Clinicopathologic features and prognosis of synchronous and metachronous multiple primary colorectal cancer.

PURPOSE: Multiple primary colorectal cancers (MPCCs) are different from solitary colorectal cancers in many aspects, which are not well studied. The aim of this study was to clarify the clinicopathological features and prognosis of MPCCs. METHODS: The data of 64 patients with MPCCs out of 2300 patients with colorectal cancers (CRCs) from January 2009 to December 2017 were retrospectively analyzed. Stratified analysis was conducted based on subtypes and microsatellite status. RESULTS: The overall incidence of MPCC was 2.8% and the median follow-up duration was 51.5 (range 1-120) months. Metachronous CRCs (MCRCs) are more likely to appear in the right colon (p < 0.05). However, no significant differences regarding age, sex, BMI, tumor size, smoking/drinking history, TNM stage, family history of cancer, and 5-year survival rate were observed between synchronous CRC (SCRC) and MCRC. Advanced TNM stage (III) and the presence of polyps were found to be independent poor prognostic factors for MPCCs. The prevalence of mismatch repair deficiency (dMMR) in MPCCs was 28.1%. Deficient MMR is more likely to appear in younger, lighter MPCC patients with polyps (p < 0.05). Of four mismatch repair proteins, MLH-1, MSH-2, MSH-6, and PMS-2 were negative in nine, nine, five, and nine patients, respectively. The 5-year survival rate did not differ significantly between MMR-proficient (pMMR) and dMMR groups (p = 0.752). CONCLUSIONS: Synchronous CRC (SCRC) and MCRC might represent similar disease entities with different courses. Deficient MMR is more likely to appear in younger, lighter MPCC patients with polyps and it is an essential indicator for screening Lynch syndrome.

Minimally invasive transanal surgery is safe after incomplete polypectomy of low risk T1 rectal cancer: a systematic review.

AIM: In patients who have undergone a polypectomy of a malignant rectal polyp without histopathological risk factors other than an involved or unclear resection margin, additional local excision is often performed. Evidence to support this approach is lacking. The aim of this systematic review and meta-analysis was to determine the outcome in terms of local recurrence, disease-free survival (DFS) and overall survival (OS) of additional local excision following incomplete polypectomy for low risk T1 rectal cancer. METHODS: A comprehensive search for published studies was performed. Only studies in which there was incomplete (or ≤ 1 mm) removal of pT1 rectal polyps or in which the resection plane could not be assessed were included. For each included study data on tumour stage, histological factors, surgical technique, local recurrence rate, 5-year DFS and 5-year OS were extracted. The PROSPERO registration number is CRD42017062702. RESULTS: A total of 580 studies were retrieved by the search in the MEDLINE database, Embase and the Cochrane Library. After careful appreciation, four studies were included in the analysis, comprising 102 patients of whom the majority had undeterminable (Rx) resection margins. Local excision via transanal endoscopic microsurgery was reported most frequently. Only 1% of patients developed a local recurrence. One study reported 5-year DFS and 5-year OS of 96% and 87% respectively. CONCLUSION: This study supports the use of additional local excision techniques for rectal cancer patients who underwent an incomplete polypectomy for a malignant rectal polyp in the absence of risk factors other than an uncertain resection margin.

Endoscopic management of mucosal lesions in the gastrointestinal tract.

With the increasing role of endoscopy in patient evaluation, more mucosal lesions, including gastric, duodenal and colonic polyps, are encountered during routine examinations. It is imperative for gastroenterologists to become familiar with the endoscopic management of these various gastrointestinal lesions. In this article, various resection techniques will be discussed, including hot/cold forceps polypectomy, hot/cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection. The article will also discuss the evidence regarding the efficacy and safety of these techniques and the future direction of endoscopic management of mucosal lesions in the gastrointestinal tract.

Endoscopic and surgical treatment of malignant colorectal polyps: a population-based comparative study.

BACKGROUND: Long-term population-based data comparing endoscopic therapy (ET) and surgery for management of malignant colorectal polyps (MCPs) are limited. OBJECTIVE: To compare colorectal cancer (CRC)-specific survival with ET and surgery. DESIGN AND SETTING: Population-based study. PATIENTS: Patients with stage 0 and stage 1 MCPs were identified from the Surveillance Epidemiology and End Results (SEER) database (1998-2009). Demographic characteristics, tumor size, location, treatment modality, and survival were compared. Propensity-score matching and Cox proportional hazards regression models were used to evaluate the association between treatment and CRC-specific survival. INTERVENTIONS: ET and surgery. MAIN OUTCOME MEASUREMENTS: Mid-term (2.5 years) and long-term (5 years) CRC-free survival rates and independent predictors of CRC-specific mortality. RESULTS: Of 10,403 patients with MCPs, 2688 (26%) underwent ET and 7715 (74%) underwent surgery. Patients undergoing ET were more likely to be older white men with stage 0 disease. Surgical patients had more right-sided lesions, larger MCPs, and stage 1 disease. There was no difference in the 2.5-year and 5-year CRC-free survival rates between the 2 groups in stage 0 disease. Surgical resection led to higher 2.5-year (97.8% vs 93.2%; P < .001) and 5-year (96.6% vs 89.8%; P < .001) CRC-free survival in stage 1 disease. These results were confirmed by propensity-score matching. ET was a significant predictor for CRC-specific mortality in stage 1 disease (hazard ratio 2.40; 95% confidence interval, 1.75-3.29; P < .001). LIMITATIONS: Comorbidity index not available, selection bias. CONCLUSIONS: ET and surgery had comparable mid- and long-term CRC-free survival rates in stage 0 disease. Surgical resection is the recommended treatment modality for MCPs with submucosal invasion.

Colorectal surgery in kidney transplant recipients: a decade of trends and outcomes in the United States.

There is paucity of data evaluating the trends and outcomes of colorectal surgery (CRS) in kidney transplant recipients (KTRs). Using the Nationwide Inpatient Sample 2001 to 2010, a retrospective review of CRS performed in KTRs was performed. Trends, demographics, indications, and outcomes were examined for elective and emergent cases and compared with the general population (GP) on multivariate logistic regression. A total of 2616 KTRs underwent CRS, 50 per cent of which were done emergently. KTRs developed colon and rectal cancer at a younger age and had significantly higher incidence of comorbidities compared with the GP. Diverticular disease was the most common indication for surgery (48%) followed by cancer (30.6%). Compared with the GP, KTRs had higher rates of mortality (6.29 vs 3.64%), wound complications (8.02 vs 5.37%), and acute renal failure (ARF) (17.14 vs 7.10%) (all P < 0.05). No difference was seen in the incidence of anastomotic leak. On multivariate analysis, KTRs had higher associated odds of ARF (odds ratio, 2.02; P < 0.001), whereas the odds of mortality, wound, and anastomotic complications were similar to the GP. Emergency surgery in KTRs was associated with worse outcomes compared with the elective setting. KTRs undergoing CRS have unique characteristics that are different than the GP. They are at an increased risk of complications, especially acute renal failure.

Nuclear orphan receptor NR4A2 confers chemoresistance and predicts unfavorable prognosis of colorectal carcinoma patients who received postoperative chemotherapy.

BACKGROUND: NR4A2, an orphan nuclear receptor essential in neuron generation, has been recently linked to inflammatory and metabolic pathways of colorectal carcinoma (CRC). However, the effects of NR4A2 on chemo-resistance and postoperative prognosis of CRC remain unknown. METHODS: NR4A2 was transfected into CRC cells to investigate its effects on chemo-resistance to 5-fluorouracil and oxaliplatin and chemotherapeutics-induced apoptosis. We also investigated prostaglandin E2 (PGE2)-induced NR4A2 expression and its effect on chemo-resistance. Tissue microarrays including 51 adenoma, 14 familial adenomatous polyposis with CRC, 17 stage IV CRC with adjacent mucosa and 682 stage I-III CRC specimens were examined immunohistochemically for NR4A2 expression. Median follow-up time for stage I-III CRC patients was 53 months. RESULTS: Ectopic expression of NR4A2 increased the chemo-resistance, and attenuated the chemotherapeutics-induced apoptosis. Transient treatment of PGE2 significantly up-regulated NR4A2 expression via protein kinase A pathway and increased the chemo-resistance. NR4A2 expression in epithelials consecutively increased from adenoma, adjacent mucosa to CRC (P(trend)<0.001). In multivariate Cox regression analyses, high NR4A2 expression in cancer nuclei (immunoreactive score ≥ 4) significantly predicted a shorter disease-specific survival (DSS) of CRC patients (hazard ratio [HR]=1.88, P=0.024). High NR4A2 expression specifically predicted a shorter DSS of colon cancer patients (dichotomisation, HR=2.55, log-rank test P=0.011), especially for those who received postoperative 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX) chemotherapy (3-score range, HR=1.86, log-rank test P=0.020). CONCLUSION: High expression of NR4A2 in CRC cells confers chemo-resistance, attenuates chemotherapeutics-induced apoptosis, and predicts unfavorable prognosis of colon cancer patients, especially for those who received postoperative chemotherapy. NR4A2 may be prognostic and predictive for colon cancer.

Management of malignant colonic polyps: a population-based analysis of colonoscopic polypectomy versus surgery.

BACKGROUND: The management of colon polyps containing invasive carcinoma includes surgical resection or colonoscopic polypectomy. To date, there are very limited population-based data comparing outcomes with the 2 management approaches. METHODS: Using the linked Surveillance Epidemiology and End Results-Medicare database, we identified 2077 patients aged ≥66 years with an initial diagnosis of stage T1N0M0 malignant polyp from 1992-2005. Patients were categorized as surgical or polypectomy depending on the most invasive treatment. To adjust for potential selection bias in treatment assignment, using multivariate analysis, patients were divided into quintiles of likelihood of polypectomy (propensity scores), and outcomes were compared in each quintile. RESULTS: Surgical resection was performed in 1340 (64.5%) patients and polypectomy was performed in 737 (35.5%) patients. Predictors for undergoing polypectomy (P<.001) included older age, greater comorbidity, no history of polyps, diagnosis in 2002 or later, left colon site of cancer, well-differentiated tumors, and colonoscopy performed in an outpatient setting. Both 1-year and 5-year survival were higher in the surgical group (92% and 75%, respectively) than in the polypectomy group (88% and 62%, respectively). The unadjusted hazard ratio was 1.51 (95% confidence interval [CI], 1.31-1.74). After adjusting for propensity quintile, the hazard ratio was 1.15 (95% CI, 0.98-1.33). Within each propensity quintile, the risk of death was similar between the 2 groups (interaction test P = .96). CONCLUSIONS: In this large, population-based sample, more than one-third of patients with malignant polyps were treated with colonoscopic polypectomy. Outcomes were similar to surgical patients with comparable clinical characteristics and could be offered to patients who meet appropriate clinical criteria.

Clinical management of small (6- to 9-mm) polyps detected at screening CT colonography: a cost-effectiveness analysis.

OBJECTIVE: The primary aim of this model analysis was to compare the clinical and economic impacts of immediate polypectomy versus 3-year CT colonography (CTC) surveillance for small (6- to 9-mm) polyps detected at CTC screening. MATERIALS AND METHODS: A decision analysis model was constructed incorporating the expected advanced neoplasia prevalence, frequency of measurable growth, colorectal cancer (CRC) prevalence and risk, CTC performance, and costs related to CRC screening and treatment. CRC risk was assumed to be independent of advanced adenoma size, which intentionally overestimates the risk related to small polyps. Clinical effectiveness and costs for 3-year CTC surveillance versus immediate colonoscopic polypectomy were compared for a concentrated cohort of patients with 6- to 9-mm polyps. For the CTC surveillance strategy, only cases with measurable growth (> or = 1 mm) at follow-up CTC were referred for polypectomy. RESULTS: Without any intervention, the estimated 5-year CRC death rate from 6- to 9-mm polyps in this concentrated cohort was 0.08%, which is a sevenfold decrease over the 0.56% CRC risk for the general unselected screening population. The death rate was further reduced to 0.03% with the CTC surveillance strategy and to 0.02% with immediate colonoscopy referral. However, for each additional cancer-related death prevented with immediate polypectomy versus CTC follow-up, 9,977 colonoscopy referrals would be needed, resulting in 10 additional perforations and an incremental cost-effectiveness ratio of $372,853. CONCLUSION: For patients with small (6- to 9-mm) polyps detected at CTC screening, the exclusion of large polyps (> or = 10 mm) already confers a very low risk of CRC. The high costs, additional complications, and relatively low incremental yield associated with immediate polypectomy of 6- to 9-mm polyps support the practice of 3-year CTC surveillance, which allows for selective noninvasive identification of small polyps at risk.

[Screening of colorectal neoplasm]. / Screening des kolorektalen Karzinoms.

In Germany approximately 29,000 people died of colorectal carcinoma (CRC) in 2002; the risk of getting CRC is 4-6% in Germany, rising with age from the 50th year of life. About one third of all people over 50 years of age have polyps with the potential for malignant transformation in the colorectum, which is a sufficiently high prevalence rate to justify screening. In contrast to most other cancer diseases, in the case of CRC it is possible to prevent the cancer and not only to detect it at an early stage. Application of the test for occult blood in persons between their 45th and 80th years can reduce the mortality of CRC by 14%. We can assume that already regular sigmoidoscopies with consistent performance of polypectomy when needed could reduce the incidence of CRC by 50-70%. There is no doubt that coloscopy is the technique of choice for secondary prevention, as it unites the possibility of complete diagnosis and treatment with a justifiably low level of risk. The economic advantages of an avoidance strategy compared with the treatment of CRC, which is certainly expensive, have been documented. On the basis of all the data reported, in the case of CRC preventive strategies can be emphatically recommended.

Small-bowel tumors.

BACKGROUND: The rarity, delayed presentation, and diagnostic difficulty of small-bowel tumors prompted this study. STUDY DESIGN: Charts were reviewed retrospectively for 85 patients with 89 small-bowel tumors (22 primary malignant, 23 primary benign, and 44 metastatic) over a 10-year period (1986-1996) at Louisiana State University Medical Center-Shreveport and two affiliated hospitals in Shreveport. RESULTS: Of the primary malignant tumors, 10 carcinoids and 11 duodenal adenocarcinomas were identified. Most primary benign tumors were adenomatous or hyperplastic polyps, diagnosed by esophagogastroduodenoscopy. Metastatic tumors accounted for nearly 50% of all small-bowel tumors. Across all three tumor types, the most common presenting signs and symptoms were abdominal pain and nausea and vomiting. In addition, patients with benign tumors were more commonly presented with gastrointestinal hemorrhage, and those with metastatic tumors were more likely to present with obstruction. The mean interval from the onset of signs and symptoms to operation was 54 days for primary malignant tumors and 330 days for primary benign tumors. Esophagogastroduodenoscopy and computed tomography of the abdomen were occasionally helpful in diagnosis. Among the 22 primary malignant tumors, curative resections were performed in 11 patients (for 9 carcinoids and 2 adenocarcinomas) and palliative resections were performed in 10 patients (for 9 adenocarcinomas and 1 myxoliposarcoma). One patient had carcinomatosis from colon cancer and an incidentally discovered ileal carcinoid; this carcinoid was not included in this group of resections for primary malignant small-bowel tumors. All operations for 39 (of 44) patients with metastatic tumors were palliative. The remaining 5 (of 44) patients had metastatic duodenal cancer (confirmed by esophagogastroduodenoscopy or endoscopic retrograde cholangiopancreatography with biopsy) and did not undergo laparotomy. Surgical complications occurred more commonly with metastatic than with primary malignant tumors. Patients with primary malignant tumors had a 5-year survival rate of 36%. CONCLUSIONS: These findings demonstrate that small-bowel tumors are difficult to diagnose because of delayed presentation, nonspecific signs and symptoms, and lack of accurate diagnostic studies. If the overall survival of patients with small-bowel tumors is to be improved, clinicians must have a high index of suspicion and be willing to perform exploratory celiotomy early.

Long-term survival after treatment of malignant colonic polyps.

PURPOSE: This study was designed to evaluate the long-term outcome and survival of patients treated for malignant colonic polyps. METHODS: A retrospective review of 15,975 cases of colonoscopies with 8,685 endoscopic polypectomies performed between 1972 and 1990 was undertaken. In 65 patients, the polypectomy specimens contained invasive carcinoma. Six patients were excluded (follow-up, <6 months). Polyp data, operative findings, and follow-up on the remaining 59 patients were recorded. RESULTS: Malignant polyps were found in 35 males and 24 females who had an average age of 64 (range, 39-81) years. Follow-up ranged from 12 to 202 (mean, 90) months. Tumor differentiation was poor in one and well or moderately differentiated in 58 patients. Positive or indeterminate margins were found in 13 patients. Thirty-seven (63 percent) patients were managed with polypectomy and surveillance. Four of these (with rectal tumors) also had an additional local excision for questionable margins. One recurrence was noted in a patient who refused surgery, which was recommended because of indeterminate margins. Twenty-two patients (37 percent) underwent colectomy. Indications included Haggitt Level 3 or 4 invasion (19), inadequate margins (7), patient preference (1), and poor differentiation (1). Residual disease was found in colectomy specimens of three patients (14 percent). There were no cancer-related deaths in either treatment group. Life table analysis demonstrated a five-year survival of 82 percent for the colectomy group and 95 percent for the polypectomy group (P = 0.15). CONCLUSION: Treatment of patients with malignant polyps must be individualized based on evolving criteria. Patients in whom polypectomy margins are inadequate should undergo colectomy. With appropriate selection criteria, patients selected for colectomy had a five-year survival rate similar to the rate of those treated by polypectomy alone.

[Mason paracoccygeal trans-sphincteric approach to the rectum: good outcome only in highly selective indications?]. / Der paracoccygeale transsphinctere Zugang zum Rectum nach Mason: Gute Ergebnisse nur bei hochselektiver Indikationsstellung?

From 3/1985 until 10/1993, a total of 10 patients were operated using the Mason approach. Four patients undergoing resection of flat villous adenomas situated on the anterior wall of the lower and mid third of the rectum, and one patient with adenoma situated on the posterior wall of the upper third, all of them with reconstruction using intact rectal wall portions, enjoyed a smooth postoperative course, continence and absence of recurrence. Two patients operated for presacral local recurrence following rectal excision and rectal prolapse, respectively, suffered recurrence after a smooth early course. Two patients undergoing resection of villous adenomas situated on the posterior wall of the lower and mid third with reconstruction using denudated muscle wall and one patient undergoing segmental resection for radiogenic rectovaginal fistula developed complex fecal fistulae. On the basis of these experiences and the pertinent literature, indications promising uniformly good results were defined.

[10 years experiences with transanal endoscopic microsurgery. Histopathologic and clinical analysis]. / 10 jährige Erfahrungen mit der transanalen endoskopischen Mikrochirurgie. Histopathologische und klinische Analysen.

The clinical and long-term results encountered from July 1983 to December 1992 are subject of this study. Contrary to other (transanal and transabdominal) surgical treatments the endorectal system permits therapeutic local excisions of large, rectal adenomas and early rectal carcinomas of the "low-risk" type within the entire rectum with minimal morbidity. A superior or comparable rate of adenoma recurrence (4.8%, n = 228) as well as a more favourable operative result (complication rate 3.9%; lethality 0.6%; n = 348) can be achieved with the transanal endoscopic microsurgery. Under palliative conditions, transanal endoscopic surgery is more effective than other conservative treatments in cases of circumscribed, non-stenotic carcinomas of the rectum. Thorough surgical training is required in order to successfully practice transanal endoscopic surgery.

Endoscopically removed malignant colorectal polyps: clinicopathologic correlations.

BACKGROUND/AIMS: Treatment options for patients with endoscopically removed malignant colorectal polyps are polypectomy alone vs. polypectomy followed by surgery. The aim of this study was to define histopathologic parameters that can be used for clinically relevant treatment decisions. METHODS: Five pathologists evaluated 140 polyps for the presence or absence of unfavorable histology. Unfavorable histology was tumor at or near (< or = 1.0 mm) the margin and/or grade III and/or lymphatic and/or venous invasion. Adverse outcome was recurrent and/or local cancer and/or lymph node metastasis. RESULTS: Adverse outcome was 19.7% (14 of 71), 8.6% (2 of 23), and 0% (0 of 46) when unfavorable histology was present, indefinite (lack of agreement), and absent, respectively (P < 0.0005, present vs. absent). Four patients with cancer > 1.0 mm from the margin had an adverse outcome (2 with lymphatic invasion and 2 indefinite for lymphatic invasion). Four patients with negative resections later developed distant metastases. Eight patients (6.3%) died of disease, and 2 of 69 without unfavorable histology (both indefinite for lymphatic invasion) had an adverse outcome. Interobserver strength of agreement was substantial to almost perfect for margin, grade, and venous invasion and fair to substantial for lymphatic invasion. CONCLUSIONS: This system is usable clinically. Patients with unfavorable histology are probably best managed by resection postpolypectomy, whereas in the absence of unfavorable histology, they probably can be treated by polypectomy only.

Small bowel tumors.

Small bowel tumors include adenocarcinomas, carcinoids, lymphomas, and sarcomas, as well as a variety of benign polyps, which should be excised to rule out malignancy. Although small bowel tumors are traditionally difficult to diagnose, a heightened index of suspicion should be combined with improved diagnostic techniques to increase yield and decrease delays in identification. The management of bioactive carcinoid tumors has rapidly advanced over the past year. Increasing experience with the stable somatostatin analogue octreotide has enabled regulation of hormonal secretion by these tumors both chronically and during acute "carcinoid crisis." In addition, early identification may be facilitated by the use of isotopically labeled variants of the compound. Although the development of sophisticated pharmacotherapeutic probes has improved the management of secretory small intestinal tumors, the prognosis for adenocarcinomas, lymphomas, and sarcomas still primarily reflects on the time of delay in diagnosis and awaits an improved understanding of the pathobiology of these malignant lesions.

Gastroduodenal polyps in familial adenomatous polyposis.

A retrospective review of the medical records of 30 patients with familial adenomatous polyposis who underwent oesophagogastroduodenoscopy was performed to evaluate the spectrum of gastroduodenal polyps. Twenty-five patients (83%) had gastroduodenal polyps. Eighteen patients (60%) had gastric polyps and 21 patients (70%) had duodenal polyps. Five patients (17%) had gastric and 20 patients (67%) had duodenal adenomatous polyps. Three patients (10%) died from an upper gastrointestinal tract adenocarcinoma. Three of nine patients with periampullary adenomas had a normal-appearing papilla of Vater. Since gastroduodenal polyps are common in familial adenomatous polyposis, oesophagogastroduodenoscopy should be performed at the time of diagnosis. Biopsy of polyps as well as biopsy of a normal-appearing papilla of Vater should be performed. Due to their malignant potential, if identified, gastroduodenal adenomatous polyps should be destroyed.

Fast-growing cancer of the colon and rectum.

Recently, the existence of a flat, colorectal cancer has been proposed. This cancer is completely different in appearance from ordinary polyp cancer and is believed to invade deeply into the submucosa, even in its early stages. Its characteristics are quite different from cancers that follow the adenoma-cancer sequence, and it requires a greater search to detect. The authors observed four cases of fast-growing cancer that were relatively flat in appearance, contained no adenomatous component, and were invasive, even in their early stages.

Relationship of polyps to cancer of the large intestine.

BACKGROUND: Pathologic and epidemiologic evidence indicates that patients with sporadic (nonfamilial) adenomatous polyps of the large intestine are at high risk of developing colorectal cancer. PURPOSE: Our primary goal in this study was to evaluate the colorectal cancer mortality rate among persons who have had a histologically confirmed benign colorectal polyp. METHODS: We used the retrospective follow-up method to evaluate the risk of death from colorectal cancer in 2872 Rhode Island men and women who were 24 through 79 years of age at the time of surgery for benign polyps in the years 1959 through 1975. RESULTS: Among 2872 subjects, the mortality from colorectal cancer, standardized for age, sex, and calendar time, was estimated as 1.74 (95% confidence interval = 1.44-2.09) times the rate in the general population of Rhode Island residents. Colorectal cancer mortality was higher in the first 5 years of follow-up than it was later. There was little relationship between the numbers of polyps and colorectal cancer mortality, and there was only a modest association between the size of polyps and mortality. Colorectal cancer mortality was more than twice as high in subjects whose polyps were proximal to the sigmoid compared with those with sigmoid or rectal polyps. The observed elevation of risk of colorectal cancer was almost entirely confined to subjects who had an adenomatous polyp. The risk increased strongly with the percentage of villous features in the polyp and was about twice as high in subjects with villous adenoma than in those with other adenomatous polyps. CONCLUSIONS: Our results support the suspected relationship between colorectal polyps and cancer incidence and extend the association to colorectal cancer mortality.