Toshiki Matsubara

Pancreaticobiliary maljunction and carcinogenesis to biliary and pancreatic malignancy

BackgroundIt is widely accepted that congenital choledochal cyst is associated with pancreaticobiliary maljunction (PBM). But, PBM is an independent disease entity from choledochal cyst. PBM is synonymous with “abnormal junction of the pancreaticobiliary ductal system”, “anomalous arrangement of pancreaticobiliary ducts”, “anomalous union of bilio-pancreatic ducts”, etc. Cases with PBM not associated with biliary duct dilatation are often found, and these cases are frequently complicated gallbladder cancer. The Japanese Study Group of Pancreaticobiliary Maljunction was started in 1983, and defined diagnostic criteria and nationwide registration system of PBM cases was started. PBM is defined as a union of the pancreatic and biliary ducts which is located outside the duodenal wall. Bile and pancreatic juice reflux and regurgitate mutually.Biliary carcinogenesisThe most bothersome problem is biliary carcinogenesis. Gallbladder cancers arise in 14.8% and bile duct cancers arise in 4.9%. The incidence of the gallbladder carcinoma of PBM without bile duct dilatation is 36.1%. Many investigators have tried to clarify the carcinogenic process, from various aspects. The biliary epithelia are injured by harmful substances, and in the course of repair, multiple alterations of oncogenes and tumor suppressor genes are followed, and they lead to carcinoma through multistage interaction. In the biliary epithelia of PBM, incidence and degree of hyperplasia are characteristic. K-ras gene mutations are observed in the cancerous as well as noncancerous lesions of biliary tract of PBM patients. Mutations of p53 gene and overexpression of p53 protein are also found in the cancerous and noncancerous lesions. These changes are called “hyperplasia–carcinoma sequence”.TreatmentTotal excision of the extrahepatic bile duct with gallbladder followed by hepaticojejunostomy, Roux-en-Y, or end-to-side hepaticoduodenostomy are treatment of choice, even for cases with not dilated bile duct, because the incidence of cancer in the nondilated bile duct is not negligible, and genetic changes are seen in a nondilated bile duct.

Risk of Second Primary Malignancy After Esophagectomy for Squamous Cell Carcinoma of the Thoracic Esophagus

PURPOSE To assess the risk of subsequent malignancies after esophagectomy for squamous cell carcinoma of the thoracic esophagus for the establishment of an adequate follow-up program. PATIENTS AND METHODS We statistically analyzed clinical factors in 114 cases of second malignancy after esophagectomy that developed in 94 of 679 patients who underwent curative resection. The cancer incidence rates in the general population estimated by the Research Group for Population-Based Cancer Registration in Japan were used as standards for comparison. RESULTS The 10-year cumulative risk of second malignancy was 34.5%, and the overall relative risk (RR) was 2.98 (95% CI, 2.41 to 3.65). The risk of head and neck cancer was markedly elevated (RR, 34.9; 95% CI, 24.3 to 48.6), followed by the risks of lung cancer (RR, 3.24; 95% CI, 1.89 to 5.19) and stomach cancer (RR, 2.00; 95% CI, 1.17 to 3.21). Multifactor analysis demonstrated that independent factors affecting the risk of subsequent malignancies were presence of other malignancies detected before esophagectomy and any of the following factors: masculine sex, alcohol consumption, and smoking. The 5-year survival rate after detection of subsequent malignancy was 45%. The outcome in patients with subsequent head and neck cancer was significantly less favorable as a result of difficulty in early detection. CONCLUSION Patients had a remarkably high risk of subsequent cancer of the upper aerodigestive tract after esophagectomy, in particular, head and neck cancer. Minute postoperative surveillance is strongly recommended, especially in patients with a history of malignancies before esophagectomy. Early detection of second malignancies allowed less invasive treatment with favorable outcome.

Treatment of thoracic esophageal carcinoma invading adjacent structures

T4 esophageal cancer is defined as the tumor invading adjacent structures, using tumor–node–metastasis (TNM) staging. For clinically T4 thoracic esophageal carcinoma, multimodality therapy, that is, neoadjuvant chemoradiotherapy (CRT) followed by surgery or definitive CRT, has generally been performed. However, the prognosis of patients with these tumors remains poor. Another strategy is needed to achieve curative treatment. In the present article, the treatment strategies employed to date are reviewed. Furthermore, the strategies for these malignancies are reassessed, based on our experiences. R1/2 and R0 resections are regarded as those with residual and no tumor after surgery. The present data show that patients who underwent R1/2 resection after neoadjuvant CRT experienced little survival benefit, while complete response (CR) cases after definitive CRT had comparatively better results. Therefore, curative surgery should not be attempted without down‐staging, and definitive CRT should be the initial treatment. Then surgery is indicated for the eradication of residual cancer cells. Close surveillance is essential for early detection of relapse even after CR, because the operation will gradually become increasingly difficult due to post‐CRT fibrosis. In conclusion, multimodality therapy consists of definitive CRT followed by R0 resection, which can be the treatment of choice for T4 esophageal carcinoma. These challenging treatments have the potential to constitute the most effective therapeutic strategy. (Cancer Sci 2007; 98: 937–942)

Metastasis to the Forearm Skeletal Muscle from an Adenocarcinoma of the Colon: Report of a Case

Abstract While the liver and lung are primary targets for distant metastasis from colorectal carcinoma, metastasis in other distant sites is rarely found. We report herein an unusual case of metastasis to the skeletal muscle of the right forearm from an adenocarcinoma of the transverse colon. A 60-year-old man was originally admitted to our hospital for surgical treatment of an intestinal obstruction caused by a transverse colon carcinoma. Transverse colon resection along with lymph node dissection was performed and no evidence of distant metastatic foci was found. Angiography-enhanced computed tomography scanning done 14 months after the first operation revealed multiple hepatic metastases which were resected. A metastasis was subsequently detected in the right extensor carpi ulnaris muscle 2 years after the primary resection, and a major part of the right extensor carpi ulnaris and the extensor digiti minimi muscle were resected, warranting a sufficient margin of 5 cm of normal tissue from the tumor. Reattachment of the residual muscles into the ulna was performed. Metastases to bone and/or soft tissues from colorectal carcinomas are extremely rare and to our knowledge, only eight other cases have been reported in the world literature. This low incidence may be related to the anatomical characteristics and/or the biochemical environment of the skeletal muscle, but it is also possible that the true incidence is underestimated. Recent improvements in interventional radiological procedures may facilitate a diagnosis of skeletal muscle metastasis being made more frequently.

Minute gastric carcinoid tumor with regional lymph node metastasis

We report a patient with a minute gastric carcinoid tumor with lymph node metastasis, and a small gastric cancer. A 50-year-old man having a diagnosis of an elevated lesion on the anterior wall of the gastric body, detected by a series of upper gastrointestinal examinations, was referred to the Cancer Institute Hospital. Careful upper fluoroscopy disclosed a small superficial depressed lesion with converging folds and a superficial elevated lesion covered with nonspecific gastric mucosa. With a final preoperative diagnosis of depressed early cancer and minute carcinoid tumor of the stomach, made by upper gastrointestinal examinations including biopsy, the patient underwent segmental gastrectomy and perigastric lymph node dissection. Histological examination of the resected specimen revealed a lymph node metastasis from a gastric carcinoid tumor of 5-mm diameter, in addition to an early gastric cancer of poorly differentiated adenocarcinoma. Small gastric carcinoid tumors have been regarded as being benign neoplasms biologically. However, the case we present suggests that attention should be paid to the possibility of metastasis at the time of treatment for a minute sporadic gastric carcinoid tumor. We therefore discuss the malignant potential of these tumors, mainly from the viewpoint of histopathological classification, to gain understanding so that the patients can be treated adequately.

Multiple perforated ulcers of the small intestine associated with allergic granulomatous angiitis: report of a case.

Although allergic granulomatous angiitis (AGA) is occasionally associated with gastrointestinal lesions, multiple perforated ulcers of the gastrointestinal tract are uncommon. We report herein a case of AGA associated with multiple perforated ulcers that erupted in the small intestine during corticosteroid therapy. A 31-year-old Japanese man was admitted to our hospital with epigastralgia, edema of the bilateral lower extremities, and general malaise. He had a persistent high fever, abdominal pain, and watery diarrhea. Laboratory data showed remarkable eosinophilia. The abdominal pain became exacerbated after the administration of oral prednisolone. Physical examination indicated positive signs of peritoneal irritation in the entire abdomen, and abdominal computed tomography scanning showed intra-abdominal free air, suggesting generalized peritonitis due to intestinal perforation. Laparotomy revealed multiple perforated ulcers in the jejunum and ileum. Histological examination indicated remarkable eosinophilic infiltration in the surrounding area of the small arteries and arterioles located in the submucosal layer, which was compatible with AGA. Although the association of intestinal perforation with AGA is relatively infrequent, intensive perioperative management is essential to ensure a favorable clinical outcome, particularly during the period on corticosteroid therapy.

Utility of preoperative chemoradiotherapy for advanced esophageal carcinoma.

Background and Aims:  The most effective treatment would be neoadjuvant chemoradiotherapy (NACRT) plus surgery with three‐field lymphadenectomy, if tolerability and complications are acceptable. The aim of this prospective study was to evaluate the tolerability of NACRT+ systematic three‐field lymphadenectomy.

Studies on Surgical Treatment for Esophageal Cancer After Gastrectomy

In the surgical treatment for postgastrectomy esophageal cancer, the issues of the reconstructive method of the alimentary tract, the management of the remnant stomach, and the appoarch to the esophagus deserve special attention. We report the surgical results.

Appropriate Range of Lymph Node Dissection for Carcinoma of the Thoracic Esophagus. Is Cervical Dissection Unnecessary for Carcinoma of the Lower Thoracic Esophagus

癌の口側がEi以下で, m3以深の胸部食道癌で頸胸腹郭清を行った31例を検討し, 胸部下部 (Ei) 癌の手術では頸部郭清は不必要か否かを検討した.頸部転移は6例 (19%) で認め, その中で4例 (13%) は頸部単独領域転移であった. 転移部位は頸部操作で郭清し得る頸胸境界部の反回神経リンパ節に多かった.m3～sm1, 4例中1例 (25%), sm2～sm3, 7例中1例 (14%), mp～a2, 19例中2例 (11%) が頸部単独領域転移であり, 表在癌でも頸部単独転移はまれではなかった. 手術操作による反回神経麻痺は4例 (13%) にあり, いずれも6か月以内に症状は改善した. 頸部再発は1例あり, 初回手術時に郭清を省略した下内深頸リンパ節に再発した. 頸部単独転移例の予後は良好であった.頸胸境界部の確実な郭清には頸部操作が必要であり, Ei以下の表在癌においても頸部郭清が望ましい.

Preoperative Assessment of Lymph Nodes on Selecting the Dissection Method for Cancer of the Thoracic Esophagus.

胸部食道癌切除198例についてリンパ節転移の術前評価と病理所見, 手術成績との関係を調べた, 術前評価は (-),(±),(+),(++) の4段階で評価した.1.画像診断上異常所見を呈しない微小転移がまれではなく, 転移診断のsensitivityには限界があった.それでも, 気管周囲, 胃上部のsensitivityは中下縦隔にくらべて良好であった.これらのリンパ節はpoor risk例で縮小手術の適応を検討する上で重要である.2.転移診断のspecificityは良好で,(+) 以上を陽性とすると95%以上であった.3.右反回神経沿線や胃上部が (+) の例や左傍気管 (±) 以上の例は他と比べて手術成績が有意に不良であった.また, 胃上部 (++) では腹部傍大動脈再発が高率であった.これらの例ではそれぞれ胸骨切開による頸胸境界部郭清や腹部左傍大動脈郭清が望ましい.4.転移陽性例の手術成績は術前評価 (++) 例を除いて術前評価との関連はみられなかった.