Mitsuhiro Nokubi

Evaluation of venous invasion by Elastica van Gieson stain and tumor budding predicts local and distant metastases in patients with T1 stage colorectal cancer.

Evaluation of pathologic predictors of metastases in T1 stage colorectal cancer may be difficult with hematoxylin and eosin (HE) staining alone. The aim of this study was to clarify the role of pathologic predictors by using immunohistochemical staining and Elastica van Gieson (EVG) staining. One hundred and twenty-four patients who underwent bowel resection for single T1 stage colorectal cancer from 1990 to 2004 in 1 institution were studied. D2-40, EVG staining, and CAM5.2 were used to detect lymphatic invasion, venous invasion, and tumor budding, respectively. These 3 factors were separately evaluated based on HE staining. Histology was reviewed by 1 pathologist. Lymph node metastases in the surgical specimen were the standard reference, and distant metastases were identified by periodic computed tomography for 2 years or more after surgery. A logistic regression model was applied to analyze risk factors for lymph node metastases and a Cox regression model for distant metastases. In predicting lymph node metastases, univariate analysis demonstrated significance for all predictors except venous invasion by HE staining. Multivariate analysis showed that venous invasion by EVG and tumor budding by HE showed significance as predictors. In predicting distant metastases, univariate analysis showed significance for lymphatic invasion shown by D2-40, tumor budding shown by CAM5.2 and HE, and lymph node metastases. Multivariate analysis showed only venous invasion by EVG stain as being significantly associated with distant metastases (P=0.001). In conclusion, venous invasion evaluated shown by EVG staining is a useful pathologic predictor for metastases in T1 stage colorectal cancer.

A comparison of conventional endoscopy, chromoendoscopy, and the optimal-band imaging system for the differentiation of neoplastic and non-neoplastic colonic polyps

BACKGROUND The diagnostic accuracy of conventional endoscopy for small colonic polyps is not satisfactory. Optimal band imaging (OBI) enhances the contrast of the mucosal surface without the use of dye. OBJECTIVE To evaluate the diagnostic accuracy for the differentiation of neoplastic and non-neoplastic colorectal polyps by using magnified OBI colonoscopy. DESIGN An open prospective study. SETTING Jichi Medical University, Japan. PATIENTS A total of 133 colonoscopy cases. MAIN OUTCOME MEASUREMENT A comparative study of the overall accuracy, sensitivity, and specificity for the differentiation of neoplastic and non-neoplastic colorectal polyps < or =5 mm in size by capillary-pattern diagnosis by using conventional colonoscopy, capillary-pattern diagnosis in OBI, and pit-pattern diagnosis in chromoendoscopy with low magnification. RESULTS A total of 107 polyps, composed of 80 neoplastic and 27 non-neoplastic polyps, were evaluated. OBI clearly showed the capillary network of the surface mucosa of neoplastic polyps at low magnification, whereas the surface mucosa of non-neoplastic polyps showed up as a pale lesion. The capillary pattern in conventional colonoscopy had 74% accuracy, 71% sensitivity, and 81% specificity for neoplastic polyps. The accuracy and sensitivity were significantly lower than those that used the capillary pattern in OBI (accuracy 87% and sensitivity 93%) and the pit pattern in chromoendoscopy (accuracy 86% and sensitivity 90%). There were no significant differences in specificity (OBI 70% and chromoendoscopy 74%). The kappa analysis indicated good agreement in both OBI and chromoendoscopy. CONCLUSIONS Capillary-pattern diagnosis in OBI is superior to that in conventional endoscopy and is not significantly different from pit-pattern diagnosis for predicting the histology of small colorectal polyps.

Cicatricial stenosis after endoscopic submucosal dissection of esophageal cancer effectively treated with a temporary self-expandable metal stent

Post-endoscopic submucosal dissection (ESD) cicatricial stenosis has become a clinical issue. In many cases, endoscopic esophageal dilation is performed in patients with post-ESD cicatricial stenosis. On the other hand, a number of recent studies have reported that stent placement is useful for the treatment of benign esophageal stenosis. 1 Here we report a case of cicatricial stenosis that failed to respond to conventional esophageal bougie dilation but was successfully dilated with a temporary self-expandable metal stent (SEMS).

Extremely well-differentiated adenocarcinoma of the gastric cardia: A unique case with columnar cells and laminated stones

Extremely well‐differentiated adenocarcinoma (EWDA) is an unusual  gastric  cancer  that  is  histologically  too  bland  to be diagnosed as malignant neoplasm, particularly using biopsy. EWDA may be a gastric counterpart of ‘adenoma malignum’ or minimal deviation adenocarcinoma (MDA) in the uterine cervix; however, the clinicopathological features of EWDA remain less apparent than those of MDA. A 60‐year‐old male was complaining of dysphagia. He had been made aware of a small submucosal tumor in the cardia 2 years before the onset of this symptom. Endoscopic ultrasonographic examination revealed a large cardiac tumor consisting of thickened layers, as observed in Borrmann type IV. Three mucosal biopsies suggested only benign changes  including  adenoma  and  hyperplastic  polyps.  At the fourth biopsy, cytologically bland columnar cells were located in the submucosa along with stromal fibrosis and laminated stones. The possibility that non‐neoplastic aberrant pancreas with lithiasis formed the tumor was denied at laparotomy by a frozen section that revealed benign‐looking glands invading the diaphragm. Immunohistochemically the cancer glands were positive for CA19‐9 and human gastric mucin, but not for p53 or MUC2. To our knowledge, this is a previously unknown combination of EWDA and psammomatous calcification in the stomach.

Successful Treatment of Esophageal Squamous Cell Carcinoma in a Patient with Fanconi Anemia

Fanconi anemia is a congenital syndrome characterized by hypoplasia of bone marrow and the development of aplastic anemia in childhood, followed by myelodysplastic syndrome and acute myelogenous leukemia in later life. We report here a patient first diagnosed with Fanconi anemia at age 10. Bone marrow transplantation was performed at age 23 and repeated after an episode of rejection at age 25. Hematologic findings returned to normal, but chronic graft-versus-host disease persisted. Esophageal cancer developed at age 35. Invasion of the bronchus and aorta by the tumor was suspected on computed tomography. Chemoradiotherapy was administered to down-stage the tumor, using low-dose cisplatin and 5-fluorouracil. After two courses of chemotherapy with cisplatin (total dose, 100 mg) and 5-fluorouracil (5000 mg) plus radiotherapy (30 Gy), Grade 3 diarrhea and bone marrow suppression developed, and treatment was discontinued. After resolution of toxicity, a good response to the neoadjuvant therapy was seen on computed tomography scan, and a subtotal esophagectomy was performed which demonstrated a complete response in the resected specimen. However, tongue cancer developed at age 40 years, and hemiglossectomy was performed. Patients with Fanconi anemia have a high risk of developing esophageal cancer while they are still young. Reduced doses of alkylating agents and radiotherapy are used in patients with Fanconi anemia. However, the optimal dosage of chemoradiotherapy and the treatment strategy for esophageal cancer in patients with Fanconi anemia remain unclear, and outcomes are generally extremely poor. In this patient, esophageal cancer associated with Fanconi anemia responded well to multidisciplinary therapy.

Spontaneous regression of symptomatic thymoma caused by infarction

We herein report a 38-year-old man who had spontaneous regression of a thymoma with repeating episodes of chest pain that initially occurred 2 years earlier when the tumor was 35 mm in the long axis. Left video-assisted thoracoscopic thymothymectomy was performed. Pathology examination showed a thymoma 15 mm in the long axis, classified B2 in the World Health Organization classification and stage II by Masaoka staging. The feeding arteriole of the tumor, occluded by organized thrombi, was suggested to be the cause of coagulation necrosis. The patient recovered well from surgery without complication and with no episodes of chest pain at the 9-month outpatient follow-up.

Atypical carcinoid of the larynx and expressions of proteins associated with molecular targeted therapy.

OBJECTIVE We reported an extremely rare case of atypical laryngeal carcinoid, and examined the expression of several proteins for application of molecular targeted therapy. METHOD Case report and review of the literature concerning atypical carcinoid arising from the larynx. The expressions of proteins were determined by immunohistochemical analysis. RESULTS We present here a case of atypical laryngeal carcinoid in a 79-year-old Japanese man, which was completely resected, and with no evidence of recurrence. On immunohistochemical analysis, neoplastic elements revealed, strong positivity for platelet-derived growth factor receptor α (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2), and epidermal growth factor receptor (EGFR), and were mild positivity for KIT. CONCLUSION Our findings suggest that atypical laryngeal carcinoid could be completely removed if it is located in the limited lesion. PDGFRα, VEGFR2, and EGFR expressions in this case provide the evidence that atypical laryngeal carcinoid is the candidate for molecular targeted therapy, although further investigations are necessary.

Placental site trophoblastic tumor (PSTT) with multiple metastases and extremely poor prognosis

Placental site trophoblastic tumor (PSTT) is a rare type of gestational trophoblastic disease. There is a wide clinical spectrum of presentation and behavior ranging from a benign condition to an aggressive disease with a fatal outcome. PSTT limited to the uterus is in a good prognosis group, but PSTT with metastasis is a lethal disease. We document a case of PSTT with multiple metastases and extremely poor prognosis. A 36-year-old woman had abnormal irregular vaginal bleeding 14 months after her third pregnancy and delivery. The mitotic count of the tumor cells was quite high (23/10 high-power fields). It would have been difficult to remove the tumor by surgery because of the tumor size and its invasion, so we suggested chemotherapy. We treated her with EMA/CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) as a first-line regimen. During the sixth cycle of EMA/CO, the disease became drug-resistant and she died 8 months after the first symptom. This was a rare case among documented patients with PSTT with metastasis, with the patient having short-term survival (<1 year). We conclude that a high mitotic count and atypical undifferentiated pathological features are significant poor prognostic factors for survival in PSTT.

Thymic clear cell carcinoma

We report a 42-year-old man with a rare thymic clear cell carcinoma. Marked nodal metastases involved right hilar, mediastinal, and left supraclavicular regions. Complete resection including thymothymectomy, cervicomediastinal nodal dissection, and right upper lobectomy with hilar lymphadenectomy was successful. Postoperative chemoradiation therapy was uneventful. The patient had no recurrence or metastasis until brain metastasis occurred 1 year after surgery.

Complete Resection of a Complicated Huge Mesenteric Lymphangioma Guided by Mesenteric Computed Tomography Angiography With Three-Dimensional Reconstruction: Report of a Case

We herein describe the case of an adult with a complicated huge lymphangioma of the small bowel mesentery. Computed tomography (CT) confirmed a 45 × 30 × 14 cm multiple and separate, mixed and solid cystic tumor without enhancement by contrast medium in the abdominal cavity. Mesenteric CT angiography with three-dimensional (3D) reconstruction showed that the tumor did not involve the first jejunal artery, although the tumor did involve the subsequent jejunal and ileal arteries and the corresponding segment of the small bowel. Under anatomic guidance based on mesenteric CT angiography with 3D reconstruction, we were able to successfully excise the tumor. Mesenteric lymphangioma should be excised even when the tumor is asymptomatic. Mesenteric CT angiography with 3D reconstruction is useful for the surgical treatment of huge mesenteric tumors.