Management of colorectal cancer in elderly patients over 80 years old

AIM: The incidence of colorectal cancer is increasing. Surgery and chemotherapy for elderly patients are also increasing. We evaluated the characteristics of elderly colorectal cancer to clarify issues related to surgical therapy for elderly patients. METHOD: We studied 67 patients (38 men, 29 women) over 80 years old on whom we operated for colorectal cancer from 1990 to 2004. We compared them with 130 patients aged from 70 to 74 who were operated on in the same period, examining clinicopathological factors, operative methods, preoperative morbidity, postoperative complications, chemotherapy and postoperative survival ratio. RESULTS: In the elderly patients aged over 80, the rate of Dukes' B was high, whereas the rate of Dukes' A was high in patients aged from 70 to 74. No significant differences were observed in operative methods for colon cancer but Hartmann's operation and transanal local excision were frequent for rectal cancer in patients aged over 80. The rate of lymph node dissection was low in patients aged over 80 with rectal cancer. A significant difference was observed in lymph node dissection of rectal cancer between patients aged over 80 and those aged from 70 to 74, but there was no significant difference in curative ratio. Preoperative morbidity were recognized in 76% of patients aged over 80. Postoperative complications occurred in 51% of patients aged over 80. There were many cases showing delirium, but no differences in other complications between patients aged over 80 and those aged from 70 to 74. There was no operative mortality in patients aged over 80. CONCLUSION: Even elderly patients can anticipate safe operations without postoperative complications or decreased quality of life, if the appropriate operative procedure is selected with regard to their general condition.     

Bladder cancer in patients over 80 years old

We studied 86 patients with bladder cancer who were 80 years old and over. All were studied at the time of their first presentation for treatment in our hospital. About 40% of then were somewhat limited in performing usual daily activities before the first treatment, and they could not come to the hospital by themselves. Tumors in patients were larger, of higher grade and more invasive than those in younger patients. Transurethral resection of the bladder tumor (TUR-Bt) was done in 94% of patients with a superficial tumor and in 56% of those an invasive tumor. The recurrence rates after TUR-Bt for superficial tumor were 48%, 64% and 89% in 1 year, 3 years and 5 years, respectively. Recurrence rates were significantly different in younger patients. Overall cancer related survival rates were 86%, 60%, and 56% in 1 year, 3 years and 5 years, respectively. The outcome were significantly worse in patients over 80 years old than in those under 79 years old. To improve the outcome of treatment for bladder cancer in patients over 80 years old, cooperation among doctors, patients and families was important.     

Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity

Pathway-specific therapy is the future of cancer management. The oncogenic phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in solid tumors; however, currently, no reliable test for PI3K pathway activation exists for human tumors. Taking advantage of the observation that loss of PTEN, the negative regulator of PI3K, results in robust activation of this pathway, we developed and validated a microarray gene expression signature for immunohistochemistry (IHC)-detectable PTEN loss in breast cancer (BC). The most significant signature gene was PTEN itself, indicating that PTEN mRNA levels are the primary determinant of PTEN protein levels in BC. Some PTEN IHC-positive BCs exhibited the signature of PTEN loss, which was associated to moderately reduced PTEN mRNA levels cooperating with specific types of PIK3CA mutations and/or amplification of HER2. This demonstrates that the signature is more sensitive than PTEN IHC for identifying tumors with pathway activation. In independent data sets of breast, prostate, and bladder carcinoma, prediction of pathway activity by the signature correlated significantly to poor patient outcome. Stathmin, encoded by the signature gene STMN1, was an accurate IHC marker of the signature and had prognostic significance in BC. Stathmin was also pathway-pharmacodynamic in vitro and in vivo. Thus, the signature or its components such as stathmin may be clinically useful tests for stratification of patients for anti-PI3K pathway therapy and monitoring therapeutic efficacy. This study indicates that aberrant PI3K pathway signaling is strongly associated with metastasis and poor survival across carcinoma types, highlighting the enormous potential impact on patient survival that pathway inhibition could achieve.     

80岁以上患者外科急腹症的诊治特点

目的分析≥80岁外科急腹症住院患者的诊治特点。方法将2002年1月1日至2009年12月31日外科急腹症入院治疗的5426例患者按年龄分为≥80岁组和〈80岁组。观察≥80岁急腹症患者人数、所占比例、病种分布、伴发疾病等特点;统计分析手术比率、治疗效果、病死率、住院时间和住院花费。结果我院8年来纳入患者5426例,≥80岁患者420例,数量和所占百分比总体呈逐年增加趋势。患者从症状发作到就诊时间差2h至21d不等。常伴发多种疾病,以呼吸和心血管系统疾病居多。≥80岁组与〈80岁组比较,急诊手术率下降（48．09％比64．19％,P〈0．01）,病死率增加（3．33％比1．38％,P〈0．01）,住院时间延长[（16．76±11．49）d比（14．50±16．08）d,P〈0．01）],人均住院花费增加[（23733．11±30571．75）元比（18530．83±29637．46）元,P〈0．01）]。结论根据t〉80岁患者的发病特点制定个体化诊治方案;在制定卫生经济学政策和医疗保险制度时,注意考虑年龄对住院患者病死率、住院时间和治疗费用的影响。     

70岁以上老年胃癌患者临床特点及预后

目的探讨70岁以上高龄胃癌患者的临床表现、诊治方法和预后特点。方法回顾性分析我院1997年～2010年间128例胃癌患者临床资料,比较两组患者(≥70岁,高龄组;<70岁,低龄组)的临床特点和预后。结果高龄组48例,占37.5%,与低龄组患者相比,其男性发病率(93.7%vs 76.2%)、心脏病发生率(70.8%vs 27.5%)、脑血管病发生率(20.8%vs 6.3%)、二重癌发生率(6.3%vs 1.3%)及无症状发病率(20.8%vs 11.2%)显著增高(P<0.001～0.035),但吸烟率(18.7%vs 37.5%)较低(P=0.025)。高龄组贲门胃底癌多见,占27.1%,中-高分化癌占31.2%,而低龄组胃窦癌占42.5%,多为低分化-未分化癌(80.0%);发病时两组TNM分期未见显著差异,但长期随访高龄组肿瘤远处转移发生率显著低于低龄组(8.3%vs 35.0%,P=0.0048)。两组共75.0%的患者接受手术治疗,两组根治性切除率相似(60.4%vs 61.25%,P=0.21);而接受化疗的高龄组患者显著低于低龄组(56.2%vs 85.0%,P<0.001),其中因不良反应终止化疗高龄组患者占10.4%,略高于低龄组(6.2%),但差异无统计学意义。高龄组患者中位生存时间(27.8个月)较低龄组患者(19.3个月)有延长趋势,但差异无统计学意义(P=0.062)。结论 70岁以上胃癌患者男性多见,多无症状起病或缺乏典型症状,贲门胃底癌多见,中-高分化癌比例超过70岁以下患者,较少发生远处转移。虽高龄患者有较高的心脑血管疾病合并率,但多数可耐受规范的根治性手术和术后化疗。积极治疗可有效延长老年患者的平均生存时间。     

The prognosis of dysphagia patients over 100 years old

Several reports have recently been published regarding dysphagia in very elderly patients, and centenarian dysphagia patients have become more common in Japan. The aim of this study was to assess the prognosis of dysphagia in very elderly patients. Participants were 24 centenarian dysphagia patients. For each patient, we collected information on age, care level, past medical history, and changes in oral intake according to the Functional Oral Intake Scale (FOIS). Patients were divided into two groups based on the mode of food intake at the time of transfer or discharge: the per oral-only group (the PO-only group, i.e., oral intake alone) and the tube feeding-dependent group (the TF-dependent group, i.e., combination of oral intake and tube feeding, or tube feeding alone). In both groups, the FOIS score decreased significantly from pre-hospitalization to the time of transfer or discharge (p = 0.006 for both). The FOIS score at initial assessment was higher in the PO-only group with the TF-dependent group (p = 0.0004). Furthermore, the frequency of a FOIS score of 4 at initial assessment was significantly higher in the PO-only group, and the frequency of a FOIS score of 1 was significantly higher in the TF-dependent group (p = 0.0006). These findings collectively suggest that oral intake can be recovered if the FOIS score is ≥4 at initial assessment, is difficult if the score is 1, and may be possible with a FOIS score of 2.     

Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients

AIM:To investigate the clinicopathologic characteristics and prognostic implications associated with loss of CDX2 expression in colorectal cancers(CRCs).METHODS:We immunohistochemically evaluated CDX2 expression in 713 CRCs and paired our findings to clinicopathologic and molecular characteristics of each individual.Endpoints included cytokeratin 7 and CK20 expression,microsatellite instability,Cp G island methylator phenotype,and KRAS and BRAF mutation statuses.Univariate and multivariate survival analysis was performed to reveal the prognostic value of CDX2 downregulation.RESULTS:CDX2 expression was lost in 42(5.9%) patients.Moreover,loss of CDX2 expression was associated with proximal location,infiltrative growth,advanced T,N,M and overall stage.On microscopic examination,loss of CDX2 expression was associated with poor differentiation,increased number of tumor-infiltrating lymphocytes,luminal serration and mucin production.Loss of CDX2 expression was also associated with increased CK7 expression,decreased CK20 expression,Cp G island methylator phenotype,microsatellite instability and BRAF mutation.In a univariate survival analysis,patients with loss of CDX2 expression showed worse overall survival(P < 0.001) and progression-free survival(P < 0.001).In a multivariate survival analysis,loss of CDX2 expression was an independent poor prognostic factor of overall survival [hazard ratio(HR) = 1.72,95%CI:1.04-2.85,P = 0.034] and progression-free survival(HR = 1.94,95%CI:1.22-3.07,P = 0.005).CONCLUSION:Loss of CDX2 expression is associated with aggressive clinical behavior and can be used as a prognostic marker in CRCs.     

Esophagectomy in patients aged over 80 years with esophageal cancer

BACKGROUND/AIMS: Esophagectomy for esophageal cancer is one of the most invasive surgical procedures. However, with the recent aging of the population, clinicians are increasingly encountering patients with advanced age (over 80 years) who require treatment for esophageal cancer. Patients in this age group tend to be regarded as at high risk in terms of surgical treatment. In the present study, the authors examined perioperative complications and clinical outcome in esophagectomy in patients aged over 80 years compared with those aged 70-79 and discuss the risk and appropriateness of esophagectomy in the older group. METHODOLOGY: Of patients with esophageal cancer at our institute, 25 were aged over 80 years, while 95 were aged 70-79 years. We statistically compared those who underwent esophagectomy; 8 in the older group and 62 in the younger group. The oldest patient was an 84-year-old man. Among the 8 older patients, 7 were male and 1 was female. All cases were histologically confirmed as squamous cell carcinoma and this series included 1 case in Stage 0, 3 in Stage I and 4 in Stage III. Total thoracic esophagectomy was performed in 5 patients, transhiatal blunt dissection in 2 and lower thoracic esophagectomy in 1. RESULTS: Rate of surgical treatment was significantly lower in the older group than in the younger group (32.0% vs. 65.3%, p < 0.001). No significant difference was observed in postoperative complications or mortality. Regarding clinical postoperative outcome in the older group, there were 5 deaths: 1 related to surgery, 2 to other causes (at 5 and 12 months), 2 to cancer (4 and 11 months). The remaining patients were alive at 31, 60, and 88 months. No significant difference was observed in overall or disease specific survival after surgery between the 2 groups. CONCLUSION: No statistically significant differences were apparent in morbidity, mortality or clinical outcome in the 2 groups. Since surgery seems to confer similar symptomatic improvements and survival in patients aged over 80 to those expected for patients aged 70-79, we believe that surgeons should not withhold esophagectomy in patients aged over 80 years because of advanced age alone.     

80岁以上老年高血压病的临床分析

目的探讨80岁以上老年高血压的降压治疗方法及安全性。方法回顾分析80岁以上老年高血压患者[男性55例,女性70例,平均年龄（83．72±3．84）岁]血压控制的临床资料。结果选用1种降压药占32％,2种以上占68％;用CCB占52％、8受体阻滞剂占55．2％、利尿剂占19．2％、ACEI占24％、ARB占46．4％。血压由（175．64±19．31）／（99．13±13．11）mmHg,降至（125．15±14．55）／（73．70±8．83）mmHg,治疗前、后比较差异有统计学意义（P〈0．01）,未见体位性低血压。结论老年人降压应个体化,平均血压降至125／74mmHg也安全。     

Poor prognosis of young patients with colorectal cancer: a retrospective study

Purpose

The present study aimed to explore the survival outcomes of patients with colorectal cancer (CRC) aged 35 years and younger.

Methods

This retrospective cohort study included a total of 995 patients with CRC treated between January 2003 and September 2011. The patients were assorted into the young (aged 18–35 years) and older (aged 36–75 years) groups. The clinical characteristics and survival outcomes of the patients in the young group were compared with those of the patients in the older group for evaluation.

Results

Compared with the older group, a significantly higher number of patients in the young group had right-sided colon cancer (30.9 vs. 19.6%, P = 0.026), high histologic grade tumor (14.7 vs. 6.4%, P = 0.021), and stage III disease (50.0 vs. 35.5%, P = 0.016). In stage III disease, compared with the older group, the patients in the young group had worse survival outcome in terms of 5-year overall survival (OS, P = 0.007), cancer-specific survival (CSS, P = 0.010), and disease-free survival (DFS, P = 0.039). Multivariate analysis revealed that age ≤35 years was an independent risk factor in terms of 5-year OS (hazard ratio [HR] = 1.68; 95% confidence interval [CI]: 1.12–2.54; P = 0.012), CSS (HR = 1.74; 95% CI: 1.15–2.65; P = 0.009), and DFS (HR = 1.58; 95% CI: 1.06–2.35; P = 0.024).

Conclusions

The young patients with CRC aged 35 years and younger had worse prognosis compared with older patients, especially for stage III disease.

     

Colorectal cancer in patients over 80 years of age

Between January 1, 1973, and December 31, 1986, 1,734 patients underwent colorectal resections for carcinoma. Patients were divided into two groups: Group I included 163 patients aged 80 years on first presentation; Group II comprised 1,571 patients aged <80 years. The total perioperative mortality rates for the elderly and young group were 15.3 percent and 5 percent, respectively (P <0.001). The surgical mortality rates after elective operations in Groups I and II were 7.4 and 4.5 percent, respectively, and were not statistically different. Emergency surgery was associated with a significantly higher incidence of perioperative deaths at any age (P <0.001). In the elderly group, most deaths (88 percent) resulted from complications of coexisting medical disorders or thromboembolic complications. The 5-year survival for the young and elderly group were 46.2 percent and 35 percent, respectively (P <0.05). However, excluding patients dying from nonmalignant disease, the 5-year survival rate did not differ significantly between the two groups of patients (49.5 percent vs. 41.2 percent).     

The BRAF mutation is associated with the prognosis in colorectal cancer

Background

Two members of the Ras/Raf signaling pathway, KRAS and B-raf, are suspected to be involved in the stepwise progression of colorectal cancer (CRC) tumorigenesis.

Objective

We compared the KRAS and BRAF mutation status of CRC patients with their clinicopathological characteristics and examined the effect of mutation status on survival rates.

Methods

DNA was extracted from 164 samples, and the mutation statuses of KRAS and BRAF were assessed using peptide PNA clamp real-time PCR method. The presences of mutation were compared with clinicopathological factors and 5-year survival rate.

Results

Among the 164 CRC cases, KRAS mutation as detected in 71 cases (43.3 %), respectively, with no relationship with clinicopathological factors of the patients. On Kaplan–Meier survival analysis, KRAS mutation was not significantly associated with survival (p = 0.971). BRAF mutation was detected in 26 cases (15.9 %) and not associated with clinicopathological factors of the patients. However, the 5-year survival rate of BRAF mutations was significantly decreased (p = 0.02).

Conclusions

The presence of KRAS mutation did not correlate with the various clinicopathological factors of CRC patients or the survival rate. However, the survival rate was reduced in BRAF-mutated CRC patients. Therefore, BRAF mutation could be an important prognostic factor in CRC patients.     

Sialyl Tn antigen expression is associated with the prognosis of patients with advanced colorectal cancer

BACKGROUND/AIMS: One of the main problems in multimodal cancer treatment is the lack of prognostic parameters for the individual patient. This study was conducted to clarify the prognostic factors in patients with advanced colorectal cancer. METHODOLOGY: We examined DNA ploidy, Ki-67-derived growth fraction and the expression of CA 19-9, Sialyl Tn (STN) and carcinoembryonic antigens (CEA), along with standard clinicopathological variables including age, sex, tumor location, tumor size, cell differentiation, depth of invasion, and lymph node metastasis in 78 patients with advanced colorectal carcinoma, who underwent curative surgical resection. In addition, we determined the prognostic significance of these parameters. RESULTS: Forty-six patients (59.0%) showed aneuploidy and 32 (41.0%) showed diploidy. The Ki-67 labeling index ranged from 13.9-40.3% with a mean of 24.9%. The index was not correlated with standard clinicopathological variables. There was no significant correlation between seropositive rates for CEA, CA 19-9, or STN and standard clinicopathological variables except for age. In tumor tissue, the positive rates for these antigens were 62.8% for CA 19-9, 67.1% for STN, and 96.2% for CEA. There was no significant correlation between positive rates and clinicopathological variables. The expression of STN in serum had the strongest association with survival, followed by lymph node metastasis and expression of STN in tissue. CONCLUSIONS: We conclude that not only lymph node metastasis but also STN expression are important prognostic factors in patients with advanced colorectal carcinoma who undergo curative surgical resection.     

Deficient DNA mismatch repair is associated with favorable prognosis in Thai patients with sporadic colorectal cancer

AIM:To determine the prognostic significance of deficient mismatch repair(d MMR) and BRAF V600 E in Thai sporadic colorectal cancer(CRC) patients.METHODS:We studied a total of 211 out of 405 specimens obtained from newly diagnosed CRC patients between October 1,2006 and December 31,2007 at Siriraj Hospital,Mahidol University.Formalinfixed paraffin-embedded blocks of CRC tissue samples w e re a n a l y ze d fo r d M M R b y d e t e c t i o n o f M M R protein expression loss by immunohistochemistry or microsatellite instability using polymerase chain reaction(PCR)-DHPLC.BRAF V600 E mutational analysis was performed in DNA extracted from the same archival tissues by two-round allele-specific PCR and analyzed by high sensitivity DHPLC.Associations between patient characteristics,MMR and BRAF status with diseasefree survival(DFS) and overall survival(OS) were determined by Kaplan-Meier survival plots and log-rank test together with Cox’s proportional hazard regression.RESULTS:d MMR and BRAF V600 E mutations were identified in 31 of 208(14.9%) and 23 of 211(10.9%) tumors,respectively.d MMR was more commonly found in patients with primary colon tumors rather than rectal cancer(20.4% vs 7.6%,P =0.01),but there was no difference in MMR status between the right-sided and left-sided colon tumors(20.8% vs 34.6%,P = 0.24).d MMR was associated with early-stage rather than metastatic disease(17.3% vs 0%,P = 0.015).No clinicopathological features such primary site or tumor differentiation were associated with the BRAF mutation.Six of 31(19.3%) samples with d MMR carried the BRAFmutation,while 17 of 177(9.6%) with proficient MMR(p MMR) harbored the mutation(P = 0.11).Notably,patients with d MMR tumors had significantly superior DFS(HR = 0.30,95%CI:0.15-0.77; P = 0.01) and OS(HR = 0.29,95%CI:0.10-0.84; P = 0.02) compared with patients with p MMR tumors.By contrast,the BRAF V600 E mutation had no prognostic impact on DFS and OS.CONCLUSION:The prevalence of d MMR and BRAF V600 E in Thai sporadic CRC patients was 15% and 11%,respectively.The d MMR phenotype was associated with a favorable outcome.     

大肠癌与抑癌基因相关性的研究现状

大肠癌是常见的高危害消化系恶性肿瘤,全球每年新发病例约为120万例.近年来,随着人们生活水平的提高,饮食习惯和结构的改变,我国大肠癌的发病率和死亡率增长迅速,而且,发病年龄明显提前,目前,我国大肠癌中位发病年龄为58岁,比欧美等国家提前12-18年.大肠癌的发生是一个多阶段多步骤的、涉及多个基因改变的复杂过程.许多研究表明,结直肠癌变是一个涉及原癌基因激活、抑癌基因失活等多基因、多阶段、多步骤渐进演化的积累过程.与结直肠癌相关的抑癌基因有p53、APC、DCC、MMR等,原癌基因有k-ras、c-myc等.本文就以上基因改变与大肠癌的发生发展相关性的研究现状作一简单复习.     

Outcome of cardiac and thoracic aortic operation in patients over 80 years old

A retrospective analysis was performed to determine the early outcome of cardiac and thoracic aortic surgery in patients over 80 years old. Between 1994 and 2000, 41 octogenarians (mean age, 82.6 +/- 2.5 years) underwent coronary artery bypass grafting (25), valve surgery (8), thoracic aortic aneurysm repair (7), or combined valve and bypass surgery (1). Overall hospital mortality was 9.8%. Mortality rates for specific procedures were 12% for coronary bypass, 0% for valve surgery, and 14% for thoracic aortic aneurysm repair. Major postoperative complications affected 27% of patients and included severe low cardiac output, respiratory failure, and acute renal failure, with a low incidence of perioperative stroke (2.4%). Cardiac and thoracic aortic operations can be performed with acceptable mortality and morbidity when appropriately applied in selected octogenarians.