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Background Neuroendocrine tumors (NETs) of the gallbladder are rare and generally considered low-grade malignancies. We herein describe a case of a patient with a 0.8-cm clear cell NET G1 of the gallbladder with nodal involvement. Case presentation A 65-year-old man with no medical history indicative of von Hippel-Lindau (VHL) disease underwent laparoscopic cholecystectomy for cholecystolithiasis. There was a 0.8-cm tumor in the neck of the gallbladder. Histologic examination revealed nests or trabecular growth of clear cells with small round-to-oval nuclei. Immunohistochemically, tumor cells showed positivity for chromogranin A and synaptophysin; Ki-67 index was

A 64-year-old man was admitted to our hospital because of epigastralgia. Gastrointestinal endoscopyrevealed a submucosal tumor with ulceration in the upper bodyof the stomach. The tumor was histologicallydiagnosed as a neuroendocrine carcinoma. CT showed that the tumor had directlyinfiltrated the pancreas and splenic vessels. The patient underwent onlyan exploratorylaparotomybecause the tumor seemed to involve the celiac artery. Chemotherapywas conducted using CPT-11/ CDDP. After 15 courses of chemotherapy, a significant tumor reduction was obtained. We performed total gastrectomy with D2 lymphadenectomy, distal pancreatectomy and splenectomy. Histopathological examination of surgical specimens showed that onlyfew carcinoma cells remained in the stomach and pancreas. Neoadjuvant chemotherapycan be a useful treatment for unresectable locallyadvanced neuroendocrine carcinoma of the stomach.

Patients who have received subtotal esophagectomy for thoracic esophageal cancer must be closely monitored for second primary malignancies. The purpose of this study is to review and assess patients who developed a second primary esophageal cancer in the residual cervical esophagus. Between 1996 and 2010, 10 patients were diagnosed in our hospital with esophageal squamous cell cancer in the residual cervical esophagus after undergoing thoracic esophagectomy and were treated with endoscopic or surgical resection. Data from these patients were reviewed retrospectively. Seven of the 10 patients (70%) had multiple primary carcinoma lesions at the time of their esophagectomy. A second primary cancer in the residual cervical esophagus was detected in eight patients during follow-up endoscopic examinations while the patients were still asymptomatic. Seven of the patients underwent endoscopic resection for a superficial cancer. None of those patients experienced any complications, and all are currently alive and cancer-free. The remaining three patients underwent resection of the cervical esophagus with regional lymph node dissection. Two of those patients experienced severe complications; one subsequently died (hospital death) from pneumonia, 12 months after surgery, while the other died from recurrence of his cancer. The third patient is alive and cancer-free. Early detection of a second primary malignancy in the residual cervical esophagus followed by endoscopic resection is the best treatment strategy for patients who previously received subtotal esophagectomy for thoracic esophageal cancer. Surgical resection puts patients at high risk of mortality or morbidity.

The type of anastomosis and its outcome can affect postoperative morbidity, mortality, and quality of life after esophagectomy. We compared the outcomes of cervical hand-sewn anastomosis (CHS) and intrathoracic stapled anastomosis (ITS) performed after esophagectomy and gastric reconstruction. Thirty-two patients with middle or lower thoracic esophageal cancer were prospectively randomized to undergo CHS (n = 18) or ITS (n = 14) after esophagectomy. We compared clinical data, postoperative symptoms, and long-term survival in the two groups. The rates of anastomotic leak and stricture in the CHS and ITS groups were 16.7% versus 7.1% and 0% versus 14.2%, respectively, which do not represent significant differences. The respective rates of recurrent laryngeal nerve palsy were 38.8% versus 7.1% (P < 0.05), and proximal esophageal resection was 15 mm longer (P < 0.05) in the CHS group. There were no significant differences in symptoms 6 months after surgery, or in the overall 5-year survival rates (72.2% and 85.7%, respectively). The two methods of anastomosis yielded similar anastomotic outcomes. Although the incidence of recurrent laryngeal nerve injury was higher after CHS, and proximal esophageal resection was longer, this had little impact on postoperative symptoms and long-term survival.

Summary Lung injury, including pneumonia, can occur in the early postoperative period following thoracic surgery. Pulmonary oxygen consumption is thought to increase in patients with pulmonary infection. This study measured oxygen consumption in relationship to lung injury in the early postoperative period after thoracic surgery. Thirty-five patients who underwent thoracoabdominal oesophagectomy for oesophageal cancer were studied. Measured oxygen-consumption was obtained by indirect calorimetry and calculated oxygen-consumption was simultaneously determined by the reverse Fick method. The difference in oxygen consumption was attributed to pulmonary oxygen consumption. The difference in oxygen consumption increased to 23.1 ml.min )1 .m )2 on postoperative day 2. In patients with pneumonia the difference in oxygen consumption increased significantly to 39.0 ml.min )1 .m )2 the day before clinical onset of pneumonia, and it increased further to 65.7 ml.min )1 .m )2 on the day that pneumonia became clinically apparent. These findings suggest that the difference in oxygen consumption may be useful for estimating the extent of lung injury and for predicting pulmonary complications in the postoperative period.

Background For thoracic esophageal cancer patients with a history of gastrectomy, esophageal reconstruction using segments of colon was often accomplished using the anterior mediastinal route to avoid fatal complications related to colon necrosis. Our aim was to review our experience with reconstruction by the posterior mediastinal route and assess the surgical outcomes. Methods Between 1989 and August 2006, 34 esophageal cancer patients at Akita University Hospital underwent esophageal reconstruction accomplished by colon interposition by the posterior mediastinal route. Data from these patients were reviewed. Results Colon conduits consisted of left colon segments in 4 patients and right colon segments in 30. The grafts were supplied with blood by the left colonic artery in 13 patients, the middle colonic artery in 20, and the right colonic artery in 1. The esophagocolic (pharyngocolic) anastomosis was located in the neck in 33 patients (97%) and in the thorax in 1. No patient died during the initial hospital stay. There were no instances of colon necrosis. An anastomotic fistula occurred in 3 patients (9%). Proximal anastomotic strictures occurred in 2 patients (6%). No late graft redundancies resulting in significant dysphagia occurred. Reductions in body weight did not differ from those seen when the gastric tube was used for reconstruction, and alimentary function was good after surgery. The 1-, 2-, 3-, and 5-year survival rates were 66%, 52%, 48%, and 48%, respectively. Conclusions Colon interposition by the posterior mediastinal route provides a good outcome and is considered the route of first choice.

A 55-year-old man underwent subtotal esophagectomy with extended three-field lymph node dissection for squamous cell carcinoma of the middle thoracic esophagus (histological stage pT3N4(3b)M0, pStage IVa). About 9 months later, contrast-enhanced computed tomography showed recurrence in several lymph nodes in the anterior mediastinum and the right side of the neck. We treated the recurrence by dissecting the affected nodes, followed by chemoradiotherapy. At the time of writing, 5 years later, the patient was well, without any further evidence of recurrence. Although the indications for resection of recurrent esophageal cancer are controversial and we cannot generalize about the best treatment for these patients, this case highlights the possibility of using salvage surgical resection to treat recurrent esophageal cancer with anterior mediastinal lymph node involvement in selected patients.

The aim of the present study was to assess the outcome of treatment for patients with recurrent mid- and lower-thoracic esophageal cancers in whom recurrence was localized to the lymph nodes of the neck, and to determine the best strategy for further treatment. Between 1989 and 2001, 270 patients with mid- and lower-thoracic esophageal cancer underwent curative esophagectomy; 90 of those patients had a cancer recurrence. Our focus was on lymph node recurrence, especially when the recurrent cancers were localized to the lymph nodes in the neck. The outcomes of those patients and the efficacy of the strategies used to treat the recurrent cancers were determined. In 43 patients (48%), recurrent cancer initially appeared in the lymph nodes. Among the 43 patients, 15 (35%) had localized neck recurrence. The time between tumor recurrence and death among the 15 patients with localized neck recurrence was significantly longer than among the 28 patients with other recurrence patterns. In addition, 15 patients underwent lymph node resection, while 28 patients were treated non-surgically. The time between tumor recurrence and death was significantly longer in patients treated surgically. Of the 15 patients in whom recurrence affected the neck lymph nodes only, 10 (67%) were treated surgically; their 2-year survival rate after recurrence was 45%. The outcomes of recurrent esophageal cancers localized to the lymph nodes of the neck were better than those seen with other recurrence patterns, and salvage resection followed by chemoradiation therapy would seem to be indicated for those patients.

Compelling evidence indicates that the small intestine is the primary source of factors inducing lung injury after major surgery and that the lymphatic system is the major route by which these gut-derived factors reach the pulmonary circulation. This study investigated the mechanism of lung edema induced by surgical stress. After subjecting male, fasted, pathogen-free Sprague-Dawley rats to surgical stress (laparotomy and intestinal handling for 5 min), followed by ventilation for 5 h, we measured H 2 O 2 production in the mucosa of small intestine and in the lung using 2',7'-dichlorofluorescein and intravital fluorescence microscopy. In addition, H 2 O 2 in mesenteric lymph was measured using a quantitative assay; lung permeability was assessed as a function of extravasation of Evans blue dye; neutrophil accumulation was visualized by intravital fluorescence microscopy and assessed as a function of myeloperoxidase activity; and TNF-a levels were measured using a specific ELISA. The intensity of 2',7'-dichlorofluorescein fluorescence in the mucosa of small intestine, H 2 O 2 levels of mesenteric lymph, and lung permeability were all significantly higher in rats subjected to surgical stress than in control animals. Moreover, all of these effects were blocked by pretreatment with a specific xanthine oxidase inhibitor. Surgical stress did not increase neutrophil accumulation or TNF-a production in the lung. In conclusion, surgical stress induces xanthine oxidase-dependent H 2 O 2 production in the small intestine. The H 2 O 2 then enters the mesenteric lymph and travels to the lung, where it increases capillary permeability and thus induces edema.

Background and Objectives A substantial body of evidence suggests that allogeneic blood transfusion increases the rate of recurrence of resected malignancies. The present study was conducted with the aim of understanding better the clinical characteristics of recurrent esophageal cancer and determining whether any survival advantage is conferred by transfusing autologous instead of allogeneic blood during the esophagectomy for the original malignancy. Methods We retrospectively analyzed 123 patients who received blood transfusion while undergoing esophagectomy for thoracic esophageal cancer between January 1991 and February 1998. We focused on those patients in whom the malignancy recurred. Of them, 23 patients received allogeneic blood and 18 received autologous blood. Compared were the clinico-pathological factors influencing prognosis as well as the disease-free survival periods and the period of survival after recurrence of the cancer. Results The clinico-pathological factors that influenced prognosis were similar in the two groups. There was also no significant difference in the rate at which the esophageal cancer recurred, or in survival time once it had recurred. On the other hand, disease-free survival prior to recurrence was significantly prolonged in the autologous blood transfusion group. Conclusion Use of autologous instead of allogeneic blood prolongs disease-free survival of esophageal cancer patients. J. Surg. Oncol. 2004;87:26–31. © 2004 Wiley-Liss, Inc.

症例は42歳の男性で, つかえ感を主訴に受診し, 上部消化管造影および内視鏡検査にて胸部中部食道に長径4cmの全周性狭窄を認めたが, 粘膜病変は見られなかった. CTで腫瘍は左主気管支, 下行大動脈に浸潤し, 悪性腫瘍が示唆された. 2度の消化管内視鏡下生検で確定診断をえられず, 胸腔鏡下腫瘍生検術を施行した. その結果, びまん性B細胞リンパ腫と診断された. 化学 (CHOP療法) および放射線 (40Gy) 療法を施行し, 完全寛解をえた. 治療後3年経過したが, 再発を認めていない. 確定病理診断の下, 化学放射線療法で3年の完全寛解をえた食道原発悪性リンパ腫の1例を報告した.

Purpose: There is evidence that blood transfusion is associated with an increased rate of tumor recurrence. This study was conducted to assess the survival advantage of giving autologous blood instead of allogeneic blood during surgery for esophageal cancer. Methods: We retrospectively analyzed 62 patients who underwent esophagectomy for thoracic esophageal cancer between January 1991 and February 1995 and received allogeneic blood transfusion, and 61 patients operated on between March 1995 and February 1998, who received autologous blood transfusion. The clinicopathological factors and survival rates were compared between the two groups. Results: The clinicopathological factors that influenced prognosis were similar in the two groups; however, a definite survival advantage was evident in the autologous blood transfusion group. According to multivariate analyses, the transfusion of allogeneic blood was an independent prognostic factor (P = 0.0222), as was the presence of metastatic lymph nodes. Patients who received allogeneic blood transfusions perioperatively had more than a twofold greater risk (Hazard ration 2.406) of death over patients who received autologous blood transfusions. Conclusion: Autologous blood transfusion appears to be an independent prognostic factor for the survival of patients with esophageal cancer.

Aims/background Rat liver perfused with an oxygenated buffered solution alone results in degenerative changes even when the perfusion flow is accelerated to give a sufficient oxygen supply. On the other hand, perfusion media supplemented with red blood cells (RBCs) preserve the viability of the liver. The present study was conducted to clarify how RBCs protect the isolated perfused liver. Methods The liver was perfused with and without RBCs in a perfusate equilibrated with supra-physiological oxygen tension at regulated inflow pressures, and controlled hepatic oxygen consumption. We examined alanine aminotransferase and purine nucleoside phosphorylase activity in the perfusate as specific markers of liver cells injury. Hydrogen peroxide (H2O2) production and morphological changes were determined using cerium electron microscopy. Apoptosis was detected by measuring CPP 32 protease activity and using TdT-mediated dUTP-digoxigenin nick end-labeling. Results When the liver was perfused with RBC-free buffer, H2O2 production and consequent injury progressing to apoptosis were initiated in the sinusoidal endothelial cells (SECs). After SECs were injured, H2O2 appeared in the hepatocytes. H2O2 production and associated degenerative changes were attenuated both morphologically and enzymatically by the addition of RBCs, a specific xanthine oxidase (XOD) inhibitor and the H2O2 radical scavenger, catalase. Conclusions In the liver perfused with RBC-free buffer, H2O2 production and consequent injury were initiated in SECs. RBCs attenuate liver injury by scavenging XOD-dependent H2O2.

This study investigates whether the pressure parameters obtained from the Swan-Ganz catheter (SGC) accurately reflect the circulating blood volume just after en bloc resection of the thoracic esophagus with regional lymph node dissection. It is well known that this operation induces severe hemodynamic changes and although the pressure parameters obtained from the SGC are an accepted means of monitoring circulating blood volume, we have often experienced a discrepancy between the SGC data and the clinical state. We examined the pressure parameters and diameter of the inferior vena cava (IVC) and left ventricle (LV), and the central venous compliance using SGC and echocardiography in ten patients who underwent esophagectomy for esophageal cancer. The central venous pressure, pulmonary arterial mean pressure, and pulmonary artery wedged pressure were significantly increased just after the operation compared with the preoperative levels, while the diameters of the IVC and LV decreased just after the operation. The compliances of the IVC decreased significantly just after the operation. The hemodynamic shift to the third space after esophagectomy induces decrement of the compliances of IVC. As the CVP does not always reflect the circulating blood volume, measuring the diameter of the IVC using echocardiography is extremely useful for monitoring circulating blood volume just after esophagectomy.

Bcl-2 is now recognized as a potent inhibitor of apoptotic cell death. It has been reported that Bcl-2 is located in the mitochondria, endoplasmic reticulum, and nuclear membrane in some cell lines, and it is not expressed in normal human and rat liver. An earlier study showed that Bcl-2 is an inner mitochondrial membrane protein. On the contrary, the following investigations using immunoelectron microscopy demonstrated that Bcl-2 resides predominantly in the mitochondrial outer membrane. In this study, using a cryo-sectioning immunogold labeling technique and immunoblotting, we carefully determined the subcellular localization of Bcl-2. Here we report that Bcl-2 is expressed in normal rat liver, and it is located predominantly in the inner membrane and crista rather than in the outer membrane of mitochondria.

Background & Aims: Evidence is accumulating that hypoxic liver injury involves not only necrosis but also apoptosis. Reactive oxygen species can cause apoptosis. This study examined the hypothesis that H 2 O 2 induces apoptosis in hypoxic rat liver. Methods: Blood-perfused rat livers were made hypoxic by reducing the perfusion flow. H 2 O 2 was detected by both 2',7'-dichlorofluorescein fluoroimaging and cerium electron-microscopic methods. To evaluate the apoptosis, the liver was stained with the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method. To further investigate the involvement of H 2 O 2 in hypoxia-induced liver cell apoptosis, small pieces of liver in the cultured media were exposed to 0.5 mmol/L of reagent H 2 O 2 and stained with the TUNEL method. Results: In the hypoxic liver, H 2 O 2 was produced predominantly by hepatocytes, and the number of apoptotic nonparenchymal cells was significantly increased, particularly in the midzone. All the apoptotic cells were positively stained with monoclonal antibody against the hepatic sinusoidal endothelial cells (SECs). In incubated liver pieces, reagent H 2 O 2 induced apoptosis selectively in SECs. Conclusions: Low-flow hypoxia induces H 2 O 2 production in hepatocytes, and this H 2 O 2 induces apoptosis selectively in SECs in the rat liver. GASTROENTEROLOGY 1998;114:153-163

Patients who have undergone major surgery such as esophagectomy may develop peripheral edema in the immediate postoperative period, the cause of which is not fully understood. The purpose of this study was therefore to determine the mechanism of this phenomenon. Finger edema was measured as a marker for peripheral edema before and after esophagectomy in eight patients. Plasma interleukin-6 (IL-6) was also measured by an enzyme-linked immunosorbent assay. Finger edema markedly increased in the immediate postoperative period and remained significantly elevated until after postoperative day (POD) 3 compared to the preoperative value (P0.05). Plasma IL-6 also markedly increased in the immediate postoperative period and remained significantly elevated on POD 2 compared to the preoperative value (P0.05). The degree of finger edema highly correlated with the level of plasma IL-6 (r = 0.71, P = 0.0001). These findings indicate that peripheral edema after esophagectomy might be caused by a proinflammatory cytokine response.

Total resection of the gastric tube with lymphadenectomy is standard and reliable treatment for gastric tube cancer. However the risk associated with totally removing a gastric tube previously reconstructed through the posterior mediastinal route is significant, given the need to lyse a significant number of adhesions in order to reach the mediastinum. As a less invasive procedure, we used distal gastrectomy to treat superficial gastric tube cancer in 2 patients. The distal gastric tube was mobilized and resected with preservation of the right gastroepiploic artery, and the Roux-en-Y gastrojejunostomy was used for reconstruction. This procedure was curative with less surgical stress.

The data on 272 patients with esophageal cancer who underwent resection in our department between 1984 and 1994, were reviewed to assess the postoperative infection caused by MRSA, MRSA were isolated from 48 (17.6%) patients, and in the latest 3 years MRSA were isolated from 4 or 5 patients every year. The incidence of patients who had clinical symptons of the infection was 62.5%, and pneumonia, pyothorax and wound infection were common. MRSA were isolated within 5 postoperative days in many patients, and the number of symptomatic patients was high (73.3%) in these patients. In patients with postoperative complications (bleeding, anastomosis insufficiency), MRSA were isolated much more frequently than in patietns without postoperative complications (25.2% v.s. 12.7%). Other pathogens were isolated with MRSA in 64.3% of patients, and the incidence of symptomatic patients was higher in cases with polymicrobial infections than in cases with infectins caused by MRSA alone (68.5% v.s. 43.3%). The most common pathogens isolated with MRSA were gram-negative rods (62.3%). Pseudomonous aeruginosa isolated with MRSA has gradually become resistant to antibiotics. In conclusion, these data indicate that the strict prevention of hospital acquired infections in the early postoperative period and the avoidance of postoperative complications by adequate selection of operation methods and skilled technics are necessary to prevent postoperative infections caused by MRSA in patients with esophageal cancer. The next problem is to come up with a strategy against the polymicrobial infection caused by MRSA and pseudomonous aeruginosa, which is resistant to antibiotics.

This study was conducted to examine the long-term outcome of 500 patients who underwent surgery for cancer of the thoracic esophagus during the past 20 years. Favorable results were obtained with postoperative adjuvant radiation and chemotherapy and there were no surgical deaths in the last 5 years. The mortality rate decreased from 17% prior to 1980 to 5% between 1981 and 1993, this being most probably attributable to the decreased incidence of suture leakage. With respect to changes in surgical techniques, during the initial years we performed intrathoracic anastomosis, after which sternal manubrium resection with anterior mediastinal esophagogastrostomy was carried out. Subsequently, we invented a technique for performing esophagogastrostomy via the posterior mediastinum. The posterior mediastinum was selected as the most physiologic route, based on measurement of tissue oxygen tension. Using blood flow determinations obtained by laser-Doppler velocimetry, we concluded that the effectiveness of thicker gastric tubes was superior to that of thin tubes. Esophagogastrostomy was performed in a shallow field in the cervical region, with the anastomosis ultimately positioned in the superior mediastinum and covered with mediastinal pleura.

We report on a case of thoracic esophageal cancer following total gastrectomy (rho-Roux-en-Y reconstruction) with metastasis to the mesojejunal lymph nodes. Subtotal esophagectomy with reconstruction using pedicled colon and dissection of two lymph node fields was performed. During the operation, we found three lymph nodes showing metastasis at the rho-Roux loop of the mesentery, and resected the rho-Roux loop. The route of the lymphatic drainage to the abdomen from the thoracic tumor seemed to have been changed by the prior gastrectomy. Based on the pathological findings, the case was diagnosed with T2N4M0, Stage IVa. We did not confirm that the distant metastases skipped the mesojejunal lymph nodes preoperatively; the distant metastases were detected accidentally by lymphoscintigraphy using technetium-99m tin colloid. We believe this case highlights the need for detailed examinations in esophageal cancer patients who have had prior gastrectomy.

We successfully performed off-pump coronary artery bypass grafting (OPCAB) with concomitant esophagectomy in a 77-year-old man with esophageal cancer and severe stenosis of the anterior descending branch of the left coronary artery. Off-pump coronary artery bypass grafting was performed via median sternotomy and esophagectomy was done via the left thoracoabdominal approach. The patient was discharged with a patent graft 8 weeks after surgery. The benefits of OPCAB include that it is less invasive and heparinization can be avoided. This case report demonstrates that simultaneous OPCAB and esophagectomy is advantageous for a selected population with surgically correctable coronary artery disease and resectable esophageal cancer.

Benign esophageal strictures are generally treated with medication and balloon dilation; however, when repeated dilations fail, surgery is the only option. When performing surgery for benign esophageal stricture in young patients, it is important to consider not only the surgical stress and likelihood of complications but also digestive function after reconstruction, the durability of the reconstruction, and the potential for cancerous change in the reconstructed organs. We describe how we treated a 14-year-old boy with benign esophageal stricture by performing transhiatal esophagectomy assisted by mediastinoscopy, preserving the whole stomach and vagus nerve, and interposing pedicled jejunum between the cervical esophagus and stomach through a posterior mediastinal route, with good long-term results.

A rare case of esophageal schwannoma is presented. A 63-year-old woman was admitted to our hospital with a 5-year history of dysphagia. The barium esophagogram showed a protrusive smooth tumor in the upper thoracic esophagus. The tumor was removed through right thoracotomy. There was no anatomical relationship between the tumor and vagal nerve trunk. From pathologic findings and positive immunohistochemical staining for S-100 protein, the diagnosis of esophageal schwannoma was made.

症例は27歳, 男性.検診にて胸部X線写真上, 右下肺野に腫瘤影を指摘された.胸部X線, CT, 気管支造影において, 腫瘤影は肥厚した胸膜に接し弧状の気管支・血管収束像 (comet tail sign) を伴っていた.Round atelectasis を最も疑ったが腫瘤影の増大を認め, 悪性腫瘍をも否定できず右下葉切除術を施行した.腫瘤は肥厚した胸膜に覆われ, 組織学的には中心融解壊死を伴う多核巨細胞性肉芽腫であった.結核菌は証明されなかったが, 家族歴より結核性胸膜炎を一次的原因としたRound atelectasisと推測された.本症の本邦報告例は自験例を含め20例であり, 自験例が最も弱年例であった.本症は悪性腫瘍との鑑別が問題となり, その特徴的X線像 (下葉基底部に好発, 限局性胸膜肥厚, comet tail sign 等) により確診のつく場合もあるが, 各種検査にても確診が得られない場合は積極的に生検もしくは開胸手術を行うべきと考えられた.

We administered chemoradiotherapy consisting of 5-fluorouracil and cisplatin combined with radiation (59.8 Gy) to a patient with locally advanced esophageal cancer (T4 (left main bronchus) N2M0, stage IVa). The cancer disappeared completely after the chemoradiotherapy. However, because an esophagobronchial fistula occurred, an esophageal bypass was performed according to the method of Postlethwait. Thereafter, multiple lung metastases appeared, which we treated with paclitaxel 120-210 mg/body during a total of 23 chemotherapy treatments over more than 2 years. For a lesion that recurred in a cervical paraesophageal lymph node, we administered 60 Gy of radiation. With these combined therapies, this patient survived 50 months as an outpatient with high quality of life. It is difficult to treat patients in whom there is direct invasion of the trachea or main bronchus by esophageal cancer, and we cannot generalize about the best treatment for these patients. This case, however, highlights how to treat such a patient so that he retains a high quality of life.

Background: Thanks to significant recent progress in the application of chemoradiotherapy (CRT) in the treatment of esophageal cancer, the numbers of operations on patients who have undergone preoperative CRT are increasing. In these patients, preoperative CRT often leads to formation of an unstable, scleroid layer comprised of what appears to be scar tissue around the tracheobronchial wall. This scleroid layer must be removed with the tumor, thereby weakening the wall. Method: We performed preventive intrathoracic transposition of a pedicled latissimus dorsi muscle flap on 6 patients with clinically T4 esophageal cancer (6 males; age: 63–75 years). All 6 patients had undergone preoperative CRT (median, 43.0 Gy; range, 32.0–60.0 Gy; with cisplatin + 5-fluorouracil infusion) to relieve direct invasion of the airway. Results: In 6 patients, preventive use of a pedicled latissimus dorsi muscle flap resulted in uneventful recovery from the tracheobronchial wall weakness. Anastomotic leakage, recurrent nerve paralysis and pneumonia occurred in 2 patients each (33.3%); there were no life-threatening complications or operation-related deaths, however. Conclusions: When performing an esophagectomy for thoracic esophageal squamous-cell cancer in patients who have received preoperative CRT, the weakened tracheobronchial wall can potentially be reinforced using a pedicled latissimus dorsi muscle flap.

Objective: The purpose of this study was to detect lymphatic drainage into the superior mediastinum and neck in thoracic esophageal cancer patients using ferumoxides-enhanced magnetic resonance imaging (MRI), and to have this information assist in determining the appropriate extent of lymphadenectomy. Methods: Nine male patients with T2–T3 mid- and lower-thoracic esophageal cancer with lymph node metastasis were examined. The day before surgery, ferumoxides was endoscopically injected into the submucosal layer of the peritumoral lesion. Thereafter, lymph nodes in the superior mediastinum and neck, which were shown to be ferumoxides-enhanced on MRI, were harvested and evaluated; magnetic force from all harvested lymph nodes was measured ex vivo. Results: MRI of the superior mediastinum and neck revealed l(median) ferumoxides-enhanced lymph nodes in eight (89%) patients, and there was laterality in the lymphatic mapping in both areas. Of the 15 lymph nodes into which drainage was detected by enhanced MRI, 12 (80%) were magnetite-positive. In six patients (67%), magnetic resonance enhanced lymph nodes corresponded completely with the ex vivo magnetite examination, and in 3 patients (33%) there was partial agreement In 3 (60%) of the 5 patients that showed paratracheal and/or supraclavicular lymph node metastases, all of the affected nodes were detected by MRI; in one patient some of the affected nodes were detected. Conclusion: Ferumoxides-enhanced MRI is useful for visualizing lymphatic drainage to the superior mediastinum and neck in thoracic esophageal cancer. It is an adequate procedure to form an estimate on the appropriate extent of lymphadenectomy.

The mechanism underlying the immunomodulation caused by blood transfusion has yet to be elucidated. The aim of the present study was to determine whether the transfusion of a soluble or insoluble factor present in stored blood can induce immunomodulation, which would thereby promote solid tumor growth.C57Bl/6J mice were subcutaneously inoculated with B16-CG melanoma cells, which secrete beta-human chorionic gonadotropin (beta-hCG). Following inoculation, each of three different products of allogeneic and syngeneic blood were transfused on days 0 and 1: fresh whole blood, stored whole blood, and supernatants from the stored blood. Tumor growth was then monitored by measuring urinary beta-hCG. All mice were killed on day 15, and the tumor weight and volume were measured.Transfusion of all allogeneic blood products enhanced tumor growth, as did the stored syngeneic whole blood. Neither fresh syngeneic blood nor the supernatant from stored syngeneic blood promoted tumor growth. Although the tumors were not visually detectable until day 10 after inoculation, by day 7 the levels of urinary beta-hCG were significantly higher in the mice that received allogeneic blood supernatant than in the mice that received saline.A soluble alloantigen enhances solid tumor growth, as does an insoluble factor present in stored syngeneic whole blood. The immunomodulation associated with this factor begins to enhance tumor growth within 7 days after transfusion.

We report a case of esophageal varices caused by an arteriovenous fistula between an artery of the thyroid gland and the submucosal venous network of the esophageal wall. The fistula developed in a 51-year-old woman 24 years after she received subtotal thyroidectomy to treat Graves' disease. At the same time, gastrointestinal endoscopy revealed the presence of uncommon esophageal varices that were limited to the cervical and upper thoracic esophagus. Angiography confirmed the presence of both an arteriovenous fistula of the peripheral residual thyroid gland and the esophageal varices, after which we successfully treated the varices by surgical resection of the fistula.

Background Recent advances in the treatment of thoracic esophageal cancer have afforded it a better prognosis. As a consequence, increasing attention is being paid to the outcomes with postoperative monitoring for second primary malignancies after esophagectomy, but no recent study has focused on the longterm followup and outcomes in these patients. Study design In 1989, we began intensive prospective screening and surveillance designed to detect cancers of the head and neck, lung, stomach, residual esophagus, and colon/rectum after esophagectomy. Between 1989 and 2001, 365 patients underwent esophagectomy for thoracic squamous cell esophageal carcinoma in our department. Of those, 200 were followed up as part of this program. Excluded were patients in whom esophageal cancer recurred, patients with other prior or simultaneous malignancies, and patients who died within a year of operation. Clinicopathologic profiles and treatment outcomes were determined for 33 patients who developed a second primary malignancy after esophagectomy. Results The interval between the primary esophageal cancer and the secondary carcinoma was 49 ± 40 months (median, 48 months). The second primary malignancies were located in the stomach (30%), head and neck (24%), lung (24%), colon/rectum (9%), liver (6%), pancreas (3%), and blood (6%). Twenty-one patients (64%) were classified as stage 0, I, or II; 10 (30%) were stage III or IV. Overall, the 2-year, 3-year, and 5-year survival rates following diagnosis of a second primary malignancy were 58.0%, 58.0%, and 48.6%, respectively. Of the 19 patients (58%) in whom second primary malignancies were detected before symptoms developed, the 5-year survival rate was 70.7%, which was significantly greater than that among patients whose secondary malignancies were discovered after symptoms developed (17.1%). Conclusions Good outcomes in the treatment of second primary malignancies after esophagectomy for thoracic squamous cell esophageal carcinoma can be obtained with longterm, intensive followup and active surgical intervention for detected malignancies.

To determine whether the clinical presentation of pulmonary edema following esophagectomy can be objectively determined by changes in X-ray density in the lung field on chest radiography.Sixteen patients who underwent esophagectomy for thoracic esophageal cancer and five patients who underwent less radical surgery at Akita University Hospital between July 2000 and March 2001 were recruited to the thoracic esophageal cancer and control groups, respectively. Chest radiography was carried out using five aluminum disks (15, 20, 25, 30 and 35 mm thickness) placed in upper right corner of the film and X-ray density for the disks and chest lung field was measured using a densitometer until POD 7.In the thoracic esophageal cancer group, X-ray density in the lung field, body weight, and respiratory index increased significantly in the immediate postoperative period. The X-ray density in the lung field peaked on POD 2, and remained constant to POD 6. Correlations were found among changes in X-ray density in the lung field, body weight, and respiratory index.The measurement of X-ray density on a chest radiograph is useful for prediction as well as early management of patients with pulmonary edema following esophagectomy for thoracic esophageal cancer.

Recent advances in the treatment of esophageal cancer have afforded better prognosis for patients. Despite the increased need to monitor the progress of patients with reconstructed digestive tracts over the long-term, no reliable prospective studies have yet been conducted. This prospective study determined secondary disease of the reconstructed gastric tube after esophagectomy for esophageal cancer.One hundred and fourteen patients who underwent esophagectomy and reconstructed gastric tube via the posterior mediastinal route between April 1992 and March 1999 at Akita University Hospital, were followed up. Follow-up endoscopy was carried out once a year to determine the incidence and characteristics of secondary disease of the reconstructed gastric tube.Fifty-four (47%) patients were found to have secondary gastric abnormalities. Of these, 4 patients (3.5%) had carcinoma of the gastric tube, 12 patients (10.5%) had benign gastric tumor, 7 patients (6.1%) had gastric ulcers, and 40 patients (35.1%) had erosive or hemorrhagic gastritis. Three patients found to have early gastric cancer upon periodic follow-up endoscopy underwent successful complete resections.Annual follow-up endoscopy is vital to the detection of early, curative secondary gastric cancer and ulceration in patients following esophagectomy for esophageal cancer.

Objective: To investigate the mechanism by which methylprednisolone protects the liver from hypoxia-induced injury. Design: Prospective control study using the isolated rat liver. Setting: Animal research facility. Subjects: Male, fasted, pathogen-free Sprague-Dawley rats. Interventions: Low-flow hypoxia was produced by reducing afferent perfusate pressure from 10 to 2.5 cm H 2 O; isolated livers were portally perfused for 2 hrs. Measurements and Main Results: We measured mitochondrial membrane potential and hydrogen peroxide production by imaging rhodamine 123 and 2'-7'-dichlorofluorescein fluorescence, respectively. Leakage of mitochondrial enzymes was also monitored by assaying mitochondrial aspartate aminotransferase activity in the outflow perfusate, and the radical-scavenging effect of methylprednisolone was assessed by measuring luminol-dependent hydrogen peroxide chemiluminescence. Apoptosis in liver cells was determined by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling. Rhodamine 123 fluorescence was significantly diminished in the hypoxic liver, especially in the region of the terminal hepatic venules, which is indicative of membrane depolarization in the mitochondria in those areas. Hypoxia-induced mitochondrial dysfunction was indicated by leakage of aspartate aminotransferase into the outflow perfusate, and increased 2'-7'-dichlorofluorescein fluorescence indicated increased hydrogen peroxide levels, particularly in the midzone. Pretreatment with 30, 10, or 3 mg/kg of methylprednisolone inhibited the hypoxia-induced mitochondrial membrane depolarization and enzyme leakage, although hydrogen peroxide levels and apoptosis in sinusoidal endothelial cells were unaffected. Conclusions: Methylprednisolone does not protect the liver from hypoxia-induced injury by suppressing hydrogen peroxide production. Instead, the beneficial effect of methylprednisolone seems to be related to its ability to protect against mitochondrial membrane depolarization under hypoxic conditions.

Background . Low-flow hypoxia induces xanthine oxidase-dependent hydrogen peroxide production by hepatocytes in the midzone of blood-perfused rat livers and apoptosis in sinusoidal endothelial cells (SECs). As Bcl-2 is a potent inhibitor of apoptotic cell death and is localized mainly in the inner mitochondrial membrane and crista, the purpose of this study was to determine whether cell-specific changes in mitochondrial Bcl-2 levels could account for the hypoxia-induced apoptosis in SECs. Materials and methods . A low-flow hypoxia model was generated in isolated rat livers by reducing perfusate inflow pressure from 10 to 2.5 cmH 2 O for 2 h. Apoptosis was then evaluated using the TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. Mitochondrial Bcl-2 protein levels were determined in hepatocytes and SECs using cryosectioning immunogold labeling electron microscopy. Results . TUNEL-positive nonparenchymal cells, identified as SECs, were observed predominantly in the midzone of low-flow hypoxic rat livers, whereas few parenchymal cells were stained. Mitochondrial Bcl-2 levels were higher in SECs than in hepatocytes under control conditions, but they declined significantly during hypoxia, though no morphological signs of apoptosis were apparent. In hepatocytes, by contrast, Bcl-2 levels were unaffected by hypoxia. Pretreatment with a specific xanthine oxidase inhibitor, sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo [1,5- a ]-1,3,5-triazine-4-olate monohydrate, which blocks production of hydrogen peroxide, also blocked both the hypoxia-induced apoptosis and the decline in mitochondrial Bcl-2 in SECs. Conclusion . Hydrogen peroxide-dependent declines in Bcl-2 induce apoptosis in SECs in the hypoxic rat liver.

There is evidence that blood transfusion is associated with an increased rate of tumor recurrence. This study was conducted to assess the survival advantage of giving autologous blood instead of allogeneic blood during surgery for esophageal cancer.We retrospectively analyzed 62 patients who underwent esophagectomy for thoracic esophageal cancer between January 1991 and February 1995 and received allogeneic blood transfusion, and 61 patients operated on between March 1995 and February 1998, who received autologous blood transfusion. The clinicopathological factors and survival rates were compared between the two groups.The clinicopathological factors that influenced prognosis were similar in the two groups; however, a definite survival advantage was evident in the autologous blood transfusion group. According to multivariate analyses, the transfusion of allogeneic blood was an independent prognostic factor ( P = 0.0222), as was the presence of metastatic lymph nodes. Patients who received allogeneic blood transfusions perioperatively had more than a twofold greater risk (Hazard ration 2.406) of death over patients who received autologous blood transfusions.Autologous blood transfusion appears to be an independent prognostic factor for the survival of patients with esophageal cancer.

We report a case of gastrobronchial fistula that developed after esophagectomy for esophageal cancer. The fistula was repaired successfully by transposing a pectoralis major muscle flap. Complete healing was confirmed histologically by epithelialization of the fistula site and at autopsy 12 months after surgery. Muscle flap transposition effectively repairs gastrobronchial fistula.

Objective: We studied optimum surgery for carcinoma of the cervical esophagus extending to the thoracic esophagus (Ce-Ut carcinoma).Methods: Subjects were 13 patients diagnosed with Ce-Ut carcinoma treated at our institute from January 1989 to December 1998. Clinicopathologic information such as surgical procedures, pathologic findings, and postoperative complications were analyzed.Results: In 10, laryngoesophagectomy was conducted due to tracheal invasion by the tumor. In 7, mediastinal tracheostomy was done because of the extended resection of the proximal trachea. In 3, the larynx was preserved and, in 2, cricopharyngeal myotomy was added. Lymph node metastasis was found only in the neck and the upper mediastinum at surgery and recurrences were all lung metastasis. The incidence of postoperative complications was very high (76.9%), and 1 patient died due to widespread tracheal necrosis. The cumulative 5-year survival rate for the group was 33.3% and that for the 9 curative cases was 50%, but most of the cases who underwent noncurative resection and/or who received preoperative therapy for widespread invasion to surrounding organs died within a year.Conclusion: The prognosis of patients who undergoing curative extended resection of the proximal trachea and suitable lymph node dissection in the neck and upper mediastinum may improve, and larynx-preserving surgery is recommended for patients without tracheal invasion. Despite preoperative chemoradiotherapy, the prognosis of patients with widespread invasion to surrounding organs was very poor, and clinical studies on new therapeutic strategies for these advanced cases are needed to improve the prognosis of Ce-Ut carcinoma patients.

OBJECTIVE To investigate the heat shock protein (HSP) 72 expression and apoptosis induced by hydrogen peroxide in hypoxic rat liver. DESIGN Prospective control study using the isolated rat liver. SETTING Animal research facility. SUBJECTS Fasted, pathogen-free specific, male Sprague-Dawley rats. INTERVENTIONS A low-flow hypoxia model was made by reducing an afferent pressure from 10 to 2.5 cm H2O, and by perfusing the isolated rat liver for 2 hrs. MEASUREMENT AND MAIN RESULTS We investigated the hydrogen peroxide production by using the 2'-7' dichlorofluorescein image, the induction of HSP 72 by using immunohistochemistry, and apoptosis by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling method in the low flow hypoxic rat liver. In low-flow hypoxia, hydrogen peroxide production, HSP 72 expression, and apoptosis were induced in the midzone of rat liver. Prevalence of HSP 72 expression was higher in the sinusoidal endothelial cells (SEC) than in the hepatocytes. All apoptotic cells were SEC with expression of HSP 72. Hydrogen peroxide was derived from hepatocytes. Pretreatment with the specific xanthine oxidase inhibitor, sodium(-)-8-(3-methoxy-phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4-olate monohydrate significantly attenuated hydrogen peroxide production, HSP 72 expression, and apoptosis of SEC in the midzone. CONCLUSION Xanthine oxidase-dependent hydrogen peroxide induces midzonal and SEC-dominant HSP 72 expression and apoptosis in hypoxic rat liver.