Unrecognized Value of Carcinoembryonic Antigen in Recurrent Rectal and Sigmoid Colon Cancer: Case Series.

INTRODUCTION: Carcinoembryonic antigen (CEA) surveillance is recommended in patients with colorectal cancer for detection of potentially resectable metastases. In patients with appropriate symptoms, a highly increased CEA concentration (> 5 times the upper limit of normal) is considered strongly suggestive of cancer. Despite the recognized value, the test is neither absolutely sensitive nor specific for recurrent cancer. Generally, a greater diagnostic value has been assigned to elevated CEA levels, most commonly greater than 5 ng/mL. Fluctuations within the established normal CEA range are not customarily analyzed. CASE PRESENTATIONS: We report here on 11 patients (8 women, 3 men) who, during the postoperative follow-up period, received a diagnosis of recurrent cancer despite their CEA levels exhibiting very subtle increases. Our cohort shared several similar characteristics such as a nonsmoking status, younger age (median, 52 years at initial diagnosis), and exclusive localization of the cancer to the rectosigmoid region. DISCUSSION: This important clinical observation may expand a prognostic value of CEA in a certain category of patients with colorectal cancer.

Immunotherapy for pulmonary squamous cell carcinoma and colon carcinoma with pembrolizumab: A case report.

RATIONALE: Novel treatment strategies such as immunotherapy are being evaluated to further improve the outcomes of colorectal cancer patients. To our knowledge, this is the first report to show both the successful treatment of pulmonary squamous cell carcinoma (SCC) with pembrolizumab alongside histological and immunohistochemical findings of resected colon cancer under immunotherapy for lung cancer. PATIENT CONCERNS: This patient was a 70-year-old man who presented with a right lung tumor and simultaneous adenocarcinoma of the sigmoid colon. DIAGNOSES: Biopsy examination revealed squamous cell carcinoma in the right lung and adenocarcinoma of the sigmoid colon. INTERVENTIONS: The patient underwent successful pembrolizumab treatment as first-line immunotherapy for lung cancer, as demonstrated by computed tomography, and the sigmoid colon tumor was excised during an immunotherapy-free window. OUTCOMES: No unusual tumor growth in the right lung or abnormal abdominal signs was observed during the 9-month follow-up. LESSONS: Microscopically, the resected colon cancer specimen was characterized by numerous lymphoid cells in the partial stroma, with a large number of infiltrating lymphocytes consisting of CD3+, CD8+ T cells. In summary, this case demonstrates how immunotherapy affects PD-L1-negative colon cancer and indicates future treatment prospects.

[CA19-9 Producing Gastric Cancer with Early Recurrence of Multiple Colon Metastases Following Gastrectomy-A Case Report].

A 90-year-old male underwent total gastrectomy for gastric cancer 10 months earlier. The cancer was pathologically diagnosed as Stage ⅢA. Preoperative serum CA19-9 level was as high as 1,326 U/mL, but quickly decreased after surgery. Although the serum CA19-9 level gradually re-increased, CT did not reveal recurrence of the disease. Ten months following surgery, the patient visited our hospital due to vomiting, and ileus was suspected because of finding of sigmoid colon tumors in the abdominalCT. Colonoscopy showed a circumferentialtumor with severe stenosis in the sigmoid colon, which was diagnosed as tubular adenocarcinoma by biopsy. After preoperative diagnosis of multiple colon cancers, sigmoidectomy was performed. A total of 4 tumors were revealed in the resected specimen. Pathological findings showed cancer cells with nuclear atypia in all tumors, which was very similar to findings in the previous gastric cancer. Immunohistochemical staining confirmed high expression of CA19-9 in both gastric and colon tumors. We concluded that the tumors were metastases of the CA19-9 producing gastric cancer.

Collision tumor of recto-sigmoidian junction - case presentation.

Collision tumors of the colon are rare. A 64-year-old man was referred on Emergency County Hospital, Craiova, Romania for the evaluation of intestinal obstruction. Colonoscopy demonstrates the presence of about 9/5 cm sized mass in the rectosigmoid junction. After surgical resection, the rectosigmoid lesion was histopathologically composed of two distinct lesions: mucoid adenocarcinoma in the superficial layer and poorly differentiated neuroendocrin carcinoma in the deeper layer. A rectosigmoid tumor showed two distinct tumors with no admixture or transposition of two neoplastic components. A lymph node metastatic deposit contained both tumors. Immunohistochemical stainings were consistent with mucinous adenocarcinoma and neuroendocrine carcinoma of the two neoplasms. We report this case of colonic collision tumor (mucoid adenocarcinoma and neuroendocrine carcinoma) and review of the literature.

[Serpins in hyperplastic colon tissue].

The purpose of the study was to define α-2-macroglobulin (α-2M) and α-1-proteinase inhibitor (α-1PI) in tissues of malignant tumors and polyps of the lower parts of the colon. 28 patients had malignant tumors of the sigmoid colon or rectum (T3N0-1M0-2), 29 had polyps of the same location. Content of α-2M and α-1PI was studied in cytosols of the central, peripheral and conditionally healthy tissues (of resection line) of the mentioned hyperplasias by the ELISA method using standard test kits. Suppression of a-2M and increase of α-1PI (perifocal zone) were found in malignant tumor tissue, as well as α-1PI maintenance in tumorous focus. Increase of α-2M and decrease of α-1PI were detected in polyp tissue. Changes in physiological balance of serpins were assessed by α-1PI/α-2M ratio in comparison with the resection line. The risk of distortion of proliferation and differentiation processes increases in polyps in ineffective inhibition of proteolysis under the influence of released factors of malignancy. Endogenous or medicamentous restoration of balance of interaction of trypsin-like proteases and kallikrein with inhibitors will probably play the crucial role.

Late recurrence of sigmoid carcinoma mimicking primary vulvar cancer: case report and review of the literature.

OBJECTIVE: To demonstrate a unique case report about late and isolated vulvar metastasis of sigmoid adeno-carcinoma with review of the literature. MATERIAL-METHOD: 57 year old postmenopausal patient with prior sigmoid colon cancer history was admitted with isolated vulvar mass. Immunohistochemistry (IHC) and KRAS gen mutation analysis following surgery were performed to discriminate the metastasis from a vulvar primary malignancy. Further imaging techniques were also performed to exclude additional tumours. RESULTS: Immunohistochemistry (IHC) and KRAS gene mutation analysis revealed isolated metastasis of the colonic adeno-carcinoma in the vulva. CONCLUSION: Isolated and late occurring vulvar metastasis of colonic origin is very unusual. Careful evaluation and IHC is useful for such cases.

Vaginal stump metastasis from sigmoid colon cancer.

BACKGROUND: Vaginal metastasis from organs other than the uterus is rare. Generally, patients with vaginal metastasis from colorectal cancer have a dismal prognosis. Although biopsy is the best method to make the diagnosis, massive bleeding may occur. On the other hand, liquid-based cytology (LBC) has the utility to perform immunocytochemistry on additional unstained slides: we can make a diagnosis with several immunocytochemical findings. CASE: A 67-year-old postmenopausal female presented to our hospital with vaginal bleeding. The patient had undergone colectomy because of her stage III sigmoid colon cancer 3 years earlier. The patient had also undergone hysterectomy for cervical cancer 30 years earlier. LBC from the vaginal stump revealed adenocarcinoma. Immunocytochemically, cancer cells were negative for cytokeratin 7 and positive for cytokeratin 20, which suggested metastasis from the sigmoid colon cancer; the diagnosis was made without a biopsy. CONCLUSION: When the patient has a metastatic lesion from colon adenocarcinoma, LBC with immunocytochemistry is useful in making a diagnosis.

Perivascular epithelioid cell tumor of the sigmoid colon with transcription factor E3 expression.

We describe here a 62-year-old woman who presented with a perivascular epithelioid cell tumor arising in the sigmoid colon. Computed tomography revealed a 5-cm-sized intraluminal fungating mass. Histologically, the tumor consisted of plump, epithelioid cells with abundant clear-to-lightly eosinophilic cytoplasm and round nuclei, arranged in an alveolar or trabecular pattern. The tumor cells were strongly positive for HMB-45 and TFE3, but negative for vimentin, cytokeratin, smooth muscle actin, S100 protein, CD117, CD34, synaptophysin, chromogranin, CD10, hepatocyte antigen, CD1a, and desmin. The tumor cells had a high Ki-67 labeling index (up to 20%). Fluorescent in situ hybridization showed no evidence of the EWS rearrangement. Based on these histologic and immunohistochemical features, our patient was diagnosed with a perivascular epithelioid cell tumor of the sigmoid colon.

A bioinformatics workflow for variant peptide detection in shotgun proteomics.

Shotgun proteomics data analysis usually relies on database search. However, commonly used protein sequence databases do not contain information on protein variants and thus prevent variant peptides and proteins from been identified. Including known coding variations into protein sequence databases could help alleviate this problem. Based on our recently published human Cancer Proteome Variation Database, we have created a protein sequence database that comprehensively annotates thousands of cancer-related coding variants collected in the Cancer Proteome Variation Database as well as noncancer-specific ones from the Single Nucleotide Polymorphism Database (dbSNP). Using this database, we then developed a data analysis workflow for variant peptide identification in shotgun proteomics. The high risk of false positive variant identifications was addressed by a modified false discovery rate estimation method. Analysis of colorectal cancer cell lines SW480, RKO, and HCT-116 revealed a total of 81 peptides that contain either noncancer-specific or cancer-related variations. Twenty-three out of 26 variants randomly selected from the 81 were confirmed by genomic sequencing. We further applied the workflow on data sets from three individual colorectal tumor specimens. A total of 204 distinct variant peptides were detected, and five carried known cancer-related mutations. Each individual showed a specific pattern of cancer-related mutations, suggesting potential use of this type of information for personalized medicine. Compatibility of the workflow has been tested with four popular database search engines including Sequest, Mascot, X!Tandem, and MyriMatch. In summary, we have developed a workflow that effectively uses existing genomic data to enable variant peptide detection in proteomics.

[An autopsy case of alpha-fetoprotein-producing carcinoma of the sigmoid colon resulting in sudden death].

A 63-year-old woman was admitted to our hospital with complaints of abdominal distention and bilateral cervical masses. Her serum AFP was 11700 ng/dl. AFP was confirmed immunohistochemically by biopsy of a sigmoid colon tumor, yielding a diagnosis of AFP-producing carcinoma of the sigmoid colon, accompanied by multiple liver metastases, and systemic multiple lymph node metastases. Due to her poor general condition with mitral regurgitation, the patient began S-1 treatment. The patient's general condition rapidly worsened after 1 course of S-1 had no effect. She died on the 59th hospital day and a pathological autopsy was performed. We examined 67 cases of AFP-producing colon cancer in Japan, including our own, and report the findings with references.

ß-Catenin and its relation to VEGF and cyclin D1 expression in pT3 rectosigmoid cancers.

BACKGROUND/AIMS: ß-Catenin is a critical component of the Wnt signaling pathway that regulates cell proliferation and differentiation. Wnt signaling leads to the stabilization of cytosolic ß-catenin and to translocation to the nucleus, where it binds with T-cell factor and promotes the transcription and changes in target gene expression, including vascular endothelial growth factor and cyclin D1. The aim of this study was to assess the expression of cyclin D1 and vascular endothelial growth factor and to correlate them with ß-catenin expression and some clinicopathologic parameters. METHODS: In this study, we analyzed paraffin-embedded specimens from 42 patients with pT3 rectosigmoid cancer for ß-catenin, vascular endothelial growth factor and cyclin D1 expression using immunohistochemistry. RESULTS: Thirty-six (85.7%) and 24 (57.1%) tumors expressed vascular endothelial growth factor and cyclin D1, respectively. Nuclear expression of ß-catenin was detected in only 26.1% of tumors. It was revealed that cytoplasmic ß-catenin expression was significantly related to vascular endothelial growth factor expression (p=0.011). No association was found between nuclear or cytoplasmic ß-catenin and cyclin D1 expression. No significant association was seen between ß-catenin, vascular endothelial growth factor or cyclin D1 expression and some investigated clinicopathologic features. CONCLUSIONS: Our results may contribute to knowledge regarding the functional interaction between ß-catenin and vascular endothelial growth factor. We suggest that the overexpression of cyclin D1 in rectosigmoid cancers may be more complicated than purely upregulation by ß-catenin. Further larger studies on Wnt/ß-catenin and target gene activity and protein expression are necessary to better understand and define their roles in the pathogenesis of colorectal carcinoma.

Mitochondrial genome alterations in rectal and sigmoid carcinomas.

The scarce studies on the molecular pathways involved in the pathogenesis of rectal cancer indicate that these may vary, at least in part, from those relevant for colon cancer. Mitochondrial DNA alterations have been described in several human cancers. We aimed to study D310, ND1 and ND5 microsatellite sequence alterations and nuclear microsatellite instability in a series of 38 rectal carcinomas as compared to a series of 25 sigmoid carcinomas. D310 sequence alterations were observed in 34.3% and 37.5% of rectal and sigmoid carcinomas, respectively, whereas ND1 mutations were present in 2.6% in RC and ND5 mutations were detected in 5.3% and 8% of rectal and sigmoid carcinomas, respectively. A trend toward an association between nuclear and mitochondrial microsatellite instability was observed in sigmoid but not in rectal cancers. In conclusion, mitochondrial genome alterations are common in both rectal and sigmoid carcinomas and may contribute to their pathogenesis.

Study of intra-abdominal fat distribution in sigmoid colon cancer in Japanese patients by use of MDCT data.

To assess the relationship between intra-abdominal fat and sigmoid colon cancer, we investigated the intra-abdominal fat distribution in 172 examples of sigmoid colon cancer and 767 examples of various other pathologies by using data from multidetector-row computed tomography. One significant finding was that the intra-abdominal fat area in sigmoid colon cancer presents a small secondary peak in the pelvis on the profile of the intra-abdominal fat, which we called the pelvic sub-peak. The presence or absence of the pelvic sub-peak was determined based on the sub-peak ratio, which was calculated by dividing the maximum peak by the sub-peak value on the profile of the intra-abdominal fat area. The pelvic sub-peak was defined as having a sub-peak ratio >or=0.1. The pelvic sub-peak frequency was higher for all male patients than for female patients. The frequency of the pelvic sub-peak in sigmoid colon cancer was 77.5% (79/102) for men and 50.0% (35/70) for women. Among both men and women, frequencies of the pelvic sub-peak were significantly higher in patients with sigmoid colon cancer than in non-tumor cases (P < 0.001). Furthermore, the frequency of the pelvic sub-peak was almost the same in sigmoid colon cancer as in rectal cancer. No causal relationship between sigmoid colon cancer and a pelvic sub-peak could be confirmed in the present study; however, patients with sigmoid colon cancer tended to exhibit a unique pattern of fat accumulation.

[Unexpected focal bowel 18-FDG uptake sites: should they be systematically investigated?]. / Hyperfixations intestinales focales de découverte fortuite sur la TEP au 18-FDG : faut-il proposer une exploration de façon systématique ?

The purpose of the present study was to retrospectively evaluate the nature and significance of unexpected focal 18-FDG uptake localized by PET/CT within the intestinal tract. Methods. The data of 4,033 PET/CT were retrospectively reviewed. One hundred and eighty PET/CT showed unexpected focal uptakes (patients with known intestinal neoplasia were excluded). Among them, 42 patients corresponding to 47 focal uptake sites were investigated by endoscopy or surgery. Results. Height endoscopy results were negative (17%). We found 25 adenomatous polyps (53.2%), 10 neoplasms (21.3%) and 4 inflammatory lesions (8.5%). 18-FDG uptake values were not statistically different between the 4 groups. Conclusion. Eighty-three percent of unexpected intestinal foci of hypermetabolism are either inflammatory, malignant or premalignant lesions. These results justify systematic investigation of these lesions.

Human mass balance study of the novel anticancer agent ixabepilone using accelerator mass spectrometry.

Ixabepilone (BMS-247550) is a semi-synthetic, microtubule stabilizing epothilone B analogue which is more potent than taxanes and has displayed activity in taxane-resistant patients. The human plasma pharmacokinetics of ixabepilone have been described. However, the excretory pathways and contribution of metabolism to ixabepilone elimination have not been determined. To investigate the elimination pathways of ixabepilone we initiated a mass balance study in cancer patients. Due to autoradiolysis, ixabepilone proved to be very unstable when labeled with conventional [14C]-levels (100 microCi in a typical human radio-tracer study). This necessitated the use of much lower levels of [14C]-labeling and an ultra-sensitive detection method, Accelerator Mass Spectrometry (AMS). Eight patients with advanced cancer (3 males, 5 females; median age 54.5 y; performance status 0-2) received an intravenous dose of 70 mg, 80 nCi of [14C]ixabepilone over 3 h. Plasma, urine and faeces were collected up to 7 days after administration and total radioactivity (TRA) was determined using AMS. Ixabepilone in plasma and urine was quantitated using a validated LC-MS/MS method. Mean recovery of ixabepilone-derived radioactivity was 77.3% of dose. Fecal excretion was 52.2% and urinary excretion was 25.1%. Only a minor part of TRA is accounted for by unchanged ixabepilone in both plasma and urine, which indicates that metabolism is a major elimination mechanism for this drug. Future studies should focus on structural elucidation of ixabepilone metabolites and characterization of their activities.

Significant increase of colonic mutated crypts correlates with age in sporadic cancer and diverticulosis cases, with higher frequency in the left- than right-side colorectum.

Mild periodic acid-Schiff (mPAS) staining can discriminate non-O-acetylated (mPAS-positive) from O-acetylated (mPAS-negative) epithelial sialoglycoproteins in human colonic mucosa, allowing the three haplotypes expressed from a single polymorphic autosomal gene (oat) to be distinguished. In heterozygotes, we previously demonstrated wholly mPAS-positive (stem cell mutated) crypts and clusters of two or more mPAS-positive crypts to be significantly increased with duration of ulcerative colitis. To establish whether such an increase in the number of mutated crypts with age also occurs in normal individuals or in cases with diverticulosis, the O-acetylation phenotype in the non-cancerous colonic mucosa of 47 sporadic colorectal cancer patients who were heterozygotes for oat was tested with mild-PAS staining. PAS-positive crypts were assessed histologically in relation to age and compared between the left (sigmoid colon and rectum) and right (cecum and ascending colon) sides of the colorectum. Wholly mPAS-positive (stem cell mutated) crypts and foci in heterozygotes were found to be increased significantly (P < 0.0001) in the left side with aging (r = 0.598 and 0.643, respectively). Such a positive correlation with aging was also confirmed in 19 diverticulosis cases without cancer (r = 0.797 and 0.793, respectively). The frequency of mutated crypts and foci on the right side was significantly lower than on the left side in both spontaneous colorectal cancer and diverticulosis cases. The results provide support for an intimate relationship between accumulation of mutated crypts with aging, possibly with significance for colorectal cancer development. Furthermore, the environment in the right side of the colon may be different from that in the left side in this regard.

Increased proliferation activity measured by immunoreactive Ki67 is associated with survival improvement in rectal/recto sigmoid cancer.

AIM: To assess the expression of Ki67 as prognosticator in rectal/recto sigmoid cancer. METHODS: Samples from 146 patients with rectal and recto sigmoid cancer were studied for expression of Ki67 and its prognostic significance in comparison with clinico-pathological predictors of survival. Formalin-fixed, paraffin-embedded tissues from 6 (4.1%) patients with T1, 26 (17.8%) with T2, 94 (64.4%) with T3, and 20 (13.7%) with T4 tumors were studied. Ki67 expression was determined immunohistochemically. Samples were divided according to mean value into high (>40%) and low (< or =40%) expression. Areas of extensive proliferation (>50%) were defined as "hot spot" areas. RESULTS: Hot spot areas were present in samples regardless of histopathological grade. Lower TNM and Dukes stage and higher expression of Ki67 and presence of Ki67 hot spot areas in histopathological samples were associated with better survival, whereas no association was observed with histopathological grade (P = 0.78). In Cox multivariate regression analysis, significant prognostic factors were Dukes stage (P<0.001), presence of lymph node metastases (P = 0.015), age (P = 0.035) and presence of Ki67 hot spot areas (P = 0.044). CONCLUSION: Proliferative activity as measured by Ki67 in rectal cancer is associated with survival improvement compared with patients with low Ki67. Areas of prognostically significant increased proliferation were found independently of histopathological tumor grade.

A case of metastatic epithelioid angiosarcoma in the lamina propria of a sigmoid tubulovillous adenoma.

Epithelioid angiosarcoma is an extremely rare tumor. It is generally a secondary tumor and the preferred sites of such metastases are the heart, pericardium, lung, breast, liver, spleen, bone, and brain. In rare cases the lung has been described as the primary site. The prognosis of this neoplasm is extremely poor. We report a case of epithelioid angiosarcoma with multiple bilateral lung infiltration, bone metastasis, and metastasis of the lamina propria of a tubulovillous adenoma of the colon.