Metachronous urothelial cancer in bilateral upper urinary tracts and bladder associated with hereditary nonpolyposis colorectal cancer

A 40-year-old man had undergone right hemicolectomy and sigmoidectomy under the diagnosis of ascending and sigmoid colon cancer and right nephroureterectomy under the diagnosis of right ureteral cancer, in 1997 and in 2002, respectively. In 2007, He visited our hospital with a complaint of bloody stool and hematuria. Colon fiberscopy, ureteropelvicscopy and cystoscopy demonstrated colon cancer, left renal pelvis cancer and bladder cancer, respectively, as diagnosed by biopsies, followed by restative colectomy, left nephroureterectomy and cystectomy. The final histopathological examination showed well differentiated adenocarcinoma (pSM) in the colon, and urothelial carcinoma in the left renal pelvis (pT2) and the bladder (pT1). Since his uncle and elder brother had suffered from stomach cancer and colon cancer, respectively, he was diagnosed with hereditary nonpolyposis colorectal cancer (HNPCC : Lynch syndrome). He has been well doing without recurrence for 3 years after the surgery.     

Metachronous colorectal cancer

OBJECTIVE: Although the diagnosis of metachronous colorectal cancer have increased, due primarily to improvements in diagnostic modalities, the potential risk factors for these tumours are not well known. We compared the characteristics of patients with metachronous and sporadic primary colorectal cancer to determine risk factors for its occurrence. PATIENTS AND METHODS: We reviewed the records of 5447 patients with colorectal cancer, who had been treated at Asan Medical Centre between July 1989 and January 2004. A metachronous cancer was defined as a secondary colorectal cancer occurring more than 6 months after the index cancer. RESULTS: Metachronous colorectal cancer occurred in 39 (0.7%) patients. Their average age was 53 years, somewhat younger than the average age of sporadic colorectal cancer patients (58 years). In patients with metachronous cancer, the cancer was more likely to be located in the right colon (P < 0.03), and the incidence of synchronous polyps or cancer was significantly higher (P < 0.001). The relative distributions of histological grades and clinicopathological characteristics were similar in index and metachronous cancers. Metachronous cancers were diagnosed more frequently at an early stage. The time interval between index and metachronous cancer ranged from 6 to 215 months (mean 39 months), with 13 (33.3%) patients diagnosed with metachronous cancer after 5 years. CONCLUSION: We found that in patients aged < 50 years, existence of synchronous polyps or cancer influence on the development of metachronous colorectal cancer. Regular follow-up is necessary for early detection, even after 5 years, for these patients.     

Metachronous sarcomas in a patient with bilateral retinoblastomas. A case report

This is the first reported case of two metachronous sarcomas developing in a patient after treatment of bilateral retinoblastomas. The histogenesis of the tumours is not clear.     

错配修复在遗传性非息肉性结直肠癌中的研究进展

遗传性非息肉性结直肠癌是最具遗传特性的一种大肠癌,随着分子遗传学检测方法的发展,目前已经能够应用多种方法检测出突变的错配修复基因,并应用于遗传性非息肉性结直肠癌患者的筛选.在此分别就MSH2、MLH1、MSH6、PMS1、PMS2、MLH3和EX01等错配修复基因与遗传性非息肉性结直肠癌相关性研究进展进行综述.     

Two cases of bladder cancer with hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by an excess of extracolonic malignancies including those of the urinary tract. We report two cases of bladder tumor associated with HNPCC. The reported cases were compatible for Amsterdam criteria II for HNPCC. It is important to obtain a family history of cancer in patients with urothelial carcinoma. A patient with a strongly positive cancer history must be carefully examined for HNPCC and HNPCC associated cancers.     

Metachronous bilateral adrenal metastases following curative treatment for colorectal carcinoma

A delayed, metachronous presentation of bilateral adrenal metastases following colorectal cancer has never previously been reported. We describe the case of a 68-year-old man who underwent curative surgery and adjuvant chemotherapy for a locally invasive sigmoid adenocarcinoma, only to be diagnosed with metachronous bilateral adrenal metastasis necessitating further resection and chemotherapy. We discuss the literature surrounding this pathology and highlight the importance of continual, vigilant radiological surveillance of the adrenal glands after curative treatment of colorectal carcinoma with or without subsequent adrenal metastasis.     

Metachronous colorectal cancer risk in patients with a moderate family history

Aim Lifetime risk of a metachronous colorectal cancer (mCRC) is 0.6–3% following sporadic colorectal cancer (CRC) and 15–26% in Lynch syndrome. The lifetime incidence of CRC in individuals with moderate familial risk is 8–17%. Risk of mCRC is unknown. Method A retrospective longitudinal study of the Regional Familial CRC Registry was performed. Patients who had at least one CRC were categorized as follows: moderate risk (n = 383), Lynch syndrome (n = 528) and average (population) risk (n = 409). The Kaplan–Meier estimate (1‐KM) and the cumulative incidence function were used to calculate the risk of mCRC. The 1‐KM gives the risk for individuals remaining at risk (alive) at a given time point and thus is useful for counselling. The cumulative incidence function gives the risk for the whole population. Results The 1‐KM and the cumulative incidence function demonstrated that the risk of mCRC was significantly higher in moderate‐risk patients compared with average (population)‐risk patients (1‐KM, P = 0.008; cumulative incidence function, P = 0.00097). However, the risk of mCRC was higher in patients with Lynch syndrome than in moderate‐risk or average (population)‐risk patients. The 1‐KM in moderate‐risk patients was 2.7%, 6.3% and 23.5% at 5, 10 and 20 years, respectively. In average (population)‐risk patients, the 1‐KM was 1.3%, 3.1% and 7.0% at 5, 10 and 20 years, and the cumulative incidence function was 0.3%, 0.6% and 2.4% at the same time points, respectively. Conclusion These data indicate that the risk of mCRC is significantly higher in patients with a moderate family history of CRC than in those with an average (population) risk. This justifies proactive lifelong surveillance.     

遗传性非息肉病性大肠癌家系研究

目的;分析遗传性非息肉病性大肠癌家系肿瘤的基因表达及特点,诊治经验。方法：分析24个遗传性非息肉病性大肠癌家系的诊断,治疗和随访结果。记录恶性肿瘤部位,确诊年龄,同时性和（或）异时性癌,肿瘤的病理学资料,应用聚合酶链反应和单链构像多态性方法检查家族成员hMLH1和hMSH2各外显子,对可疑突变片段测序。结果：24个家系中共有患者75例,共诊断各种恶性肿瘤125个,主要有大肠癌,胃癌,子宫内膜癌等,本组诊断大肠癌患者64例（异时性多原发大肠癌16例）,24％的大肠癌患者首次手术10年内再发异时性大肠癌,发现2个家系携带hMSH2基因,1个家系携带hMLH1基因种系突变,均产生截短蛋白,3个家族中已发现12例突变基因携带者,结论：本病主要特点是恶性肿瘤早发,多发;结肠直肠癌,尤其是右侧结肠癌为主,多原发癌,尤其是多原发性大肠癌多见,家族发病年龄逐代提前,常规肠段切除手术可能不适于此类大肠癌的治疗。已发现2个家系有hMSH2基因,1个家系有hMLH1基因突变。     

遗传性非息肉病性大肠癌的临床特征分析

目的 探讨遗传性非息肉病性大肠癌（HNPCC）的临床特征,为大肠癌的靶向筛检、早期诊断提供依据。方法 通过家族调查、系谱分析、手术病理和定期随访等手段追踪调查4个HNPCC家系,共计15岁以上成员84人。结果 确诊患者23例（A组）,与确切无家族史者（B组）30例相比：（1）平均发病年龄：A组43．0岁,B组61．4岁,平均年轻18．4岁;低于50．0岁者：A组78．3％（18／23）,B组26．7％（8／30,P＜0．01）;第1、2、3代平均年龄分别为67．8、45．3、32．5岁,逐代比较差异有显著性意义（P＜0．05和P＜0．01）。（2）病变部位：右半结肠A组73．9％（17／23）,B组36．7％（11／30,P＜0．01）,（3）合并腺瘤：A组0,B组23．3％（7／30,P＜0．05）。（4）低分子腺癌：A组76．2％（16／21）,B组36．7％（11／30,P＜0．01）。结论 HNPCC患者临床并非少见,且具有典型的遗传特征。     

Genetic testing for hereditary nonpolyposis colorectal cancer

Approximately 80 per cent of patients with colorectal cancer have sporadic disease whereas the remaining 20 per cent seem to have a genetic component. Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common autosomal dominant hereditary syndrome predisposing to colorectal cancer. Various methods have been described to screen for HNPCC and to directly test for mismatch repair gene mutations. This study evaluates the initial results of 1) microsatellite instability (MSI) and immunohistochemistry (IHC) staining of tumors and 2) genetic sequencing for mismatch repair gene mutations in patients suspected to have HNPCC. Appropriate patients for HNPCC testing were identified through a high-risk colorectal cancer clinic. Of those patients screened only those who met Amsterdam criteria (AC) for HNPCC or were young age onset (YAO) (<40 years of age) were eligible for testing. The tumors underwent testing for MSI and had IHC performed in those patients with available tumor specimens. MSI was performed on the five markers approved by the NIH consensus conference. MSI-High (MSI-H) was defined as two or more markers being unstable. IHC was done with commercially available stains for MLH1 and MSH2. All patients had sequencing of the MLH1 and MSH2 genes performed to search for mutations by a commercial laboratory. Genetic counseling was provided and written informed consent was obtained. Fourteen patients were part of kindreds that met the AC. An additional 10 patients were <40 years of age at diagnosis of colorectal cancer but lacked any family history. Testing for MSI and IHC was performed on those available tissue blocks. Of the AC patients five had MSH2 mutations and two had MLH1 variants. Of the five with MSH2 mutations three of four had MSI-H tumors and all four had loss of expression of MSH2 on IHC. Of the MLH1 variants only one had MSI-H tumor and lacked expression of MLH-1 on IHC. Of those patients with no mutation identified three of six had MSI-H tumors. For those patients YAO no genetic mutations were identified. Two of the seven had MSI-H tumors. Genetic testing for HNPCC even in those patients fulfilling the rigid AC yielded mutations in only five of 14 patients with variants of unknown significance being found in an additional two patients. Only one MSH2 variant of unknown significance was identified in the 10 YAO patients, which would suggest that screening in this group of patients with MSI and/or IHC would be appropriate.     

Metachronous bilateral testicular cancer: report of two cases

We report two cases of metachronous bilateral testicular tumors. In the first case (48 years old), and the second case (39 years old) the contralateral tumor developed 106 months and 63 months after the initial therapy, respectively. In both cases, the primary and the contralateral tumors were stage I seminomas. The patients underwent high inguinal orchiectomy and adjuvant retroperitoneal irradiation for the primary tumor, and only high inguinal orchiectomy for the contralateral tumor. There was no recurrence following the second operation in either case. In the second case, preoperative cryopreservation of the semen was performed for future artificial insemination. Long-term follow-up of contralateral testis is necessary for patients with testicular cancer, even if good prognosis is expected. The quality of life of the patients with bilateral testicular tumors should be maintained by preserving fertility and replacing androgen.     

Metachronous colorectal carcinoma

During the period 1943-67, 903 Danish patients aged less than 40 years had colorectal carcinoma. The patients were followed up for up to 41 years and during this period 44 of 501 (9 per cent) operated on for cure developed a metachronous colorectal carcinoma. The cumulative risk of a metachronous colorectal carcinoma was 30 per cent after up to 41 years of observation. The occurrence of a metachronous colorectal carcinoma was evenly distributed in the observation period. The cumulative survival rate after operation for a metachronous colorectal carcinoma was 41 per cent after 20 years of observation. We propose a lifelong follow-up programme after resection of colorectal carcinoma for cure in this age group, including annual Hemoccult test and colonoscopy at 3-year intervals.     

Value of histopathology in predicting microsatellite instability in hereditary nonpolyposis colorectal cancer and sporadic colorectal cancer

Identification of colorectal carcinomas with high levels of DNA microsatellite instability (MSI-H) is important because of the suggested prognostic and therapeutic significance associated with MSI. The role of histology in identifying MSI-H colorectal carcinomas has been suggested by some studies but not confirmed by others. Furthermore, previous studies assumed that hereditary nonpolyposis colorectal cancer (HNPCC)-associated MSI-H tumors and sporadic MSI-H tumors have similar histology. This assumption, however, has been challenged by more recent studies. In this report, we first analyzed the value of various histologic features in predicting MSI-H in a series of 218 colorectal carcinomas containing mixed HNPCC and sporadic cases [77 tumors (35%) were MSI-H by polymerase chain reaction (PCR) method]. Then, we evaluated the various histologic features comparatively in two groups extracted from the 218 cases. Group A was composed of 84 tumors from 82 patients obtained based on a strong family history (HNPCC/HNPCC-like group) (male to female ratio, 42:40; age range, 23-80 years, median, 53.5 years). Thirty-one of the 84 tumors (41.7%) were MSI-H by PCR, and all 31 cases were HNPCC by Amsterdam criteria. Group B was composed of 109 patients with no family history of colorectal cancer or HNPCC-associated cancer, obtained from surgical clinics (sporadic group) (male to female ratio, 65:69; age range, 31-84 years, median, 65 years). Thirty-five of the 109 tumors (32.1%) were MSI-H by PCR. Our results showed that, overall, poor tumor differentiation, medullary type, mucinous type, signet-ring cell component, histologic heterogeneity, and increased tumor-infiltrating lymphocytes (TILs) were features more commonly seen in MSI-H tumors than in non-MSI-H tumors. Comparative analyses showed that the overall TIL count was significantly higher in HNPCC/HNPCC-like group, and mucinous type appeared to be more frequent in HNPCC MSI-H tumors than in sporadic MSI-H tumors. However, there was no significant difference in the odds ratio for predicting MSI-H status for any of the analyzed histologic features between HNPCC/HNPCC-like group and sporadic group, indicating that differences between HNPCC and sporadic MSI-H tumors did not significantly impact on the informative value of histology in predicting MSI in the two different clinical settings. TIL counts followed by histologic heterogeneity provided the greatest sensitivity and specificity in predicting MSI status in both HNPCC/HNPCC-like and sporadic cases. Using a stepwise logistic regression model, a formula was generated that could be used to calculate the probability of a colorectal carcinoma being MSI-H based on morphologic features.     

A case of bladder cancer with bilateral ureteral carcinoma in situ

A case of bladder cancer with bilateral ureteral carcinoma in situ (CIS) is presented. A 55-year-old male had gross hematuria and urinary retention. Cystoscopy revealed diffuse broad-based papillary tumors, which proved to be transitional cell carcinoma (G2) with CIS and submucosal invasion microscopically. Excretory urography showed normal upper urinary tracts except stasis of bilateral lower ureters. Neither lymph node swelling nor distant metastasis was found by computed tomography. Therefore the patient underwent total cystourethrectomy, pelvic lymph-adenectomy, and construction of an ileal conduit. Histological examination of the specimens demonstrated CIS on bilateral ureteral stumps on the renal side, which, however, was not continuous to that of the bladder. Much attention should be paid to upper urinary tracts for ureteral lesions before cystectomy in such bladder tumors and the proximal stump of the ureter should be examined using frozen section at the operation, but these were not sufficient in the present case in which skip lesions of the ureters were seen apart from the bladder.     

遗传性非息肉病性大肠癌家族肠外肿瘤的特点分析

目的：探讨遗传性非息肉病性大肠癌（HNPCC）肠外肿瘤的特点,方法：对随访登记的32家系进行随访和回顾,结果：在12个典型HNPCC家系中,6家系发生8例肠外肿瘤,20家系非典型的HNPCC家系中,1家族中有1例肠外肿瘤发生,肠外肿瘤最常见为子宫内膜癌和胃癌,结论：大肠外肿瘤为HNPCC肿瘤谱中的重要成员,中国人的大肠外肿瘤胃癌,子宫内膜癌较多见。     

遗传性非息肉病性结直肠癌家族多原发癌的特点

目的 探讨中国人遗传性非息肉病性结直肠癌（HNPCC）家族多原发癌的临床特点。方法 对登记的32个家系进行随访和回顾分析。结果 在32个家系91例患中,共9个家系10例患（11．0％）发生异时性多原发癌,无同时性多原发癌发生,其中8例（15．7％）来自典型的HNPCC家系,2例（5．0％）来自非典型的家系。第1个癌为结直肠癌患9例,第2个癌为结直肠癌3例,肝癌、卵巢癌、子宫内膜癌各2例,脑胶质瘤1例。有2例患发生3次癌,其后2次癌发生的间隔时间为60－108个月,中位数68个月。第2个癌除2例肝癌外均行手术治疗,手术切除率为80．0％。结论 中国人HNPCC家系中多原发癌的患明显增加。对HNPCC患要加强随访,以冀早期发现多原发癌,争取较好的疗效。     

遗传性非息肉病性大肠癌家系的临床特征分析

目的　探讨遗传性非息肉病性大肠癌(HNPCC)家系的临床特征。方法　对符合Amsterdam标准的4 5个HNPCC家系共2 6 4个患者绘出其家系图,确定年龄、性别、肿瘤部位、同时和异时癌等。结果　4 5个家系中2 6 4例患者,男14 2例,女12 2例,均为常染色体显性遗传;确诊时的中位年龄为5 0岁。30 5个原发癌灶中,大肠癌灶180个,大肠多发癌2 8例,肠外癌12 5个。结论　HNPCC垂直传递特征突出,肠外癌以肺癌、子宫内膜癌、胃癌最多见,同时多原发癌和异时多原发癌比较多见。