Naoya Yokomakura

Expression of p53R2 Is Related to Prognosis in Patients with Esophageal Squamous Cell Carcinoma

Purpose: The p53 gene and its family are important factors for carcinogenesis, prognosis, and chemoresistance in esophageal squamous cell carcinoma. A recently identified ribonucleotide reductase, p53R2, is regulated by p53 for supplying nucleotides to repair damaged DNA. In the present study, we analyzed the expression and clinicopathologic significance of p53 and p53R2 in esophageal squamous cell carcinoma. Experimental Design: We immunohistochemically investigated the relationship between p53 and p53R2 expressions in surgical specimens of primary tumors in 222 patients with esophageal squamous cell carcinoma. Results: The positive expression rate of p53 was 47.1% and that of p53R2 was 61.7%. Positive p53R2 expression was significantly correlated with depth of invasion, lymph node metastasis, stage, and poor prognosis. In the p53-negative group, the 5-year survival rate was better in patients with negative p53R2 expression than in those with positive p53R2 expression. Multivariate analysis indicated that the negative expression of both p53 and p53R2 was an independent prognostic factor along with tumor depth nodal metastasis and stage. Conclusions: We showed that positive p53R2 expression was related to tumor development and that alteration of p53R2 expression in p53-negative tumors was closely related to prognosis. Evaluation of the expressions of p53 and p53R2 proteins should be useful for determining the tumor properties, including prognosis, in patients with esophageal squamous cell carcinoma.

Overexpression of vascular endothelial growth factor-C correlates with lymph node micrometastasis in submucosal esophageal cancer

Lymph node metastasis, including lymph node micrometastasis (LMM), is one of the most important prognostic factors in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor C (VEGF-C) plays a key role in the process of lymphangiogenesis. We examined VEGF-C expression and tumor microvessel density of the primary tumors in ESCC and analyzed relationships between VEGF-C expression and clinicopathologic findings including LMM in submucosal ESCC. The subjects were 87 patients with submucosal ESCC. Immunohistochemical staining of VEGF-C and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. Microvessel density was calculated from CD34 expression, and LMM was detected by cytokeratin staining. VEGF-C overexpression significantly correlated with depth of tumor invasion, lymphatic invasion, and lymph node metastasis (P<0.05, P<0.0001, and P<0.0001, respectively). High microvessel density also correlated with lymphatic invasion and lymph node metastasis (P<0.005 and P<0.05, respectively). LMM was detected in 8 cases and 14 lymph nodes by cytokeratin staining. VEGF-C overexpression and high microvessel density were found in tumors with lymph node metastasis and/or LMM, compared with tumors without nodal metastasis or LMM (P<0.0001 and P<0.01, respectively). The present findings indicate that in ESCC with submucosal invasion, VEGF-C overexpression of the primary tumor is a strong high risk factor for lymph node metastasis, including LMM.

EGFR mutations and human papillomavirus in lung cancer

Our previous study reported a frequent detection of human papillomavirus (HPV) genome in primary lung adenocarcinomas of the recurrent patients who were responsive to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, suggesting that HPV presence in lung cancer may be related to a genetic background related to EGFR mutations. The present study examined the association between the HPV presence and mutations in exons 19 and 21 of EGFR gene in Japanese lung cancer patients. Thirteen (31%) out of 42 cases had EGFR mutations. Although these mutations were tended to be observed in females, non-smokers, or adenocarcinomas, there was no statistically significant associations. HPV DNA was found in 7/42 (17%) lung tumors. The frequency of HPV presence did not differ in histological types. The presence of HPV DNA was significantly related to EGFR mutations (P=0.021), especially in adenocarcinomas of the lung (P=0.014). HPV-positive lung tumors accounted for 38% and 7% of those with and without EGFR mutations, respectively. Our results suggest that EGFR mutations are associated with HPV presence in Japanese patients with lung cancer.

A case of leptomeningeal carcinomatosis from esophageal basaloid carcinoma diagnosed by quantitative reverse transcription-polymerase chain reaction for carcinoembryonic antigen

We describe herein the case of a 68-year-old man who experienced leptomeningitis after esophagectomy from an esophageal basaloid carcinoma. Although the patient had a good operative course for the first 10 days after surgery, he suddenly had general convulsions with unconsciousness. He was placed on mechanical ventilation in an intensive care unit. Computed tomography and magnetic imaging resonance did not reveal any abnormal findings. No abnormal data in the cerebrospinal fluid were found by biochemical, virological, and cytological examination. The positive expression of carcinoembryonic antigen messenger ribonucleic acid in cerebrospinal fluid was detected by a quantitative reverse transcription-polymerase chain reaction method. Immunohistochemical staining using an anticytokeratin antibody confirmed the presence of tumor cells in the cerebrospinal fluid. Spontaneous breathing was recovered after treatment with systemic chemotherapy. Six months after surgery, computed tomography revealed multiple brain metastases. This case demonstrates that the quantitative reverse transcription-polymerase chain reaction method of analyzing carcinoembryonic antigen messenger ribonucleic acid may be a sensitive and useful method for determining leptomeningeal metastasis before the detection of tumors by cytological and imaging examinations in patients with cancer.

Individualization of lymphadenectomy in superficial esophageal squamous cell cancer

BackgroundAs the result of the development of imaging means, the incidence of discovery of superficial esophageal squamous cell cancer (ESCC) has recently increased. Various treatment methods such as endoscopic mucosal resection and reduction of lymphadenectomy have been performed to preserve the quality of life. Because lymph node metastasis occurs even in the early stage of esophageal cancer, we should carefully select the treatment method, including lymphadenectomy.MethodsWe analyzed the distribution of solitary lymph metastasis of 27 superficial esophageal cancers. To analyze the distribution of micrometastasis, a total of 1542 lymph nodes obtained from 46 patients with pN0 submucosal cancer were immunohistochemically examined by cytokeratin antibody. Sentinel node mapping was performed in 23 patients with clinical T1 tumors.ResultsThe location of lymph node metastasis in the 22 patients with solitary lymph metastasis in superficial cancer was limited to recurrent nerve nodes in the upper thoracic esophagus, recurrent nerve nodes, paraesophageal nodes, or perigastric nodes in the middle or lower thoracic esophagus. For eight patients with lymph node micrometastasis in pN0 patients with superficial esophageal cancer, the locations of micrometastasis were similar to those of solitary metastasis. In sentinel node mapping, all nodal metastasis was included in sentinel nodes with a single exception.ConclusionsIndividual lymphadenectomy in superficial ESCC will be established using methods such as analysis of past data, clinical diagnosis of lymph node metastasis by imaging, and sentinel node navigation surgery, including the diagnosis of micrometastasis.

Pulmonary Metastasectomy 31 Years After Surgery for Renal Cell Carcinoma

An 82-year-old man underwent a left upper lobectomy for a solitary tumor on suspicion of lung cancer. Histopathologic findings of the resected specimen showed clear cell renal cell carcinoma, which was diagnosed as a metastasis from kidney cancer concealed for 31 years after nephrectomy. The Ki-67 labeling index of the metastatic tumor was high (36.1%). A few cases of recurrent renal cell carcinoma after a long interval from initial diagnosis have been seen. However, pulmonary metastasectomy more than 30 years after radical nephrectomy for renal cell carcinoma has not been reported. This remarkable case provides new and valuable clinical insights into metastatic renal cell carcinoma.

Detection of alternative subpleural lymph flow pathways using indocyanine green fluorescence

PurposePulmonary lymphatic fluid predominately flows along the bronchi. However, there are reports suggesting that an alternative lymphatic pathway exist, which may result in skip metastases. The aim of this study was to evaluate the subpleural lymph flow in vivo using indocyanine green (ICG) fluorescence.MethodsOne hundred cases were enrolled. ICG was injected into the macroscopically healthy subpleural space. Intraoperative fluorescence images were then observed in real time.ResultsICG fluorescence was observed moving through subpleural channels in 58/100 cases. ICG flowed into adjacent lobes over interlobar lines in 18 cases and flowed from the visceral pleura directly into the mediastinum in 5 cases. The frequency of mediastinal detection without hilar lymph node detection was significantly higher in the left lung compared to the right (p < 0.05). The subpleural lymph flow detection rates were significantly lower in patients with smoking pack-years ≥ 40 than those with < 40 (p < 0.05).ConclusionsThe flow of lymphatic fluid directly into the mediastinum suggests one mechanism of skip metastasis. In addition, the reduction of the subpleural lymph flows in smokers with ≥ 40 pack-years suggests that smoking might modify lymph flow patterns. These findings may assist in selecting the optimal therapy for patients with possible skip metastasis.

Successful closure of a tracheocutaneous fistula after tracheostomy using two skin flaps: a case report.

A tracheocutaneous fistula may develop when a tracheostomy orifice epithelializes during a prolonged course of healing or undernutrition. Various techniques for closing such fistulae have been reported. However, a standard procedure has not yet been established. We, herein, present a case involving a 35-year-old woman who developed a tracheocutaneous fistula after tracheostomy. We closed the fistula using two skin flaps to cover the tracheal lumen and skin defect, respectively. The advantage of this technique is that it allows the tracheal lumen to be covered by inversed skin epithelium and ensures that the suture line of the skin does not match up with that of the subcutaneous tissue.

A case of resected plasma cell type castleman's disease with intramediastinal lymph nodes spread.

We report a case of resected plasma cell (PC) type Castlemans disease (CD) in a 21-year-old female who had an anterior mediastinal mass with additional surrounding nodules. She was aware of low-grade fever and fatigue for several years. From hematological and biochemical examinations, elevated inflammatory responses and levels of serum IgG (2908 mg/dL) and IL-6 (22.2 pg/mL) were observed. She was diagnosed with PC type CD by needle biopsy under computed tomography (CT) guidance. It was thought that the lesion was localized in the mediastinum. Then, mediastinal adipose tissue including the tumor, additional nodules and thymus were removed. The histological findings of PC type CD were found not only in the main tumor but also in surrounding swollen lymph nodes. Her symptoms improved and inflammatory responses decreased after the operation. No recurrence has been observed for 5 years after the operation.