Evaluation of the learning curve for conformal sphincter preservation operation in the treatment of ultralow rectal cancer.

BACKGROUND: To investigate the learning curve of conformal sphincter preservation operation (CSPO) in the treatment of ultralow rectal cancer and to further explore the influencing factors of operation time. METHODS: From August 2011 to April 2020, 108 consecutive patients with ultralow rectal cancer underwent CSPO by the same surgeon in the Department of Colorectal Surgery of Changhai Hospital. The moving average and cumulative sum control chart (CUSUM) curve were used to analyze the learning curve. The preoperative clinical baseline data, postoperative pathological data, postoperative complications, and survival data were compared before and after the completion of learning curve. The influencing factors of CSPO operation time were analyzed by univariate and multivariate analysis. RESULTS: According to the results of moving average and CUSUM method, CSPO learning curve was divided into learning period (1-45 cases) and learning completion period (46-108 cases). There was no significant difference in preoperative clinical baseline data, postoperative pathological data, postoperative complications, and survival data between the two stages. Compared with the learning period, the operation time (P < 0.05), blood loss (P < 0.05), postoperative flatus and defecation time (P < 0.05), liquid diet time (P < 0.05), and postoperative hospital stay (P < 0.05) in the learning completion period were significantly reduced, and the difference was statistically significant. Univariate and multivariate analysis showed that distance of tumor from anal verge (≥ 4cm vs. < 4cm, P = 0.039) and T stage (T3 vs. T1-2, P = 0.022) was independent risk factors for prolonging the operation time of CSPO. CONCLUSIONS: For surgeons with laparoscopic surgery experience, about 45 cases of CSPO are needed to cross the learning curve. At the initial stage of CSPO, beginners are recommended to select patients with ultralow rectal cancer whose distance of tumor from anal verge is less than 4 cm and tumor stage is less than T3 for practice, which can enable beginners to reduce the operation time, accumulate experience, build self-confidence, and shorten the learning curve on the premise of safety.

Juvenile polyposis syndrome might be misdiagnosed as familial adenomatous polyposis: a case report and literature review.

BACKGROUND: Juvenile polyposis syndrome (JPS) is a rare disorder characterized by the presence of multiple juvenile polyps in the gastrointestinal tract, and germline mutations in SMAD4 or BMPR1A. Due to its rarity and complex clinical manifestation, misdiagnosis often occurs in clinical practice. CASE PRESENTATION: A 42-year-old man with multiple pedunculated colorectal polyps and concomitant rectal adenocarcinoma was admitted to our hospital. His mother had died of colon cancer. He was diagnosed with familial adenomatous polyposis (FAP) and underwent total proctocolectomy and ileal pouch anal anastomosis. Two polyps were selected for pathological examination. One polyp had cystically dilated glands with slight dysplasia. The other polyp displayed severe dysplasia and was diagnosed as adenoma. Three years later, his 21-year-old son underwent a colonoscopy that revealed more than 50 pedunculated colorectal juvenile polyps. Both patients harbored a germline pathogenic mutation in BMPR1A. Endoscopic resection of all polyps was attempted but failed. Finally, the son received endoscopic resection of polyps in the rectum and sigmoid colon, and laparoscopic subtotal colectomy. Ten polyps were selected for pathological examination. All were revealed to be typical juvenile polyps, with cystically dilated glands filled with mucus. Thus, the diagnosis of JPS was confirmed in the son. A review of the literatures revealed that patients with JPS can sometimes have adenomatous change. Most polyps in patients with JPS are benign hamartomatous polyps with no dysplasia. A review of 767 colorectal JPS polyps demonstrated that 8.5% of the polyps contained mild to moderate dysplasia, and only 0.3% had severe dysplasia or cancer. It is difficult to differentiate juvenile polyps with dysplasia from adenoma, which could explain why juvenile polyps have been reported to have adenomatous changes in patients with JPS. Therefore, patients with JPS, especially those with concomitant dysplasia and adenocarcinoma, might be easily diagnosed as FAP in clinical practice. CONCLUSIONS: Juvenile polyp with dysplasia is often diagnosed as adenoma, which might lead to the misdiagnosis of JPS as FAP. The differential diagnosis of JPS versus FAP, should be based on comprehensive evaluation of clinical presentation, endoscopic appearance and genetic investigations; not on the presence or absence of adenoma.

Lower peripouch fat area is related with increased frequency of pouch prolapse and floppy pouch complex in inflammatory bowel disease patients.

BACKGROUND: Pouch prolapse is a rare pouch complication which often leads to pouch failure in inflammatory bowel disease (IBD) patients. Its exact cause remains unknown. Floppy pouch complex (FPC) was defined as the presence of any one of the following pouch disorders: pouch prolapse, afferent limb syndrome (ALS), redundant loop, and pouch folding. We aimed to explore the role of peripouch fat area in the occurrence of pouch prolapse and FPC. METHODS: Pouch patients with available pouchoscopy and abdominal CT scans who were followed up between 2011 and 2017 in Cleveland Clinic were reviewed. Peripouch fat was measured on CT images. RESULTS: Of the 93 included patients, 31 were females; 87 had J pouches and 6 had S pouches. The median duration of pouch was 8.0 (interquartile range [IQR] 5.0-16.5) years. A total of 18 cases (19.4%, 18/93) were identified as FPC, including 12 pouch prolapse, 5 ALS, 1 redundant loop, and 3 pouch folding. Patients with pouch prolapse had lower peripouch fat area (13.6 (9.3-18.5) vs. 27.6 (11.0-46.2)cm2, P = 0.022) than those without. Patients with FPC had lower peripouch fat area (15.4 (11.4-20.6) vs. 27.6 (11.0-46.9)cm2, P = 0.040) than those without. Univariate and multivariate analyses demonstrated that lower peripouch fat area, lower weight, and family history of IBD were independent predictors of pouch prolapse and FPC. CONCLUSIONS: A lower peripouch fat area was observed in inflammatory bowel disease patients with pouch prolapse and FPC. Longitudinal studies are needed to further elucidate the role of peripouch fat in the pathogenesis of pouch prolapse and FPC.

Pouch wall thickness and floppy pouch complex.

BACKGROUND: Floppy pouch complex (FPC) consists of disease phenotypes in patients with ileal pouches, including pouch prolapse, afferent limb syndrome, enterocele, redundant loop, and pouch folding. Our recent study demonstrated that lower body weight, lower peripouch fat, family history of inflammatory bowel disease (IBD), female gender, and dyschezia are risk factors for FPC patients with IBD. The aims of this study were to assess the relationship between pouch wall thickness and FPC, and to investigate the association between inflamed and non-inflamed pouch wall thickness. METHODS: This case-control study included all eligible patients with FPC from our prospectively maintained, IRB-approved Pouchitis Registry from 2011 to 2017. We measured pouch wall thickness of fully distended pouches on cross-sectional abdominal and pelvic imaging. Patients with stoma and non-distended pouches were completely excluded. Risk factors for FPC were analyzed. RESULTS: A total of 140 out of 451 patients from our were found to have fully distended pouches on imaging. Of the 140 patients, 36 (25.7%) were diagnosed as having FPC. We analyzed pouch wall thickness for each subcategory of FPC as well as non-FPC conditions. The thickness of pouch wall was follows: pouch prolapse (N = 19): 1.5 mm (1.5-2.0), afferent limb syndrome (N = 12): 1.5 mm (1.1-2.0), folded pouch (N = 4): 1.5 mm (1.1-1.9), and redundant pouch (N = 2): 1.3 mm (1.0-1.3). The control group (N = 104) consisting of normal pouch, pouchitis, cuffitis, Crohn's disease of the pouch, and pouch sinus with median pouch wall thickness of 1.5 mm, 2.3 mm, 2.0 mm, 2.0 mm, and 1.5 mm, respectively. There were significant differences in pouch wall thickness between normal or non-inflamed pouch versus pouchitis versus cuffitis versus Crohn's disease of the pouch with p values of 0.01, 0.04, 0.05, and 0.049, respectively. CONCLUSION: Patients with FPC were shown to have thin pouch wall, which those with inflammatory conditions of the pouch tended to have thick pouch wall. These findings will have implications in both diagnosis and investigation of etiopathogenesis of these disorders.

Greater Peripouch Fat Area on CT Image Is Associated with Chronic Pouchitis and Pouch Failure in Inflammatory Bowel Diseases Patients.

BACKGROUND: The causes of chronic antibiotic refractory pouchitis (CARP) and pouch failure in inflammatory bowel disease (IBD) patients remain unknown. Our previous small study showed peripouch fat area measured by MRI was associated with pouchitis. AIMS: To explore the relationship between peripouch fat area on CT imaging and pouch outcomes. METHODS: This is a historical cohort study. Demographic, clinical, and radiographic data of IBD patients with abdominal CT scans after pouch surgery between 2002 and 2017 were collected. Peripouch fat areas and mesenteric peripouch fat areas were measured on CT images at the middle pouch level. RESULTS: A total of 435 IBD patients were included. Patients with higher peripouch fat areas had a higher prevalence of CARP. Univariate analyses demonstrated that long duration of the pouch, high weight or body mass index, the presence of primary sclerosing cholangitis or other autoimmune disorders, and greater peripouch fat area or mesenteric peripouch fat area were risk factors for CARP. Multivariable analyses demonstrated that the presence of primary sclerosing cholangitis or autoimmuned disorders, and greater peripouch fat area (odds ratio [OR] 1.031; 95% confidence interval [CI] 1.016-1.047, P < 0.001) or mesenteric peripouch fat area were independent risk factors for CARP. Of the 435 patients, 139 (32.0%) had two or more CT scans. Multivariable Cox proportional hazard analyses showed that "peripouch fat area increase ≥ 15%" (OR 3.808, 95%CI 1.703-8.517, P = 0.001) was an independent predictor of pouch failure. CONCLUSIONS: A great peripouch fat area measured on CT image is associated with a higher prevalence of CARP, and the accumulation of peripouch fat is a risk factor for pouch failure. The assessment of peripouch fat may be used to monitor the disease course of the ileal pouch.

Characterization of risk factors for floppy pouch complex in ulcerative colitis.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis can be associated with a variety of complications, including floppy pouch complex (FPC). FPC is defined as the presence of pouch prolapse, afferent limb syndrome, enterocele, redundant loop, and folding pouch on pouchoscopy or contrasted pouchogram. The main symptoms of patients with FPC are dyschezia, incomplete evacuation, and bloating. The aims of the study were to evaluate the relative frequency of each disorder of FPC and to characterize its risk factors. METHODS: This case-control study included all eligible patients with FPC from our prospectively maintained, IRB-approved Pouchitis Registry from 2011 to 2017. The control group included the patients without any of the above conditions. Univariate and multivariate analyses were performed. RESULTS: A total of 437 eligible patients were analyzed including 97 (22.2%) with FPC and 340 (77.8%) without FPC, 188 (43.0%) being female, 360 (82.4%) being Caucasians, and 66 (15.1%) having a family history of inflammatory bowel disease (IBD). There were 427 patients (97.7%) having J pouches and 10 (2.2%) having S pouches and the median duration from pouch construction to data sensor was 6.0 years (interquartile range 0.962-1.020). In the whole cohort, 64 (66.0%) patients had pouch prolapse, 38 (39.2%) patients had afferent limb syndrome, 10/42 (23.8%) patients had redundant loop, and 3/42 (7.1%) had folding pouch. In multivariable analysis, lower body weight (odds ratio [OR] 0.944; interquartile range; 95% confidence interval [CI] 0.913-0.976, P = 0.001) and the presence of family history of IBD (OR 4.098; 95% CI 1.301-12.905, P = 0.013) were associated with a higher risk of FPC. CONCLUSION: We found that pouch prolapse and afferent limb syndrome are the most common forms of FPC. A lower body weight as well as family history of IBD was found to be risk factors for FPC. The findings will have implications in both diagnosis and investigation of etiopathogenesis of this group of challenging disorders.

Clinical significance of multiple gene detection with a 22-gene panel in formalin-fixed paraffin-embedded specimens of 207 colorectal cancer patients.

BACKGROUND: Simultaneous detection of multiple molecular biomarkers is helpful in the prediction of treatment response and prognosis for colorectal cancer (CRC) patients. METHODS: A 22-gene panel consisting of 103 hotspot regions was utilized in the formalin-fixed paraffin-embedded (FFPE) tissue samples of 207 CRC patients, using the next-generation sequencing (NGS)-based multiplex PCR technique. Those 22 genes included AKT1, ALK, BRAF, CTNNB1, DDR2, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, KRAS, MAP2K1, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, STK11, and TP53. RESULTS: Of the 207 patients, 193 had one or more variants, with 170, 20, and 3 having one, two, and three mutated genes, respectively. Of the total 414 variants identified in this study, 384, 25, and 5 were single-nucleotide variants, deletion, and insertion. The top four frequently mutated genes were TP53, KRAS, PIK3CA, and FBXW7. There was high consistency between the results of NGS-PCR technique and routine ARMS-PCR in KRAS and BRAF mutation detection. Univariate and multivariate analyses demonstrated that advanced TNM stage, elevated serum CEA, total variants number ≥ 2, AKT1 and PTEN mutation were independent predictors of shorter DFS; poor differentiation, advanced TNM stage, total variants number ≥ 2, BRAF, CTNNB1 and NRAS mutation were independent predictors of shorter OS. CONCLUSIONS: It is feasible to detect multiple gene mutations with a 22-gene panel in FFPE CRC specimens. TNM stage and total variants number ≥ 2 were independent predictors of DFS and OS. Detection of multiple gene mutations may provide additional prognostic information to TNM stage in CRC patients.

Comparisons of the surgical outcomes and medical costs between transferred and directly admitted patients diagnosed with intestinal obstruction in an American tertiary referral center.

PURPOSE: Intestinal obstruction is a leading cause of patient mortality and the most common reason for emergent operation in colorectal surgery. The influence of inter-hospital transfer on patients' outcomes varies greatly in different diseases. We aimed to compare the surgical outcomes and medical costs between transferred and directly admitted patients diagnosed with intestinal obstruction in an American tertiary referral center. METHODS: All intestinal obstruction patients operated in Cleveland Clinic from Jan 2012 to Dec 2016 were collected from a prospectively maintained database. Preoperative characteristics; surgical outcomes, including intraoperative complication, postoperative complication, readmission, reoperation, and postoperative 30-day mortality; and medical cost were collected. All parameters were compared between two groups before and after propensity score match. Multivariate logistic analysis was used to explore risk factors of surgical outcomes. RESULTS: A total of 576 patients were included, with 75 in the transferred group and 501 in the directly admitted group. Before match, the transferred patients had longer waiting interval from admission to surgery (p < 0.001), more contaminated or infected wounds (p = 0.02), different surgical procedures (p = 0.02), and similar surgical outcomes and total medical cost (all p > 0.05), compared with the directly admitted group. Multivariate analysis showed that inter-hospital transfer was not an independent predictor of any surgical outcome. After matching to balance the preoperative characteristics between two groups, no significant differences were identified in all surgical outcomes and total medical cost between two groups (all p > 0.05). CONCLUSIONS: Compared with directly admitted patients, transferred intestinal obstruction patients are associated with similar surgical outcomes and similar medical costs.

Expression of ZNF148 in different developing stages of colorectal cancer and its prognostic value: a large Chinese study based on tissue microarray.

BACKGROUND: It has been speculated that zinc finger protein 148 (ZNF148) is a tumor suppressor. However, to the authors' knowledge, little is known about the clinical significance of ZNF148 expression in patients with colorectal cancer (CRC). The objective of the current study was to clarify the association between ZNF148 expression and the postoperative prognosis of patients with CRC. METHODS: Tissue microarrays containing 56 normal mucosa, 51 adenoma, 742 CRC (TNM stage I-IV), 16 familial adenomatous polyposis, and 21 metastatic CRC specimens were examined immunohistochemically for ZNF148 expression. RESULTS: Expression of ZNF148 was found to increase consecutively from normal mucosa to stage I CRC, and then decreased consecutively from stage I to stage IV CRC. Lower expression of ZNF148 in tumors was found to be significantly associated with lymph node metastases, advanced TNM disease stage, poor differentiation, higher rate of disease recurrence, worse overall survival (OS), and shorter disease-free survival. High expression of ZNF148 was also associated with improved OS (P = .025) and disease-free survival (P = .042) in patients with stages II to III CRC. On multivariate Cox analysis, lower ZNF148 expression in tumors, advanced TNM stage, colon cancer, and elevated serum carbohydrate antigen 19-9 (CA19-9) were found to be significant factors for a worse OS. In 16 patients with familial adenomatous polyposis, ZNF148 expression was upregulated at steps toward carcinogenesis. In 21 patients with metastatic CRC, although ZNF148 expression was higher in primary tumors compared with adjacent mucosa, its expression in metastatic tumors was significantly lower than that in primary tumors. CONCLUSIONS: Although ZNF148 expression is related to colorectal carcinogenesis, high ZNF148 expression in patients with CRC appears to be inversely associated with malignant phenotypes and may serve as a significant prognostic factor after surgery for patients with CRC.

Downregulation of ATP-binding cassette subfamily C member 4 increases sensitivity to neoadjuvant radiotherapy for locally advanced rectal carcinoma.

OBJECTIVE: This study was designed to verify the effect of ATP-binding cassette subfamily C member 4 on radiosensitivity of locally advanced rectal carcinoma. SETTING: The expression of ATP-binding cassette subfamily C member 4 protein in 121 pretreatment tissue samples from locally advanced rectal carcinoma patients was detected by immunohistochemistry. DESIGN: Pathological response to radiotherapy was evaluated according to tumor regression grading by postoperative histological examinations after they received long-course preoperative neoadjuvant radiotherapy, and the association between clinicopathological data and tumor regression grading was analyzed retrospectively. For further validation, short hairpin RNA was constructed and transfected into colorectal carcinoma cell line HT29. The knockdown efficiency was confirmed at both RNA and protein levels. The altered radiosensitivity was evaluated by methylthiazolyl tetrazolium assay, colony formation assay, flow cytometry, and Hoechst 33258 staining. RESULTS: Univariate analysis revealed that ATP-binding cassette subfamily C member 4 expression (p < 0.001), P53 type (p = 0.069), and CEA (p = 0.100) were possibly associated with tumor regression grading, and multivariate analysis demonstrated that ATP-binding cassette subfamily C member 4 expression (p < 0.001) and P53 type (p = 0.039) were positively correlated with response to neoadjuvant radiotherapy in locally advanced rectal carcinoma patients. Lentiviral vector was successfully introduced into HT29 cells and inhibited ATP-binding cassette subfamily C member 4 expression efficiently and persistently. Downregulation of ATP-binding cassette subfamily C member 4 expression significantly enhanced inhibition of cell proliferation, decreased colony formation capacity, and increased cell apoptosis induced by irradiation, as examined by a series of experiments in vitro. In addition, radiobiological parameters calculated according to the single-hit multitarget model were also decreased significantly. CONCLUSIONS: Our data indicate that ATP-binding cassette subfamily C member 4 may be a useful molecular marker in predicting radiosensitivity, and a potential target in improving the response to neoadjuvant radiotherapy in locally advanced rectal carcinoma patients.

Erratum: miR-365a-3p regulates ADAM10-JAK-STAT signaling to suppress the growth and metastasis of colorectal cancer cells: Erratum.

[This corrects the article DOI: 10.7150/jca.42731.].

Re-recognition of BMPR1A-related polyposis: beyond juvenile polyposis and hereditary mixed polyposis syndrome.

Background: Bone morphogenetic protein receptor type 1A (BMPR1A) is responsible for two individual Mendelian diseases: juvenile polyposis syndrome and hereditary mixed polyposis syndrome 2, which have overlapping phenotypes. This study aimed to elucidate whether these two syndromes are just two subtypes of a single syndrome rather than two isolated syndromes. Methods: We sequenced the BMPR1A gene in 186 patients with polyposis and colorectal cancer, and evaluated the clinicopathological features and phenotypes of the probands and their available relatives with BMPR1A mutations. Results: BMPR1A germline mutations were found in six probands and their three available relatives. The numbers of frameshift, nonsense, splice-site, and missense mutations were one, one, two, and two, respectively; two of the six mutations were novel. Typical juvenile polyps were found in only three patients. Two patients had colorectal cancer rather than any polyps. Conclusions: Diseases in BMPR1A germline mutation carriers vary from mixed polyposis to sole colorectal cancer, and typical juvenile polyps do not always occur in these carriers. The variety of phenotypes reflected the features of BMPR1A-mutation carriers, which should be recognized as a spectrum of one syndrome. Genetic testing may be a good approach to identifying BMPR1A-related syndromes.

Investigating anorectal function using postoperative MRI-based fibrosis score in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy: a two-center study.

PURPOSE: This study aimed to develop a postoperative MRI-based fibrosis scoring system and to assess its correlation with anorectal function in locally advanced rectal cancer (LARC) cases administered neoadjuvant chemoradiotherapy (nCRT). METHODS: Pathologically confirmed LARC cases administered nCRT and radical resection were assessed retrospectively. Based on postoperative magnetic resonance imaging (MRI) findings, anastomotic fibrosis score (AFS) and perirectal fibrosis score (PFS) were determined to evaluate the extent of fibrosis. The Wexner continence score for anorectal function was obtained 2 years postoperatively and assessed for correlation with MRI fibrosis scores. The cases were divided into 2 groups by the median Wexner score. Univariable and multivariable analyses were adopted for building a nomogram model, whose diagnostic performance was estimated by receiver operating characteristic (ROC) and decision curve analyses (DCA). RESULTS: Finally, 144 patients with LARC were included in cohort 1 (training set). 52 patients were enrolled in cohort 2 (external validation set). Spearman correlation analysis indicated that AFS and PFS were positively correlated with the Wexner score. Univariable and multivariable analyses revealed age, tumor height, AFS, and PFS were independent predictors of anorectal function. The nomogram model achieved a good diagnostic performance, with AUCs of 0.800 and 0.827 in the training and validation sets, respectively; its predicting value was also confirmed by DCA. CONCLUSION: The present study showed AFS and PFS derived from postoperative MRI are positively correlated with Wexner score. In addition, the new scoring system was effective in predicting anorectal function in LARC cases administered nCRT.

Changing trends, clinicopathological characteristics, surgical treatment patterns, and prognosis of schistosomiasis-associated versus non-schistosomiasis-associated colorectal cancer: a large retrospective cohort study of 31 153 cases in Shanghai, China (2001-2021).

BACKGROUND: With the elimination of schistosomiasis in China, its role in the pathogenesis of colorectal cancer (CRC) has decreased. However, the trends, clinicopathological features, surgical treatment patterns, and prognosis of schistosomiasis-associated CRC (SACRC) versus non-schistosomiasis-associated CRC (NSACRC) in China remain unclear. MATERIALS AND METHODS: The percentage trend of SACRC in CRC patients in China was analyzed using data retrieved from the Pathology Registry of Changhai Hospital (2001-2021). Clinicopathological characteristics, surgical treatment patterns, and prognosis-related parameters were compared between the two groups. Multivariate Cox regression analyses were performed for disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 31 153 CRC cases were included, with 823 (2.6%) cases of SACRC and 30 330 (97.4%) cases of NSACRC. The average percentage of SACRC cases has decreased continuously from 3.8 to 1.7% (from 2001 to 2021). Compared with the NSACRC group, the SACRC group had more men, older age at diagnosis, lower BMI, fewer symptoms; higher rates of rectal cancer, comorbidities, KRAS mutation, multiple primary CRC and concomitant polyps; less lymph node metastasis, distant metastasis, vascular invasion, and tumor budding; less preoperative radiotherapy and preoperative chemotherapy; and more positive resection margins and postoperative targeted therapy. There were no significant differences between the two groups regarding laparoscopic surgery, palliative resection, extended radical resection, or ostomy. Moreover, the SACRC group had adverse DFS and similar OS compared with the NSACRC group. In multivariate analyses, schistosomiasis was not an independent predictor of DFS or OS. CONCLUSION: The percentage of SACRC in CRC (2.6%) in our hospital was very low, and it decreased continuously over the last two decades, indicating that schistosomiasis is no longer an important risk factor for CRC in Shanghai, China. Patients with SACRC have distinct clinicopathological, molecular, and treatment-related features and survival rates similar to those with NSACRC.

Whether, when, and who to disclose bad news to patients with cancer: a survey in 150 pairs of hospitalized patients with cancer and family members in China.

OBJECTIVE: The purpose of this study is to determine how to disclose bad news to patients with cancer in China. METHODS: One hundred fifty pairs of hospitalized patients and their family members were investigated using a self-designed questionnaire. RESULTS: More patients than their families believed that patients should be informed of their illnesses (98.0% vs. 66.7%, p < 0.001), that patients should be informed of their condition completely (69.3% vs. 18.7%, p < 0.001), that patients should be informed as soon as the diagnoses were confirmed (49.3% vs. 14.7%, p < 0.001), and that patients should be informed by doctors (55.3% vs. 10.7%, p < 0.001). κ coefficients between patients and their families on "whether, when and who to disclose" ranged from -0.084 to 0.004. Univariate logistic analyses demonstrated that farmer patients and patients with lower education and lower income were less likely to prefer to be informed completely; farmer patients and patients without an intended curative operation history were less likely to prefer to be informed immediately and directly by doctors. Multivariate analyses showed that farmer patients were less likely to prefer to be informed completely, immediately, and directly by doctors. CONCLUSIONS: There was poor or slight concordance in disclosure preferences between patients with cancer and their families. More patients than their families wanted to be informed completely, immediately, and directly by doctors. Farmer patients with cancer were less likely to prefer to be informed completely, immediately, and directly by doctors.

DNA topoisomerase II alpha: a favorable prognostic factor in colorectal caner.

PURPOSE: There is a lack of study concerning expression of Topoisomerase IIα (Topo IIα) and long-term results in colorectal cancer patients. We aimed to investigate the relationship between expression of Topo IIα and clinicopathological parameters including overall survival in colorectal cancer. METHODS: Paraffin-fixed specimens from a large prospective cohort of colorectal cancer patients who had been followed up for 4 years were assayed immunohistochemically. RESULTS: Of 490 colorectal cancer patients accessible for Topo IIα expression, expression of Topo IIα was scored as (-) in 4 (0.8%) patients, (+) in 41 (8.4%) patients, (++) in 396 (80.8%) patients, and (+++) in 49 (10.0%) patients. Overexpression of Topo IIα was found to be related with lower T stage (p = 0.042), lower N stage (p = 0.038), and a lower incidence of recurrence with nearly significance (p = 0.053). Kaplan-Meier analyses showed that overexpression of Topo IIα was related with prolonged overall survival (p = 0.022) and disease-free survival (p = 0.036). Multivariate analyses showed that elevated serum CEA (p < 0.001), elevated serum CA199 (p = 0.002), poor differentiation (p = 0.001), advanced Dukes stage (p < 0.001), and lower expression of Topo IIα (p = 0.017) were independent predictive factors for poor prognosis. CONCLUSIONS: Topo IIα expression is a valuable prognostic indicator for colorectal cancer and would be useful in treatment selection for early colorectal cancer and malignant colorectal polyps resected under endoscopy, especially when it is used in combination with serum CEA, CA199, and differentiation.

Implantation metastasis from sigmoid colon cancer to rectal anastomosis proved by whole exome sequencing and lineage inference for cancer heterogeneity and evolution analysis: Case report and literature review.

It was estimated that 70% of patients with colorectal cancer were found to have viable exfoliated malignant cells in adjacent intestinal lumen. Exfoliated malignant cells had been reported to implant on raw surfaces, such as polypectomy site, anal fissure, anal fistula, hemorrhoidectomy wound, and anastomotic suture line. Tumors at anastomosis could be classified into four groups: local recurrence, local manifestation of widespread metastasis, metachronous carcinogenesis, and implantation metastasis. However, all of the previous studies only reported the phenomena of implantation metastasis at anastomosis. No study had proved the origin of anastomotic metastasis by genomic analysis. In this study, a 43-year-old woman presented with persistent hematochezia was diagnosed as having severe mixed hemorrhoids. She was treated by procedure for prolapse and hemorrhoids (PPH), without receiving preoperative colonoscopy. Two months later, she was found to have sigmoid colon cancer by colonoscopy due to continuous hematochezia and received radical sigmoidectomy. Postoperative histological examination confirmed the lesion to be a moderately differentiated adenocarcinoma (pT3N1M0). Six months later, she presented with hematochezia again and colonoscopy revealed two tumors at the rectal anastomosis of PPH. Both tumors were confirmed to be moderately differentiated adenocarcinoma without lymph node and distant metastasis and were finally removed by transanal endoscopic microsurgery (TEM). Pathological examination, whole exome sequencing (WES), and Lineage Inference for Cancer Heterogeneity and Evolution (LICHeE) analysis demonstrated that the two tumors at the rectal anastomosis were probably implantation metastases arising from the previous sigmoid colon cancer. This is the first study to prove implantation metastasis from colon cancer to a distal anastomosis by WES and LICHeE analysis. Therefore, it is recommended to rule out colorectal cancer in proximal large bowel before performing surgery with a rectal anastomosis, such as PPH and anterior resection. For patients with a suspected implanted tumor, WES and LICHeE could be used to differentiate implantation metastasis from metachronous carcinogenesis.

Trends, clinicopathological features, surgical treatment patterns and prognoses of early-onset versus late-onset colorectal cancer: A retrospective cohort study on 34067 patients managed from 2000 to 2021 in a Chinese tertiary center.

BACKGROUND: In recent decades, the incidence of early-onset colorectal cancer (EOCRC) has reportedly increased in several developed countries, whereas that of late-onset colorectal cancer (LOCRC) has decreased continuously. The trends, clinicopathological features, surgical treatment patterns, and prognoses of EOCRC and LOCRC in China remain unclear. MATERIALS AND METHODS: This retrospective cohort study was performed in China using data from our pathology registry collected in 2000-2021. Pathologically confirmed cases of colorectal cancer (CRC) were analyzed. The average annual percentage change (AAPC) was estimated to quantify the secular trends. Clinicopathological features, surgical treatment patterns, and prognoses were compared between the two groups. Multivariate Cox regression analyses were performed for disease-free survival and overall survival. RESULTS: A total of 34,067 cases of CRC were included, with 6,369 cases of EOCRC and 27,698 cases of LOCRC. Overall, the numbers of EOCRC (AAPC = 8.4%), LOCRC (AAPC = 11.6%), and CRC (AAPC = 11.0%) cases increased significantly from 2000 to 2021. Compared to the LOCRC group, the EOCRC group had fewer men, comorbidities, concomitant cancers, polyps, and KRAS mutations; more symptoms, rectal cancers, multiple primary CRCs, deficient mismatch repair tumors, poorly differentiated, mucinous adenocarcinoma or signet ring cell carcinoma, advanced TNM stage, vascular invasion, perineural invasion; less laparoscopic surgery and sphincter-preserving surgery; more extended radical resection, perioperative chemoradiotherapy and targeted therapy; and similar disease-free and overall survival rates. CONCLUSION: The numbers of EOCRC and LOCRC cases have continuously increased over the last two decades. The EOCRC group has more aggressive features, advanced TNM stage, intensified surgical treatment and perioperative treatment than the LOCRC group, but similar disease-free and overall survival rates. More CRC screening programs are recommended for younger adults to combat the rapidly increasing trend of EOCRC.

Role of Perirectal Fat in the Carcinogenesis and Development of Early-Onset Rectal Cancer.

Purpose: The incidence of early-onset rectal cancer (EORC) has been increasing since the past decade, while its underlying cause remained unknown. This study was aimed at clarifying the relationship between perirectal fat area (PFA) and EORC. Patients and Methods. All patients with rectal cancer who received radical excision between January 2016 and December 2017 at our hospital were included. The fat series images of pelvic magnetic resonance imaging scans were obtained and PFA at the ischial spine level was calculated using the ImageJ software. Results: A total of 303 patients were finally included and divided into two groups according to the median PFA: Group 1 (<20.2 cm2, n = 151) and Group 2 (≥20.2 cm2, n = 152). PFA positively correlated with body weight and body mass index. PFA increased with invasion depth, lymph node metastasis, TNM stage, tumor deposits, and vascular invasion. Patients with EORC had higher PFA than those with late-onset rectal cancer (LORC; P = 0.009). Among patients with stage I-III rectal cancers, those in Group 2 had significantly shorter disease-free survival (P = 0.010) and overall survival (P = 0.034) than those in Group 1, and PFA was an independent predictor of disease-free survival (OR: 1.683 [1.126-3.015], P = 0.035) and overall survival (OR: 1.678 [1.022-2.639], P = 0.046). Conclusions: Patients with EORC had significantly higher PFA than those with LORC. PFA is positively correlated with T stage, N stage, TNM stage, tumor deposit, and vascular invasion and is an independent predictor of disease-free survival and overall survival. Therefore, perirectal fat may be involved in the carcinogenesis and development of EORC.

Local recurrence after intended curative excision of presacral lesions: causes and preventions.

OBJECTIVE: This study was designed to explore causes for local recurrence of presacral lesions after intended curative surgery and discuss prevention strategies. METHODS: Medical data of presacral lesions in our hospital from January 2001 to September 2009 were retrospectively studied, including preoperative examinations, intraoperative findings, and postoperative histopathologies. RESULTS: Of 39 patients (29 women and 10 men) with presacral lesions, who ranged in age from 14 to 71 (mean, 39.56) years, 7 patients were diagnosed with recurrent presacral lesions on admission. Preoperative pelvic MRI, pelvic CT, and endorectal ultrasonography (ERUS) were performed in 23, 22, and 8 cases, respectively. MRI/CT showed that five cases had two coexisting lesions and three cases had lobulated or dumbbell shaped lesions, all of which were confirmed by intraoperative findings. ERUS suspected involvement of the rectal wall in three cases: adhesion to the rectal wall in two cases, and tumor invasion in the remaining case. During the operation, 26, 8, and 2 cases were resected by the transsacral, transabdominal, and combined abdominosacral approach, respectively. Four patients underwent simultaneous coccygectomy, and three patients received simultaneous resection of the sacrum and coccyx. Simultaneous partial resection of the invaded sigmoid colon or rectum was performed in two patients, respectively. By postoperative pathological examination, three cases were found to have ruptured cystic lesions, three had previous cyst rupture history, and five had infected lesions. CONCLUSIONS: Presacral lesions are likely to be multiple, lobulated, infected, ruptured, and adhesive to the sacrococcyx and rectum, which contribute to the high local recurrence rate. Preoperative CT/MRI/ERUS and careful intraoperative exploration are required to direct surgical treatment and to reduce local recurrence. Optimal selection of surgical approach also is very important to reduce local recurrence. Presacral lesions attached to the sacrococcyx or rectum require simultaneous partial resection of the sacrococcyx or rectum to reduce local recurrence.