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1.

Purpose

The type of surgery or surgical approach for transverse colon cancer treatment largely depends on the tumor location or surgeon’s preference. However, extensive lymphadenectomy appears to improve the long-term outcomes of locally advanced colon cancers. This study was designed to compare the short- and long-term outcomes after surgery via the laparoscopic or open approach with radical D3 lymph node dissection in patients with stage II and III transverse colon cancer.

Methods

Patients were treated for stage II and III transverse colon cancer between May 2006 and December 2014. This retrospective study evaluated data collected prospectively at a tertiary teaching hospital. Radical D3 lymphadenectomy included the principal middle colic artery nodes.

Results

The study included 144 patients among whom 118 (81.9%) underwent laparoscopic surgery. Significantly more patients in the laparoscopic group underwent extended right hemicolectomy compared with the open group (90.7 vs. 65.4%, p = 0.005). The operative time was longer in the laparoscopic group (151.3 vs. 131.2 min, p = 0.021), and the open group had a greater estimated blood loss volume (160.8 vs. 289.3 ml, p = 0.011). Although the groups differed in terms of tumor size (5.8 vs 7.9 cm, p = 0.007), other pathologic outcomes did not differ. The groups did not differ regarding postoperative parameters or disease-free, overall, and cancer-specific survivals.

Conclusion

Despite differences in surgical methods and related factors, no long-term differences in outcomes were observed between laparoscopic and open approaches to radical D3 lymphadenectomy in patients with stage II and III transverse colon cancer.
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2.

Aim

This study is to analyze the clinicopathological differences between right- and left-sided colonic tumors and to evaluate the impact upon the patient’s survival.

Methods

In a period of 5 years (2004–2009), 453 patients were diagnosed with colorectal cancer.

Results

From a total of 453 patients diagnosed with colon cancer, 56.5% of them were men, while 43.5% of them were women. Right-sided colonic tumors were diagnosed in 54.53% of the patients compared to the 45.47% of patients with left-sided colonic tumors. The size of colonic tumors is statistically significant greater in right-sided colonic tumors compared to left ones (P < 0.001). Left-sided colon cancer patients identified to have a statistically significant better overall 5-year survival rate compared to right-sided ones (P < 0.001).

Conclusion

Based upon our results, there is a different biological profile between right- and left-sided colonic tumors.
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3.

Background

This study aimed to investigate the prognostic factors of patients with stage IIA (T3N0M0) colon cancer in terms of macroscopic serosal invasion and small tumor size.

Methods

We enrolled 375 stage IIA colon cancer patients who underwent curative resection between January 2004 and December 2011. Macroscopic serosal invasion was defined as tumor nodules or colloid changes protruding the surface of the serosa. The clinicopathologic characteristics were analyzed to identify independent prognostic factors.

Results

The median follow-up was 47 months (range, 1–90 months). On multivariate survival analysis, macroscopic serosal invasion (adjusted hazard ratio [HR]?=?4.750; p?=?0.013), tumor size <?5 cm (adjusted HR?=?3.112, p?=?0.009), perineural invasion (adjusted HR?=?3.528; p?=?0.002), <?12 retrieved lymph nodes (adjusted HR?=?4.257; p?=?0.002), and localized perforation (adjusted HR?=?7.666; p?=?0.008) were independent risk factors for recurrence.

Conclusion

We found novel prognostic factors of stage IIA colon cancer, including macroscopic serosal invasion and small tumor size (<?5 cm). Further studies are needed to evaluate the benefit of adjuvant chemotherapy in patients with these prognostic factors.
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4.

Background

Oral administration of lysophosphatidic acid (LPA) was shown to attenuate gastric ulceration in rats and mice but aggravate intestinal tumorigenesis in mice.

Aims

The present study examined whether dietary LPA induces or prevents development of colorectal tumor in rats.

Methods

Kyoto Apc Delta rats fed high-fat diet with or without an LPA-rich soybean phospholipid mixture (LSP, 0.1 or 1%) were treated with azoxymethane and dextran sodium sulfate to induce colorectal tumorigenesis. Rats were killed 15 weeks after azoxymethane treatment, and size, total number, location, and severity of colorectal tumors were assessed. Expression of mRNA of LPA receptors in rat colon tissue was assayed.

Results

Rats fed the diet supplemented with 1% LSP had a higher number of tumors 2–4 mm long compared than those with or without 0.1% LSP. The mean distance of tumors >4 mm long from the anus was significantly higher than those of tumors <2 and 2–4 mm long in rats fed 1% LSP-supplemented diet. Supplementation of the diet with 0.1% LSP decreased mRNA expression of LPA5 in colon tumors of rats.

Conclusions

Dietary supplementation of LPA-rich phospholipids dose-dependently augmented colorectal tumorigenesis. Decreased expression of LPA5 in colon tumors may be relevant to augmented tumorigenesis.
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5.

Purpose

To investigate whether radiotherapy for prostate cancer increases the risk of therapy-related rectal cancer and colon cancer.

Methods

A systematic literature search was carried out using the Medline (PubMed), EMBASE, and the Cochrane Library to identify studies examining the association between radiotherapy for prostate cancer and secondary colorectal cancer (rectal cancer and colon cancer) published before March 19, 2018. The risk of second colorectal cancer after radiotherapy was summarized using unadjusted odds ratio (OR) and adjusted hazard ratio (HR) with their 95% confidence interval (CI). Subgroup and sensitivity analyses were conducted to detect potential bias and heterogeneity.

Results

After study selection, 16 reports were retrieved for analysis. When patients received radiotherapy compared with those unexposed to radiation, there was an increased risk of the rectal cancer (OR 1.37, 95%CI 1.01 to 1.85), but not colon cancer. According to adjusted HR, there was an increased risk of the rectal cancer (HR 1.64, 95%CI 1.39 to 1.94), and colon cancer (HR 1.33, 95%CI 1.02 to 1.76). The OR for rectal cancer showed an increased risk with longer latent period (5 years lag time versus 10 years lag time, OR: 1.56 versus 2.22). Brachytherapy had no association with second cancer across all analyses.

Conclusions

Radiotherapy was associated with an increased risk of subsequent rectal cancer compared with patients unexposed to radiation. Colon may be free from the damage of radiation. Brachytherapy had no association with second rectal cancer or colon cancer.
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6.

Introduction

In acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon.

Materials and Methods

We will review here the evidence available regarding the characteristic thyroid and colon complications in acromegaly.

Results

This review summarizes the published data observing noncancerous structural abnormalities (thyroid nodules, colonic polyps) and thyroid and colon cancer in patients diagnosed with acromegaly.

Conclusion

Thyroid micro-carcinomas are probably over-diagnosed among acromegalic patients. In regard to colon cancer, there is no sufficient data to suggest that colon cancer risk is higher in acromegaly compared to the general population.
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7.

Puprpose

Benign polyps that are technically challenging and unsafe to remove via polypectomy are known as complex polyps. Concerns regarding safety and completeness of resection dictate they undergo advanced endoscopic techniques, such as endoscopic mucosal resection or surgery. We provide a comprehensive overview of complex polyps and current treatment options.

Methods

A review of the English literature was conducted to identifyarticles describing the management of complex polyps of the colon and rectum.

Results

Endoscopic mucosal resection is the standard of care for the majority of complex polyps. Only polyps that fail endoscopic mucosal resection or are highly suspicious of invasive cancer but which cannot be removed endoscopically warrant surgery.

Conclusion

Several factors influence the treatment of a complex polyp; therefore, there cannot be a “one-size-fitsall” approach. Treatment should be tailored to the lesion’s characteristics, the risk of adverse events, and the resources available to the treating physician.
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8.

Background

Screening for colon cancer (CC) may not only reduce its occurrence but has also the potential to reduce the overall mortality. So far, there has been little evidence that detection of colon cancer by screening colonoscopy results in different survival rates compared to symptomatic patients.

Patients and methods

Clinical, histological, diagnostic, and survival data of 1016 consecutive patients with CC from a prospectively expanded single-institutional database were analyzed for diagnostic, treatment, and prognostic factors. Findings were then stratified according to detection by screening colonoscopy vs. patients who became symptomatic prior to further diagnostic work-up.

Results

7.1 % of all patients were identified by screening colonoscopy for colon cancer. Screened patients were younger (68.2 vs. 64.8 years), had smaller T stage (p?=?0.032), lower tumor stage (p?=?0.009), and a tendency to less lymph node metastasis. Overall survival was superior in screened patients, and stage-specific survival showed a tendency to improved survival, which was not statistically significant. Furthermore, a higher percentage of screened patients underwent adjuvant chemotherapy (84.6 vs. 55.0 %, p?=?0.032).

Conclusion

Survival outcome and enrollment in a multimodal treatment was higher in screening-detected patients compared to patients diagnosed after the onset of clinical symptoms. Besides a potential occurrence of lead time bias, these findings strongly support the need for continued improvement of screening programs and the recruitment of more patients for colorectal cancer screening.
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9.

Purpose

The relationship between emergency colon cancer resection and long-term oncological outcomes is not well understood. Our objective was to characterize the impact of emergency resection for colon cancer on disease-free and overall patient survival.

Methods

Data on patients undergoing resection for colon cancer from 2006 to 2015 were collected from a prospectively maintained clinical and administrative database. The median follow-up time was 4.4 years. Cox proportional hazards models were used to estimate the hazard ratios for recurrence and death for patients treated with surgery for an emergent presentation. Differences in initiation of, and timeliness of, adjuvant chemotherapy between emergently and electively treated patients were also examined.

Results

Of the 1180 patients who underwent resection for stages I, II, or III colon cancer, 158 (13%) had emergent surgery. After adjustment for patient, tumor, and treatment characteristics, the HR for recurrence was 1.64 (95% CI 1.12–2.40) and for death was 1.47 (95% CI 1.10–1.97). After adjustment for tumor characteristics, patients who underwent emergency resection were similarly likely to receive adjuvant chemotherapy (OR 1.1; 95% CI 0.70–1.76). The time from surgery to initiation of adjuvant chemotherapy was also similar between the groups.

Conclusions

Emergency surgery for localized or regional colon cancer is associated with a greater risk of recurrence and death. This association does not appear to be due to differences in adjuvant treatment. A focus on screening and colon cancer awareness in order to reduce emergency presentations is warranted.
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10.

Aim

In this study, we present our patients with metachronous colorectal cancer.

Patients and methods

In the period between 1990 and 2009, 670 patients with colorectal cancer were treated.

Results

Metachronous cancer was developed in 4 (0.6%) patients. The time interval between index and metachronous cancer was 28 months to 22 years (mean 146 months).

Conclusion

Metachronous colorectal cancer is a potential risk that proves the necessity of postoperative colonoscopic control of all patients with colorectal cancer.
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11.

Purpose

Colon cancers in male and female patients are suggested to be oncologically different. The aim of this study is to elucidate the prognostic impact of lymph node dissection (LND) in male and female colon cancer patients.

Methods

A total of 5941 stage I-III colon cancer patients who were curatively operated on during the period from 1997 to 2007 were retrospectively studied. Cancer-specific survival (CSS) was individually compared between for male and female patients treated with D3, D2, and D1 LND. Background differences of the patients were matched using propensity scores.

Results

D3, D2, and D1 LND were performed in 3756 (63 %), 1707 (29 %), and 478 (8 %), respectively, and more extensive LND was indicated for younger patients and more advanced disease. D2 LND was significantly associated with decreased cancer-specific mortality compared to D1 LND in male patients (HR 0.54, 95 % CI 0.32–0.89, p?=?0.04), but not in female patients. D3 LND did not correlate to an improved prognosis compared to D2 LND both in male and female patients.

Conclusions

D2 LND was associated with an improved CSS in male, but not female colon cancer patients, compared to D1 LND. This suggested that colon cancer in male and female patients might be oncologically different, and that the prognostic impact of the extent of surgical intervention for colon cancer might therefore be different between sexes.
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12.

Purpose

Proximal and distal colon cancers differ in terms of epidemiology, clinical presentation, and pathologic features. The aim of our study was to evaluate the impact of right-sided (RC), transverse (TC), and left-sided (LC) colon cancer on morbidity rates and oncological outcomes.

Methods

A retrospective analysis of patients with resected colon cancer between 2004 and 2014 was conducted. Cox proportional hazard models were used to assess predictors of overall (OS), and disease-specific survival (DSS), as well as disease-free survival (DFS).

Results

A total of 1189 patients were included. RC patients (n?=?618) were older, predominantly women, and had a higher comorbidity rate. LC (n?=?454) was associated with symptomatic presentation and increased rates of laparoscopic surgery. Multivisceral resections were more frequently performed in TC tumors (n?=?117). This group was admitted 1 day longer and had a higher complication rate (RC 35.6% vs. TC 43.6% vs. LC 31.1%, P0.032). Although the incidence of abscess/leak was similar between the groups, the necessity of readmission and subsequent reoperation for a leak was significantly higher in LC patients. Pathology revealed more poorly differentiated tumors and microsatellite instability in RC. Kaplan-Meier curves demonstrated worse 5-year OS for right-sided tumors (RC 73.0%; TC 76.2%. LC 80.8%, P0.023). However, after adjustment, no differences were found in OS, DSS, and DFS between tumor location. Only pathological features were independently correlated with prognosis, as were baseline characteristics for OS.

Conclusion

Tumor location in colon cancer was not associated with survival or disease recurrence. Pathological differences beyond tumor stage were significantly more important.
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13.

Background

The aim of this study was to identify risk factors for lymph node positivity in T1 colon cancer and to carry out a surgical quality assurance audit.

Methods

The sample consisted of consecutive patients treated for early-stage colon lesions in 15 colorectal referral centres between 2011 and 2014. The study investigated 38 factors grouped into four categories: demographic information, preoperative data, indications for surgery and post-operative data. A univariate and multivariate logistic regression analysis was performed to analyze the significance of each factor both in terms of lymph node (LN) harvesting and LN metastases.

Results

Out of 507 patients enrolled, 394 patients were considered for analysis. Thirty-five (8.91%) patients had positive LN. Statistically significant differences related to total LN harvesting were found in relation to central vessel ligation and segmental resections. Cumulative distribution demonstrated that the rate of positive LN increased starting at 12 LN harvested and reached a plateau at 25 LN.

Conclusions

Some factors associated with an increase in detection of positive LN were identified. However, further studies are needed to identify more sensitive markers and avoid surgical overtreatment. There is a need to raise the minimum LN count and to use the LN count as an indicator of surgical quality.
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14.

Purpose

With an increasing demand for more accurate preoperative staging methods for colon cancer, we aimed to compare preoperative tumour (T)- and nodal (N)-stage in patients with left-sided colon cancer by endoscopic ultrasonography (EUS) and computed tomography (CT) with post-operative histology as gold standard.

Methods

A total of 44 patients were prospectively recruited at Herlev and Roskilde University Hospitals during November 2014–January 2016. Thirty-five patients were included in the final analysis and underwent EUS, CT and surgery within 2 weeks. Diagnostic values were evaluated for “low risk” (T1+T2+T3 with ≤5 mm extramural invasion) and “high risk” (T3 with >5 mm of extramural spread + T4) colonic cancer.

Results

Sensitivity and specificity in “low risk” colonic cancer evaluated with EUS was 0.90 [0.74;0.98] and 0.75 [0.19;0.99] and with CT 0.96 [0.80;0.99] and 0.25 [<0.01;0.81]. EUS and CT were poor in predicting N0 or N+ disease.

Conclusions

The sensitivity of EUS and CT were good and comparable regarding T-stage evaluation, while EUS had a significantly higher specificity in the evaluation of “low risk” tumours. The results obtained for “high risk” colonic cancer were difficult to evaluate due to small patient numbers. EUS could be considered as a supplement to CT scans in selecting patients for neoadjuvant therapies, or local transmural treatment, in the future.

Trial registration

NCT02324023
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15.

Purpose

Multidrug resistance (MDR) has been linked to sphingolipid metabolism and preclinical data ascribe glucosylceramide synthase (GCS) a major role for MDR especially in breast cancer cells but no profound data are available on the expression of this potential therapeutic target in clinical breast cancer specimens.

Methods

We analyzed microarray data of GCS expression in a large cohort of 1,681 breast tumors.

Results

Expression of GCS was associated with a positive estrogen receptor (ER) status, lower histological grading, low Ki67 levels and ErbB2 negativity (P < 0.001 for all). In univariate analysis there was a benefit for disease free survival for patients with tumors displaying low levels of GCS expression but this significance was lost in multivariate Cox regression.

Conclusions

Our results suggest ER positive tumors may be the most promising candidates for a potential therapeutic application of GCS inhibitors.
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16.
17.

Purpose

Para-aortic lymph node (PALN) metastasis from colorectal cancer is rare and often not suitable for surgery. However, in selected patients, radical resection may bring about longer survival. The aim of this study was to evaluate long-term outcomes of resection of left-sided colon or rectal cancer with simultaneous PALN metastasis.

Methods

The study included 2122 patients with left-sided colon or rectal cancer (30 patients with and 2092 patients without PALN metastasis) who underwent resection with curative intent between 2002 and 2013. Clinicopathological characteristics, long-term outcomes of resection, and factors related to poor postoperative survival in patients with PALN metastasis were investigated.

Results

Of a total of 2122 total patients, 16 of 50 patients (32.0%) with lymph node metastasis at the root of the inferior mesenteric artery had PALN metastasis. The 5-year overall survival rates for 18 patients who underwent R0 resection and 12 patients who did not were 29.1 and 10.4%, respectively (p = 0.017). Factors associated with poor postoperative survival among patients who underwent R0 resection were presence of conversion therapy, lack of adjuvant chemotherapy, carcinoembryonic antigen >20 ng/mL, and lateral lymph node metastasis in rectal cancer patients. The 5-year recurrence-free survival rate was 14.8%.

Conclusions

Although recurrence was frequent, R0 resection for left-sided colon or rectal cancer with PALN metastasis was associated with longer survival than R1/R2 resection. Furthermore, the 5-year overall survival rate in the R0 group was relatively favorable for stage IV. Therefore, R0 resection may prolong survival compared with chemotherapy alone in selected patients.
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18.

Background

Endoscopic polypectomy is widely used for colorectal polyps. However, for giant pedunculated colorectal polyps (≥3 cm), conventional techniques are so difficult with en bloc resection that patients had to be transferred to surgery. We had firstly reported our first experience with an insulated-tip knife to successfully remove a giant pedunculated polyp in the sigmoid colon. In this study, our aim was to explore safety and feasible of insulated-tip knife endoscopic polypectomy (IT-EP) for difficult pedunculated colorectal polyps.

Methods

A total of seven consecutive patients with giant pedunculated colorectal polyps (≥3 cm) were prospectively enrolled. IT-EP was conducted with the help of clips for all the seven patients, and data of them was recorded and analyzed.

Results

Of seven patients, five were men and two were women with a mean age 61 years (49–72 years). The mean diameter of polyp head and stalk was 36.4 ± 4.9 mm (30–42 mm) and 14.6 ± 3.6 mm (10–20 mm), respectively. All the polyps were successfully removed with IT-EP, with a mean operation time of 14.9 ± 3.5 min (11–20 min). No serious bleeding or perforation was experienced, and no surgery was needed. There was no recurrence or residual of polyps at a mean 8.1-month follow-up.

Conclusions

Insulated-tip knife endoscopic polypectomy is a safe and feasible alternative for difficult pedunculated colorectal polyps.
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19.

Introduction

Laparoscopy in T4 colon cancers is not widely advocated due to concerns regarding safety and oncologic efficacy. We conducted this study to compare the short- and long-term oncological outcomes between laparoscopic and open approaches in T4 colon cancers.

Methods

A retrospective analysis of all patients who underwent surgery for T4 colon cancer from 2008 to 2014 was performed. Margin positive rate, lymph node yield, local or distant recurrence and overall survival were analysed.

Results

A total of 59 patients received open surgery, whilst 93 underwent laparoscopic surgery, with a conversion rate of 8.6%.There was no difference in the various measured outcomes between the laparoscopic and open groups. The relative risks of positive margins and inadequate lymph node yield for staging were 0.95 (0.74–1.23, p = 0.692) and 1.01 (0.97–1.05, p = 0.710), respectively, for the laparoscopic group when compared to the open approach.Regarding long-term outcomes, the relative risk of local recurrence in the laparoscopic group was 0.99 (0.96–1.02, p = 0.477), whilst there were also no increased risks of developing distal recurrences at the liver (RR 1.19, 0.51–2.82, p = 0.684), lungs (RR 1.20, 0.50–2.87, p = 0.678) and peritoneum (RR 1.22, 0.51–2.95, p = 0.653) in the laparoscopic group.There was also no difference in the overall survival (RR 0.70, 0.42–1.16, p = 0.168). Patients were followed up for a median of 73.3 months (range 34.8–144.7).

Conclusion

Laparoscopic surgery does not compromise oncological outcomes in T4 colon cancers compared to the open approach. Because of its proven associated benefits, laparoscopy should be considered in selected T4 colon cancers.
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20.

Background

Vasculogenic mimicry (VM) is the formation of vascular channels by tumor cells or tumor cell-derived, trans-differentiated cells in highly aggressive, solid tumors. However, the disease features and prognostic value of VM for overall survival of cancer patients remain controversial.

Method

To systematically investigate the roles of VM in cancer progression and its prognostic values, we performed a meta-analysis based on 36 studies (33 eligible articles) including 3609 patients. The pooled hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) were used to assess the relationship between VM and overall survival in cancer patients.

Results

Vasculogenic mimicry was significantly associated with cancer differentiation, lymph node metastasis, distant metastasis, and TNM stage. The prognostic value of VM was significant in overall survival (HR 2.16; 95 % CI 1.98–2.38; P < 0.001). Analyses stratified by confounders, such as cancer type, ethnicity, VM detection methods, sample size, and Newcastle–Ottawa quality score, found similar significant results.

Conclusions

The presence of VM predicts poorer survival outcomes in cancer patients.
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