Evaluating complete response prediction rates in locally advanced rectal cancer with different radiomics segmentation approaches.

Purpose: Studies examining prediction of complete response (CR) in locally advanced rectum cancer (LARC) from pre/post chemoradiotherapy (CRT) magnetic resonance imaging (MRI) are performed mostly with segmentations of the tumor, whereas only in two studies segmentation included tumor and mesorectum. Additionally, pelvic extramesorectal region, which is included in the clinical target volume (CTV) of radiotherapy, may contain information. Therefore, we aimed to compare predictive rates of radiomics analysis with features extracted from segmentations of tumor, tumor+mesorectum, and CTV. Methods and materials: Ninety-three LARC patients who underwent CRT in our institution between 2012 and 2019 were retrospectively scanned. Patients were divided into CR and non-CR groups. Tumor, tumor+mesorectum and CTV were segmented on T2 preCRT MRI images. Extracted features were compared for best area under the curve (AUC) of CR prediction with 15 machine-learning models. Results: CR was observed in 25 patients (26.8%), of whom 13 had pathological, and 12 had clinical complete response. For tumor, tumor+mesorectum and CTV segmentations, the best AUC were 0.84, 0.81, 0.77 in the training set and 0.85, 0.83 and 0.72 in the test set, respectively; sensitivity and specificity for the test set were 76%, 90%, 76% and 71%, 67% and 62%, respectively. Conclusion: Although the highest AUC result is obtained from the tumor segmentation, the highest accuracy and sensitivity are detected with tumor+mesorectum segmentation and these findings align with previous studies, suggesting that the mesorectum contains valuable insights for CR. The lowest result is obtained with CTV segmentation. More studies with mesorectum and pelvic nodal regions included in segmentation are needed.

Reliability and validity of the Turkish version of the New Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire.

PURPOSE: This study aims to adapt and validate the Cleveland Clinic Colorectal Cancer Quality of Life Questionnaire (CCF-CaQL) in Turkish, addressing the significant need for reliable, language-specific QoL measures for colorectal cancer (CRC) in Turkiye. This effort fills a critical gap in CRC patient care, enhancing both patient-provider communication and disease-specific QoL assessment. METHODS: The CCF-CaQL was translated into Turkish, verified for accuracy, and reviewed for clarity and relevance. Eligible patients who underwent colorectal surgery for cancer between July 2021 and July 2022 from six hospitals completed the CCF-CaQL and SF-36 questionnaires. For analysis, confirmatory factor analysis using Smart PLS 4 and descriptive statistics were employed. The questionnaire's reliability and validity were assessed using Cronbach alpha, composite reliability, and the heterotrait-monotrait (HTMT) ratio, along with multicollinearity checks and factor loadings. Nonparametric resampling was used for precise error and confidence interval calculations, and the Spearman coefficient and split-half method were applied for reliability testing. RESULTS: In the study involving 244 colorectal cancer patients, confirmatory factor analysis of the CCF-CaQL indicated effective item performance, with one item removed due to lower factor loading. The questionnaire exhibited high internal consistency, evidenced by a Cronbach alpha value of 0.909. Convergent validity was strong, with all average variance extracted (AVE) values exceeding 0.4. Discriminant validity was confirmed with HTMT coefficients below 0.9, and no significant multicollinearity issues were observed (VIF values < 10). Parallel testing with the SF-36 scale demonstrated moderate to very strong correlations, affirming the CCF-CaQL's comparability in measuring quality of life. CONCLUSION: The Turkish version of the CCF-CaQL was validated for assessing quality of life in colorectal cancer patients. This validation confirms its reliability and cultural appropriateness for use in Turkiye. The disease-specific nature of the CCF-CaQL makes it a useful tool in clinical and research settings, enhancing patient care by accurately monitoring treatment effects and interventions in the Turkish colorectal cancer patient population.

Neoadjuvant intermediate-course versus long-course chemoradiotherapy in T3-4/N0+ rectal cancer: Istanbul R-02 phase II randomized study.

Radiation therapy (RT) is typically applied using one of two standard approaches for preoperative treatment of resectable locally advanced rectal cancer (LARC): short-course RT (SC-RT) alone or long-course RT (LC-RT) with concurrent fluorouracil (5-FU) chemotherapy. The Phase II single-arm KROG 11-02 study using intermediate-course (IC) (33 Gy (Gray)/10 fr (fraction) with concurrent capecitabine) preoperative chemoradiotherapy (CRT) demonstrated a pathologically complete response rate and a sphincter-sparing rate that were close to those of LC-CRT. The current trial aim to compare the pathological/oncological outcomes, toxicity, and quality of life results of LC-CRT and IC-CRT in cases of LARC. The prescribed dose was 33 Gy/10 fr for the IC-CRT group and 50.4 Gy/28 fr for the LC-CRT group. Concurrent chronomodulated capecitabine (Brunch regimen) 1650 mg/m2/daily chemotherapy treatment was applied in both groups. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer Module (EORTC QLQ-CR29) was administered at baseline and at three and six months after CRT. A total of 60 patients with LARC randomized to receive IC-CRT (n = 30) or LC-CRT (n = 30) were included in this phase II randomized trial. No significant difference was noted between groups in terms of pathological outcomes, including pathological response rates (ypT0N0-complete response: 23.3% vs. 16.7%, respectively, and ypT0-2N0-downstaging: 50% for each; p = 0.809) and Dworak score-based pathological tumor regression grade (Grade 4-complete response: 23.3 vs. 16.7%, p = 0.839). The 5-year overall survival (73.3 vs. 86.7%, p = 0.173) rate was also similar. The acute radiation dermatitis (p < 0.001) and any hematological toxicity (p = 0.004) rates were significantly higher in the LC-CRT group, while no significant difference was noted between treatment groups in terms of baseline, third month, and sixth month EORTC QLQ-CR29 scores.

Clinical outcomes of obstructive colorectal cancer patients during the coronavirus disease 2019 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has affected all aspects of clinical care including diagnosis and treatment of colorectal cancers (CRCs) globally, including in Türkiye. During the initial peak of the pandemic, elective surgeries and outpatient clinics were restricted in addition to the government-imposed lockdown, resulting in a decrease in the number of colonoscopies being performed and patients admitted to inpatient wards for treatment of CRCs. In this study, we aimed to investigate whether the pandemic has affected presentation characteristics and outcomes of obstructive colorectal cancer in this period. METHODS: This is a single-center, retrospective cohort study based on all CRC adenocarcinoma patients that underwent surgical resection in a high-volume tertiary referral center in Istanbul, Türkiye. Patients were divided into two groups before and after 15 months of identification of 'patient-zero' in Türkiye (March 18, 2020). Patient demographics, initial presentation characteristics, clin-ical outcomes, and pathological cancer stages were compared. RESULTS: Overall, 215 patients underwent resection for CRC adenocarcinoma during 30 months (COVID era: 107, pre-COVID era: 108). Patient characteristics, tumor location, and clinical staging were comparable between two groups. During the COVID period, the number of obstructive CRCs (P<0.01) and emergency presentations (P<0.01) increased significantly compared to the respective pre-COVID period. However, there were no differences between 30-day morbidity, mortality, and pathological outcomes (P>0.05). CONCLUSION: Although the results of our study indicate a significant increase in emergency presentation and a decrease in elective admissions of CRCs during the pandemic, patients treated during the COVID period were not at a significant disadvantage in terms of post-operative outcomes. Further efforts should be made to decrease risks related to an emergency presentation of CRCs for future adverse events.

Malignant Colorectal Polyps: Are Pathology Reports Sufficient for Decision Making?

AIM: This study aims to assess the completeness of pathology reports of T1 colorectal cancers from different healthcare centers and the change of treatment decision after reevaluation of the polyps. MATERIALS AND METHODS: In this single-center retrospective cohort study, several pathology reports of endoscopically excised malignant colorectal polyps at diverse healthcare centers in Turkey were reassessed at a comprehensive cancer center in Istanbul. Reassessment was mainly focused on core elements such as the size of invasive carcinoma, histologic type and grade, tumor extension, surgical margin (deep and mucosal), and lymphovascular invasion. RESULTS: Sixty-seven endoscopically resected malignant polyps were analyzed. The mean age of patients was 62.2 years and 38 (58%) patients were males. Tumor size, histologic type and grade, surgical margin (deep and mucosal), and lymphovascular invasion were reported in 11%, 100%, 31%, 9%, and 19%, respectively. All 5 prognostic factors were reported only in 1 (1.5%) pathology report. Because of the missing (incomplete) data, the pathologic examination of 59 (88%) patients was determined to be inadequate to make an accurate treatment decision. CONCLUSION: Several variables are not considered and frequently missing for decision-making, suggesting the reassessment of the specimen by a second pathologist at a high-volume comprehensive cancer center.

BRAF, NRAS, KIT, TERT, GNAQ/GNA11 Mutation Profile and Histomorphological Analysis of Anorectal Melanomas: A Clinicopathologic Study.

OBJECTIVE: Primary anorectal melanomas (AMs) are uncommon neoplasms with aggressive behavior. Molecular profile and clinicopathologic features of AMs are still not well established. In this study, we aimed to investigate BRAF, NRAS, KIT, TERT, and GNAQ/GNA11 mutation status and clinicopathologic features of AMs. MATERIAL AND METHOD: All diagnostic slides of 15 AMs were reviewed. Histopathological and follow-up information were documented. Mutations in exon 15 of the BRAF gene; exons 2 and 3 of the NRAS gene; exons 9, 11, 13, 17, and 18 of the KIT gene; and exons 4 and 5 of the GNAQ/GNA11 genes and mutations in the promoter region of the TERT gene (chr.5, 1,295,228C > T and 1,295,250C > T) were analyzed. RESULTS: BRAF(V600E) and KIT(V555I and K642E) mutations were observed in one (7%) and two cases (14%), respectively. NRAS, TERT and GNAQ/GNA11 mutations were not detected. The mean age was 65. Patients presented with rectal mass, rectal bleeding, pain, and weight loss. 73% of the lesions were macroscopically polypoid. The most common tumor cell type was epithelioid. Mean tumor thickness was 10.4 mm. One third of the cases lacked pigmentation. In situ melanoma was present in one third of the cases. Among 14 patients with follow-up data, 12 succumbed to disease. The mean overall survival was 36 months. CONCLUSION: AMs are uncommon tumors with dismal survival, usually occurring in the elderly in various gross and microscopic appearances. In terms of molecular profile, BRAF and KIT mutations are rarely detected. Profiling of larger cohorts is required to elucidate the pathogenesis and to identify potential molecular indicators that may contribute to the development of individualized targeted therapies.

The Role of FDG Positron Emission Tomography/Contrast--Enhanced Computed Tomography in Preoperative Staging and Postoperative Follow-up in Rectal Cancer Surgery.

<b> Introduction:</b> F-18 fluorodeoxyglucose (F18-FDG) positron emission tomography-computed tomography (PET/CT) is a valuable functional imaging modality for the clinical diagnosis which provides physiological information based on the altered tissue metabolism. </br></br> <b> Aim:</b> This study aims to investigate the effectiveness of F-18 fluorodeoxyglucose (F18-FDG) positron emission tomography-computed tomography (PET/CT) in preoperative staging and postoperative local recurrence and distant metastases in patients with rectal cancer. </br></br> <b> Material and methods:</b> The imaging of 726 patients with rectal cancer who were operated on at Istanbul University, Istanbul School of Medicine and had F18-FDG PET/CT, CT, and magnetic resonance imaging (MRI) scans between September 2005 and October 2016 were retrospectively analyzed. Of these patients, 170 who had pre- and postoperative PET/CT scans, had their CT scans included in the study. The sensitivity and specificity of PET/CT in preoperative staging and detection of postoperative local recurrence and distant metastases were analyzed. </br></br> <b> Results:</b> Of the patients, 101 were males and 69 were females with a median age of 62.27 (range, 31 to 89) years. The sensitivity and specificity of preoperative PET/CT in detecting liver metastases were 100% (confidence interval [CI]: 66.37-100%) and 94.2% (CI: 89.72-100%), respectively (Cohen's kappa [κ]: 1.00; P < 0.001). The sensitivity and specificity of postoperative PET/ CT in diagnosing liver metastases were 100% (CI: 88.06-100%) and 98% (CI: 9-100%), respectively (Cohen's κ: 1.00; P < 0.001). The sensitivity and specificity of preoperative PET/CT in detecting lung metastases were 100% (CI: 66.37-100%) and 91.8% (CI: 89.72-100%), respectively (Cohen's κ: 1.00; P < 0.001). The sensitivity and specificity of postoperative PET/CT in detecting lung metastases were 100% (CI: 91.4-100%) and 96% (CI: 95.8-100%), respectively (Cohen's κ: 1.00; P < 0.001). The sensitivity and specificity of PET/CT in preoperative staging of pathological pelvic lymph nodes were 100% (CI: 63.06-100%) and 94.29% (CI: 80.84-99.3%), respectively (Cohen's κ: 0.860; P < 0.001). The sensitivity and specificity of postoperative PET/CT in detecting local recurrences were 100% (CI: 78.2-100%) and 76.74% (CI: 61.37-88.24%), respectively (Cohen's κ: 0.219; P < 0.08). </br></br> <b>Results:</b> Given the fact that PET/CT can detect all primary rectal cancer in preoperative staging, it can be effectively used in selected cases, particularly in those suspected of local and advanced disease and with metastases (T3N0, T3N1, and/or T4N1). Due to a relatively low specificity in detecting local recurrences postoperatively, PET/CT can be combined with further modalities.

Is Having Inflammatory Bowel Disease a Risk Factor for Severe Acute Respiratory Syndrome Coronavirus 2?

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 virus was found to have effects not only in the lungs but also in many different organs. We aimed to evaluate the management of our patients with inflammatory bowel disease in this pandemic, the incidence of coronavirus disease 2019 in terms of clinical, medical treatment, and features of inflammatory bowel disease, and to investigate the effects of the severe acute respiratory syndrome coronavirus 2 on this particular group of patients. METHODS: During the coronavirus disease 2019 pandemic, 207 patients who had inflammatory bowel disease for at least 6 months were questioned for coronavirus disease 2019 at their outpatient clinic admissions, and their medical records were evaluated prospectively. RESULTS: Of the 207 patients, 146 had Crohn's disease. The mean disease duration was determined as 118.15 ± 72.85 months. Of the patients, 127 (61.4%) were using mesalazine, 110 (53.1%) azathioprine, and 148 (71.5%) biological agents. It was found that 66 (31.9%) patients changed their medications during the coronavirus disease 2019 pandemic. As a medication change, anti-Tumor Necrosis Factor (TNF) dose was observed to be omitted most frequently at a rate of 80%. Diarrhea was present in 20.8%, abdominal pain in 20.3%, nausea in 10.6%, anorexia in 13.5%, and weight loss in 15.9% of the patients. Twelve (5.79%) patients were diagnosed with coronavirus disease 2019. Lung involvement was present in 11 (91.7%) of the patients diagnosed with coronavirus disease 2019. Of the patients diagnosed and not diagnosed with coronavirus disease 2019, 75% vs. 71.6% were using biological agents (P = .80), respectively. Half of the patients diagnosed with coronavirus disease 2019 were active in terms of inflammatory bowel disease at the time of diagnosis, and 2 of these patients were severely active. CONCLUSION: The incidence of coronavirus disease 2019 infection in patients with inflammatory bowel disease was not different from the general population during the severe acute respiratory syndrome coronavirus 2 pandemic. Coronavirus disease 2019 infection does not progress with poor prognosis in patients with inflammatory bowel disease who receive immunosuppressive therapy including biological agents.

Complete Response Evaluation of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiotherapy Using Textural Features Obtained from T2 Weighted Imaging and ADC Maps.

BACKGROUND: The prediction of pathological responses for locally advanced rectal cancer using magnetic resonance imaging (MRI) after neoadjuvant chemoradiotherapy (CRT) is a challenging task for radiologists, as residual tumor cells can be mistaken for fibrosis. Texture analysis of MR images has been proposed to understand the underlying pathology. OBJECTIVE: This study aimed to assess the responses of lesions to CRT in patients with locally advanced rectal cancer using the first-order textural features of MRI T2-weighted imaging (T2-WI) and apparent diffusion coefficient (ADC) maps. METHODS: Forty-four patients with locally advanced rectal cancer (median age: 57 years) who underwent MRI before and after CRT were enrolled in this retrospective study. The first-order textural parameters of tumors on T2-WI and ADC maps were extracted. The textural features of lesions in pathologic complete responders were compared to partial responders using Student's t- or Mann-Whitney U tests. A comparison of textural features before and after CRT for each group was performed using the Wilcoxon rank sum test. Receiver operating characteristic curves were calculated to detect the diagnostic performance of the ADC. RESULTS: Of the 44 patients evaluated, 22 (50%) were placed in a partial response group and 50% were placed in a complete response group. The ADC changes of the complete responders were statistically more significant than those of the partial responders (P = 0.002). Pathologic total response was predicted with an ADC cut-off of 1310 x 10-6 mm2/s, with a sensitivity of 72%, a specificity of 77%, and an accuracy of 78.1% after neoadjuvant CRT. The skewness of the T2-WI before and after neoadjuvant CRT showed a significant difference in the complete response group compared to the partial response group (P = 0.001 for complete responders vs. P = 0.482 for partial responders). Also, relative T2-WI signal intensity in the complete response group was statistically lower than that of the partial response group after neoadjuvant CRT (P = 0.006). CONCLUSION: As a result of the conversion of tumor cells to fibrosis, the skewness of the T2-WI before and after neoadjuvant CRT was statistically different in the complete response group compared to the partial response group, and the complete response group showed statistically lower relative T2-WI signal intensity than the partial response group after neoadjuvant CRT. Additionally, the ADC cut-off value of 1310 × 10-6 mm2/s could be used as a marker for a complete response along with absolute ADC value changes within this dataset.

Adjuvant Treatment of Gastric Cancer in the D2 Dissection Era: A Real-life Experience from a Multicenter Retrospective Cohort Study.

BACKGROUND: The role of radiotherapy in the adjuvant treatment of gastric cancer (GC) remains to be elucidated. This study aimed to assess the additional benefit of radiotherapy in the adjuvant treatment of GC. MATERIALS AND METHODS: In this retrospective cohort study, we included 230 gastric adenocarcinoma patients who underwent D2 dissection between January 2004 and December 2019. Patients without R0 resection, who underwent metastasectomy at surgery, and treated with the neoadjuvant treatment were excluded. The co-primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were the locoregional and distant metastasis risk and adverse events (AEs) leading to treatment discontinuation. RESULTS: One hundred and sixty-six and 64 patients were included in the chemoradiotherapy (CRT) and chemotherapy (ChT) arms, respectively. The median OS was 135.8 months [interquartile range (IQR): 99.4-172.2] and 97 months (IQR: 59.7-134.3) in the CRT and the ChT arms, respectively. No statistical significance was observed between the arms in OS (p = 0.3). Locoregional or distant recurrence rates were similar in each group. AEs leading to treatment discontinuation were higher in the CRT arm than in the ChT arm (13.2 vs 9.3%), and the difference between the arms was not statistically significant (p = 0.4). CONCLUSION: In this real-life study, we established that there was no additional benefit of RT in GC patients who underwent D2 dissection. HOW TO CITE THIS ARTICLE: Yekedüz E, Dogan I, Birgi SD, et al. Adjuvant Treatment of Gastric Cancer in the D2 Dissection Era: A Real-life Experience from a Multicenter Retrospective Cohort Study. Euroasian J Hepato-Gastroenterol 2021;11(2):51-58.

Evaluating the Validity of the Clavien-Dindo Classification in Colectomy Studies: A 90-Day Cost of Care Analysis.

BACKGROUND: The Clavien-Dindo classification is widely used to report postoperative morbidity but may underestimate the severity of colectomy complications. OBJECTIVE: The purpose of this study was to assess how well the Clavien-Dindo classification represents the severity of all grades of complications after colectomy using cost of care modeling. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a comprehensive cancer center. PATIENTS: Consecutive patients (N = 1807) undergoing elective colon or rectal resections without a stoma performed at Memorial Sloan Kettering Cancer Center between 2009 and 2014 who were followed up for ≥90 days, were not transferred to other hospitals, and did not receive intraperitoneal chemotherapy were included in the study. MAIN OUTCOME MEASURES: Complication severity was measured by the highest-grade complication per patient and attributable outpatient and inpatient costs. Associations were evaluated between patient complication grade and cost during 3 time periods: the 90 days after surgery, index admission, and postdischarge (<90 d). RESULTS: Of the 1807 patients (median age = 62 y), 779 (43%) had a complication; 80% of these patients had only grade 1 or 2 complications. Increasing patient complication grade correlated with 90-day cost, driven by inpatient cost differences (p < 0.001). For grade 1 and 2 patients, most costs were incurred after discharge and were the same between these grade categories. Among patients with a single complication (52%), there was no difference in index hospitalization, postdischarge, or total 90-day costs between grade 1 and 2 categories. LIMITATIONS: The study was limited by its retrospective design and generalizability. CONCLUSIONS: The Clavien-Dindo classification correlates well with 90-day costs, driven largely by inpatient resource use. Clavien-Dindo does not discriminate well among patients with low-grade complications in terms of their substantial postdischarge costs. These patients represent 80% of patients with a complication after colectomy. Examining the long-term burden associated with complications can help refine the Clavien-Dindo classification for use in colectomy studies. See Video Abstract at http://links.lww.com/DCR/B521. EVALUACIN DE LA VALIDEZ DE LA CLASIFICACIN DE CLAVIENDINDO EN ESTUDIOS DE COLECTOMA ANLISIS DEL COSTO DE LA ATENCIN EN DAS: ANTECEDENTES:La clasificación de Clavien-Dindo es utilizada ampliamante para conocer la morbilidad posoperatoria, pero puede subestimar la gravedad de las complicaciones de la colectomía.OBJETIVO:Evaluar que tan bien representa la clasificación de Clavien-Dindo la gravedad de todos los grados de complicaciones después de la colectomía utilizando un modelo de costo de la atención.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLÍNICO:Centro oncológico integral.PACIENTES:Pacientes consecutivos (n = 1807) sometidos a resecciones electivas de colon o recto sin estoma realizadas en el Memorial Sloan Kettering Cancer Center entre 2009 y 2014 que fueron seguidos durante ≥ 90 días, no fueron transferidos a otros hospitales y no recibieron quimioterapia intraperitoneal.PRINCIPALES MEDIDAS DE VALORACION:Gravedad de la complicación medida por la complicación de mayor grado por paciente y los costos atribuibles para pacientes ambulatorios y hospitalizados. Se evaluó la asociación entre el grado de complicación del paciente y el costo durante 3 períodos de tiempo: posterior a la cirugía (hasta 90 días), a su ingreso y posterior al egreso (hasta 90 días).RESULTADOS:De los 1807 pacientes (mediana de edad de 62 años), 779 (43%) tuvieron una complicación; El 80% de estos pacientes tuvieron solo complicaciones de grado 1 o 2. El aumento del grado de complicación del paciente se correlacionó con el costo a 90 días, impulsado por las diferencias en el costo de los pacientes hospitalizados (p <0,001). Para los pacientes de grado 1 y 2, la mayoría de los costos se incurrieron después del alta y fueron los mismos entre ambas categorías. Entre los pacientes con una sola complicación (52%), no hubo diferencia en el índice de hospitalización, posterior al alta o en el costo total de 90 días entre las categorías de grado 1 y 2.LIMITACIONES:Diseño retrospectivo, generalizabilidad.CONCLUSIONES:La clasificación de Clavien-Dindo se correlaciona bien con los costos a 90 días, impulsados en gran parte por la utilización de recursos de pacientes hospitalizados. Clavien-Dindo no discrimina entre los pacientes con complicaciones de bajo grado en términos de sus costos sustanciales posterior al alta. Estos pacientes representan el 80% de los pacientes aquellos con una complicación tras la colectomía. Examinar la carga a largo plazo asociada a las complicaciones puede ayudar a mejorar la clasificación de Clavien-Dindo para su uso en estudios de colectomía. Consulte Video Resumen en http://links.lww.com/DCR/B521.

Fragmentation Analysis of Plasma DNA Reveals Its Prognostic Value in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is a common cause of cancer-related deaths. The poor clinical outcome in GC patients is partially associated with a lack of appropriate diagnostic and prognostic biomarkers. In the present study, we evaluated the diagnostic and prognostic values of cell-free DNA (cfDNA) integrity and the concentration of circulating nucleosomes (cNUCs). METHODS: In the study, 40 GC patients and 55 GC-free individuals were enrolled. Cell-free DNA integrity was calculated as the ratio of concentration of the longer ACTB (beta-actin) gene fragment to that of the shorter ACTB fragment, measured using quantitative PCR. Circulating nucleosomes were measured by an ELISA-based approach. RESULTS: We found that cfDNA integrity is higher in GC patients than in the control subjects (relative median values 0.51 vs. 0.38, respectively, P = .56) indicating prominent abundance of longer fragments in the patients. The patients with larger tumors (T3-4) had significantly higher cfDNA integrity than those with T1-T2 tumors. We also found GC patients to have higher concentrations of cNUCs in their plasma (relative median values 3.64 vs. 3.1). Importantly, the patients with high cfDNA integrity (i.e., lower fragmentation) had longer overall survival rates at 3 years than those with lower cfDNA integrity (76.5% vs. 38.9%, P = .02). CONCLUSION: Cell-free DNA fragmentation has a prognostic value. However, it has no diagnostic value in GC.

The Value of Preoperative Ultrasound in the Detection of Contralateral Occult Inguinal Hernia in the Treatment of Symptomatic Inguinal Hernia.

BACKGROUND: The true incidence of contralateral occult inguinal hernia (OIH) is a debate. The repair of contralateral OIH in the treatment context of clinical symptomatic unilateral inguinal hernia (IH) is controversial. This study aimed to assess the effect and clinical benefit of preoperative ultrasound (US) in the diagnosis of contralateral OIH performed before surgery. METHODS: The retrospective data of 155 consecutive male patients who underwent IH repair between January 2014 and January 2020 were analyzed. The surgical procedures for IH and the clinical outcomes of the US were evaluated. RESULTS: Of 155 patients, 29 (18.7%) presented with bilateral IH. Preoperative US was performed in 73 cases of clinical unilateral IH (n=126), and 30 (23.8%) patients were found to have a contralateral OIH. The totally extrapreperitoneal (TEP) or Lichtenstein repair was conducted. Bilateral IH repair was proposed for all, but only 28 agreed and underwent bilateral repair. Patients with clinically bilateral hernia had more complications compared with patients diagnosed to have occult contralateral IH after the US (n=3 vs. n=0). In the overall group, the TEP procedure resulted in shorter hospital stay (P=0.001) and less pain (P=0.021). CONCLUSIONS: The preoperative US may be recommended to assess the presence of a contralateral OIH as it is a noninvasive, radiation-free, widely available, relatively cheap diagnostic method. The preoperative US may change the surgical approach in up to 1/4 patients with a clinical unilateral IH. Either Lichtenstein repair or TEP repair can be performed with an acceptable complication rate in the case of OIH.

What are the predictors for recurrence of Crohn's disease after surgery?

ABSTRACT: Surgical resection is an unavoidable part of the current treatment options for Crohn's disease (CD), and more than half of patients develop recurrence. The aim of this study was to investigate the predictors for recurrence in the long-term follow-up of CD patients after surgery.Medical records of consecutive CD patients who were operated on between January 2003 and January 2015 were retrospectively analyzed. Data including demographic and clinical characteristics of the patients were recorded. Recurrence was evaluated based on the Crohn's Disease Activity Index or endoscopic findings.The majority of 112 patients were males (n = 64, 57.1%), and 61 (54.4%) of them were active smokers. The median follow-up was 113 (range: 61-197) months. Disease recurrence occurred in 16 (14.3%) patients at a median of 13.5 months. The endoscopic recurrence rate was 8% (n = 9) at 1 year, 12.5% (n = 14) at 5 years, and 13.4% (n = 15) at 10 years. One (0.9%) patient underwent colonoscopic balloon dilatation at 1 year, and 7 (6.3%) patients needed re-resection at a median of 36 months. The age of the patient at the time of diagnosis (P = .033), penetrating disease behavior (P = .011), intra-abdominal abscess (P = 0.040) and, concomitant fistula and intra-abdominal abscess (P = .017) were associated with disease recurrence.Our study results suggest that the patients' age at the time of diagnosis, penetrating disease, intra-abdominal abscess, and concomitant fistula and abscess are the risk factors for CD recurrence after surgery.

Satellite 2 repeat DNA in blood plasma as a candidate biomarker for the detection of cancer.

BACKGROUND AND AIM: Currently, cancer biomarkers are associated with low diagnostic performance, and the notion of using cell-free DNA (cfDNA) as a surrogate cancer biomarker is a subject of ongoing research efforts. Pericentromeric satellite repeats were shown to expand in tumor cells. Here, we hypothesized that the increased release of satellite DNA into the circulation might be a basis for developing a biomarker for the detection of cancer. MATERIALS AND METHODS: The study included patients with different cancer types, and controls without cancer. Human satellite 2 repeat (HSATII) from chromosomes 1, 10, or 16 was amplified using extracted DNA from plasma or direct application of diluted plasma in PCR. RESULTS: We first showed that HSATII DNA levels were higher in patients with cancer than in controls relative to LINE1 element, with chr10-HSATII being the most relevant. Absolute quantification in digital PCR showed much higher levels of chr10-HSATII in patients with breast cancer compared with healthy individuals. Subsequently, employing diluted plasma also revealed that HSATII DNA was present in increased levels in patients with cancer including breast, gastric, lung or bile cancers, sarcoma or Hodgkin's lymphoma than in controls with an AUC of 94% in the ROC curve. CONCLUSIONS: This proof-of-concept study reveals the high potential of HSATII DNA as a surrogate cancer biomarker.

Intracorporeal Anastomoses in Minimally Invasive Right Colectomies Are Associated With Fewer Incisional Hernias and Shorter Length of Stay.

BACKGROUND: Intracorporeal anastomosis is associated with several short-term benefits. However, it is a technically challenging procedure with potential risk OBJECTIVE:: The purpose of this study was to investigate differences in short-term complications and long-term incisional hernia rates after robotic right colectomy with intracorporeal versus extracorporeal anastomoses and standardized extraction sites. DESIGN: This was a historical cohort study. SETTINGS: The study was conducted at a single institution. PATIENTS: All of the patients undergoing robotic right colectomy with intracorporeal anastomosis and a Pfannenstiel extraction site or extracorporeal anastomosis with a vertical midline extraction site from 2013 to 2017 were eligible. Exclusion criteria were conversion to laparotomy for tumor-related reasons or lack of follow-up. INTERVENTION: Intracorporeal or extracorporeal anastomosis was performed, based on availability of the robotic stapler and appropriate bedside assistance. MAIN OUTCOME MEASURES: The primary outcome was incisional hernia, diagnosed either clinically or on postoperative imaging, and analyzed using time-to-event analysis. A Cox proportional hazards model was used for multivariable analysis. Secondary outcomes were analyzed using parametric and nonparametric tests. Statistical significance was set at p < 0.05. RESULTS: Of 164 patients who met all inclusion criteria, 67 had intracorporeal and 97 had extracorporeal anastomoses. Median follow-up time was similar in both groups (14 vs 15 mo; p = 0.73). The 1-year estimated incisional hernia rate was 12% for extracorporeal and 2% for intracorporeal anastomoses (p = 0.007); this difference was confirmed by multivariable modeling. The severity of postoperative complications was similar between the groups, but there was an increase in incisional infections and a shorter length of stay (1 day) for intracorporeal cases. LIMITATIONS: The study was limited by its retrospective, single-surgeon nature. CONCLUSIONS: Right colectomy with intracorporeal anastomosis and a Pfannenstiel extraction site may reduce the rate of incisional hernias compared with extracorporeal anastomosis with a vertical midline extraction site. The intracorporeal approach was also associated with a decreased length of stay but an increase in incisional surgical site infections. These findings have implications for healthcare use and patient-centered outcomes. See Video Abstract at http://links.lww.com/DCR/B147. ANASTOMOSIS INTRACORPÓREAS EN COLECTOMÍAS DERECHAS MÍNIMAMENTE INVASIVAS SE ASOCIAN CON MENOS HERNIAS INCISIONALES Y UNA ESTADÍA HOSPITALARIA MÁS BREVE: nastomosis intracorpórea se asocia con varios beneficios a corto plazo. Sin embargo, es un procedimiento técnicamente desafiante con riesgos potenciales.nvestigar las diferencias en las complicaciones a corto plazo y las tasas de hernia incisional a largo plazo después de la colectomía robótica derecha con anastomosis intracorpórea versus extracorpórea y sitios de extracción estandarizados.Estudio de cohorte histórico.cirujano individual, institución única.Todos los pacientes sometidos a colectomía robótica derecha con anastomosis intracorpórea y un sitio de extracción de Pfannenstiel o anastomosis extracorpórea con un sitio de extracción vertical de la línea media de 2013-2017 fueron elegibles. Los criterios de exclusión fueron la conversión a laparotomía por razones relacionadas con el tumor o la falta de seguimiento.nastomosis intracorpórea o extracorpórea, según la disponibilidad de grapadora robótica y la asistencia adecuada quirúrgica.El resultado primario fue la hernia incisional, diagnosticada clínicamente o en imágenes postoperatorias, y analizada mediante análisis de tiempo hasta el evento. Se usó un modelo de riesgos proporcionales de Cox para el análisis multivariable. Los resultados secundarios se analizaron mediante pruebas paramétricas y no paramétricas. La significación estadística se estableció en p < 0,05.De 164 pacientes que cumplieron con todos los criterios de inclusión, 67 tenían anastomosis intracorpóreas y 97 tenían anastomosis extracorpóreas. La mediana del tiempo de seguimiento fue similar en ambos grupos (14 versus 15 meses, p = 0,73). La tasa de hernia incisional estimada para un año fue del 12% para las anastomosis extracorpóreas y del 2% para las anastomosis intracorpóreas (p = 0,007); esta diferencia fue confirmada por el modelado multivariable. La gravedad de las complicaciones postoperatorias fue similar entre los grupos, pero hubo un aumento de las infecciones incisionales y una estancia más corta (un día) para los casos intracorpóreos.Retrospectiva, cirujano único.a colectomía derecha con anastomosis intracorpórea y un sitio de extracción de Pfannenstiel puede reducir la tasa de hernias incisionales en comparación con la anastomosis extracorpórea con un sitio de extracción vertical en la línea media. El enfoque intracorpóreo también se asoció con una disminución de la duración de la estadía, pero con un aumento de las infecciones del sitio quirúrgico incisional. Estos hallazgos tienen implicaciones para la utilización de recursos médicos y beneficios para pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B147. (Traducción-Dr. Adrian Ortega).

Plasma Histone H4 and H4K20 Trimethylation Levels Differ Between Colon Cancer and Precancerous Polyps.

BACKGROUND/AIM: No blood-based biomarkers are available to differentiate between colonic tumors and precancerous polyps. Previously we demonstrated levels of trimethylated H4K20 (H4K20me3) to be lower in blood plasma from patients with colon cancer than those from cancer-free individuals. Herein, we added individuals with precancerous polyps for the first time in order to analyze and investigate the usefulness of plasma H4K20me3 and histone H4 to discriminate colon tumors from precancerous polyps. MATERIALS AND METHODS: The study included a cohort of 185 individuals undergoing colonoscopy. H4K20me3 and histone H4, measured by an enzyme-linked immunosorbent assay-like assay in plasma, were analyzed according to colonoscopy findings. RESULTS: Levels of H4K20me3 were lower in patients with colon cancer than in individuals with normal colonoscopy and those with precancerous polyps (p=0.02 and p=0.01, respectively). In contrast, highest quantities of histone H4 were measured in those with colon cancer compared to other groups (all p<0.01). CONCLUSION: Beside H4K20me3, plasma histone H4 is a useful marker to discriminate colonic tumors from precancerous polyps and other conditions.

Assessment of the Value of Comorbidity Indices for Risk Adjustment in Colorectal Surgery Patients.

BACKGROUND AND PURPOSE: Comorbidity indices (CIs) are widely used in retrospective studies. We investigated the value of commonly used CIs in risk adjustment for postoperative complications after colorectal surgery. METHODS: Patients undergoing colectomy without stoma for colonic neoplasia at a single institution from 2009 to 2014 were included. Four CIs were calculated or obtained for each patient, using administrative data: Charlson-Deyo (CCI-D), Charlson-Romano (CCI-R), Elixhauser Comorbidity Score, and American Society of Anesthesiologists classification. Outcomes of interest in the 90-day postoperative period were any surgical complication, surgical site infection (SSI), Clavien-Dindo (CD) grade 3 or higher complication, anastomotic leak or abscess, and nonroutine discharge. Base models were created for each outcome based on significant bivariate associations. Logistic regression models were constructed for each outcome using base models alone, and each index as an additional covariate. Models were also compared using the DeLong and Clarke-Pearson method for receiver operating characteristic (ROC) curves, with the CCI-D as the reference. RESULTS: Overall, 1813 patients were included. Postoperative complications were reported in 756 (42%) patients. Only 9% of patients had a CD grade 3 or higher complication, and 22.8% of patients developed an SSI. Multivariable modeling showed equivalent performance of the base model and the base model augmented by the CIs for all outcomes. The ROC curves for the four indices were also similar. CONCLUSIONS: The inclusion of CIs added little to the base models, and all CIs performed similarly well. Our study suggests that CIs do not adequately risk-adjust for complications after colorectal surgery.

Inflammatory bowel disease and mycobacteria: how much can we trust isoniazid prophylaxis during antitumor necrosis factor therapy?

OBJECTIVES: Isoniazid (INH) prophylaxis is recommended for the prevention of tuberculosis (TB) reactivation before or/and during initiation of treatment with tumour necrosis factor antagonists (anti-TNF agents). Nonetheless, the long-term effectiveness of chemoprophylaxis is not clear. In this study, we aimed to evaluate the characteristics of patients who developed TB reactivation in spite of INH prophylaxis associated with anti-TNF treatment. PATIENTS AND METHODS: In this retrospective study, medical records of 1263 patients with inflammatory bowel disease were reviewed. Baseline TB screening tests (purified protein derivative test and/or QuantiFERON-TB Gold test) were performed on all patients before initiation of anti-TNF therapy. Patients with purified protein derivative of more than 5 mm and/or a positive result of the QuantiFERON-TB Gold test received INH prophylaxis for 9 months. We analysed the data of patients diagnosed with TB reactivation during the anti-TNF treatment despite INH chemoprophylaxis. RESULTS: Overall, 175 patients underwent anti-TNF treatment. Sixty of these 175 patients had pretreatment testing showing latent TB infection and therefore were treated concomitantly with INH for 9 months in addition to their anti-TNF treatment. TB reactivation occurred in four of these 60 co-INH/anti-TNF treated patients. Active TB was diagnosed after 37.5±27 (range: 18-84) months of anti-TNF treatment. In two of the four patients that active TB was diagnosed, was also detected other Mycobacterium spp.: M. bovis in one patient and M. genavense in the other one. CONCLUSION: INH chemoprophylaxis may not prevent the reactivation of TB during anti-TNF therapy in the long-term. Patients should be carefully and periodically screened for TB reactivation during anti-TNF therapy.

Variation in the Thoroughness of Pathologic Assessment and Response Rates of Locally Advanced Rectal Cancers After Chemoradiation.

BACKGROUND: Pathologic complete response (pCR) is associated with better prognosis and guides management for patients with advanced rectal cancer. Response rates vary between series for unclear reasons. We examine whether the thoroughness of pathologic assessment explains differences in pCR rates. METHODS: We retrospectively reviewed pathology reports from patients with stage II/III rectal cancer who underwent chemoradiation and resection in a prospective, multicenter trial. We utilized a novel measure for the thoroughness of pathologic assessment by dividing residual tumor size by the number of cassettes evaluated (tumor size to cassette ratio, TSCR), and evaluated whether TSCR is associated with pCR. We validated our findings using a separate cohort. RESULTS: From the trial cohort, 71 of 247 (29%) patients achieved pCR. The pCR rate ranged from 0 to 45% and mean TSCR ranged 0.29 to 0.87 across 12 institutions. Within each institution, a lower TSCR was associated with pCR, demonstrating a higher degree of thoroughness used for tumors that achieved pCR. Moreover, across all samples, low TSCR was independently associated with pCR on multivariable analysis. This finding was corroborated in a separate cohort of 201 tumors evaluated by five pathologists; each pathologist had a lower mean TSCR for pCR calls compared with non-pCR calls. However, the mean TSCR for an institution was not associated with its overall pCR rate. CONCLUSIONS: Pathologists assess rectal cancers that have responded significantly to neoadjuvant therapy more thoroughly. Thoroughness does not appear to explain differences in pCR rates between institutions. Our results suggest pCR is not a sampling artifact.