrospectively reviewed the clinical using DLH+T dissection compared with the conventional dissection since January 2018 at a single tertiary care institution. Postoperative short-term outcomes were investigated after the procedure including mucosal flap creation time, dissection time, dissection speed, en bloc resection rate, and perioperative complications. RESULTS: 28 lesions were in DLH+T dissection group and 39 lesions in the conventional dissection group. The outcomes including en bloc resection rate, dissection speed, and complication between the two groups were similar. The mean mucosal flap creation time (p = 0.035) and the mean dissection speed (p = 0.041) of the DLH+T dissection group was significantly shorter and faster. CONCLUSION: DLH dissection followed by loop-clip traction (DLH+T) technique is a useful technique for safe, efficient, and adequate mucosal flap creation, which can increase the dissection speed and may prevent complication, especially in biopsy-related submucosal fibrosis.

Shared decision-making and patient decision aids in choosing first-line targeted therapy for metastatic colorectal cancer in Taiwan.

INTRODUCTION: In Taiwan, given the discrepancy between current treatment guidelines and reimbursement options, patients might require a tool to support their decision-making process when selecting a regimen for metastatic colorectal cancer, especially therapeutic strategies, and subsequent costs, along with efficacy and safety outcomes. Therefore, we developed a patient decision aid (PDA) to support patients in choosing between treatment options recommended based on the current evidence and those reimbursed by the Taiwanese National Health Insurance. METHODS: By carefully reviewing the updated data and then interpreting the clinical tool, we conducted a needs assessment using a serial questionnaire to test for a step-by-step adjustment of the PDA. RESULTS: Patients, their relatives, and medical team members were most concerned about outcomes, such as overall survival, progression-free survival, objective response rate, tumor shrinkage to resectable status, total medical cost, severe gastrointestinal perforation, and severe skin reaction. After a serial alpha test for quality, we performed quantitative evaluation and beta tests, revealing average scores of more than 4 points (on a scale of 1-5) for both perceptibility and utility. CONCLUSIONS: The present findings suggest that PDAs are useful and supplement the shared decision-making practice, helping patients make decisions about preferences and consider the pros and cons of treatment regimens, along with insurance reimbursement options.

Ichthyosis with superimposed mycosis fungoides, a rare case of generalized erythema with malaise.

Ichthyosiform eruption of mycosis fungoides is rare, and ichthyosis with superimposed mycosis fungoides is scarcely ever seen; only a few cases have been documented in the medical literature. Furthermore, the patients with ichthyosiform lesions may indicate the presence of an underlying systemic disease, paraneoplastic syndrome, or an atypical manifestation of cutaneous T-cell lymphoma. Thus, determining the accurate etiology is important to establish the correct diagnosis and subsequently facilitate its management. They should be evaluated thoroughly, and a skin biopsy is essential to rule out the possibility of ichthyosiform mycosis fungoides.

Real-Time Gauging of the Gelling Maturity of Duck Eggs Pickled in Strong Alkaline Solutions.

Although many ultraviolet-visible-near-infrared transmission spectroscopy techniques have been applied to chicken egg studies, such techniques are not suitable for duck eggs because duck eggshells are much thicker than chicken eggshells. In this study, a high-transmission spectrometer using an equilateral prism as a dispersive element and a flash lamp as a light source was constructed to nondestructively detect the transmission spectrum of duck eggs and monitor the pickling of eggs. The evolution of egg transmittance was highly correlated with the albumen during pickling. The transmittance exponentially decays with time during this period, and the decay rate is related to the pickling rate. The colors of the albumen and yolk remain almost unchanged in the first stage. A multiple linear regression analysis model that realizes a one-to-one association between the days of pickling and the transmission spectra was constructed to determine the pickling duration in the second stage. The coefficient of determination reached 0.88 for a single variable, wavelength, at 590 nm. This method can monitor the maturity of pickled eggs in real time and does not require the evolution of light transmittance.

Kinetics of hepatitis B surface antigen and estimated glomerular filtration rate in telbivudine-treated hepatitis B patients with different rescue strategies.

This study investigated the kinetics of estimated glomerular filtration rate (eGFR) and quantitative hepatitis B surface antigen (qHBsAg) in telbivudine (LdT)-treated chronic hepatitis B (CHB) patients whose treatment was subsequently adjusted with the adding on adefovir or by switching to tenofovir disoproxil fumarate (TDF) as rescue. Of 295 CHB patients initially treated with LdT, 102 of them who subsequently receiving either adding-on adefovir (group A, n = 58) or switching to TDF (group B, n = 44) for more than 24 months were enrolled. Serial eGFR and qHBsAg levels (3 to 6 monthly) in both LdT monotherapy and rescue therapy periods were analyzed retrospectively. Subsequent decline of qHBsAg especially in rescue therapy period were noted (p<0.001 and p = 0.068 in group A and B). However, patients in group B achieved a significant increase of eGFR (p = 0.010) in LdT monotherapy period but had a significant decline of eGFR (p<0.001) in rescue therapy period. In contrast, patients in group A maintained eGFR levels in both periods. Meanwhile, switch to TDF (hazard ratio: 3.036; 95% confidence interval: 1.040-8.861; p = 0.042) was the sole factor related to the decrease of eGFR>20% from baseline. Both rescue therapies achieved subsequent declines of qHBsAg over time but caused different changes in eGFR. LdT-based rescue therapy maintained eGFR but TDF switching therapy descended eGFR. Therefore, it is essential to monitor patient's renal function intensively when switching from LdT to TDF as a rescue strategy.

Rapid determination of isoflavones and other bioactive compounds in soybean using SWATH-MS.

Isoflavones are the major bioactive components in soybeans. Sequential window acquisition of all theoretical fragment ions (SWATH) is a kind of data-independent acquisition (DIA), such that all fragments of each precursor will be preserved in a SWATH-Mass Spectrometry (SWATH-MS) run. In this study, a high-throughput SWATH-MS method for the determination of 12 isoflavones in soybeans was established. Furthermore, amino acids, saponins can be semi-quantitated from the same SWATH-MS data. Combination of targeted quantification and untargeted profiling with SWATH, all bioactive compounds were analyzed within 5 min in 10 min run time, and the method had good linear regression with r2 > 0.99. The precisions (RSD %) of the intra-day and inter-day analyses ranged from 2.11% to 18.7%, and the accuracies (RE%) ranged from -14.39% to 17.48%. The matrix effect ranged from 88.66% to 114.82%. Moreover, 7 varieties of soybeans were analyzed and compared with this robust screening method.

Endoscope rotating technique is useful for difficult colorectal endoscopic submucosal dissection.

BACKGROUND: Conventional lesion-up colorectal ESD has the potential risk of iatrogenic perforation due to the knife's direction toward the muscular layer of the bowel wall. If we rotate the endoscope to the proper position, the mucosal flap is easy to be lifted down by tip attachment and the knife is easy to approach the proper dissection plane, which may prevent the perforation and facilitate difficult ESD. METHODS: We aimed to retrospectively assess the safety and efficacy of this rotating technique compared with the conventional lesion-up dissection regardless of shape, location, or size of the tumor, and investigated in short- and long-term outcomes following the ESD procedure. RESULTS: 41 lesions were enrolled into rotating technique group and 37 lesions in lesion-up group. The dissection speed was significantly faster in the rotating technique group (p = 0.023). R0 resection rate was significantly higher in rotating technique group (p = 0.008). The rate of perioperative complication was significantly higher in lesion-up method group (p = 0.003). Local recurrence was higher in lesion-up group (p = 0.001). Recurrence-free rate was higher in rotating technique group (p = 0.018). CONCLUSION: The endoscope rotating is a useful technique for difficult colorectal ESD due to easy approaching the proper dissection plane. This technique also increases the rate of en bloc resections, R0 resections regardless of size, shape, and location and improves dissection speed without increasing the incidence of adverse events.

Risk factors for Barrett's esophagus in young adults who underwent upper gastrointestinal endoscopy in a health examination center.

BACKGROUND: Barrett's esophagus (BE) is a premalignant condition with increased incidence worldwide both in old and young individuals. However, the role of certain potential risk factors remains unclear in young adults (< 50 years). We aimed to determine the risk factors of BE in young adults. METHODS: A total of 4943 young adults who underwent upper gastrointestinal endoscopy at our health check-up center were enrolled. The diagnosis of BE was based on histological confirmation. We analyzed demographic factors, laboratory data, potential risk factors such as smoking, alcohol consumption, presence of gastroesophageal reflux disease (GERD) symptoms, and metabolic syndrome for the risk of BE by using binary logistic regression analysis. RESULTS: The prevalence of BE was 1.8% (88/4943). Male sex, the presence of GERD symptoms, and smoking were three significant risk factors related to BE. Furthermore, participants who had smoked for 10 pack-years or more had increased risk of BE with dose-dependent phenomenon (p trend < 0.001). The proportion of BE in male participants with both GERD symptoms and a smoking history of 10 pack-years or more was as high as 10.3% (16/155). CONCLUSIONS: Significant risk factors of BE in young adults are male sex, the presence of GERD symptoms, and smoking. The risk also increases with an increase in cumulative exposure to smoking.

Role of Fatty Liver Index and Metabolic Factors in the Prediction of Nonalcoholic Fatty Liver Disease in a Lean Population Receiving Health Checkup.

OBJECTIVES: Some metabolic factors and noninvasive markers, including fatty liver index (FLI), are used to predict nonalcoholic fatty liver disease (NAFLD) in obese patients. Despite the increasing prevalence of NAFLD in lean patients (lean-NAFLD), the risk factors and predictors are not well determined in this population. We investigated factors associated with lean-NAFLD and validated their predictive ability. METHODS: From 9,293 examinees who underwent routine health checkups, we enrolled 4,000, aged ≥20 years, with a body mass index <24 kg/m in our lean-NAFLD study population. NAFLD diagnoses were made according to the patients' histories, laboratory values, and sonographic criteria. Clinical variables, serum sugar, lipid, and liver profiles were evaluated using multiple logistic regression analysis. The predictive ability and optimal cutoff values for NAFLD were determined according to the area under the receiver operating characteristic curve. RESULTS: Overall, 18.5% (n = 740) of the lean population had NAFLD. Male sex, body mass index, body fat mass, fasting plasma glucose, uric acid, alanine aminotransferase, triglyceride, and FLI values were associated with NAFLD. FLI had the best discriminative ability to predict lean-NAFLD compared to the other biochemical markers. We further used the Youden index test and found an optimum cut-off value for FLI of 15 with the highest discriminant ability than other values. DISCUSSION: The prevalence of lean-NAFLD was not low. FLI was superior to other predictors including sex, liver function, and other metabolic factors, in the prediction of lean-NAFLD. FLI may be considered an easy to use, noninvasive marker to screen for lean-NAFLD.

Incidence and Clinical Outcomes of Gonadal Artery Injury during Colorectal Surgery in Male Patients.

BACKGROUND: Gonadal artery is susceptible to accidental injury due to their anatomical proximity to the colon and rectum. There are few literature reviews focusing on this injury during colorectal surgery. We conduct a retrospective study to evaluate the incidence and the clinical significance of these injuries in terms of testicular size and testicular enhancement on the contrast CT scan. METHODS: Patients' characteristic data included age, body mass index (BMI), diagnosis, operation type, cause of gonadal artery injury, side of injury, level of injury, method of vessel ligation, and follow-up period. We measured the testicular sizes before and after gonadal artery injury and measured the enhancement level by recording the mean attenuation value on the injury side and non-injury side of the testis on the CT scan. RESULTS: The incidence of gonadal artery injury was 3.61% and 15 male patients with this injury were enrolled. There were 5 patients with iatrogenic injury and 10 patients with non-iatrogenic injury due to advanced tumor or inflammation. No patients had any complaints of testicular discomforts or atrophy after the surgery. The testicular sizes before and after the surgery showed no significant difference (p = 0.877). The mean attenuation values of the injury side and non-injury side of the testis also showed no significant difference (p = 0.79). CONCLUSIONS: Gonadal artery injury during colorectal surgery is not a rare complication. To prevent this injury, knowledge of the anatomy and staying in the proper plane of dissection are the key points. In patients with gonadal artery injury during colorectal surgery, sacrifice of the gonadal artery is safe without clinical significance in terms of testicular size and testicular enhancement on the contrast CT scan.

Placement of SurgiWrap® adhesion barrier film around the protective loop stoma after laparoscopic colorectal cancer surgery may reduce the peristomal adhesion severity and facilitate the closure.

PURPOSE: A temporary loop stoma is often created after laparoscopic colorectal cancer surgery. Peristomal adhesions may make stoma closure into a complicated operation. We demonstrated how to place the SurgiWrap® adhesion barrier film and evaluated the peristomal adhesion severity and feasibility of stoma closure. METHODS: This is a retrospective case-control study. Patients were divided into a study group (placement of adhesion barrier film) and a control group (no placement). Patient characteristics, operative data, and severity of adhesions were recorded. We used logistic regression to probe the association between the variables and the adhesion severity. RESULTS: A total of 180 patients were identified with 60 in the study group and 120 in the control group. In the study group, the adhesion severity (p < 0.001), operative time (p = 0.025), and time to flatus (p = 0.042) are significantly reduced. In logistic regression analysis, placement of the film (p < 0.001), neoadjuvant concurrent chemoradiotherapy (p = 0.041), and time interval between stoma creation and closure ≧ 12 weeks (p = 0.038) are three significant factors influencing the peristomal adhesion. CONCLUSION: The placement of SurgiWrap® adhesion barrier film around the loop stoma after laparoscopic colorectal cancer surgery may reduce the peristomal adhesion severity and facilitate the stoma closure in terms of operative time and time to flatus.

Anticancer effects of methotrexate in combination with α­tocopherol and α­tocopherol succinate on triple­negative breast cancer.

Triple­negative breast cancers (TNBCs) lack the estrogen receptor, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Therefore, hormone or targeted therapies are not effective in the treatment of TNBC and thus the development of novel therapeutic strategies is crucial. Methotrexate (MTX), a folate antagonist, has been used in the treatment of various types of cancer; however, the anticancer effects of MTX treatment on breast cancer have thus far been ineffective. Vitamin E variants and derivatives have been applied for cancer therapy. Previous studies have indicated that vitamin E variants and derivatives exert distinct anticancer effects on different types of cancer. However, whether MTX plus vitamin E variants or its derivatives can inhibit TNBC remains unclear. The aim of the present study was to examine the anticancer effects and mechanisms of action of MTX in combination with vitamin E variants (α­tocopherol) and derivatives (α­tocopherol succinate) on TNBC. In the present study, MTT assay and western blot analysis were used to determine the cell survival rates and protein levels. The results demonstrated that combination treatment with MTX and α­tocopherol suppressed TNBC cell proliferation. In addition, various concentrations of MTX exerted distinct cytotoxic effects on α­tocopherol succinate­treated cells. Furthermore, high­dose MTX enhanced α­tocopherol succinate­induced anticancer activity; however, low­dose MTX inhibited α­tocopherol succinate­induced anticancer activity. The present study also demonstrated that caspase­3 activation and poly(adenosine diphosphate­ribose) polymerase cleavage were observed in the α­tocopherol succinate/MTX­treated cells. In conclusion, the findings of the present study demonstrated that high­dose MTX enhanced anticancer activity in α­TOS­treated TNBC, while low­dose MTX reduced anticancer activity in α­TOS­treated TNBC.