Morphogenesis of nonpolypoid colorectal adenomas and early carcinomas assessed by cell proliferation and apoptosis

Nonpolypoid neoplasms, as well as ordinary polypoid tumours, are occasionally found in the colorectum. To clarify whether cell kinetic status affects the macroscopic morphology of colorectal neoplasms, we investigated proliferative indices (PI), apoptotic indices (AI), and the expression of apoptosis-related gene products. We examined 110 colorectal neoplasms comprised of 36 polypoid, 38 flat elevated and 36 depressed tumours. According to WHO’s criteria these tumours consisted of 61 adenomas with low grade dysplasia (LGD), 30 adenomas with high grade dysplasia (HGD) and 19 carcinomas with submucosal invasion. Apoptotic cells were detected by TUNEL staining. Proliferating cells and apoptosis-related gene products were assessed by immunohistochemistry for Ki-67, p53, Bcl-2, and Bax antigens. AI were closely associated with macroscopic morphology in adenomas but not in carcinomas. PI were relatively constant among the three macroscopic types in adenomas and carcinomas. Median AI values of polypoid, flat elevated and depressed tumours were 1.8%, 2.1% and 4.6% for adenomas with LGD, 0.8%, 2.4% and 6.2% for adenomas with HGD and 2.9%, 4.0% and 3.6% for carcinomas, respectively. Overall PI were significantly higher in carcinomas than in adenomas with LGD, whereas AI were not different. Although the incidence of expression was significantly higher in carcinomas for p53 and in adenomas for Bcl-2 than the others, the expression of apoptosis-related gene products (p53, Bcl-2 and Bax) was similar among polypoid, flat elevated and depressed tumours. Macroscopic morphology of colorectal adenomas is determined by the apoptosis not by proliferation, and high apoptosis found in depressed adenomas implies their low net growth. Received: 1 July 1999 / Accepted: 17 January 2000     

α2，6-唾液酸转移酶（ST6GalⅠ）的表达对结肠癌细胞唾液酸化的影响

目的 研究结肠癌细胞LS174T转染正义和反义的α2，6唾液酸转移酶(ST6GalⅠ)cDNA对结肠癌细胞表面唾液酸化及肿瘤细胞粘附功能的影响．方法 结肠癌细胞株LS174T转染正义ST6GalⅠcDNA或反义ST6GalⅠcDNA的部分序列的表达载体pcDNA3.1，以RT—PCR检测转染子ST6GalⅠmRNA的表达．流式细胞仪检测细胞表面α2，6唾液酸含量．结果 转染正义ST6GalⅠcDNA的克隆显示ST6GalⅠmRNA的表达增强以及接骨木凝集素(SNA)与细胞表面成分的结合增加；而转染反义ST6GalⅠcDNA的部分序列的细胞克隆的ST6GalⅠmRNA的表达减少．SNA与细咆表面成分的结合力降低．结论 ST6GalⅠ的表达直接影响细胞表面α2．6-连接的唾液酸水平并调节肿瘤细胞的粘附功能利用反义核酸技术抑制ST6GalⅠ的表达并降低肿瘤细咆表面α2，6-唾液酸水平可能成为减少癌细胞转移的一种手段．     

Normal colon of Sprague-Dawley rats

Summary The patterns of expression of the human-tumor-associated antigens, CO17-1A, GA73-3, BR55-2, GICA19-9, CA50 and carcino-embryonic antigen (CEA) were studied in the normal colonic mucosa (the last three also in the serum) of Sprague-Dawley rats. Four immunohistochemically different segments were identified: caecum, ascending colon, transverse colon and descending colon. The immunohistochemical reactions of the cells at the lower part of the crypt were essential for the distinction of the four segments. In the caecum, the MAbs 17-1A, 73-3 and 19-9 stained the glycocalyx of the cells of the lower part of the crypts and the Golgi apparatus of the intercalated cells (IC). MAb55-2 stained very weakly the goblet-like cells (GLC) of the lower part of the crypt of transverse colon, in addition to a nearly complete lack of reaction in the upper part of the crypts. In the ascending colon, the lower part of the crypts showed a characteristic diffuse staining of the intercalated cells with MAb55-2. The perinuclear and mucosal staining observed in the GLC of the transverse colon with MAbs 17-1A, 73-3 and 19-9 as against the supranuclear and Golgi zone staining observed in the GLC/goblet cells (GC)/columnar cells (CC) of the lower part of crypts of the descending colon with the same MAbs, distinguished the former segment from the latter. The IC demonstrated by immunohistochemistry in the lower parts of the crypts of caecum and ascending colon appear to correspond to the replicating cells of the colonic crypts.     

Responses of sacral visceral afferents from the lower urinary tract,colon and anus to mechanical stimulation

The discharge characteristics of sacral visceral afferents supplying the urinary bladder, urethra, colon and anus to mechanical stimuli were analyzed in the anaesthetized cat. The stimuli used were passive distension (urinary bladder, colon), isovolumetric contraction (urinary bladder), movements of the urethral catheter and mechanical shearing stimuli (mucosal skin of the anal canal). (1) In total 245 afferent units which projected in the pelvic nerve were isolated from the sacral dorsal roots. From one of the following organs, urinary bladder, colon, urethra and anus 117 afferent units were activated. By these stimuli from the bladder, urethra and anus 122 afferent units could not be activated, and as far as tested also not from the colon; in 6 afferent units the classification was unclear. (2) Afferent units from the urinary bladder and the colon responded consistently to passive distension of the respective organ. The units from the urinary bladder showed graded responses at intraluminal pressures of about 10–70 mm Hg and responded also to isovolumetric contractions of the organ. The thresholds of the units from the bladder to passive distension and contraction varied from about 5 to 20 mm Hg intravesical pressure. (3) The afferent units from the urethra and the anus did not react or showed some weak phasic and irregular responses to distension and contraction applied to the urinary bladder or to distension of the colon. They were consistently excited by low threshold mechanical stimulation of the urethra and anus, respectively. (4) The axons from the bladder, urethra and anus were presumably myelinated (conduction velocity above 2 m/s) and conducted at 10.3±6.1 m/s (n=34, mean±SD), 26.3±9.3 m/s (n=13) and 9.5±5.1 m/s (n=37), respectively. The axons from the colon conducted at about 0.5 to 16 m/s (n=20), 13 of them conducting at less than 2 m/s. About 75% of the axons which could not be activated by mechanical stimulation of the visceral organs were presumably unmyelinated (conduction velocity below 2 m/s). (5) Some ongoing activity was found in 9 out of 26 afferent units from the anus but, with one exception, the afferent units from the bladder, urethra and colon were silent. (6) It is concluded that the pelvic afferent units from the urinary bladder, urethra, colon and anus consist of distinct populations with characteristic response patterns. There is no indication from this investigation that the urinary bladder is supplied by sacral afferents which are only recruited at high intravesical pressures during passive distension and isovolumetric contractions and which are possibly associated with pain.Supported by the Deutsche Forschungsgemeinschaft     

Tissue zinc levels in precancerous tissue in the gastrointestinal tract of azoxymethane (AOM)-treated rats

Alterations in tissue zinc levels have been documented in patients with gastrointestinal tract malignancies and more frequently, in those with colonic cancer. However, the precise role of tissue zinc in carcinogenesis is not well elucidated. This study, using a well-established colon cancer model in rats, was designed to investigate the relationship of tissue zinc to the carcinogenic process. The aim was to examine tissue zinc levels in the preneoplastic tissues and to study the changes that occur during transition of mucosa from normal to preneoplastic state. Six-week old rats were given a single dose subcutaneous injection of azoxymethane (AOM) (30mg/kg body weight) and sacrificed after 1, 2, 5, and 9 months of the treatment. Plasma zinc levels showed a significant decrease (p<0.05) at 9 months compared with controls. Tissue zinc levels showed a significant decrease in the large intestine at 1 and 2 months (p<0.05) and at 5 and 9 months (p<0.01), in the small intestine at 2, 5, and 9 months (p<0.05), and in the stomach at 5 and 9 months (p<0.05). The maximum percent decrease (45%) in tissue zinc was observed in the large intestine at 9 months. Tissue copper zinc super oxide dismutase (CuZnSOD) activity was assessed in the body of the stomach, small intestine, and large intestine and compared with the control group. There was a significant fall in CuZnSOD levels in the small intestine at 9 months (p<0.05) and in the large intestine at 5 and 9 months (p<0.01). Two of these six rats showed histological evidence of precancerous lesions in the mucosa of the colon. This study suggests that the decrease in plasma zinc, tissue zinc and activity of CuZnSOD is associated with development of preneoplastic lesions in the colonic mucosa.     

Extrapelvic colon--areas of failure in a reoperation series: implications for adjuvant therapy

A total of 230 patients had planned single or multiple reoperative procedures following "curative" resection of colorectal cancer at the University of Minnesota. The site of the primary lesion was extrapelvic in 91, and later evidence of cancer was found in 58 patients (64%) at re-operation and/or other follow-up. Eight of the 58 (14%) were converted to disease-free status. Incidence and patterns of failure were correlated with initial operative-pathologic extent of disease (87 of the 91 at risk had initial tumor extension beyond the bowel wall, involved nodes or both) and comparisons were made with the previously analyzed rectal reoperation patients. While a component of local-regional failure was more common with rectal lesions (48/74 at risk, 65%), it was not uncommon with extrapelvic primaries (44/91-48%). The incidence of hematogenous metastasis (DM) was equal, but the pattern of initial DM differed (extrapelvic colon--primarily liver; rectum--liver and lung). Peritoneal seeding was a more common component of failure with the extrapelvic primaries (19/91--21% vs 3/74-4%). Since surgery alone is inadequate treatment for many patients with colon as well as rectal cancer, the rationale of adjuvant radiation and systemic therapy, alone or in combination, is discussed.     

Metastatic renal cell carcinoma involving colon with unusual histologic features and diagnostic challenges: A case report

Introduction and importanceRenal cell carcinoma (RCC) accounts for 3% of all malignancies in adults, on its own being the 3rd most common urologic malignancy. Commonly RCC metastasizes to lung, bone, liver, brain but rarely to colorectum. Here we present the metastasis of RCC to colon with unusual histologic features.Case presentationA 40-year-old woman presented with abdominal pain and constipation. Colonoscopy showed an ulcerative mass 30 cm from anal verge. Subsequently, she underwent abdominoperineal resection of the involved portion of colon and the biopsy was sent to us for histopathological analysis. Grossly, it was a large fungating mass. Microscopic examination revealed a malignant neoplasm with polygonal cells, abundant eosinophilic cytoplasm, eccentric nuclei and prominent nucleoli. Immunohistochemistry confirmed the diagnosis of RCC.Clinical discussionColon rarely infiltrated by metastasis from RCC and so far, around 25 of such cases have been reported in the literature. Most common metastatic type of RCC to gastrointestinal tract is clear cell type. In our patient, the type of the metastatic RCC to colon was RCC with rhabdoid features. RCC with rhabdoid features is rare (3–5% of all RCC), but it is highly aggressive with higher chance of metastasis, extra renal invasion and poorer prognosis.ConclusionRCC should be considered as one of the differential diagnosis of colorectal cancers. Appropriate immunohistochemical workup would then reveal the correct diagnosis.     

Colo-colic intussusception secondary to colon lipoma: A case report

Introduction and importanceIntestinal intussusception is rare in adults and it is associated with lead points affecting the colon in around 17% of patients. Lipomas are very rare benign tumors which may act as lead points for intestinal intussusception. Indeed, the incidence of intestinal intussusception is much rare when caused by lipomas.Case presentationOur patient is a 29-year-old male, previously healthy and admitted for severe right lower quadrant abdominal pain of 2-day duration. Computed tomography (CT) scan of the abdomen and pelvis showed large mass of fat consistency containing colon structure.Clinical DiscussionUrgent laparotomy was opted during which colo-colic intussusception was diagnosed and right hemicolectomy with primary ileocolic anastomosis was performed. Pathology report showed that intussusception was induced by a colon lipoma. Patient had an uneventful hospital stay and was discharged on post-operative day 5.ConclusionThus we recommend that colo-colic intussusception caused by lipoma be considered in the differential when diagnosing adults with right lower quadrant pain.     

Metachronous ileal cancer after surgery for ascending colon cancer in a patient with Lynch syndrome: A case report

Introduction and importanceColorectal surveillance via colonoscopy in patients with Lynch syndrome reduces the mortality of colorectal cancer. On the other hand, it is unclear whether surveillance for other malignancies, including small bowel cancer, is beneficial. We report a patient with Lynch syndrome who developed ileal cancer after surgery for ascending colon cancer.Case presentationA 47-year-old man visited our hospital for a check-up for positive fecal occult blood. He was diagnosed with ascending colon cancer and met the clinical criteria for the diagnosis of Lynch syndrome based on his past and family history. The Bethesda markers demonstrated high-frequent microsatellite instability. Laparoscopy-assisted right hemicolectomy was performed. He received follow-up colonoscopy the next year, which revealed ileal cancer near the anastomosis. He underwent resection of the second cancer via a laparoscopic approach, and has been free from recurrence for five years.Clinical DiscussionSmall bowel cancer has a dismal prognosis because a high percentage of patients were diagnosed at advanced stages. The diagnosis of metachronous ileal cancer by the first follow-up colonoscopy after surgery for ascending colon cancer offered a long disease-free survival in our patient.ConclusionThe clinical course suggested the importance of inspecting the small bowel in Lynch syndrome patients, especially when colorectal cancer is diagnosed.