Multivariate Analysis of Predictive Factors for Early Postoperative Death After Colorectal Surgery in Patients with Colorectal Cancer and Synchronous Unresectable Liver Metastases

Purpose Surgery of the primary tumor in patients with colorectal cancer and unresectable synchronous liver metastases remains controversial. This study was designed to evaluate predictive preoperative factors of early postoperative death (<3 months) in such patients. Methods This study included 80 patients who underwent colorectal resection (n = 56) or diversion stoma (n = 24) for colorectal cancer with unresectable liver metastases. Twenty-two patients (28 percent) died during the first three months after surgery with two (2.5 percent) in-hospital postoperative deaths. Analysis of predictive preoperative factors for three-month postoperative death risk was performed. Results In univariate analysis, age older than 75 years (P = 0.01), American Society of Anesthesiologists grade > II (P = 0.009), symptomatic patient (P = 0.01), bowel obstruction (P = 0.03), aspartate aminotransferase serum level >50 (1.5 N) IU/L (P = 0.008), and alkaline phosphatase >200 (2 N) IU/L (P = 0.02) were prognostic risk factors for three-month death after surgery. In multivariate analysis, age older than 75 years (relative risk = 7.9; P = 0.04) and aspartate aminotransferase serum level >50 IU/L (relative risk = 8.3; P = 0.03) were independent risk factors. Conclusions In patients with colorectal cancer and synchronous unresectable liver metastases, the three-month mortality rate was high (28 percent). Thus, better knowledge of risk factors could help select patients who could possibly benefit from surgery. The study suggested that age older than 75 years and liver cytolysis (>1.5 N) are associated with an increased three-month postoperative death risk. In these patients, surgery should be avoided. Read at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, April 30 to May 5, 2005.     

Significance of Follow-up Total Colonoscopy after Resection for Colorectal Cancer

Abstract: This is a retrospective study of the results of total colonofiberscopy performed on 180 postoperative patients with colorectal cancer. We divided the patients into two groups: “Group A” that had no concurrent polyp and/or synchronous multiple carcinoma besides the main lesion at the time of surgery and “Group B” that had a concurrent polyp and/or synchronous multiple carcinoma besides the main lesion at the time of surgery, and compared them. Colorectal polyps were found in 77 patients (42.8%), recurrent cancers in 9 patients (5.0%). and metachronous cancers in 6 patients (3.3%). respectively. In Group A, no abnormality was found in 65.7% (69/ 105), which was significantly higher compared with 33.3% (25/75) of Group B (p< 0.0001). The detection ratio of polyps in Group B was significantly higher than that of Group A (61.3% versus 29.5%. p<0.0001). The number of detected polyps in Group B was also large. As for the time required to detect the polyps, no difference was found between the two groups. There was no certain tendency for the location in which the polyp developed, and polyps were found in any portion of the residual colon and rectum. The development of metachronous cancer was found in 3 patients (2.8%) in Group A and 3 patients (4.0%) in Group B, which indicated a higher ratio for Group B, but statistically no significant difference was confirmed. In the metachronous cancer group, more than half were in the early stage, and even with the advanced cancers, the diameter of the tumor was small. In all of them, a curative resection were performed, and they were found to be Dukes’A and B in which no spreading was found to the lymphnodes. From the above, we can conclude that a follow-up using total colonoscopy is useful, and that a postoperative follow-up total colonofiberscopy should be performed on postoperative patients with colorectal cancer within 6 months after surgery regardless of the presence of a concurrent polyp and/or synchronous multiple carcinoma besides the main lesion at the time of surgery. Also a follow-up schedule must be conducted once a year after the first follow-up using the endoscopic method. (Dig Endosc 1994; 6: 7–16)     

Follow-up Study of Early Colorectal Cancer After Endoscopic Resection

Abstract: This study was conducted to determine the significance of long-term follow-up observation of early colorectal cancer following endoscopic resection. The subjects included 100 patients who had undergone early colorectal cancer resection by endoscopic polypectomy with prior injection of the base (73 patients with mucosal carcinoma (m cancer), 24 Patients with submucosal carcinoma (sm cancer), and 3 patients with multiple early colorectal cancers. Posttherapeutic observation was carried out by endoscopy. The results were, briefly, as follows: 1) No cases of local recurrence or metastasis were observed during the follow-up observation period for up to a period of 14 years. 2) 3 cases (3%) of metachronous carcinoma were detected, 2 of these patients had early carcinoma and 1 had advanced carcinoma. The mean period which elapsed before the detection of metachronous cancers was 35.0 ± 15.3 months. 3) The incidence of adenoma during the follow-up period was 40%, the frequency of newly detected adenoma was relatively high among the patients with coexisting adenoma at the time of treatment for early carcinoma and among the elderly patients aged 60 years or over, 4) No cancer was detected after establishing a clean colon, and the incidence of adenoma in such cases was relatively low, i. e., 14.5%. The mean period of time which elapsed until the detection of the adenoma was 24.4 ± 18.0 months. The results of this study indicated that endoscopic examination is necessary and useful for surveillance of local recurrence or metachronous carcinoma as well as the detection of adenoma.     

Surveillance-Detected Hepatic Metastases From Colorectal Cancer Had a Survival Advantage in Seven-Year Follow-Up

PURPOSE Colorectal cancer is a common cause of cancer-related death. The liver is the most common site of distant metastases and the most amenable to potentially curative surgery. The aim of this study was to determine whether hepatic metastases detected by surveillance following colonic resection were associated with higher resectability rates and to determine whether there was any impact on survival rates.METHODS A retrospective study of 211 patients who presented to the liver unit between February 1990 and July 1996 with hepatic metastases following colonic resection for adenocarcinoma was performed. Patients were divided into two groups: Group A (n = 154), hepatic metastases diagnosed by carcinoembryonic antigen or by radiology; and Group B (n = 57), patients with symptomatic presentation.RESULTS Potentially curative operations were possible in 51.3 percent (79/154) of Group A patients and 28.1 percent (16/57) of Group B patients (P = 0.0043, chi-squared test). In Groups A and B, 24 percent (37/154) and 43.9 percent (25/57) of patients, respectively, were inoperable. The three-year and five-year survival rates after detection of liver metastases were 26.8 percent (41/153) in Group A and 12.5 percent (7/56) in Group B, and 5.9 percent (9/153) in Group A and 8.9 percent (5/56) in Group B, respectively. Log-rank analysis resulted in P = 0.05, Breslow test in P = 0.01.CONCLUSION Our study shows that patients with hepatic metastases from colorectal cancer detected by follow-up were significantly more likely to have a potentially curative operation. Our medium-term survival data show a statistically significant survival benefit in patients with surveillance-detected metastases.     

Risk of Dissemination With Biopsy of Colorectal Liver Metastases

PURPOSE: Liver surgeons usually recommend against biopsy of colorectal liver metastases because of the risk of local dissemination. To date, only case reports describing this problem have been published. This study is an attempt to quantify the risk of biopsy-related dissemination. METHODS: A multicenter, retrospective review was undertaken of cases of colorectal liver metastases presenting for surgery that had undergone a preoperative biopsy. RESULTS: Two hundred thirty-one cases of colorectal liver metastases presenting for surgery were identified. Forty-three cases had undergone a preoperative biopsy (18.6 percent). Seven patients had evidence of dissemination related to the biopsy, giving a risk of dissemination of 16 percent (95 percent confidence interval, 7–30 percent). The risk of dissemination was not related to the type of biopsy. Within the follow-up period (median, 21 months), 3 of the 7 cases with evidence of dissemination and 11 of the 35 without dissemination were alive without disease. Twenty-five percent of the 36 cases without dissemination were resected, whereas 6 of the 7 cases with dissemination were resected. CONCLUSIONS: There is a significant risk of local dissemination with biopsy of colorectal liver metastases. In this series this was independent of the type of biopsy. There was no demonstrated effect on resectability or survival, but numbers were small, and the median follow-up was short.     

Accuracy of Investigations for Asymptomatic Colorectal Liver Metastases

PURPOSE: The aim of this study was to prospectively assess the accuracy of the most promising imaging and tumor marker tests in liver metastasis diagnosis on follow-up of asymptomatic colorectal cancer patients during a median of 57 months after primary tumor resection. METHODS: One hundred patients, who were considered free of liver metastases after primary colorectal cancer resection and conventional follow-up, were screened for liver metastases by computerized tomography, magnetic resonance and ultrasound scans, ultrasound Doppler and isotope assessment of changes in hepatic arterial and portal venous flow, and serum estimation of carcinoembryonic antigen. Patients were followed up during a median of 41 months to identify those who developed liver metastases. RESULTS: The most sensitive technique was computerized tomography (sensitivity 0.67, specificity 0.91). Computerized tomography and magnetic resonance but not ultrasound were 100 percent accurate in differentiating liver metastases from other hepatic lesions. Techniques based on changes in hepatic arterial and portal venous flow had lower diagnostic accuracies (Doppler perfusion index, sensitivity 0.58, specificity 0.57; hepatic perfusion index, sensitivity 0.50, specificity 0.55), whereas ultrasound scanning identified only 43 percent (sensitivity 0.43, specificity 0.96) and serum carcinoembryonic antigen 33 percent (sensitivity 0.33, specificity 0.81) of patients with asymptomatic liver metastasis. Sensitivity could be improved by using tests in combination but this reduced specificity. CONCLUSIONS: Computerized tomography was the most sensitive test for asymptomatic colorectal liver metastases, but only 67 percent of affected patients were identified.     

Delayed and Synchronous Recurrence of Breast Cancer Metastases in Multiple Organs

The most common sites of breast cancer metastasis include the lymph nodes, bones, lungs, liver, and brain. Gastrointestinal tract metastasis is rarely seen, and hypopharyngeal metastasis is extremely rare. We herein report a case of late distant recurrence of breast cancer and synchronous metastasis to the hypopharynx, stomach, ileum, bones, and lymph nodes almost 24 years after surgery. To our knowledge, this is the first case of synchronous metastasis to the hypopharynx, gastrointestinal tract, and other organs, especially after a long interval following primary mastectomy.     

Endoscopic Features of Duodenal Metastases from Breast Cancer

Abstract: The endoscopic appearance of gastrointestinal metastasis from breast cancer is demonstrated in this report. A patient with breast cancer was found by panendoscope examination to have duodenal metastases. The endoscopic characteristic was that of multiple umbilicated submucosal tumors in the bulb and second portion of the duodenum. The imprint cytology of duodenal biopsy specimens, which revealed malignant cells identical to those found in the breast lump aspiration previously, supported the initial endoscopic diagnosis of metastatic breast cancer. The histology of these lesions subsequently revealed many tumor emboli in the mucosal and submucosal lymphatic channels. A laparotomy conducted to perform an intestinal bypass disclosed a large fixed metastatic tumor in the upper retroperitoneum with extension to the mesentery, the mesocolon of the transverse colon and the third portion of the duodenum. The findings at laparotomy and the histologic evidence of tumor emboli in the lymphatics of the mucosal and submucosal layers indicated a retrograde lymphatic spread of the tumor from the large retroperitoneal mass to the duodenal wall. A literature review in this report discusses the differential diagnosis from metastatic disease to second primary malignancy and benign disease of the gastrointestinal system.     

Timing of Resection for Synchronous Liver Metastases from Colorectal Cancer

Background  

This study aimed to compare the surgical outcome and long-term survival between simultaneous and delayed resection of liver metastases from colorectal cancer (LM), and to identify the factors influencing hepatic disease-free survival in patients with synchronous LM.     

Present Status of Early Colorectal Cancer in Japan

We examined and clinicopathologically analyzed 422 patients with early colorectal cancer that we encountered, and discussed the problems typical of early colorectal cancers in Japan. In Japan we define early colorectal cancer as consisting of intramucosal cancer and cancer with submucosal invasion. Because histopathologists subjectively diagnose patients with intramucosal cancer, their diagnoses for the same specimen often differ from each other. The only way to avoid such confusion caused by diagnostic differences and to reach a consensus on the diagnosis of intramucosal cancer is to make a diagnosis of intramucosal cancer only in those patients who clearly show the structural atypia and/or the cellular atypia, that are typical of cancer. No one will deny the importance of the depressed type early cancer, the number of cases of which have recently been increasing in Japan. However, it is also important to assert that endoscopically-discovered depressed neoplastic lesions are not always cancer. In the depressed neoplastic lesions discovered in our patients, the number of adenoma was almost three times that of cancer. Forty percent of the patients with depressed type early cancer also had an adenoma component. Therefore, at this moment we cannot conclude that early cancer with a depression is de-novo-genetic colorectal cancer. Eighty percent of early colorectal cancers are discovered to be the protruded type of early cancer. Twenty-six percent of early cancers with submucosal invasion, including early cancers with massively submucosal invasion, are 6 to 10 mm in diameter and 76% of these are protruded early cancers. These facts indicate that colorectal tumors, protruded or depressed, which are more than 6 to 10 mm in diameter should be endoscopically removed to prevent them from becoming advanced cancers.     

Early-Age-at-Onset Colorectal Cancer and Microsatellite Instability as Markers of Hereditary Nonpolyposis Colorectal Cancer

PURPOSE: Early-age-at-onset colorectal cancer and microsatellite instability are characteristic features of hereditary nonpolyposis colorectal cancer. Our aim was therefore to investigate whether these features might be useful markers in screening for hereditary nonpolyposis colorectal cancer and mismatch repair gene mutations. METHODS: From 1,132 consecutive patients who underwent surgery for colorectal cancer at our department between 1980 and 1999, we selected all patients 40 years of age or younger (study group, n = 59) and a subset of patients 40 years of age or older (control group, n = 60) who were matched for gender and pathologic TNM stage. Patients for whom a complete family cancer history or microsatellite status was unavailable were excluded from the study. Family cancer histories, retrieved from archival charts, were reassessed. Microsatellite status was investigated with the five microsatellites from the Bethesda recommended panel (BAT-26, BAT-25, D2S123, D5S346, and D17S250). On the basis of the number of altered microsatellites ( 2, 1, or 0), tumors were considered as having high or low instability or microsatellite stability, respectively. Mutation analysis for MLH1 and MSH2 genes was performed only in cases of high instability. DNA was investigated for mutations by single-strand conformational polymorphism and sequencing analysis. RESULTS: Data from 95 patients (study group: n = 37, 18 males, mean age 35 years; control group: n = 58, 29 males, mean age 62 years) were available for analysis. Four patients (study group, n = 3; control group, n = 1) fulfilled the Amsterdam II criteria for hereditary nonpolyposis colorectal cancer. Of the 37 study group tumors, 12 (32.4 percent) showed high-frequency microsatellite instability, and 25 had microsatellite stability, whereas among the 58 control group tumors, 4 (7 percent) showed high-frequency microsatellite instability, and 54 had microsatellite stability (P < 0.002). Mismatch repair gene mutation analysis was performed in 12 cases (study group, n = 7; control group, n = 5). We found four mutations (MSH2 119delG, MLH1 ex9 684insT, MSH2 Gln239Stop, and MLH1 del0.8 Kb) in the study group patients and none in the control group. Of four hereditary nonpolyposis colorectal cancer patients who underwent mismatch repair gene mutation analysis, one had a mutation. CONCLUSIONS: Early-age-at-onset colorectal cancer is significantly correlated with high-frequency microsatellite instability tumor status and is a useful criterion to identify hereditary nonpolyposis colorectal cancer patients. Moreover, when used in association with high-frequency microsatellite instability status, it is effective in selecting patients for mismatch repair gene mutation analysis.     

结直肠癌患者血液和组织中鸟氨酸脱羧酶活性和腐胺含量的测定

本文用改良分光光度法测定３１例经结肠镜及活检病理确诊的结直肠癌患者血液和组织中鸟氨酸脱羧酶（ＯＤＣ）活性和腐胺（ＰＵＴ）含量，并与２５例轻度结肠炎患者对照。结果显示结直肠癌患者血液和组织中ＯＤＣ活性，以及血液中ＰＵＴ含量均极显著地高于对照组，分别为４．２３±０．４０对２．４０±０．３０，Ｐ＜０．００１；１１．７５±１．３２对７．３６±０．９０μｇ／ｍｇ蛋白质，Ｐ＜０．００１；和８４．９７±６．１０对６１．３６±６．０１μｇ％，Ｐ＜０．０１。组织中ＰＵＴ含量两组间差异无显著性。这些结果表明结直肠癌患者ＯＤＣ活性增强，多胺合成增多。测定这些指标可能有助于结直肠癌的诊断。     

The Incidence,Distribution and Clinicopathology of Missed Colorectal Cancer After Diagnostic Colonoscopy

Background: Colonoscopy does miss some lesions that may be later diagnosed as post-colonoscopy colorectal cancers (PCCRCs). We evaluated the rate of PCCRCs in a cohort of our patients.Methods: The data of patients diagnosed with first primary colorectal cancers (CRCs) between July 2014 and June 2017 were analyzed. Colorectal cancers were considered to be missed if they occurred among patients who have had an index colonoscopy between 7 and 36 months prior to their diagnosis. The incidence of missed lesions and the distribution of such lesions in the large bowel are presented.Results: In the study, 399 of the total 541 patients whose CRCs were diagnosed by colonoscopy were included. The median age of the patients (213 males and 186 females) was 75.3 (32.4-82.1) years. Seven patients with diagnosis of primary CRCs had undergone index colonoscopy between 7 and 36 months prior to their diagnostic colonoscopy. Therefore, the PCCRC rate in this cohort was 1.8% (7/399 × 100). The mean time interval between the false negative colonoscopy (index colonoscopy) and diagnostic colonoscopy was 18.7 (9.1-34.9) months. Missed CRCs were located in the ascending (2), transverse (1), descending (1), and sigmoid colon (2) and in the rectum (1).Conclusion: Our PCCRC rate was 1.8%, which is lower than the usually reported rate.     

Expression of Hippo Pathway in Colorectal Cancer

Background/Aims:

Hippo pathway plays a crucial role in cell proliferation, apoptosis, and tumorigenesis. This study aimed to investigate the expression of Hippo pathway components in the progression and metastasis of colorectal cancer (CRC).

Materials and Methods:

Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the mRNA expression levels of MST1, LATS2, YAP, TAZ, TEAD1, CDX2, and OCT4, and western blot (WB) was used to examine the protein expression levels of MST1, YAP, TEAD1, and CDX2 in 30 specimens of human colorectal adenomas, 50 pairs of human CRC tissues, and adjacent nontumorous tissues from CRC patients. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as the housekeeping gene in qRT-PCR.

Results:

The mRNA expression levels of MST1 and LATS2 showed an increasing tendency from CRC to adjacent nontumorous tissues (P < 0.001). Conversely, the mRNA expression levels of YAP, TAZ, TEAD, and OCT4 showed a decreasing tendency from CRC to adjacent nontumorous tissues (P < 0.001). MST1 protein was downregulated and YAP and TEAD1 proteins were upregulated in CRC (all P < 0.001). The mRNA and protein expression levels of CDX2 in CRC were significantly lower than those in colorectal adenomas and adjacent nontumorous tissues (P < 0.001), but there was no significant difference between the latter two groups (qRT-PCR, P = 0.113; WB, P = 0.151). Furthermore, statistical analysis showed that the expression levels of Hippo signal pathway components were associated with tumor differentiation, lymph node metastasis, and TNM stage.

Conclusion:

Hippo pathway is suppressed in the progression from colorectal adenomas to CRC and is associated with CRC progression and metastasis. This study suggests the components of Hippo pathway might be prognostic indicators for CRC patients.     

A Systematic Review of Hepatic Artery Chemotherapy After Hepatic Resection of Colorectal Cancer Metastatic to the Liver

PURPOSE Colorectal cancer metastatic to the liver, when technically feasible, is resected with a moderate chance of cure. The most common site of failure after resection is in the remaining liver. To enhance survival, chemotherapy has been delivered directly to the liver postresection via the hepatic artery. This study was designed to assess the effect of posthepatic resection, hepatic artery chemotherapy on overall survival.METHODS Trials were sought in Medline, the Cochrane Controlled Trial Register, The Cochrane Hepatobiliary Group Trials Register, and through contact of trial authors and reference lists using key words: colorectal, cancer, hepatic metastases, hepatic artery, chemotherapy, and randomized. Trials were chosen in which patients having resection of colorectal cancer metastatic to the liver were randomized to hepatic artery chemotherapy or any alternative treatment. Survival data were obtained principally from abstraction from survival curves in published studies using the method of Parmar to calculate a study-specific, log-hazard ratio and then combined-effect, log-hazard ratio, as well as a combined Kaplan-Meier survival probability curve.RESULTS Overall survival at five years in the hepatic artery group was 45 percent and 40 percent in the control group. Forty-three individuals developed recurrent liver metastases in the hepatic artery chemotherapy group, and 97 developed liver recurrence in the control group. However, no significant advantage was found in the meta-analysis for hepatic artery chemotherapy measuring overall survival and calculating survival based on intention to treat (log-hazard ratio = 0.0848, favoring the control group; 95 percent confidence interval = ±0.2037). Adverse events related to hepatic artery therapy were common, including five therapy-related deaths.CONCLUSIONS Although recurrence in the remaining liver happened less frequently in the hepatic artery chemotherapy group, overall survival was not improved. The log-hazard ratio even favored the control group, although not significantly. This added intervention for the treatment of metastatic colorectal cancer cannot be recommended at this time.