Small Cell Type of Esophageal Neuroendocrine Carcinoma Resembling a Submucosal Tumor.

We report a rare case of primary small cell type esophageal neuroendocrine carcinoma with a unusual endoscopic form similar to a submucosal tumor with the results of the histological and immunohistochemical analyses. A 57-year-old woman with dysphagia was referred to our hospital for further examination and treatment, and was diagnosed as type 1s esophageal carcinoma in the middle thoracic esophagus. Endoscopy revealed a protruding esophageal carcinoma resembling a submucosal tumor with an irregular and nodular surface covered by non-neoplastic epithelium stained with iodine. Analysis of the esophageal biopsy specimen revealed poorly differentiated squamous cell carcinoma. Based on a diagnosis of type 1s carcinoma in the middle thoracic esophagus that was 5 cm in size longitudinally, a radical esophagectomy with three-field lymph node dissection was performed. The pathological examination with histological and immunohistochemical analysis of the resected specimen revealed a small cell type neuroendocrine carcinoma overlaid by a non-neoplastic epithelium, extending into the adventitia without lymph node metastasis (T3, N0, M0, Stage II). However, multiple metastases in the brain and lung developed 3 months postoperatively, and the patient died of the cancer 7 months after the operation. This was a rare case of a highly malignant primary small cell type esophageal neuroendocrine carcinoma showing extremely rare form.

Small Intestinal Metastasis from Esophageal Squamous Cell Carcinoma Presenting with Perforated Peritonitis.

Metastatic tumors of the small intestinal tract from extra-abdominal sites are rare. We report herein a rare case of small intestinal metastasis from esophageal carcinoma that presented with perforated peritonitis. A 71-year-old man with dysphagia was referred to our hospital for further examination and treatment, and was diagnosed with type 3 advanced esophageal squamous cell carcinoma of the lower thoracic esophagus. Based on a diagnosis of Stage II cancer, a radical esophagectomy with three-field lymph node dissection was performed after neoadjuvant chemotherapy composed of 5-fluorouracil plus cisplatin. Pathological examination of the resected specimen revealed a moderately differentiated squamous cell carcinoma, extending into the adventitia with lymph node metastasis (T3, N2, M0, Stage III). During postoperative adjuvant chemotherapy, the patient complained of abdominal pain and was found to have perforated peritonitis. Emergency laparotomy was performed. A jejunal perforation with a submucosal nodule approximately 80 cm distal from the ligament of Treitz was detected, and completely resected by jejunal partial resection. Histopathology of the specimen showed a perforation of the small intestine due to metastasis of esophageal squamous cell carcinoma with mesenteric lymph node metastasis. The patient died of cancer 9 months after surgery. An extremely rare case of small intestinal metastasis from esophageal carcinoma presenting with perforated peritonitis was described.

Liposome-encapsulated hemoglobin accelerates gastric wound healing in the rat.

BACKGROUND: Liposome-encapsulated hemoglobin, a nanometer-sized artificial O2 carrier with a high O2 affinity (h-LEH), may facilitate O2 delivery to surgical wounds and thereby accelerate healing after gastrointestinal surgery. METHODS: Ten mL/kg of h-LEH (n = 25), empty liposome (n = 21) or homologous washed red blood cells (RBC, n = 22) was intravenously infused prior to the creation of a 10 mm incision and interrupted suture closure of the gastric wall in rats. After two and four days, the stomach was excised and the bursting pressure was determined by gradually inflating the stomach with air. This procedure was followed by histological examinations. RESULTS: The bursting pressure of the surgical wound was significantly higher two days after surgery in the h-LEH-treated rats in comparison to the control rats that received either empty liposome or RBC transfusion (P < 0.05). The three groups displayed similar bursting pressures four days after surgery. Histological examinations revealed less neutrophil infiltration, better granulation, and more macrophage infiltration in the h-LEH-treated rats after two days; however, these differences were no longer significant four days after surgery. CONCLUSION: The results suggest that h-LEH, but not a homologous transfusion or empty liposome, may accelerate early wound healing after a gastric incision and anastomosis in a rat model.

[Recent advances of endoscopic treatment for esophageal cancer].

The indications for endoscopic treatment are limited to cases without lymph node metastasis, because it is only a local therapy. The relationship between cancer depth and lymph node metastasis has been clarified based on the pathologic analysis of lymph nodes removed during esophagectomy for early esophageal cancer. Cancer confined to the lamina propria mucosa rarely undergoes lymph node metastasis and complete endoscopic resection (ER) is indicated. ER allows the esophagus to be preserved and is less invasive, enabling specimens to be pathologically examined. Lesions extending over large area can be resected by repeating endoscopic mucosal resection (EMR), but have recently been resected using endoscopic submucosal dissection (ESD), as indicated for gastric cancer. Which of the two procedures, EMR or ESD, to be chosen depends on the difficulty, skill of the surgeon, time to be spared, and economic management. ER is now performed in SM1 without lymph node metastasis, although some patients require additional treatment after pathologic examination of resected lesions.

Early carcinoma of the esophagus associated with achalasia treated by endoscopic mucosal resection: report of a case.

A case of endoscopically resected early esophageal carcinoma associated with achalasia is reported. A 63-year-old woman was made diagnosis of esophageal achalasia, sigmoid type and grade III. The patient was operated by Tokai University method, Heller's long esophagomyectomy, Hill's posterior cardiopexy, fundoplication and selective proximal vagotomy using a laparotomy. Two years and six months after the operation, an early carcinoma of type 0-IIb, 1cm in size, was detected in the upper thoracic esophagus, and treated by endoscopic mucosal resection using EEMR-tube method. Pathological examination revealed proliferation of squamous cell carcinoma in situ (Tis: m1). The entire esophageal mucosa around the carcinoma demonstrated hyperplastic changes of stratified squamous epithelium and foci of dysplastic changes. In the patient of achalasia, food stasis in esophagus is thought to induce chronic hyperplastic esophagitis, converting eventually to malignant transformation. Achalasia is known as a risk factor of esophageal carcinoma. Early operation or good drainage of the esophageal lumen might reduce the risk. Long-term follow-up for patients of achalasia by endoscopic screening is recommended.

Clinical analysis of reflux esophagitis following esophagectomy with gastric tube reconstruction.

BACKGROUND: Recently, the rate of postoperative long-term survival has increased in cases of esophageal cancer. We report on our analysis of postoperative reflux esophagitis (RE) at Tokai University. METHODS: We enrolled 48 patients who underwent gastric tube reconstruction after esophagectomy. The diagnosis of RE was confirmed by endoscopy. RESULTS: Of the 48 patients, 28 (58.3%) were found to have RE. Among the 28 patients with RE, only four (14.3%) reported symptoms. The distribution of the severity of RE according to the Los Angeles classification in the patients was as follows: grade M, 1 (3.6%); grade A, 2 (7.1%); grade B, 6 (21.4%); grade C, 17 (60.7%); and grade D, 2 cases (7.1%). Barrett's epithelium was detected in 9 of the 28 patients (31%) with RE and in 3 of the 20 (15%) patients with no evidence of RE. CONCLUSIONS: To detect the presence of RE as well as monitor for recurrence and development of metachronous cancer, we consider it important to perform endoscopy regularly over the long term. As Barrett's epithelium is frequently encountered, care should be exercised to detect the specialized columnar epithelium showing dysplastic changes.

Effect of dermal fibroblasts on long-term maintenance of regenerating xenotransplanted human esophageal epithelial cells in immunodeficient mice.

OBJECTIVE: Artificial esophagus of various materials has been tried without satisfactory results. Effects of fibroblasts derived from human dermis on cultured human esophageal epithelial cells were investigated regarding their preservation over time. METHODS: Human esophageal epithelial cells (EE) were subcutaneously injected either alone or with human esophageal fibroblasts (EF) or human dermal fibroblasts (DF) into the flank of the BALB/cA-nu, scid mice of 8 to 12 weeks of age. At 10 days, 3, 6 and 48 weeks after transplantation, randomly chosen mice were sacrificed and the rates of nodule formation at the injected sites were compared. Nodules were examined histologically by hematoxylin and eosin staining and immunohistochemically with anti- Ki-67 and anti-p63 antibodies. RESULTS: The rate of subcutaneous epidermoid cyst formation at 10 days was 33% for EE, and 67% for EE with EF, and 100% for EE with DF transplantation. At 6 weeks after transplantation, subcutaneous cysts were not found for EE alone or EE with EF, but were detected in 100% of the mice transplanted EE with DF and still preserved at 12 months. CONCLUSIONS: Long-term preservation of regenerated esophageal epithelium in vivo after transplantation of cultured esophageal epithelial cells is possible by co-transplantation of human dermal fibroblasts.

Acceleration of the proliferative activity of esophageal carcinoma with invasion beyond the muscularis mucosae; immunohistochemical analysis using MIB-1 for the Ki-67 antigen.

Squamous cell carcinoma of the esophagus with cancer invasion beyond the muscularis mucosae is known to have lymph node metastasis and lymphatic or blood vessel invasion compared with intramucosal carcinoma. In submucosal and T2-3 carcinoma, lymph node and lymphatic/vascular involvement are shown more frequently, leading to a poor prognosis. Therefore, we examined proliferative activity of esophageal squamous cell carcinoma including early carcinoma in relation to clinicopathological findings. 77 cases of esophageal squamous cell carcinoma, including 23 cases of mucosal carcinoma (Tis+T1a), 35 cases of submucosal carcinoma (T1b) and 19 cases of advanced invasive carcinoma (T2+T3) undergoing surgical resection without preoperative treatment were studied using monoclonal antibody MIB-1 for Ki-67 antigen immunohistochemically, and the labeling index (LI) was calculated. The LI of MIB-1 positive nuclei correlated with the depth of cancer invasion was significantly increased in the cancer invading beyond the musculais mucosae. The LI at the invasive tip was significantly higher than that at the core of differentiated carcinoma. The LI values at both invasive tip and core of poorly differentiated carcinoma were higher than those of differentiated carcinoma with significant difference. The LI at the invasive tip of the carcinoma with lymph node metastasis or lymphatic invasion was significantly higher than that without them. Proliferative activities of esophageal cancer cell, immunostaining with MIB-1, had correlations to depth of tumor invasion, differentiation, lymph node metastasis and lymphatic invasion with significant difference. But if invading deeper than m3, the proliferative activity did not increase anymore.

Successful treatment of severe reflux esophagitis with erythromycin in a patient with progressive systemic sclerosis and proximal gastrectomy.

A case of severe reflux esophagitis related to progressive systemic sclerosis (PSS) and proximal gastrectomy was successfully treated with oral erythromycin (EM). A 53-year-old woman was troubled with severe heartburn related to PSS for a long period and had undergone proximal gastrectomy for a gastric cancer a few months before. She was not readily made free from heartburn by any anti-ulcer drugs and she could barely eat. Therefore she underwent continuous intravenous hyperalimentation (IVH). She was referred to our hospital for IVH. Nine months after the proximal gastrectomy, we gave oral erythromycin to her in expectation of improvement of the heartburn. Gradually she recovered from the heartburn and became able to eat small amounts. EM is an agonist of motilin which is a gastrointestinal hormone. EM acts on the stomach and intestine not through the autonomic nervous system but through the circulation system of the blood. This is the reason why EM is effective in the residual stomach and intestine. In the case of severe esophagitis which is related to PSS and/or proximal gastrectomy and which resists anti-ulcer drugs, oral EM should be considered as a second therapy.

Acute oral selenium intoxication with ten times the lethal dose resulting in deep gastric ulcer.

A 48-year-old woman presented after taking 2000 mg of selenium dioxide, corresponding to 10 times the experimental lethal dose in animals. She presented with mildly altered consciousness and hematemesis. Endoscopy revealed mucosal damage throughout the oral cavity, esophagus, and stomach. There was no evidence of perforation. After intubation and gastric lavage, hemodialysis was performed. The patient was discharged uneventfully on the 16(th) day. This case highlights a very rare acute selenium intoxication. Serum and urinary selenium levels and serum glutathione peroxidase activities during the patient's course were followed, as well as the mucosal corrosive damage caused by the selenium.

Gastrointestinal cytomegalovirus infection in collagen diseases.

Cytomegalovirus infection of the gastrointestinal tract is a rare serious complication in patients with collagen diseases receiving immunosuppressive agents. We report 3 such cases diagnosed by endoscopy followed by proper treatment. The patients include 38 and 53 years old females with systemic lupus erythematosus. They presented epigastric pain after pulse steroid therapy and combination therapy with steroids and cyclophosphamide, respectively. Their endoscopical findings were multiple small gastric erosions. The other patient was a 60-year-old female with polymyositis who developed rectal bleeding after steroid and imuran therapy. Her endoscopical finding was a discrete, irregular rectal ulcer. The diagnosis of all the patients was confirmed by biopsies of those lesions showing giant cell inclusion bodies and positive staining with anti- cytomegalovirus -antibodies. All patients were treated properly with ganciclovir. We should always keep in mind of a cytomegalovirus infection of the gastrointestinal tract in a patient with collagen disease receiving immunosuppressive agents.

Gastric tube cancer after esophagectomy for esophageal squamous cell cancer and its relevance to Helicobacter pylori.

BACKGROUND/AIMS: Improvement of surgical skills and postoperative management has allowed longer postoperative survival for patients with esophageal cancer, among those some develop gastric tube cancer. We analyzed the characteristics of such patients we encountered as well as of reported cases of Japan. Furthermore, we investigated if Helicobacter pylori plays a role in carcinogenesis of the gastric tube in our cases. METHODOLOGY: We analyzed the clinicopathological features of our 8 patients with gastric tube cancer from 1991 to 2000 as well as the status of H. pylori on the gastric tube biopsy. Moreover the features of gastric tube cancer from domestic reported cases up to the year 2000 were also summarized. RESULTS: According to the review of our cases, the frequent tumor location was the distal portion of the gastric tube. Seventy-eight percent were detected in early stage during postoperative follow-up, 71% of those were treated endoscopically. No cases showed H. pylori positivity. From the previous domestic reports, early cancer is increasing as the screening becomes popular. Type 0-IIa and 0-IIc were the most popular images for early cancer, while type 2 and 3 were for advanced cancer. CONCLUSIONS: The carcinogenesis of the gastric tube seemed not to be related to H. pylori. Subdermal route of reconstruction at esophagectomy seemed superior regarding early recognition of gastric tube cancer and easiness of its treatment.

Immunohistochemical mucin expression of short-segment Barrett's esophagus.

Barrett's mucosa consists of metaplastic columnar epithelium (specialized columnar epithelium) of the esophagus. Recently, "short-segment Barrett's esophagus (SSBE)" was proposed. In the present study, we examined immunohistochemical mucin expression and the Ki-67 labeling index (LI) of SSBE, in 5-15 mm lengths. All 27 SSBE cases showed gastric mucin (MUC5AC, HGM, MUC6). CD10 and MUC2, which were markers of intestinal phenotypes, were detected in 13 (48.1%) and 14 (51.9%) of the 27 SSBE cases. Ki-67 LI of SSBE positive cases for CD10 was 23.6 %, while that of SSBE negative cases for CD10 was 14.4 % (p < 0.05). SSBE cases were divided into two groups: one was gastric epithelium type with low Ki-67 LI, and the other was metaplastic epithelium with intestinal metaplasia and high Ki-67 LI. The latter group was suggested to be more important as a premalignant lesion of esophageal adenocarcinoma.

A case of superficial esophageal cancer complicated with idiopathic muscular hypertrophy of the esophagus.

We hereby reported a case of 60-year old man with superficial esophageal cancer complicated with idiopathic muscular hypertrophy of the esophagus. Endoscopic ultrasonography and CT showed the thickness of esophageal muscular layer, but the accurate diagnosis could not be entertained before operation. Idiopathic muscular hypertrophy of the esophagus is an entity rarely encountered, and most cases are diagnosed at postmortem examination. Only a few cases have been reported regarding its clinical symptoms and images. The etiology remains to be elucidated, and the pathologic features are characterized by significant thickness of inner circular muscular layer of esophagus without degeneration of plexus and ganglionic cells. This case report deals with superficial esophageal cancer complicated with idiopathic muscular hypertrophy of esophagus. Literature review is also included.