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1.
Am J Surg Pathol ; 35(2): 212-20, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21263241

ABSTRACT

Advanced colorectal polyps are identified based on size ≥10 mm, high-grade dysplasia, and/or villous histology. A diagnosis of tubular adenoma (TA) is recommended if villous change occupies <20% of the lesion, or tubulovillous adenoma (TVA) is recommended if there is 20% to 80% villosity. We hypothesized that even subtle villous changes (1% to 20%) would correlate with advanced molecular features. Two hundred sixty-nine colorectal adenomas were examined for KRAS and BRAF mutation and immunohistochemical staining of ß-catenin, O6-Methyl Guanine DNA Methyltransferase (MGMT), and p53. Adenomas were classified as TA1 (0% villosity, n=70), TA2 (1% to 20% villosity, n=81), or TVA (21% to 80% villosity, n=118). Clinical and molecular features were analyzed by univariate χ² and multivariate logistic regression. There was an incremental increase in KRAS mutation frequency with increasing villous compartment (17.9% TA1, 59.0% TA2, 78.4% TVA; P<0.001). MGMT was more frequently lost in TA2 (37.0%) than in TA1 (8.6%) (P<0.001) but did not differ from TVA (39.8%). p53 overexpression was more common in TA2 (38.3%) than in TA1 (10.0%) (P<0.001) but did not differ from TVA (32.2%). On multivariate analysis, TA2 adenomas were more likely to have a KRAS mutation [odds ratio (OR) 6.6, 95% confidence interval (CI), 3.0-14.2], MGMT loss (OR 6.2, 95% CI, 2.4-16.0), or p53 overexpression (OR 5.6, 95% CI, 2.3-13.7) than TA1. We have identified a subgroup of TAs based on subtle villous changes. These adenomas are more likely to show molecular features that are characteristic of TVAs than TAs. These data support the concept that any villous change may indicate increased malignant potential and may be useful to consider when assigning surveillance guidelines.


Subject(s)
Adenoma, Villous/pathology , Colonic Polyps/pathology , Colorectal Neoplasms/pathology , Adenoma, Villous/genetics , Adenoma, Villous/metabolism , Adult , Aged , Aged, 80 and over , Colonic Polyps/genetics , Colonic Polyps/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , DNA Modification Methylases/genetics , DNA Modification Methylases/metabolism , DNA Mutational Analysis , DNA Repair Enzymes/genetics , DNA Repair Enzymes/metabolism , DNA, Neoplasm/analysis , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mutation , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras) , Retrospective Studies , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , beta Catenin/genetics , beta Catenin/metabolism , ras Proteins/genetics
2.
Gan To Kagaku Ryoho ; 36(5): 867-9, 2009 May.
Article in Japanese | MEDLINE | ID: mdl-19461197

ABSTRACT

FOLFOX therapy is a commonly used chemotherapeutic regimen against recurrent and unresectable colon cancer. However, its acute neurotoxicity is rare and not well recognized. We herein report a case of mFOLFOX6-induced hyperammonemic encephalopathy in a patient having recurrent colon cancer. A 74-year-old female with a history of sigmoid colon cancer was diagnosed as liver, lung, and peritoneal recurrences by surveillance CT and PET/CT. She was initially treated with modified FOLFOX6 therapy. After completing treatment, she presented with sudden onset of confusion, cognitive disturbances, and repeated seizures. None of the other radiographic examinations and laboratory tests provided an explanation for her symptoms except hyperammonemia. She was treated with branched-chain amino acid solutions and high-volume drip infusion, 6 hours after which the encephalopathy resolved. Clinicians should be aware of the adverse hyperammonemia induced by mFOLFOX6 when patients treated with mFOLFOX6 present with neurological disorders.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Diseases, Metabolic/blood , Brain Diseases, Metabolic/chemically induced , Colonic Neoplasms/drug therapy , Hyperammonemia/blood , Hyperammonemia/chemically induced , Aged , Brain Diseases, Metabolic/pathology , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/pathology , Female , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Organoplatinum Compounds/therapeutic use , Positron-Emission Tomography , Recurrence , Tomography, X-Ray Computed
3.
J Med Case Rep ; 2: 289, 2008 Aug 28.
Article in English | MEDLINE | ID: mdl-18755014

ABSTRACT

INTRODUCTION: The occurrence of cytomegalovirus colitis is well known in immunosuppressed patients, such as neoplastic patients following chemotherapy, although its exact etiology remains unclear. CASE PRESENTATION: We present a case of cytomegalovirus colitis occurring in a 77-year-old man with vomiting and diarrhea 2 weeks after initial systemic chemotherapy consisting of 5-fluorouracil, leucovorin and irinotecan for a recurrent colorectal cancer. Initial colonoscopy revealed multiple punched-out ulcers in the transverse colon and the diagnosis of cytomegalovirus was based on positive cytomegalovirus antigen detected by indirect enzyme antibody method, although immunohistological examination of tissues biopsied at colonoscopy was negative. The symptoms ceased under ganciclovir and octreotide treatment, and the patient recovered gradually. CONCLUSION: The most probable cause of the cytomegalovirus colitis in this case was impaired immunity following chemotherapy. Cytomegalovirus infection should be included in the differential diagnosis of gastrointestinal disease in colorectal cancer patients after chemotherapy and, when suspected, the clinician should pursue appropriate diagnostic interventions including colonoscopy.

4.
Gan To Kagaku Ryoho ; 34(11): 1857-9, 2007 Nov.
Article in Japanese | MEDLINE | ID: mdl-18030024

ABSTRACT

We report a recurrent case of gastric cancer with para-aortic lymph node metastasis that showed a marked response to systemic chemotherapy consisting of S-1 alone. A 70-year-old male was admitted to our hospital with appetite loss and left abdominal pain. He had a history of distal gastrectomy due to the advanced gastric cancer. Endoscopy revealed a submucosal tumor-like elevation with central ulcer, and the biopsy specimen was poorly-differentiated adenocarcinoma histologically. CT of the abdomen demonstrated a para-aortic lymph node swelling behind the remnant stomach, indicating an unresectable recurrent gastric cancer. We initially treated the patient with S-1 chemotherapy (60 mgx2/day) by oral administration. His tumor immediately responded to the chemotherapy, and restaging abdominal CT after 2 cycles of chemotherapy showed almost complete regression of lymph node metastasis. The patient has undergone S-1 chemotherapy and currently has remained in remission for more than 21 months with no severe adverse events. The S-1 regime was effective and safe, suggesting that S-1 could be the first-line chemotherapy for recurrent gastric cancer.


Subject(s)
Adenocarcinoma/drug therapy , Antimetabolites, Antineoplastic/therapeutic use , Gastric Stump/pathology , Lymph Nodes/pathology , Oxonic Acid/therapeutic use , Stomach Neoplasms/drug therapy , Tegafur/therapeutic use , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Aged , Aorta , Drug Administration Schedule , Drug Combinations , Gastrectomy , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Remission Induction , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
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