Up-regulation of α-catenin is associated with increased lymph node involvement in colorectal cancer

AIM： To investigate the changing pattern of α-catenin expression and its relationship to clinical and pathological features of colorectal cancer （CRC） patients. METHODS： Archival tumor samples were analyzed using immunohistochemistry （IHC） for α-catenin in 91 patients with advanced CRC. RESULTS： The values of α-catenin membrane index （MI） and cytoplasmic index （CI） were significantly related to the depth of tumor invasion （P = 0.027, P = 0.020, respectively）, high indices being associated with increased depth of the primary tumor invasion （T3 and T4）. Similarly, patients with high α-catenin expression had a significantly increased risk of lymph node metastasis （32/39 vs 37/52 for MI and 37/45 vs 32/46 for CI） （P = 0.001, P = 0.0001, respectively, for LNN status）. An altered expression （i.e., cytoplasmic pattern） was also related （P = 0.047） to the response to chemotherapy; patients with low CI were more responsive （CR： 7/46） than patients with high CI values （CR： 0/45）. There was a marginal effect on survival in patients time with metastases （SWM） （P = 0.087）; patients with low CI showing slightly longer SWM, but no such effect on disease free survival （DFS） or disease specific survival （DSS）. As to co-expression with another member of the adhesion complex （β-catenin）, high α-catenin/β-catenin MI index was of marginal significance in predicting longer DSS （P = 0.063, log-rank）. CONCLUSION： The results implicate that high α-catenin expression is intimately involved in the key regulatory mechanisms leading to invasive phenotype, lymph node metastases, and progressive disease in CRC.     

Sentinel lymph node concept in gastric cancer with solitary lymph node metastasis

AIM:To study the localization of the solitary metastases inrelation to the primary gastric cancers and the feasibilityof sentinel lymph node(SLN)concept in gastric cancer.METHODS:Eighty-six patients with gastric cancer,whohad only one lymph node involved,were regardedretrospectively as patients with a possible sentinel nodemetastasis,and the distribution of these nodes wereassessed.Thirteen cases with jumping metastases werefurther studied and followed up.RESULTS:The single nodal metastasis was found in thenearest perigastric nodal area in 65.1%(56/86)of thecases and in 19.8%(17/86)of the cases in a fairly remoteperigastric area.Out of 19 middle-third gastric cancers,3 tumors at the lesser or greater curvatures had transversemetastases.There were also 15.1%(13/86)of patientswith a jumping metastasis to N2-N3 nodes without N1involved.Among them,the depth of invasion was mucosal(M)in 1 patient,submucosal(SM)in 2,proper-muscular(MP)in 4,subserosal(SS)in 5,and serosa-exposed(SE)in 1.Five of these patients died of gastric cancerrecurrence at the time of this report within 3 years aftersurgery.CONCLUSION:These results suggest that nodalmetastases occur in a random and multidirectional processin gastric cancer and that not every first metastatic node islocated in the perigastric region near the primary tumor.The rate of“jumping metastasis”in gastric cancer is muchhigher than expected,which suggests that the blindexamination of the nodal area close to the primary tumorcan not be a reliable method to detect the SLN and that aextended lymph node dissection(ELND)should beperformed if the preoperative examination indicatessubmucosal invasion.     

Cetuximab after bevacizumab in metastatic colorectal cancer: Is it the best sequence?

Background

Chemotherapy combinations and addition of cetuximab or bevacizumab to chemotherapy have been shown to improve overall survival of metastatic colorectal cancer (CRC) patients. However, the efficacy of cetuximab when administered after bevacizumab failure is still unknown.

Methods

Fifty-eight consecutive patients diagnosed with advanced colorectal cancer between treated with cetuximab following irinotecan failure were included in our analysis. A multivariate Cox model analysis was performed to estimate the effect of previous bevacizumab regimen on survival.

Results

Thirteen (22.4%) were pre-treated with anti-VEGF agents. None of them responded to cetuximab, and this subgroup presented a significantly decreased disease-specific survival as compared to treatment-naïve patients (9.1 months vs. 4.9 months; p = 0.026). This difference remained statistically significant in a multivariate Cox model after adjusting for age, sex, performance status (PS), and K-RAS status (RR = 2.2; 95% CI: 1.1–4.5, p = 0.03).

Conclusion

These study results suggest that a previous anti-VEGF therapy decrease cetuximab efficiency.     

What is the prognostic significance of metastatic lymph nodes in GIST?

BACKGROUND/AIMS: So many variables have been identified as prognostic factors influencing survival after curative resection in gastrointestinal stromal tumors (GIST), but the role of lymph node metastasis remains uncertain. METHODOLOGY: Twenty-nine patients with c-Kit positive gastric GIST who underwent surgical resection at the Brazilian National Cancer Institute between 1983 and 2004 were reviewed retrospectively. The prognostic significance of lymph node metastasis was investigated. The endpoints were overall survival and disease free survival. RESULTS: The median follow-up was 35 months. The 5-years estimate survival rate was 53%. Three patients presented lymph node metastasis and developed recurrence disease. Univariate analysis for overall survival identified the size >13.5cm (p = 0.01) and recurrence (p = 0.03) as prognostic factors. Size > 13.5cm and recurrence were independent factors (p = 0.01 and p = 0.03, respectively) in the multivariate analysis. Univariate analysis for disease free survival identified the size > 13.5cm (p = 0.04) and the grade (p = 0.04) as prognostic factors but, only the size > 13.5cm was an independent factor in the multivariate analysis. Lymph node metastasis had no prognostic significance for overall and disease free survival (p = 0.65 and p = 0.57, respectively). CONCLUSIONS: GIST lymph node metastasis was not related to poor survival in this study, but more studies are needed to identify the real incidence and the proper role of the GIST metastatic nodal disease.     

5-fluorouracil-interferon-α 2b adjuvant treatment of Dukes C colorectal cancer

PURPOSE: To determine whether interferon-α _2b can improve results of 5-fluorouracil adjuvant treatment of Dukes C colorectal cancer patients, we compared the outcome of patients receiving a fluorouracil-interferon combination to that of historic controls treated with fluorouracil alone. METHODS: Fifty-seven Dukes C colorectal cancer patients were given 5-fluorouracil-interferon-α in2b adjuvant treatment from October 1986 to September 1990. The results were compared with those obtained in 51 consecutive patients treated at the same institutions with 5-fluorouracil (5-FU) alone (used at the same doses and schedule) between 1983 and 1986. The main prognostic variables were similar in the two groups. RESULTS: No life-threatening toxicity occurred in either group. The addition of interferon (IFN) slighlty impaired tolerance to the treatment; however, the dose of IFN had to be reduced only in five patients and discontinued in one patient. Grade 3 and 4 myelotoxicity was rare and not substantially different in the two groups. Interferon-related side effects (fever, flu-like syndrome, malaise,etc.)were frequent, but, in general, mild or moderate. At the time of this analysis (July 1992), median followup was 49 (range, 20–70) months in the group of patients treated with 5-FU + IFN, and 86 (range, 68–103) months in the group receiving 5-FU alone. There were 17 recurrences and 15 cancer-related deaths among patients receiving combined treatment, and 27 deaths in the group treated with 5-FU alone. Both five-year relapse-free survival (65 percent vs.47 percent; P=0.043) and causespecific survival (64 percent vs.46 percent; P=0.038) were significantly better in the patients receiving combined treatment. After correction for the influence of prognostic pretreatment variables, 5-FU + IFN again afforded a significant advantage in terms of both relapse-free (P<0.01) and overall survival (P<0.001). CONCLUSION: 5-FU-IFN-α _2b treatment seems to improve the prognosis in Dukes C colorectal cancer patients.     

Sentinel lymph node navigation surgery for gastric cancer: Does it really benefit the patient?

Sentinel lymph node(SLN) navigation surgery is accepted as a standard treatment procedure for malignant melanoma and breast cancer. However, the benefit of reduced lymphadenectomy based on SLN examination remains unclear in cases of gastric cancer. Here, we review previous studies to determine whether SLN navigation surgery is beneficial for gastric cancer patients. Recently, a large-scale prospective study from the Japanese Society of Sentinel Node Navigation Surgery reported that the endoscopic dual tracer method, using a dye and radioisotope for SLN biopsy, was safe and effective when applied to cases of superficial and relatively small gastric cancers. SLN mapping with SLN basin dissection was preferred for early gastric cancer since it is minimally invasive. However, previous studies reported that limited gastrectomy and lymphadenectomy may not improve the patient's postoperative quality of life(QOL). As a result, the benefit of SLN navigation surgery for gastric cancer patients, in terms of their QOL, is limited. Thus, endoscopic and laparoscopic limited gastrectomy combined with SLN navigation surgery has the potential to become the standard minimally invasive surgery in early gastric cancer.     

Thymidylate synthase and cyclin d1 protein expression in lymph node negative colorectal cancer: role as prognostic factors?

Background/Aims: Thymidylate synthase (TS) is an enzyme for DNA-synthesis and the target for 5-fluorouracil whereas cyclin-D1 plays a critical role in the progression of cells through the G1 phase of the cell-cycle. There is evidence that expression of these markers may predict the outcome of patients with colorectal cancers. The aim of this study was to examine the prognostic value of TS and cyclin D1 protein expression in patients with node negative colorectal cancers. Methodology: TS and cyclin D1 protein expression from 140 patients with UICC stage I and II colorectal cancer was analyzed by immunhistochemistry in paraffin-embedded primary tumour specimens. Results: The 1-, 5- and 10-year overall-survival rates were 96%, 86% and 71%, respectively. Tumour stage and recurrence were associated with overall-survival. Low- and high TS immunoreactivity was present in 68 (48%) and 72 (52%) of cancers, respectively. Low- and high cyclin D1 immunoreactivity was present in 98 (70%) and 42 (30%) of the cancers, respectively. Patients (n=72) with high TS expressing tumours had a worse overall-survival than patients (n=68) with low TS expressing colorectal cancers (p=0.011). No difference in overall-survival was seen between patients with high and low cyclin D1 expressing cancers. Conclusions: TS may be helpful as a prognostic marker in lymph node negative colorectal cancer.     

Delivery of cancer screening: how important is the preventive health examination?

BACKGROUND: Patients and physicians strongly endorse the importance of preventive or periodic health examinations (PHEs). However, the extent to which PHEs contribute to the delivery of cancer screening is uncertain. METHODS: In a retrospective cohort study, we determined the association between receipt of a PHE and cancer testing in a population-based sample of enrollees in a Washington State health plan who were aged 52 to 78 years and eligible for colorectal, breast, or prostate cancer screening in 2002-2003 (N = 64 288). Outcomes included completion of any colorectal cancer testing (fecal occult blood testing, sigmoidoscopy, colonoscopy, or barium enema), screening mammography, and prostate-specific antigen testing. RESULTS: More than half (52.4%) of the enrollees received a PHE during the study period. After adjusting for demographics, comorbidity, number of outpatient visits, and historical preventive service use before January 1, 2002, receipt of a PHE was significantly associated with completion of colorectal cancer testing (incidence difference, 40.4% [95% confidence interval (CI), 39.4%-41.3%]; relative incidence, 3.47 [95% CI, 3.34-3.59]), screening mammography [incidence difference, 14.2% [95% CI, 12.7%-15.7%]; relative incidence, 1.23 [95% CI, 1.20-1.25]), and prostate-specific antigen testing (incidence difference, 39.4% [95% CI, 38.3%-40.5%]; relative incidence, 3.06 [95% CI, 2.95-3.18]). CONCLUSIONS: Among managed care enrollees eligible for cancer screening, PHE receipt is associated with completion of colorectal, breast, and prostate cancer testing. In similar populations, the PHE may serve as a clinically important forum for the promotion of evidence-based colorectal cancer and breast cancer screening and of screening with relatively less empirical support, such as prostate cancer screening.     

Open versus laparoscopic portal lymphadenectomy in gallbladder cancer: is there a difference in lymph node yield?

Background

Gallbladder cancer (GBC) is the most common biliary tract malignancy. Because it commonly metastasizes via lymphatics, portal lymphadenectomy should be included in oncologic resections. This study aimed to compare the oncologic equivalence of the laparoscopic versus open technique by evaluating lymph node (LN) yield.

Lateral lymph node dissection for low rectal cancer: Is it necessary?

Rectal cancer constitutes a major public health issue.Total mesorectal excision has remained the gold standard treatment for mid and low rectal tumors since its introduction in the late 1980s.Removal of all lymph nodes located in the mesorectum has indeed improved pathological and oncological outcomes.However,when cancer spreads to the lateral lymph nodes(located along the iliac and obturator arteries)Western and Japanese practices differ.Where the Western guidelines consider this condition as an advanced form of the disease and use neoadjuvant radiochemotherapy liberally,the Japanese guidelines define it as a local disease and proceed to lateral lymph node dissection with or without neoadjuvant treatment.Herein,we review the current literature regarding both therapeutic strategies,with the aim of contributing to potential improvements in treatment and outcome for patients with low and mid rectal cancer.     

Oligometastatic colorectal cancer: is single-site bony colorectal metastasis a treatable condition?

Introduction

A potentially resectable bony metastasis in the context of oligometastatic colorectal cancer is uncommon. Bony metastases are usually considered a late event with poor prognosis and generally associated with liver and/or lung metastases.

Index case

A previously healthy 33-year-old gentleman, with no family history of colorectal cancer, presented with rectal bleeding and at colonoscopy had a biopsy-proven adenocarcinoma of the rectum, 7 cm from the anal verge. Imaging also showed an isolated bone metastasis in the left ischial tuberosity. Following recovery from an anterior resection and a segment 5 metastasectomy, he underwent resection of the bony metastasis with a left type 3 internal hemipelvectomy. Three years from the bony resection, there is no evidence of recurrence on imaging.

Discussion

Osseous metastases are usually treated with palliative intent with bisphosphonates or external radiation, with surgical fixation of pathological fractures in some cases. Median survival after diagnosis of bone metastases is less than 10 months. Surgery is perhaps the only way of potentially achieving cure in patients with single-site bony metastases from colorectal cancer. Reports of such surgery in the literature are however very scant.

Conclusion

Our case is unusual and ongoing follow up is required. However, current disease-free status at conventional and functional imaging is encouraging. A multidisciplinary and indeed multicentre approach may be needed, and oligometastatic disease, even to a bone, may be amenable to curative surgical intervention in highly selected cases.

     

Simultaneous surgery for primary colorectal cancer and metastatic lesions?

Approximately 20-25% of patients with colorectal cancer present with liver metastases at the time of diagnosis. Traditionally, resection of the primary tumor has been advocated in order to prevent complications of the primary tumor colorectal cancer in patients with synchronous liver metastases. The published data concerning long-term prognosis in this group of patients are discordant. Although some of the reports show survival benefits from resection of the primary tumor, these studies are retrospective with small number of patients and using single drug chemotherapy. For patients with resectable liver metastases, new studies indicate that progression-free survival is best in patients receiving perioperative chemotherapy. In patients with synchronous nonresectable liver metastases and colorectal cancer, there is no published prospective randomized study comparing initial surgery of the primary tumor with neoadjuvant chemotherapy. However, recent publications show that in patients receiving chemotherapy based on oxaliplatin or irinotecan combined with targeted treatments, the complications associated with the primary tumor are less than 10%. The conclusion should be that today prophylactic surgery of asymptomatic primary colorectal cancer in patients with liver metastases cannot be recommended.     

Screening for colorectal cancer: What is the impact on the determinants of outcome?

Colorectal cancer screening has been introduced across the UK following several large randomised control trials and a Cochrane review that have shown a reduction in cancer specific mortality with population based Faecal Occult Blood testing. This has been attributed to the detection of more early stage disease. It is well known that in addition to stage at presentation there are a variety of other key factors that determine a patient's outcome following a diagnosis of colorectal cancer. For example there are tumour-related factors, such the presence of venous invasion and tumour necrosis, and also host-related factors, both in terms of demographic profile and an elevated circulating host inflammatory response that have been shown to be predictive of a poorer outcome. The present review summarises both the background behind the current screening programme and the observed and anticipated impact that colorectal cancer screening will have on the key determinants of outcome.