Association of resection margin distance with anastomotic recurrence in stage I-III colon cancer: data from the National Colorectal Cancer Cohort (NCRCC) study in China.

PURPOSE: Few studies have focused on anastomotic recurrence (AR) in colon cancer. This study aimed to clarify the association of resection margin distance with AR and compare the prognosis with nonanastomotic local recurrence (NAR). METHODS: This retrospective cohort study included the clinical data of patients who underwent radical colon cancer surgery between January 1, 2009, and December 31, 2019. RESULTS: A total of 1958 colon cancer patients were included in the study. 34 of whom (1.7%) had AR and 105 of whom (5.4%) had NAR. Multivariate analysis revealed that the lower distal resection margin distance, advanced N stage, and number of lymph nodes dissected were risk factors for AR. In the proximal resection margin, the risk of AR was lowest at a distance of 6 cm or greater, with a 3-year rate of 1.3%. In the distal resection margin, the 3-year AR risk increased rapidly if the distance was less than 3 cm. The prognosis of patients in the AR group was similar to that of patients in the NAR group, regardless of synchronous distant metastases. Furthermore, the radical surgery rate for AR was significantly higher than that for NAR, but the prognosis of AR was comparable to that of NAR. CONCLUSIONS: The distal resection margin distance, advanced N stage, and less number of lymph nodes dissected are associated with AR of colon cancer. The prognosis of patients with AR was similar to that of patients with NAR. TRIAL REGISTRATION: Clinical Trial Numbers NCT04074538 ( clinicaltrials.gov ), August 26, 2019, registered, retrospectively registered.

Risk factors for symptomatic anastomotic postoperative recurrence following ileo-colic resection in Crohn's disease.

AIM: Crohn's disease is a chronic inflammatory bowel disease characterized by alternating periods of exacerbation and remission. Surgical resection is not curative and postoperative recurrence (POR) remains a challenge in these patients. The aim of this study was to identify clinical variables that influence the risk of symptomatic anastomotic POR in patients with ileo-colonic Crohn's disease. METHOD: A retrospective study of Crohn's disease patients who had undergone ileo-colic resection between January 2014 and December 2018 was performed. For each patient, data including demographic information, Crohn's disease clinical setting, preoperative radiological data, operative and histological data, pre- and postoperative medication history and postoperative clinical course, including recurrence of disease, were extracted. Symptomatic anastomotic POR was defined as symptoms of Crohn's disease in the presence of confirmed anastomotic POR (endoscopic and/or radiological POR). RESULTS: For the study period, 104 patients were eligible and included for analysis. The cumulative probability of symptomatic anastomotic POR was 14%, 30%, 42%, 50% and 50% at 1, 2, 3, 4 and 5 years, respectively. Two clinical variables on multivariate analysis were associated with increased risk of symptomatic anastomotic POR, namely age <17 years at diagnosis [hazard ratio (HR) 2.17, p = 0.019] and gastrointestinal involvement (extent) >30 cm (HR 1.85, p = 0.048). CONCLUSION: This study describes the natural history of POR after ileo-colic resection for Crohn's disease, as defined by endoscopic, radiological and clinical outcomes. Age <17 years at diagnosis and gastrointestinal involvement (extent) >30 cm were independent risk factors for symptomatic anastomotic POR.

Laparoscopic redo surgery in recurrent ileocolic Crohn's disease: A standardised technique.

BACKGROUND: Despite many advances in the medical management of Crohn's disease (CD), there is still a significant risk of surgical resection for lack of response to medical management or complications during the lifetime of a patient. Laparoscopic surgery offers short-term benefits such as decreased pain, lower wound complication rates, earlier resumption of diet and bowel function, better cosmesis and shorter hospital stays, while reduced post-operative adhesions and lower incisional hernia rate may represent long-term benefits. METHODS: A modular, standardised laparoscopic approach can be applied to safely perform laparoscopic redo surgery in the hostile setting of the recurrent CD and to facilitate teaching and training of these advanced procedures. RESULTS: Laparoscopic surgery in CD can be particularly challenging due to multifocal disease with extensive inflammation and a thickened mesentery, the potential for abscesses, fistulas and phlegmons and high conversion rates have been reported in reoperative surgery for recurrent CD with abscesses and adhesions representing the main reasons for conversion. CONCLUSIONS: A standardised laparoscopic approach for redo surgery in recurrent CD has been described. Multidisciplinary management of CD is essential and bowel preservation must be the priority.

Anastomotic recurrence of colon cancer: Genetic analysis challenges the widely held theories of cancerous cells' intraluminal implantation and metachronous carcinogenesis.

BACKGROUND AND OBJECTIVES: Anastomotic recurrence (AR), whose etiopathogenesis is attributed to intraluminal implantation of cancerous cells or metachronous carcinogenesis, is a major issue for patients undergoing colon cancer (CC) resection. The objective of the study is to throw some light on AR etiopathogenesis and to identify risk factors of AR in selecting patients to undergo early endoscopy. METHODS: An analysis of clinical and histopathological parameters, including MSI and LOH of seven sites (Myc-L, BAT26, BAT40, D5S346, D18S452, D18S64, D16S402) was performed in primary CC and AR of 18 patients. They were then compared to 36 controls not developing AR. RESULTS: A genetic instability was present in 16/18 patients, with distinct genetic patterns between primaries and ARs. LOH at 5q21 and/or 18p11.23 were found in both primary and AR in >50% of cases, but this rate was no different from control population. CEA resulted as associated with AR (P = 0.03), whereas N status presented a borderline result (P = 0.08). CONCLUSIONS: Our findings challenge present theories about AR development. No "genetic marker" has been found. CEA and, to a lesser extent, N status, appear associated with AR. Rectal washout is seemingly meaningless. Iterative resection should be recommended since a long survival may be expected. J. Surg. Oncol. 2016;114:228-236. © 2016 Wiley Periodicals, Inc.

Development and Validation of a Prognostic Model for Postoperative Anastomotic Recurrence in Siewert II or III Adenocarcinomas Without Neoadjuvant Therapy in an East Asian Population.

PURPOSE: Anastomotic recurrence leads to poor prognosis in patients with Siewert II or III adenocarcinoma who undergo radical gastrectomy and do not receive neoadjuvant therapy. We aimed to establish a prognostic model to evaluate the risk of postoperative anastomotic recurrence in patients with Siewert II or III adenocarcinoma who did not receive neoadjuvant therapy. METHODS: We included 366 patients with Siewert II or III adenocarcinoma who were treated with radical gastrectomy without neoadjuvant therapy at Fujian Provincial Hospital (FPH) between 2012 and 2018 as the development cohort. Cox regression was used to verify prognostic factors for anastomotic recurrence, and a nomogram was established. The nomogram was externally validated using a combined cohort of two external centers. Patients were classified into high- or low-risk groups according to the diagnostic threshold and nomogram scores, and recurrence-related survival analysis was analyzed. RESULTS: The average age was 64.6 years, and 285 patients were male. All surgeries were successfully performed (185 open vs 181 laparoscopic). The 3-year anastomotic recurrence rate was significantly lower in the low-risk group (3.5% vs 18.8%, P < 0.001). The predictive performance was verified in the external validation cohort. This model better stratified patient survival than the American Joint Committee on Cancer (AJCC) TNM staging system. CONCLUSIONS: This novel nomogram with surgical margin, postoperative tumor node metastasis (pTNM) stage, and neural invasion as prognostic factors has a significant predictive performance for the risk of anastomotic recurrence after radical gastrectomy in patients with Siewert II or III adenocarcinoma.

Long-term outcomes of salvage transurethral high-dose-rate brachytherapy combined with external beam radiation therapy for anastomotic recurrence of prostate cancer after radical prostatectomy: A retrospective analysis.

BACKGROUND: High-dose-rate brachytherapy (HDR-BT) delivers high-dose radiation to local lesions within a short treatment period. There are no reports of salvage transurethral HDR-BT for biochemical recurrence (BCR) after radical prostatectomy. Thus, we aimed to evaluate the usefulness of salvage transurethral HDR-BT with external beam radiation therapy (EBRT) for anastomotic prostate cancer recurrence. METHODS AND MATERIALS: Patients with postoperative prostate cancer who underwent salvage transurethral HDR-BT with EBRT for anastomotic recurrence at our hospital between January 2002 and July 2009 were retrospectively evaluated. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. RESULTS: Nine patients were included in this study. The median follow-up period and age were 13.1 (range 4.3-18.4) years and 67 (range 63-78) years, respectively. The dose of HDR-BT ranged from 13 to 24 Gy per 2 to 5 fractions, while that of EBRT ranged from 30 to 44 Gy per 15 to 22 fractions. The 1-year, 5-year, and 10-year bFFF rates were 77.8%, 41.7%, and 13.9%, respectively. The 10-year and 15-year CSS rates were 100% each. The 10-year and 15-year OS rates were 100% and 64.3%, respectively. Six patients were diagnosed with BCR. Two patients experienced Grade 3 hematuria as a late adverse event. There was no exacerbation of urinary incontinence. CONCLUSIONS: No prostate cancer-related deaths were observed, even after a long-term follow-up. Salvage transurethral HDR-BT after radical prostatectomy is safe and feasible and may be a useful treatment option.

A case of lymphatic flow evaluation using indocyanine green fluorescence imaging for recurrence of anastomotic site after laparoscopic right hemicolectomy.

BACKGROUND: Anastomotic recurrence of colorectal cancer is rare, but reoperation improves prognosis. However, there is no clear evidence regarding the extent of dissection, and there are few reports on the details of surgery. We used intraoperative lymphatic flow imaging with indocyanine green (ICG) fluorescence as a reference to determine the range of additional resection. CASE PRESENTATION: The patient was a 75-year-old man who underwent laparoscopic right hemicolectomy and extracorporeal functional terminal anastomosis for ascending colon cancer 4 years ago. Histopathological examination revealed a well-differentiated tubular adenocarcinoma, T4aN0M0, pathological stageIIB. During follow-up, anemia was observed, and colonoscopy indicated anastomotic recurrence, so additional laparoscopic resection was performed. Intraoperatively, ICG was injected into the anastomotic site, and the operation proceeded under near-infrared light observation. Lymphatic vessels along the middle colonic artery were visualized down to the root of the vessel. Using this as an indicator, the vessel was ligated from the root. Using the fact that the lymphatic vessels were also depicted in the small intestinal mesentery on the oral side of the anastomosis as an indicator, the small intestine and mesentery were resected about 7 cm from the anastomosis. CONCLUSIONS: The optimal surgical approach for anastomotic recurrence of colorectal cancer has not been defined. Intraoperative ICG fluorescence imaging can provide images of lymphatic flow from the site of recurrence and may be an indicator of lymph node dissection in the case of anastomotic recurrence.

Preoperative computed tomography enterography-based radiomics signature: A potential predictor of postoperative anastomotic recurrence in patients with Crohn's disease.

BACKGROUND: More than half of patients with Crohn's disease (CD) require at least one surgery for symptom management; however, approximately half of the patients may experience postoperative anastomotic recurrence (PAR). OBJECTIVES: This study aims to develop and validate a preoperative computed tomography enterography (CTE)-based radiomics signature to predict early PAR in CD. DESIGN: A total of 186 patients with CD (training cohort, n = 134; test cohort, n = 52) who underwent preoperative CTE and surgery between January 2014 and June 2020 were included in this retrospective multi-centre study. METHODS: 106 radiomic features were initially extracted from intestinal lesions and peri-intestinal mesenteric fat, respectively; significant radiomic features were selected from them and then used to develop intestinal or mesenteric radiomics signatures, using the least absolute shrinkage and selection operator and a Cox regression model. A radiomics-based nomogram incorporating these signatures with clinical-radiological factors was created for comparison with a model based on clinical-radiological features alone. RESULTS: 68 of 134 patients in training cohort and 16 of 52 patients in test cohort suffered from PAR. The intestinal radiomic signature (hazard ratio [HR]: 2.17; 95% confidence interval [CI]: 1.32-3.58; P = 0.002) and mesenteric radiomic signature (HR: 2.19; 95% CI: 1.14-4.19; P = 0.018) were independent risk factors for PAR in the training cohort as per a multivariate analysis. The radiomics-based nomogram (C-index: 0.710; 95% CI: 0.672-0.748) yielded superior predictive performance than the clinical-radiological model (C-index, 0.607; 95% CI: 0.582-0.632) in the test cohort. Decision curve analysis demonstrated that the radiomics-based nomogram outperformed the clinical-radiological model in terms of clinical usefulness. CONCLUSIONS: Preoperative mesenteric and intestinal CTE radiomics signatures are potential non-invasive predictors of PAR in postoperative patients with CD.

Clinical significance of the KRAS G13D mutation in anastomotic recurrence of colorectal cancer.

The genetic risk factors for anastomotic recurrence (AR) after curative surgery for colorectal cancer (CRC) are unclear. The present study is a single-center retrospective observational study that aimed to elucidate the association between the KRAS G13D mutation and AR in CRC. The present study included 21 patients with AR and 67 patients with non-anastomotic local recurrence (NALR) following curative surgery for CRC between January 2005 and December 2019. KRAS G13D mutation status was examined by droplet digital polymerase chain reaction. Data of clinicopathological findings and oncological outcomes were analyzed and compared between the AR group and the matched NALR group. The prevalence of the KRAS G13D mutation was significantly higher in the AR group (AR vs. NALR, 33.3 vs. 4.8%; P=0.047). Comparing the KRAS G13D mutation-positive and KRAS G13D mutation-negative patients in the AR group, there was no significant difference in the time from initial surgery to AR or resection rate of AR; however, all patients with KRAS G13D mutation who underwent resection of AR had subsequent recurrence within 2 years after resection, and overall survival was poor (3-year survival rate: Positive vs. negative, 68.6 vs. 90.9%; P=0.02). The prevalence of the KRAS G13D mutation was significantly higher in patients with AR, and KRAS G13D-mutant patients with AR had a poorer prognosis than those that were negative for the KRAS G13D mutation. In conclusion, postoperative surveillance and treatment strategies should be considered with attention to the possibility of AR and subsequent recurrence in KRAS G13D-mutant patients.

68Ga-FAPI-04 PET for Surveillance of Anastomotic Recurrence in Postoperative Patients with Gastrointestinal Cancer: a Comparative Study with 18F-FDG PET.

PURPOSE: This study aims to compare the diagnostic efficacy of 68Ga-FAPI-04 PET and 18F-FDG PET for detecting anastomotic recurrence in postoperative patients with gastrointestinal cancer, and to characterize the signal pattern over time at surgical wounds on both PET imaging. METHODS: Gastrointestinal cancer patients who planned to 68Ga-FAPI-04 and 18F-FDG PET/CT imaging for postoperative surveillance were involved. The SUVmax at surgical wounds were assessed. Endoscopic pathology confirmed anastomotic recurrence or it was ruled out by imaging and clinical follow-up. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy of the two PET imaging in detecting anastomotic recurrence were compared. Relationships between tracer uptake at surgical wounds and postoperative time were also analyzed. RESULTS: Compared with non-recurrent patients, the recurrent patients exhibited a significantly higher anastomotic SUVmax on 68Ga-FAPI-04 PET (SUVmax: 9.92 ± 4.36 vs. 2.81 ± 1.86, P = 0.002). Sensitivity, specificity, PPV, NPV, and accuracy of detecting anastomotic recurrence were 100.0%, 87.3%, 41.7%, 100.0%, and 88.3% for 68Ga-FAPI-04 PET, and 60.0%, 81.8%, 23.1%, 95.7%, and 80.0% for 18F-FDG PET, respectively. Although 68Ga-FAPI-04 PET signal at surgical wounds showed a slight trend to decrease with time, no statistical difference was observed over months post-surgery (P > 0.05). CONCLUSIONS: Both tracers displayed high NPVs in identifying anastomotic recurrence with a higher sensitivity to 68Ga-FAPI-04. Tracer uptake at anastomotic sites does not decrease significantly over time, which results in low PPVs for both PET. Therefore, it is difficult to differentiate anastomotic recurrence from inflammation on either PET imaging.

Unexplained neoplastic anastomotic recurrence after right hemicolectomy: a case report.

BACKGROUND: Anastomotic recurrences of the colon are postulated to arise due to inadequate margins, tumor implantation by exfoliated cells, altered biological properties of bowel anastomosis, and missed synchronous lesions. In this paper, a case of unexpected early local recurrence after surgery for colon cancer is presented. CASE PRESENTATION: A 68-year-old Caucasian man underwent right hemicolectomy for invasive G2 adenocarcinoma. Two months later, endoscopy revealed a wide and well-functioning anastomosis with a hyperemic, hard, and thickened mucosal area of about 2 cm in diameter. Biopsies showed the presence of an adenocarcinoma with the same grading of the previous lesion. Ten days later, the patient underwent a new intervention; the last 10 cm of the ileum and half of the remaining transverse colon were resected, and the patient started adjuvant therapy. Specimen examination confirmed the presence of an adenocarcinoma (G2) penetrating the muscular layer of the wall; also, in this case, resection edges were free from tumoral invasion, and the removed lymph nodes were exempt from neoplastic colonization. The patient was seen in follow-up for about 5 years, and he did not show local or systemic manifestations. CONCLUSIONS: Whenever a neoplastic recurrence on the anastomotic line occurs, in the presence of negative intestinal margins, as usual in right colectomies, the implantation of neoplastic cells could be the possible cause.

Anastomotic recurrence after laparoscopic distal gastrectomy with delta-shaped anastomosis†:†report of a case.

Delta-shaped anastomosis is nowadays an increasingly performed reconstruction method in laparoscopic distal gastrectomy for early gastric cancer. To date, anastomotic recurrence at the delta-shaped anastomotic site has not been reported. Surgery for this disease is more complicated than anastomotic recurrence at the site of conventional Billroth-I anastomosis. A 68-year-old female was referred to our institute with early gastric cancer on the posterior wall of the antrum. She underwent laparoscopic distal gastrectomy with delta-shaped Billroth-I anastomosis. Follow-up gastrofiberscopy 16 months after the operation revealed suspected anastomotic recurrence, and gastric biopsy revealed signet-ring cell carcinoma. Open total gastrectomy with reconstruction with the Roux-en-Y method was performed. At the distal part of the previous anastomosis, an adequate length of the duodenum was dissected from the pancreas. Then, the duodenum was transected 3 cm distal to the anastomosis using a linear stapler. The patient recovered well and was discharged on postoperative day 14. The patient is alive without re-recurrence 3 years postoperatively. We successfully treated a patient with anastomotic recurrence of gastric cancer after delta-shaped anastomosis. Adequate resection of the duodenal stump was performed without any residual tumor or injury to the pancreas. J. Med. Invest. 67 : 211-213, February, 2020.

Prediction of risks of early anastomotic recurrence following primary bowel resection in patients with Crohn's disease based on preoperative magnetic resonance enterography / 实用医学杂志

Objective To develop a nomogram for predicting the risks of early anastomotic recurrence(EAR)after primary bowel resection in patients with Crohn's disease(CD).Methods The patients with CD under-going preoperative magnetic resonance enterography(MRE)and primary bowel resection were enrolled in this retrospective study and divided into an EAR group(18 patients)and EAR-free group(12 patients).The EAR group included the patients having an endoscopic Rutgeerts score of≥I2 month or the need for anastomotic resection within 12 months after surgery.All the 38 indexes including preoperative demographic characteristics,laboratory examina-tions,multi-parameter MRE features of the resected intestine and its adjacent mesentery,histological findings,and postoperative pharmacotherapy were analyzed.Least absolute shrinkage and selection operator(LASSO)regression and multivariate binary logistic regression analysis were performed to identify independent risk factors to be incorpo-rated into the nomogram for predicting the risks of early anastomotic recurrence and the prediction performance was evaluated.Results Mesenteric creeping fat index on MRE and comb sign were independent risks of EAR,with a concordance index of 0.882(95%CI:0.764～1).The calibration plot revealed a strong relationship between actual observation and predicted probability of EAR.Conclusions The preoperative MRE-based nomogram may be a potential tool for predicting EAR following surgery in patients with CD,which is beneficial to individual management in those patients.It provides reference for the formulation of early postoperative individualized drug adjuvant therapy in patients at high risk of EAR.

Ex vivo model for a new bilateral antimesenteric V-modified side-to-side isoperistaltic anastomosis to prevent recurrence in ileocolic Crohn's disease.

INTRODUCTION: The high rate of recurrence following ileocaecal resection for Crohn's disease may lead to repeat surgery in 20-30% of patients at five years after surgery. Recurrence usually occurs at the anastomosis and the neoterminal ileum and the association of a strictureplasty to widen the bowel lumen in the regions immediately proximal ('anastomotic inlet') and distal ('anastomotic outlet') to the anastomosis may delay or reduce the risk of surgical recurrence. MATERIALS AND METHODS: A side to side isoperistaltic anastomosis, with an associated V-modified strictureplasty on the anti-mesenteric border at the level of the anastomosis inlet and outlet has been designed. We produced a wet lab ex vivo model of the anastomosis and, to evaluate the different calibre of the anastomotic segments, we compared it with ex vivo models of three anastomotic configurations currently used in surgery for Crohn's disease: i) side to side isoperistaltic anastomosis; ii) modified side-to-side isoperistaltic anastomosis with double Heineke-Mikulicz procedure (Sasaki anastomosis); iii) anti-mesenteric functional end-to-end handsewn anastomosis (Kono-S anastomosis). RESULTS: Differences were recorded at the level of the anastomosis inlet and outlet, with a larger volume estimated in the Sasaki anastomosis and in the V-modified anastomosis. The V-modified anastomosis had a larger volume compared with the Sasaki anastomosis for a longer segment of small bowel. CONCLUSIONS: We have developed an experimental animal model for a new anastomotic technique which could be applied in surgery for Crohn's disease following small-bowel or ileocolic resection.

Predictive model construction of anastomotic thickening character after radical surgery of esophageal cancer based on CT radiomics and its application value / 中华消化外科杂志

Objective:To investigate the predictive model construction of anastomotic thickening character after radical surgery of esophageal cancer based on computed tomogralphy(CT) radiomics and its application value.Methods:The retrospective cohort study was conducted. The clinicopathological data of 202 patients with esophageal squamous cell carcinoma (ESCC) who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2013 to June 2021 were collected. There were 147 males and 55 females, aged (63±8) years. Based on random number table, 202 patients were assigned into training dataset and validation dataset at a ratio of 7:3, including 141 cases and 61 cases respectively. Patients underwent radical resection of ESCC and enhanced CT examination. Observation indicators: (1) influencing factor analysis of malignant anas-tomotic thickening; (2) construction and evaluation of predictive model; (3) performance comparison of 3 predictive models. The normality of continuous variables was tested by Kolmogorov-Smirnov method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whintney U test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher's exact probability. The consistency between subjective CT features by two doctors and measured CT numeric variables was analyzed by Kappa test and intraclass correlation coefficient (ICC), with Kappa >0.6 and ICC >0.6 as good consistency. Univariate analysis was conducted by corresponding statistic methods. Multivariate analysis was conducted by Logistics stepwise regression model. The receiver operating characteristic (ROC) curve was drawn, and area under curve (AUC), Delong test, decision curve were used to evaluate the diagnostic efficiency and clinical applicability of model. Results:(1) Influencing factor analysis of malignant anastomotic thickening. Of the 202 ESCC patients, 97 cases had malignant anastomotic thickening and 105 cases had inflammatory anastomotic thickening. The consistency between subjective CT features by two doctors and measured CT numeric variables showed Kappa and ICC values >0.6. Results of multivariate analysis showed that the maximum thickness of anastomosis and CT enhancement pattern were independent influencing factors for malignant anastomotic thickening[ hazard ratio=1.46, 3.09, 95% confidence interval ( CI) as 1.26-1.71,1.18-8.12, P<0.05]. (2) Construction and evaluation of predictive model. ① Clinical predictive model. The maximum thickness of anasto-mosis and CT enhancement pattern were used to construct a clinical predictive model. ROC curve of the clinical predictive model showed an AUC, accuracy, sensitivity, specificity as 0.86 (95% CI as 0.80-0.92),0.77, 0.77, 0.80 for the training dataset, and 0.78 (95% CI as 0.65-0.89), 0.77, 0.77, 0.80 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset ( Z=1.22, P>0.05). ② Radiomics predictive model. A total of 854 radiomics features were extracted and 2 radiomics features (wavelet-LL_first order_ Maximum and original_shape_VoxelVolume) were finally screened out to construct a radiomics predictive model. ROC curve of the radiomics predictive model showed an AUC, accuracy, sensitivity, specificity as 0.87 (95% CI as 0.81-0.93), 0.80, 0.75, 0.86 for the training dataset, and 0.73 (95% CI as 0.63-0.83), 0.80, 0.76, 0.94 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset ( Z=-0.25, P>0.05). ③ Combined predictive model. Results of multivariate analysis and radiomics features were used to construct a combined predictive model. ROC curve of the combined predictive model showed an AUC, accuracy, sensitivity, specificity as 0.93 (95% CI as 0.89-0.97),0.84, 0.90, 0.84 for the training dataset, and 0.79 (95% CI as 0.70-0.88), 0.89, 0.86, 0.91 for the validation dataset, respectively. Results of Delong test showed no significant difference in AUC between the training dataset and validation dataset ( Z=0.22, P>0.05). (3) Performance comparison of 3 predictive models. Results of Hosmer-Lemeshow goodness-of-fit test showed that the clinical predictive model, radiomics predictive model and combined predictive model had a good fitting degree ( χ2=4.88, 7.95, 4.85, P>0.05). Delong test showed a significant difference in AUC between the combined predictive model and clinical predictive model, also between the combined predictive model and radiomics predictive model ( Z=2.88, 2.51, P<0.05 ). There was no significant difference in AUC between the clinical predictive model and radiomics predictive model ( Z=-0.32, P>0.05). The calibration curve showed a good predictive performance in the combined predictive model. The decision curve showed a higher distinguishing performance for anastomotic thickening character in the combined predictive model than in the clinical predictive model or radiomics predictive model. Conclusions:The maximum thickness of anastomosis and CT enhancement pattern are independent influencing factors for malignant anastomotic thickening. Radiomics predictive model can distinguish the benign from malignant thickening of anastomosis. Combined predictive model has the best diagnostic efficacy.

Second isolated anastomotic recurrence after curative surgery for colorectal cancer.

Introduction The two mechanisms postulated for cancer recurrence at the anastomosis site ('anastomotic recurrence' (AR)) after curative surgery for colorectal cancer are: (i) intraluminal dissemination of viable cancer cells; (ii) metachronous carcinogenesis related with changes in the local milieu provoked by the materials employed to carry out the anastomosis. Case History We describe a 79-year-old female who underwent a left hemicolectomy due to a stenotic lesion shown on colonoscopy: an adenocarcinoma (pT3NO, G2). One year after surgery, control colonoscopy revealed an AR, so a new resection was carried out. Pathology showed it to be a recurrent adenocarcinoma over the staple line (pT3N0, G2). One year after the second surgical procedure, control colonoscopy evinced a new AR, resulting in a new resection. Pathology revealed a new AR. Conclusions This is only the second time that a second isolated AR after curative resection for colorectal cancer has been reported.

Local recurrences at the anastomotic area are clonally related to the primary tumor in sporadic colorectal carcinoma.

PURPOSE: Anastomotic recurrences (AR) occur in 2-10% of colorectal carcinoma cases after resection of primary tumor (PT). Currently, there are no molecular data investigating their genetic profile and multiple theories exist about their pathogenesis. The aim of our study was to compare the genomic profile of AR to that of the patients' corresponding matched PT and, when available, to a distant metastasis (DM). EXPERIMENTAL DESIGN: Thirty-six tumors from 14 patients were genotyped using a capture-based, next-generation assay to define the mutational status of 341 cancer-associated genes. All patients had R0 resection of their PT and AR occurred 1.1-7.0 years following PT resection. A DM or a second AR was analyzed in 8 patients. All tumors were microsatellite stable except in one patient with Lynch syndrome. RESULTS: A total of 254 somatic mutations were detected including 138 mutations in the microsatellite stable (MSS) cases. The most commonly mutated genes were APC, KRAS, TP53, PIK3CA, ATM and PIK3R1. In all patients with MSS tumors the AR and PT shared between 50-100% of mutations, including mutations in key driver genes, consistent with these tumors being clonally related. Genetic events private to DM were not detected in AR and phylogenetic analysis showed that ARs were more closely related to PT than DM. In the Lynch syndrome patient the PT and AR showed distinct somatic mutations consistent with independent primaries. CONCLUSIONS: ARs are clonally related to PT in sporadic colorectal carcinomas and do not appear to represent seeding of the anastomotic site by distant metastases.

Long-term survival case of a recurrent colon cancer owing to successful resection of a tumor at hepaticojejunostomy: report of a case.

With advances in surgical procedures and perioperative management, hepato-biliary-pancreatic surgery, including hepatectomy and pancreaticoduodenectomy, has been employed for recurrent colon cancer. However, no report has described a case of major hepatectomy with the combined resection of hepaticojejunostomy following pancreaticoduodenectomy for locoregionally recurrent colon cancer. Here, such a case is reported. The patient, a 37-year-old woman, had undergone pancreaticoduodenectomy for lymph node recurrence along the extrahepatic bile duct from cecal cancer. Thirteen months later, a biliary stricture was found at the hepaticojejunostomy site and right hepatectomy was performed. The resected specimen showed a papillary tumor at the hepaticojejunostomy. Based on its histological features, the pathogenesis of this tumor was considered to be intramural recurrence via lymphatic vessels. Although she underwent resection of a lymph node recurrence at her mesentery 12 months later, she has remained well thereafter, without any sign of further recurrence during 5 years of follow-up after hepatectomy.

Anastomotic Recurrence of Colon Cancer-is it a Local Recurrence, a Second Primary, or a Metastatic Disease (Local Manifestation of Systemic Disease)?

The aim of this study is to review the literature to find out the exact etiology of anastomotic cancers of colon post resection and differentiate them between a recurrence, second primary, and metastatic disease (local manifestation of systemic disease). Web-based literature search was done, and datas collected. We searched PubMed for papers using the keywords colon cancer recurrence, anastomotic recurrence, and recurrent colon carcinoma. We also searched for systematic review in the same topic. In addition, we used our personal referrence archive. Anastomotic recurrences of colon are postulated to arise due to inadequate margins, tumor implantation by exfoliated cells, altered biological properties of bowel anastomosis, and missed synchronous lesions. Some tumors are unique with repeated recurrence after repeated resection. Duration after primary surgery plays a major role in differentiating recurrent and second primary lesions. Repeated recurrences after repeated resections have to be considered a manifestation of systemic disease or metastatic disease due to the virulence of the disease. A detailed analysis and study of patients with colonic anastomotic lesion are required to differentiate it between a recurrent, a second primary lesion, and a metastatic disease (local manifestation of a systemic disease). The nomenclature is significant to study the survival of these patients, as a second primary lesion will have different survival compared to that of recurrent lesions.

The Cause and Prevention of Anastomotic Recurrence following Colectomy: An Immunohistochemical Approach for Detecting Transforming Colonocytes.

With the ability to identify the presence of transforming colonocytes in a field adjacent to an existing primary colon cancer, it is now possible to reduce if not eliminate one of the major causes leading to anastomotic tumor recurrence. In a review of those colectomy cases that presented post-surgery with anastomotic recurrence, we noted that mucosal abnormalities could readily be detected adjacent to the primary lesion. Such changes had gone unrecognized at the time of surgery, when standard histologic procedures were employed. By utilizing monoclonal antibodies (mAbs) that defined the presence of tumor immunogenic proteins, we were able to reexamine so-called normal biopsy sites adjacent to the tumor. Here, it was possible to demonstrate the presence of altered cellular activity in existing phenotypically normal appearing colonocytes that were in the process of transforming to malignancy. Eight consecutive patients that had been admitted for evaluation and resection of an anastomotic recurrence post colectomy, were studied with regard to possible etiologic factors. The original margins incorporated into the anastomosis were re-examined by immunohistochemistry employing those monoclonal antibodies (mAbs) designed to target colon tumor antigen. This antigen had previously been shown to be expressed only in colon cancer and not in adjacent normal tissue. In addition, biopsies from margins of resection in five patients free of recurrence following colectomy were also studied along with colon specimens from 50 normal patients, non-demonstrating expression of tumor antigen in the normal appearing colonocytes. In each of the patients who had presented with anastomotic recurrence, normal appearing colonocytes defined by light microscopy and found adjacent to the previously resected primary lesion, expressed tumor antigen. The antigen detected in these colonocytes proved to be identical to antigen expressed in the anastomotic recurrence giving credence to the concept that these normal appearing cells in proximity to the tumor were responsible for the regrowth of tumor in the suture line used to establish continuity of the bowel. Based on the findings of this preliminary retrospective study it is felt that at the time of performing a colectomy for a malignant lesion of the bowel, that it is important that those normal appearing colonocytes adjacent to tumor be evaluated for expression of tumor associated antigen. Excluding such cells from an anastomosis, may help to assure that tumor recurrence will be minimized if not totally eliminated.