Shigeru Lee

Hypomethylation of Alu repetitive elements in esophageal mucosa, and its potential contribution to the epigenetic field for cancerization

BackgroundAberrant hypermethylation of specific genes is present in esophageal squamous cell carcinomas (ESCCs). Such hypermethylation is also present in normal-appearing esophageal mucosae of ESCC patients and is considered to contribute to the formation of a field for cancerization. On the other hand, the presence of global hypomethylation in ESCCs or in their background esophageal mucosae is unknown.MethodWe collected 184 samples of esophageal mucosae (95 normal mucosae from healthy subjects, and 89 non-cancerous background mucosae from ESCC patients) and 93 samples of ESCCs. Methylation levels of repetitive elements (Alu, LINE1) and cancer/testis antigen genes (NY-ESO-1, MAGE-C1) were measured by bisulfite pyrosequencing and quantitative methylation-specific PCR, respectively.ResultsMethylation levels of Alu, LINE1, NY-ESO-1, and MAGE-C1 were significantly lower in ESCCs than in their background and normal mucosae. Also, in the background mucosae, a significant decrease of the Alu methylation level compared with the normal mucosae was present. In ESCCs, methylation levels of the two repetitive elements and the two cancer/testis antigen genes were correlated with each other.ConclusionThis is the first study to show the presence of global hypomethylation in ESCCs, and even in their non-cancerous background mucosae. Alu hypomethylation might reflect the severity of an epigenetic field for cancerization.

Results of video-assisted thoracoscopic surgery for esophageal cancer during the induction period

ObjectiveThe attainment of proficiency in thoracoscopic radical esophagectomy for thoracic esophageal cancer requires much experience. We aimed to master this procedure safely with our regular surgical team members under the direction of an experienced surgeon. We evaluated the efficacy of instruction during the induction period and the significance of our results.MethodsWe compared the results of 12 thoracic esophageal cancer patients who underwent thoracoscopic radical esophagectomy in our institution (group A) to those of the initial 17 patients who underwent the same operation at the director’s institution (group B).ResultsWe were able to perform complete thoracoscopic radical esophagectomies without any direction after experiencing 10 cases that were performed under adequate direction. The number of dissected lymph nodes and the duration of the procedure were similar in the two groups: 34 (22–53) vs. 26 (9–55) nodes, P = 0.23; and 327.5 (230–455) vs. 315 (190–515) min, P = 0.947, respectively. The amount of thoracic blood loss was significantly less in group A than in group B: 185 (110–380) g vs. 440 (110–2360) g, P = 0.0035. Postoperative pneumonia and atelectasis were observed in 25.0% of group A patients and in 17.6% of group B patients. The incidence of recurrent nerve palsy was 30.7% in group A and 11.7% in group B, but there was no statistically significant difference (P = 0.19). The morbidity rates in group A and group B were 41.6% and 29.4%, respectively (P = 0.694).ConclusionThoracoscopic radical esophagectomy can be mastered relatively quickly and safely under the direction of an experienced surgeon and a regular surgical team.

Granular cell tumor of the male breast: report of a case.

We treated a 35-year-old male with a granular cell tumor in the right breast. Physical examination revealed a solid, flattened, round 3.2 × 2.5-cm mass with an irregular surface, covering skin fixation and right axillary lymphadenopathy. Mammography revealed a welldemarcated high-density mass with a minimal starburst appearance. Ultrasonography revealed a hypoechoic, nonhomogeneous mass with an acoustic shadow. Several enlarged lymph nodes in the right axilla were removed at the time of breast tumor excision. Histologically, the tumor featured nests of round or polygonal cells with abundant eosinophilic cytoplasmic granules and small round nuclei, and the enlarged lymph nodes in the right axilla exhibited no metastasis. Immunohistochemically, there was positive staining for S-100 protein, neuronspecific enolase, and vimentin. The tumor also stained for macrophage CD-68, α1-antichymotrypsin, and myoglobin. These immunohistochemical findings suggested the tumor cells to be undifferentiated mesenchymal cells which demonstrated the properties of neurogenic cells and histiocytes.

Influence of incomplete neoadjuvant chemotherapy on esophageal carcinoma

BackgroundNeoadjuvant chemotherapy (NAC) involving two cycles of cisplatin plus fluorouracil is recommended in Japan as a standard treatment for resectable, locally advanced esophageal squamous cell carcinoma (ESCC). We have encountered patients who were administered incomplete chemotherapy because of adverse events or the patient’s refusal of treatment. Here, we retrospectively investigated the influence on perioperative outcomes and long-term prognosis of patients with ESCC who underwent complete (two cycles) or incomplete (one cycle) NAC.MethodsWe retrospectively investigated 133 patients with locally advanced ESCC of the thoracic esophagus who underwent NAC. We compared the perioperative results and prognoses of patients who underwent complete or incomplete NAC because of adverse events or the patient’s refusal of treatment.ResultsOf 133 patients, 37 patients did not receive the second cycle of NAC; the remaining 96 patients received the second cycle of NAC as scheduled. There were no significant differences in the clinical backgrounds, surgical results, or operative morbidity rates between the groups. Patients in both groups were similarly administered postoperative chemotherapy regimens. There was no significant difference in disease-free survival or overall survival.ConclusionsWe suggest that perioperative outcomes and long-term prognosis of patients with locally advanced ESCC were not significantly influenced, even if the patients did not receive a complete cycle of NAC. When certain adverse events occur after the first cycle of NAC, we believe that it is nevertheless possible to discontinue chemotherapy.

Attention to anomalies of the right pulmonary vein in subcarinal lymph node dissection in radical esophagectomy for cancer

Here, we report on an anomaly of the right pulmonary vein in the subcarinal area and emphasis the importance of its focus in subcarinal lymph node dissection. A 51-year-old Japanese man underwent thoracoscopic radical esophagectomy with regional lymph node dissection for esophageal carcinoma T1bN1M0, stage IIB. While dissecting the subcarinal lymph node, we encountered a thick vein crossing posterior to the intermediate right bronchus. We recognized the anomalous right pulmonary vein (anomalous V2) that drained into the left atrium from the right posterior segment (S2). We cautiously dissected the subcarinal lymph node and were able to preserve the anomalous vein. This anomalous pulmonary vein can cause serious complications. If the anomalous V2 had been injured or ligated, congestion of the right S2 or cardiac tamponade might have develop. Since anomalous pulmonary veins are easily identified by enhanced computed tomography, careful observation is essential for avoiding their unnecessary injury.

Cytomegalovirus-associated ulceration of gastric conduit after chemoradiotherapy following esophagectomy for cancer

A 64-year-old man underwent radical esophagectomy for cancer and simultaneous reconstruction using the gastric conduit through the posterior mediastinum. Two courses of adjuvant chemotherapy were performed. Twenty-eight months postoperatively, recurrence of the cancer was detected in the mediastinal lymph nodes, and he underwent concurrent chemoradiotherapy and boost chemotherapy. Endoscopy was then performed to investigate the cause of epigastralgia, and multiple ulcerations were found in the lesser curvature of the gastric conduit. Although a proton-pump inhibitor was orally administered, the ulceration was intractable. Re-examination of the original biopsy specimens and serological testing revealed positivity for cytomegalovirus. The ulcers began to heal after administration of foscarnet sodium. After the treatment, no signs of exacerbation associated with reinstitution of chemotherapy were observed.

Effect of Neutrophil Elastase Inhibitor on Coagulability in Patients after Radical Esophagectomy

食道癌術後には凝固異常が発症することが知られている。この凝固異常に対しては，現在までステロイドなどさまざまな薬剤投与が試みられてきた。今回われわれは，好中球エラスターゼの特異的阻害剤（シベレスタットナトリウム，以下SN）投与の食道癌術後の凝固能におよぼす影響について検討した。対象は食道癌切除再建を一期的に行った41例で，これら症例を術後SNを投与した21例（SN+群）と，SNを投与しなかった20例（SN-群）に分けた。SN+群でSNを，術直後より0.2mg/kg/hrで術5病日まで持続的に投与した。全例で術直前にメチルプレドニゾロン（500mg）を投与し，術7病日まで血小板数・FBG·FDP·D-Dimer·AT3·TAT·APTT·Protein C・α2PIを経時的に測定した。血小板数・FBG·FDP·D-Dimer·TATの変動には両群に差がなかった。AT3とProtein Cは術2·3病日でSN+群が有意に高値で，α2PIは術3病日でSN+群が有意に高値であった。APTTは，術3病日にSN-群で有意に高かった。食道癌術後管理におけるエラスターゼ阻害剤投与は食道癌術後の凝固異常状態を制御し，早期に回復させることが可能である。

A Case of Submucosal Basaloid Carcinoma of Cervico-thoracic Esophagus

症例は64歳の男性. 平成14年1月初旬より嚥下困難が出現し, 食道造影で頸胸境界部食道の右側に約2.5cmの隆起性病変を認め, 上部消化管内視鏡検査では, 門歯列より約20cmの食道右壁に1pl型の隆起性病変を認めた. CT, 超音波検査では明らかなリンパ節転移, 血行性転移は認めなかった. 以上より, T2N0M0, Stage IIの頸胸境界部食道癌と診断し, 平成14年5月8日に胸腔鏡下食道切除術および3領域リンパ節郭清術を施行した. 腫瘍は肉眼的に径22×16mm, 1pl型で, 病理組織診断では類基底細胞癌であった. 深達度はsmでly0, v1, pN0, pStage Ibであった. 類基底細胞癌は非常にまれであり, 予後不良とされている. リンパ節転移のない表在型は予後がよいとの報告もあるが, 頸胸境界部食道に発生した表在型類基底細胞癌は本邦では報告例がなく, また細胞増殖能が高いことより再発に留意し経過観察中である.