Serum carbohydrate antigen 19-9 (Ca19-9) is the only approved biomarker approved for the screening and diagnosis of pancreatic cancer (PC), but its value remains controversial. The aim of our study is to evaluate the role of CA 19-9 in the management of PC patients in jaundiced patients staged by both Computed Tomography (CT) and Endoscopic Ultrasound (EUS). Additionally, we evaluated traditional cholestasis marker behavior. Medical records of 73 patients have been retrospectively reviewed. We considered tumor size, tumor stage, CA 19-9, cytolysis, and cholestasis biomarkers. All patients underwent CT scan for staging. EUS +/− fine-needle biopsy (FNB) was performed in doubtful cases. Median alkaline phosphatase (ALP) and y-glutamyltransferase (GGT) levels were significantly lower compared to baseline after the biliary drainage (204 vs. 465 U/L, p < 0.0001, 204. U/L vs. 608.5, p < 0.0001, respectively), whilst no differences were observed for CA 19-9 levels. CA 19-9 showed significant association with the tumor stage in the pre-drainage setting. CT and EUS showed a low agreement in estimating tumor size (mean difference 4.8 mm 95% LoA −10.82–20.38). We did not find any significant correlation between CA 19-9 and bilirubin levels (r = −0.05, p = 0.7). In our cohort, survival rate was lower in patients with higher CA 19-9 levels (log rank p = 0.007). CA 19-9 has some limitations as a biomarker in the PC setting, thus it cannot address the treatment strategy alone. Nonetheless, it provides valuable information, and is not replaceable for the time being.

BACKGROUND:MRI and rectal endosonography (EUS) are routinely used for preoperative tumor staging and assessment of response to therapy in patients with rectal cancer. This study aimed to evaluate the accuracy of the two techniques in predicting the pathological response compared to the resected specimen and the agreement between MRI and EUS and to define the factors that could affect the ability of EUS and MRI to predict pathological responses.MATERIALS AND METHODS:This study included 151 adult patients with middle or low rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy, followed by curative intent elective surgery in the Oncologic Surgical Unit of a hospital in the north of Italy between January 2010 and November 2020. All patients underwent MRI and rectal EUS.RESULTS:The accuracy of EUS to evaluate the T stage was 67.48%, and for the N stage was 75.61%; the accuracy of MRI to evaluate the T stage was 75.97%, and that for the N stage was 51.94%. The agreement in detecting the T stage between EUS and MRI was 65.14% with a Cohen's kappa of 0.4070 and that for the evaluation of the lymph nodes between EUS and MRI was 47.71% with a Cohen's kappa of 0.2680. Risk factors that affect the ability of each method to predict pathological response were also investigated using logistic regression.CONCLUSIONS:EUS and MRI are accurate tools for rectal cancer staging. However, after Radiotherapy - Chemotherapy RT-CT, neither method is reliable for establishing the T stage. EUS seems significantly better than MRI for assessing the N stage. Both methods can be used as complementary tools in the preoperative assessment and management of rectal cancer, but their role in the assessment of residual rectal tumors cannot predict the complete clinical response.

Background: Total mesorectal excision (TME) is the gold standard to treat locally advanced rectal cancer. This monocentric retrospective study evaluates the results of laparotomic, laparoscopic and robotic surgery in “COMRE GROUP” (REctalCOMmittee). Methods: 327 selected stage I-II-III patients (pts) underwent TME between November 2005 and April 2020 for low or middle rectal cancer; 91 pts underwent open, 200 laparoscopic and 36 robotic TME. Of these, we analyzed the anthropomorphic, intraoperative, anatomopathological parameters and outcome during the follow up. Results: The length of hospital stay was significantly different between robotic TME and the other two groups (8.47 ± 3.54 days robotic vs. 11.93 ± 5.71 laparotomic, p < 0.001; 8.47 ± 3.54 robotic vs. 11.10 ± 7.99 laparoscopic, p < 0.05). The mean number of harvested nodes was higher in the laparotomic group compared to the other two groups (19 ± 9 laparotomic vs. 15 ± 8 laparoscopic, p < 0.001; 19 ± 9 laparotomic vs. 15 ± 7 robotic, p < 0.05). Median follow-up was 52 months (range: 1–169). Overall survival was significantly shorter in the open TME group compared with the laparoscopic one (Chi2 = 13.36, p < 0.001). Conclusions: In the experience of the “COMRE” group, laparoscopic TME for rectal cancer is a better choice than laparotomy in a multidisciplinary context. Robotic TME has a significant difference in terms of hospital stay compared to the other two groups.

BACKGROUND AND STUDY AIM:The traditional endoscopic therapy of anastomotic strictures (AS) after orthotopic liver transplantation (OLT) is multiple ERCPs with the insertion of an increasing number of plastic stents side-by-side. Fully covered self-expanding metal stents (cSEMS) could be a valuable option to decrease the number of procedures needed or non-responders to plastic stents. This study aims to retrospectively analyse the results of AS endoscopic treatment by cSEMS and to identify any factors associated with its success. PATIENTS AND METHODS:Ninety-one patients (mean age 55.9 ± 7.6 SD; 73 males) from nine Italian transplantation centres, had a cSEMS positioned for post-OLT-AS between 2007 and 2017. Forty-nine (54%) patients were treated with cSEMS as a second-line treatment. RESULTS:All the procedures were successfully performed without immediate complications. After ERCP, adverse events occurred in 11% of cases (2 moderate pancreatitis and 8 cholangitis). In 49 patients (54%), cSEMSs migrated. After cSEMS removal, 46 patients (51%) needed further endoscopic (45 patients) or radiological (1 patient) treatments to solve the AS. Lastly, seven patients underwent surgery. Multivariable stepwise logistic regression showed that cSEMS migration was the only factor associated with further treatments (OR 2.6, 95% CI 1.0-6.6; p value 0.03); cSEMS implantation before 12 months from OLT was associated with stent migration (OR 5.2, 95% CI 1.7-16.0; p value 0.004). CONCLUSIONS:cSEMS appears to be a safe tool to treat AS. cSEMS migration is the main limitation to its routinary implantation and needs to be prevented, probably with the use of new generation anti-migration stents.

Abstract Tumor mutational burden (TMB), defined as the number of somatic mutations per Megabase (Mb) in a neoplastic specimen measured by next-generation sequencing (NGS), is shown to increase its rate in association with higher genomic instability. Neoadjuvant chemoradiotherapy (NACRT) in locally advanced rectal adenocarcinoma (LARC) may be more active in genomically unstable tumors. However, response to NACRT is highly variable and pathological complete response is observed in only 15-25% of cases. Currently, the association of TMB with response to NACRT in LARC is unknown. The aim of this study was to investigate the role of TMB as a potential predictive biomarker of response in NACRT-treated LARC. We collected a set of pre-treatment biopsies from LARC cases, clinical stage II or III, undergoing NACRT with capecitabine combined with radiotherapy (N = 22). After DNA extraction and quality and concentration evaluation, we performed mutational profiling and assessed TMB through multigene sequencing of 409 cancer-related genes by NGS (OncomineTM Tumor Mutation Load Assay, Thermo Fisher Scientific). The most common mutations were, as expected, in KRAS, TP53 and PIK3CA. We compared our results with those of The Cancer Genome Atlas (TCGA) database and proportion was similar, with no statistically significant differences. We found three cases with TMB over 10 mutations/Mb, a threshold above which neoantigen formation occurs with higher likelihood and response to NACRT may be more efficient due to the stimulation of immune system through radiotherapy. Two cases harbored deleterious mutations in genes involved in DNA damage repair (PMS2 and NBN). Furthermore, cases with mutations in the transcription factor FBXW7 (N = 4/22) and in the receptor tyrosine kinase ERBB3 (N = 3/22) had significantly higher TMB than non-mutated ones (p-value = 0.0090 and 0.0107 respectively, false discovery rate < 0.1 for both genes). We compared TMB in major/complete responders vs. minor/non-responders as evaluated by post-surgical pathological examination (responders if Dworak tumor regression grading score, TRG, was equal to 3-4 and non-responders if TRG was equal to 0-1) and investigated the possible association of higher TMB with better response to NACRT. In our cohort we found a trend for higher TMB in responder vs. non-responder cases (5.08 mutations/Mb, IQR 3.40-9.29 vs. 4.25 mutations/Mb, IQR 2.54-5.5) (p-value = 0.05, one-sided). In conclusion, our study shows that higher TMB is correlated with a better response to NACRT in LARC and can be found in cases presenting with defects in DNA damage repair as well as enriched for specific gene mutations, notably in the receptor tyrosine kinase ERBB3. Citation Format: Martina Dameri, Gabriella Cirmena, Anna Garuti, Lorenzo Ferrando, Maurizio Gallo, Shirin Djahandideh Sheijani, Ester Cecchella, Edoardo Isnaldi, Roberto Murialdo, Valentina Barbero, Lucia Tixi, Federica Grillo, Luca Mastracci, Ciro Marrone, Andrea Massobrio, Stefano Scabini, Alberto Ballestrero, Gabriele Zoppoli. High tumor mutational burden subtends better response in locally advanced rectal adenocarcinoma undergoing neoadjuvant chemoradiotherapy and is associated with mutations in DNA damage repair genes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB032.

Standard treatment for locally advanced rectal adenocarcinoma (LARC) includes a combination of chemotherapy with pyrimidine analogues, such as capecitabine, and radiation therapy, followed by surgery. Currently no clinically useful genomic predictors of benefit from neoadjuvant chemoradiotherapy (nCRT) exist for LARC. In this study we assessed the expression of 8,127 long noncoding RNAs (lncRNAs), poorly studied in LARC, to infer their ability in classifying patients' pathological complete response (pCR). We collected and analyzed, using lncRNA-specific Agilent microarrays a consecutive series of 61 LARC cases undergoing nCRT. Potential lncRNA predictors in responders and non-responders to nCRT were identified with LASSO regression, and a model was optimized using k-fold cross-validation after selection of the three most informative lncRNA. 11 lncRNAs were differentially expressed with false discovery rate < 0.01 between responders and non-responders to NACT. We identified lnc-KLF7-1, lnc-MAB21L2-1, and LINC00324 as the most promising variable subset for classification building. Overall sensitivity and specificity were 0.91 and 0.94 respectively, with an AUC of our ROC curve = 0.93. Our study shows for the first time that lncRNAs can accurately predict response in LARC undergoing nCRT. Our three-lncRNA based signature must be independently validated and further analyses must be conducted to fully understand the biological role of the identified signature, but our results suggest lncRNAs may be an ideal biomarker for response prediction in the studied setting.

Abstract Standard treatment for clinical stage II/III rectal adenocarcinoma (READ) includes a combination of chemotherapy with pyrimidine analogues, such as capecitabine, and radiation therapy, followed by surgery after 6 to 12 weeks. Currently no predictors of benefit from neoadjuvant chemoradiotherapy (NACT) exist, and transcriptomic studies, prevalently focused on coding transcripts or miRNAs have so far failed to find clinically useful gene signatures. In the present analysis we assessed the expression levels of 8,127 long non-coding RNAs (lncRNAs), poorly studied in the context of READ, to infer whether they could stratify pre-treatment READ samples according to patients' pathological complete response (pCR). Methods: We collected and analysed with Agilent SurePrint G3 Human v2 8x60K microarrays, a consecutive series of 49 specimens from READ patients undergoing NACT with a combination of capecitabine (825 mg/m2) and radiation (50.4 Gy) cycles for 6 weeks. We performed a regularized variable selection regression (“glmnet” R package) to identify potential lncRNAs predicting pCR. We then analysed, with a bivariate correlation, the top lncRNAs predictors with the expression of 20,560 coding transcripts represented in the microarrays we used, and performed pathway enrichment analysis using Ingenuity® Pathway Analysis (Qiagen, Inc.). Results: Out of 49 patients for whom we could obtain snap-frozen biopsies with complete clinical and pathological data, we analysed 30 patients, 12 with minor or absent pathological response and 18 with major or complete response to NACT. We identified a signature of 11 lncRNAs able to successfully stratify responder vs. non-responder patients. By investigating the correlation of these 11 lncRNAs with coding transcripts, we identified one of them, lnc-ZNF-366-6, presenting an unusually high correlation with more then 1136 coding genes (FDR < 0.01). By gene enrichment analysis we found an enrichment in cancer-related pathways, especially alterations in solid and colon adenocarcinoma pathways (p < 0.01), as well as mitochondrial dysfunction, oxidative phosphorylation and sirtuin signalling pathways (p < 0.00001), defined by the positively and negatively correlated variables with lnc-ZNF-366-6. Moreover, we identified potential drivers of disease or therapeutic targets, either correlated or anti-correlated with lnc-ZNF-366-6. Conclusions: LncRNAs have the potential to classify responder versus non-responder READ patients undergoing NACT. Lnc-ZNF-366-6 deserves further experimental validation and functional analyses to clarify its exact contribution to resistance to DNA damaging agents, such as radiation, and to inhibitors of DNA/RNA synthesis, such as capecitabine. Citation Format: Lorenzo Ferrando, Gabriella Cirmena, A Garuti, Stefano Scabini, Federica Grillo, Luca Mastracci, Edoardo Isnaldi, Ciro Marrone, Roberto Murialdo, David Norman Brown, Roberto Fiocca, Emanuele Romairone, Alberto Ballestrero, Gabriele Zoppoli. Long non-coding RNA ZNF-366-6 predicts lack of response to neoadjuvant chemoradiotherapy in locally advanced rectal adenocarcinoma and presents meaningful biological associations with potential coding cancer driver transcripts related to gastrointestinal cancer pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2465.

INTRODUCTION Radiofrequency is a treatment option for patients suffering from fecal incontinence. OBJECTIVE To assess the one-year follow-up results following the radiofrequency procedure for fecal incontinence. DESIGN Prospective, single-center, observational study. MATERIALS AND METHODS Twenty-one patients underwent the SECCA® radiofrequency procedure, 19 of who completed the one-year of follow-up (Cleveland Clinic Florida Fecal Incontinence score, Fecal Incontinence Quality of Life Scale (FIQoL), anorectal manometry, and endoanal ultrasound). MAIN OUTCOME MEASURES Any change in the Fecal Incontinence Score or Fecal Incontinence Quality of Life scales post SECCA® radiofrequency procedure. RESULTS The mean Fecal Incontinence Score significantly improved at three months' follow-up from 14.5 prior to treatment to 11.9 post-treatment, and was maintained at six months (12). A slight decrease was observed at one year (12.9), which had no impact on the global satisfaction. During the same period, only 1/4 subsets of the Fecal Incontinence Quality of Life score improved. Manometry and endoanal ultrasound did not show significant changes post procedure. LIMITATIONS Limited number of patients. CONCLUSIONS Radiofrequency is a valid treatment option for patients with mild-to-moderate fecal incontinence. This treatment has demonstrated clinically significant improvements in symptoms, as demonstrated by statistically significant reductions in the Fecal Incontinence Score as well as significant improvements in Fecal Incontinence Quality of Life scores at six months, with a slight, though not clinically significant, decrease at one year follow-up.

Scabini, Stefano MD; Rimini, Edoardo; Romairone, Emanuele; Mastracci, Luca; Grillo, Federica MD; Bacigalupo, Almalina; Marrone, Ciro; Murialdo, Roberto MD; Zoppoli, Gabriele; Ballestrero, Alberto Author Information