Prognostic impact of lymphovascular invasion in lymph node-negative superficial esophageal squamous cell carcinoma.

The relationship between lymphovascular invasion (LVI) and prognosis in patients with superficial esophageal squamous cell carcinoma (SESCC) is unclear. The aim of this study is to evaluate prognostic factors in patients with lymph node-negative SESCC. A total of 195 patients with pathologically confirmed T1a-MM, T1b, and lymph node-negative SESCC were retrospectively reviewed in this study. Overall, the disease-free survival (DFS) rate was poorer in the lymphatic invasion-positive group than in the lymphatic invasion-negative group (p = 0.002) and a multivariate analysis suggested that lymphatic invasion was the only independent prognostic factor of DFS in patients with lymph node-negative SESCC (HR = 4.075, p = 0.005). Distant organ recurrence occurred in one patient (1/52, 1.9%) in the T1b-SM2 group and in six patients (6/61, 9.7%) in the T1b-SM3 group; all of these patients had LVI. LVI-positive patients had a poorer DFS than invasion-negative patients in the T1b-SM2 and SM3 groups (p = 0.026), and a multivariate analysis suggested that LVI was the only independent prognostic factor of DFS in patients with lymph node-negative SM2 and SM3 SESCC (HR = 5.165, p = 0.031). Lymph node-positive patients had a significantly poorer DFS rate than lymph node negative and LVI positive patients among the SM2 and SM3 SESCC patients (p = 0.018). The present results suggested that LVI was an independent prognostic factor in patients with SM2 and SM3 lymph node-negative SESCC; however their prognosis was not worse than that of patients with lymph node-positive SM2 and SM3 SESCC, for whom adjuvant therapy is indicated as a standard treatment.

Impact of body mass index on postoperative complications and long-term survival in patients with esophageal squamous cell cancer.

Undernutrition and cachexia have been suggested to be risk factors for postoperative complications and survival in cancer patients. The aim of this study was to investigate whether body mass index (BMI) is related to the short-term and long-term outcomes in patients who undergo an esophagectomy for the resection of esophageal squamous cell cancer (ESCC). Three hundred forty patients who underwent an esophagectomy for the resection of ESCC between 2003 and 2008 were retrospectively reviewed. The patients were divided into two groups: an L-BMI group characterized by a BMI < 18.5 kg/m(2) and an N-BMI group characterized by a BMI ≥ 18.5 kg/m(2). Clinical and pathological outcome were compared between groups. The study included 40 patients in the L-BMI group and 300 patients in the N-BMI group. A clinicopathological assessment showed that nodal involvement was seen more frequently in the L-BMI group (P = 0.016). Pulmonary complications seemed to occur more frequently in the L-BMI group (P = 0.006). The 5-year overall survival rate was higher in the N-BMI group (63.6%) than in the L-BMI group (32.3%) (P < 0.001). The 5-year disease-free survival rate was also higher in the N-BMI group (58.0%) than in the L-BMI group (33.6%) (P = 0.001). In multivariate analysis, the BMI (hazard ratio, 2.154; 95% CI, 1.349-3.440, P = 0.001) was found to be an independent prognostic factor for overall survival. Our data suggested that a lower BMI not only increased pulmonary complications but also impaired overall and disease-free survival after an esophagectomy for the resection of ESCC.

Clinicopathological significance of laminin-5γ2 chain expression in superficial esophageal cancer.

The glycoprotein laminin 5γ2 chain (LN-5γ2) has recently become a focus of increased interest and investigation as a marker of invasion in gastrointestinal malignancies. We investigated the significance of LN-5γ2 expression as a prognostic factor in superficial esophageal cancer. The study population consisted of 87 patients who had undergone a transthoracic esophagectomy and three-field lymphadenectomy for the treatment of superficial esophageal cancer at Tokai University Hospital. Formalin-fixed, paraffin-embedded sections of the resected specimens were examined using immunohistochemical staining and hematoxylin and eosin staining to assess the correlations between the LN-5γ2 expression pattern and the clinicopathological factors (age, sex, T-factor, N-factor, ly-factor, v-factor, degree of differentiation, infiltrative growth pattern, tumor node metastasis classification of malignant tumors [TNM] stage, etc.) and the patient outcome. The expression pattern of LN-5γ2 was classified into an extracellular type (E type), characterized by the staining of extracellular matrix such as the basement membrane and the stroma (31 cases, 35.6%), and a cytoplasmic type (C type), characterized by the staining of the cytoplasm in the cancer cells (56 cases, 64.6%). The expression pattern was not correlated with any of the clinicopathological factors that were assessed. However, univariate analyses of the survival analysis data showed that the N-factor (P = 0.011), TNM stage (P = 0.011), and LN-5γ2 C type (P = 0.017) were prognostic factors. A multivariate analysis revealed that the N-factor (P = 0.049) and LN-5γ2 C type (P = 0.048) were prognostic factors. In the survival analysis, a univariate analysis of the 75 T1b cases also showed that the N-factor (P = 0.048), TNM stage (P = 0.048), and LN-5γ2 C type (P = 0.029) were prognostic factors, while a multivariate analysis showed that the LN-5γ2 C type (P = 0.035) was a prognostic factor. The C type expression of LN-5γ2, i.e. confined to the cytoplasm, was correlated with an unfavorable outcome among the patients with superficial esophageal cancer in the present series. Observation of the LN-5γ2 expression pattern may be useful for the diagnosis of highly malignant tumors.

[Lymph node metastasis in superficial squamous carcinoma of the esophagus]. / Lymphknotenmetastasen bei Plattenepithelfrühkarzinomen des Ösophagus.

The definition of early carcinoma of the esophagus has changed with time on the basis of new data. As from 2007 an early carcinoma is defined as an intramucosal carcinoma with or without metastasis. In the subclassification based on invasion depth, m1 and m2 squamous cell carcinomas have no metastasis and are considered curable by endoscopic resection alone, whereas less than 10% of m3 carcinomas and some 20% of sm1 squamous cell carcinomas have lymph node metastasis. In this article the relationship between various histopathological findings and the incidence of lymph node metastasis is reviewed. The m3 and sm1 superficial squamous cell carcinomas showing 0-I and 0-III types, large tumors over 50 mm in size or those showing vessel permeation have higher incidences of lymph node metastasis. In the field of gastrointestinal surgical pathology pathologists are now expected to not only diagnose the presence or absence of malignancy but also to investigate in detail many of the histological factors related to the prevalence of lymph node metastasis.

Proteomic analyses of aortic wall in patients with abdominal aortic aneurysm.

AIM: The mechanisms underlying the formation of abdominal aortic aneurysms have yet to be fully clarified. To identify key proteins generally involved in aneurysmal formation, proteomic profiles were compared between aneurysmal and non-aneurysmal regions of aortic walls from patients with abdominal aortic aneurysm. METHODS: Aortic wall specimens were obtained from three patients with abdominal aortic aneurysm. Protein profiles of aortic wall samples including vascular media and adventitia were compared between aneurysmal and non-aneurysmal regions in each patient using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). Protein spots expressed differently between the two regions were identified by tandem mass spectrometry and verified by immunohistochemical investigations. RESULTS: Image analysis of 2D-DIGE gels revealed 22 proteins spots expressed differently between aneurysmal and non-aneurysmal regions in all three patients. Among these, five protein spots that were up-regulated in the AA regions were successfully identified as complement component C4, fragments of the fibrinogen alpha or beta subunits, and actin. Immunohistochemical studies showed massive deposition of fibrin/fibrinogen or its fragments in the media, and complement C1q component, the molecule starting the classical complement pathway, in all three layers of the aneurysmal region. CONCLUSION: Our proteomic and subsequent immunohistochemical studies revealed significant fibrinogenesis and fibrinolysis in the media, and activation of the classical complement pathway in all three layers of the aneurysmal region. These data promote understanding of mechanisms behind the formation of abdominal aortic aneurysms.

Endoscopy-assisted anastomosis: a modified technique for laparoscopic side-to-side esophagojejunostomy following a total gastrectomy.

INTRODUCTION: Esophagojejunostomy with a circular stapling device is sometimes difficult to perform in a laparoscopic setting. On the other hand, a side-to-side anastomosis with a linear stapling device is technically challenging. METHODS: Between June 2002 and March 2008, 10 consecutive patients underwent a laparoscopy-assisted total gastrectomy using a side-to-side anastomosis technique. Of these patients, four underwent a laparoscopy-assisted total gastrectomy with a modified anastomosis technique. A small wound was created on the antimesenteric side of the jejunum 5 cm distal to the resected portion and then in the lower esophagus. A peroral endoscope was advanced to the hole, and the cartridge fork was introduced into the lower esophagus under endoscopic guidance. The device (45 mm, blue) was fired to create an antiperistaltic side-to-side anastomosis. The common entry hole was closed by transecting the jejunum and the esophagus with another linear stapler and by using an endoscope as a stent. RESULTS: Four patients underwent the modified procedure and did not require an open procedure. One patient developed a pancreatic fistula, which was treated conservatively. The average operative time, reconstruction time and blood loss were 483 ± 133 minutes, 139 ± 31 minutes, and 199 ± 121 mL, respectively. An introduction of the stapler into the lower esophagus and a closure of the common entry hole were performed safely without any stress. CONCLUSION: Although several techniques must be compared to determine the ideal procedure for laparoscopic esophagojejunostomy, the modified side-to-side anastomosis technique may be useful in clinical settings.

[Paraplegia associated with acute aortic dissection complicated with pulmonary embolism and re-dissection].

Paraplegia associated with acute aortic dissection is one of the most serious complications. We experienced a case of Stanford type A acute aortic dissection with paraplegia and cardiac tamponade because the dissection was already thrombosed, conservative therapy was chosen. After drainage of pericardial effusion, a spinal drainage tube was inserted. Eleven days later, pulmonary embolism and re-dissection occurred, and an emergency operation was performed. Although the operation was successful, paraplegia did not improve. Even if type A acute aortic dissection is complicated with paraplegia, early surgical repair of aortic dissection should be considered, when paraplegia does not improve rapidly in spite of treatment.

[Treatment of a persistent postoperative chylothorax with octreotide].

Chylothorax is a serious postoperative complication in the field of thoracic surgery. To treat refractory chylothorax, various methods including surgery are employed. In this study, we report a patient with refractory chylothorax in whom treatment with octreotide acetate was successful, although the chylorrhea site could not be determined during additional thoracotomy.

Local VEGF administration enhances healing of colonic anastomoses in a rabbit model.

BACKGROUND/AIMS: Many studies report the role of vascular endothelial growth factor (VEGF) in wound healing, but few describe local VEGF administration to the digestive tract. Leakage from colonic anastomoses, including those due to ischemia, represents a major complication causing increased mortality and morbidity. Angiogenesis is crucial to anastomotic healing and restoration of blood supply, and VEGF is a potent angiogenic factor showing improved healing in various models of reconstruction and anastomosis. Here, we examine the effects of local VEGF-A(165) administration on postoperative rabbit colon anastomosis. METHODS: Two colotomies per animal were made in the sinistral colon on opposite sides of the mesentery. Randomly assigned VEGF (10 microg/0.1 ml) or saline (0.1 ml) was injected into the muscularis propria on both sides of each colonic anastomosis before closing the access laparotomy using single-layer sutures. On postoperative days 3, 4 and 7, the bursting pressure of partially healed anastomoses was measured. On postoperative day 4, anastomotic tissues were examined for the following: hydroxyproline; histopathologically for inflammatory infiltrate and tissue organization and immunohistochemically for capillary proliferation and density; vessel density of midzone collaterals around anastomoses by microangiography. RESULTS: Compared to saline, VEGF administration significantly improved bursting pressure (p = 0.014, paired t test) and increased hydroxyproline (p = 0.027, paired t test) on postoperative day 4. Inflammatory cell infiltration and fibroblast proliferation were prominent, and submucosal capillary vascular counts were significantly higher for VEGF. CONCLUSIONS: Administration of VEGF to colonic anastomosis accelerates wound healing and strengthens the anastomosis by increased angiogenesis.

Phase I/II study of twenty-four-hour infusion of irinotecan in combination with oral UFT plus leucovorin for metastatic colorectal cancer.

OBJECTIVE: Irinotecan has, in general, been administered as a 90-min infusion. However, several studies have demonstrated that continuous infusion seems to be a promising method of delivering irinotecan. This phase I/II trial was performed to evaluate the efficacy and safety of continuous infusion of irinotecan combined with UFT plus leucovorin (LV) for metastatic colorectal cancer. METHODS: Escalating doses of irinotecan (90-110 mg/m(2)) were administered by 24-hour infusion on day 1. UFT 300 mg/m(2)/day and LV 75 mg/day were administered orally, in 3 divided daily doses, on days 3-7 and 10-14. The treatment cycles were repeated every 2 weeks. RESULTS: In the phase I study, the maximum tolerated dose of irinotecan was 110 mg/m(2) and the recommended dose for the phase II study was determined to be 100 mg/m(2). Thirty-six patients, including 3 patients at the recommended dose in the phase I study, were evaluated in the phase II study. The common grade 3/4 toxicities were leucopenia, neutropenia, diarrhea and anorexia. The response rate was 63.9%, and the median progression-free and overall survival times were 8.3 and 24.6 months, respectively. CONCLUSION: A 24-hour infusion of irinotecan combined with UFT/LV is feasible and active for metastatic colorectal cancer.

[Coronary artery bypass grafting in patients with carotid artery disease; indication and early clinical outcome of coronary artery bypass grafting concomitant with carotid endarterectomy].

The purpose of this study is to assess the clinical results of coronary artery bypass grafting (CABG) in patients with carotid artery disease, especially concomitant with carotid endarterectomy (CEA). Between April 1993 and April 2008, 77 patients (aged 69.5 +/- 7.1 years, 77.9% male) with carotid artery stenotic disease underwent CABG. Cerebral hemodynamics in all patients was examined with single photon emission computerized tomography (SPECT). Treatment course was decided after through diagnostic evaluation and strategic discussion with brain surgeons. Among these, 12 patients required CEA simultaneously, because both coronary and carotid artery diseases were too serious for safe staged operation. Hospital death occurred in 3 patients (3.9%). Two patients (2.6%) had postoperative stroke, but were discharged without neurological deterioration. In 12 patients receiving CABG and CEA simultaneously, there was no intraoperative stroke or hospital death. One patient had hyperperfusion syndrome after CEA, and required adequate rehabilitation exercise. CABG concomitant with CEA is an acceptable and feasible procedure in patients with significant coronary and carotid artery diseases. In order to improve surgical outcome of combined cases, it is important to prevent occurrence or aggravation of cerebral hyperperfusion syndrome.

[Ruptured aneurysm of the sinus of Valsalva with severe liver dysfunction; report of a case].

The patient is a 59-year-old male who complained of acute palpitation, shivering and chest oppression. His laboratory data showed severe liver dysfunction (AST 3,445 IU/l, ALT 2,937 IU/l, and LDH 3,200 IU/l). By echocardiography, abnormal shunt flow was detected in the right atrium, and it was diagnosed as a ruptured aneurysm of the Valsalva sinus (Konno type IV). Suture closure of the fistula was performed from the right atrial side, and then, patch closure was performed from the aortic side with auto-pericardium to cover the whole non-coronary sinus, which was heavily calcified. The liver function rapidly restored to a normal range postoperatively. In a case of severe liver dysfunction, such cardiac disease should also be considered.

[Ball thrombus in the right atrium: report of a case].

A 63-year-old man visited our hospital because of intermittent claudication due to an embolic episode in the left femoral artery. He had a long history of arterial fibrillation but had received no anticoagulant therapy. Echocardiography showed a large floating ball-shaped shadow in the right atrium, without any sign of tricuspid stenosis. Pulmonary perfusion scintigram was normal. At the operation, the thrombus which attached to the superior atrial septum with a thin string was removed. The thrombus was 54 x 40 x 25 mm in size and 23.8 g in weight, whose cut surface was in layers. There was neither atrial septal defect nor foramen ovale to suggest possibility of paradoxical embolism. The postoperative course was uneventful and he was discharged on the 9th postoperative day. Although the mechanism of the thrombus formations is unknown, it is considered to be important to continue anticoagulant therapy to avoid reccurence of intracardiac thrombus.

[Thoracoabdominal aortic aneurysm combined with inferior mesenteric artery aneurysm and occlusion of celiac and superior mesenteric arteries].

A 56-year-old man with thoracoabdominal aortic aneurysm combined with inferior mesenteric artery aneurysm and occlusion of celiac and superior mesenteric arteries is presented. Contrast-enhanced computed tomography (CT) and aortography revealed thoracoabdominal aortic aneurysm of 6 cm in diameter, accompanied by inferior mesenteric aneurysm of 3 cm in diameter. Severe calcification of the abdominal aorta and occlusion of the celiac and the superior mesenteric arteries were also noted, whose territories were perfused by collateral circulation of the inferior mesenteric artery. At the operation, orifice of the left renal artery was stenosed by severe calcification, which was resected. Because of severe adhesion around the origins of celiac and superior mesenteric arteries, they were left unrevascularized. The thoracoabdominal aortic aneurysm was replaced with an Dacron tube graft, whose side branch was anastomosed to the inferior mesenteric artery after resection of its aneurysm. The postoperative course was uneventful, and no symptoms of intestinal ischemia were noted. As blood supply to the abdominal viscera mostly depends on the inferior mesenteric artery, careful follow-up is necessary.

Automated diagnosis of heart disease in patients with heart murmurs: application of a neural network technique.

This study was conducted to test a three-layered artificial neural network analysis of phonocardiogram recordings to diagnose, automatically and objectively, the condition of the heart in patients with heart murmurs. The data were recorded simultaneously in each of 49 patients with a heart murmur through eight microphones attached to the skin surface with adhesive tape, and were analysed by computer. The diagnosis was automated using a three-layered neural network technique. The neural network generated correct answers in over 70% of cases. Furthermore, about 80% of cases of two concurrent diseases were identified correctly. However, ventricular septal defects were incorrectly classified as aortic stenosis or aortic regurgitation, and patent ductus arteriosus was not diagnosed correctly. Accurate diagnoses can frequently be obtained using a neural network, but accuracy can be improved with further data accumulation.

Clinicopathological study of cholelithiasis following gastric cancer surgery.

The purpose of this study was to compare liver function tests preoperatively and postoperatively in 2 cohorts of patients, those that developed gallstones after gastrectomy for cancer and those that did not develop gallstones. The cohorts were taken from 698 consecutive patients who underwent curative gastrectomy for gastric cancer between April 1980 and March 1995. In comparison with 698 patients, the gallstone group was characterized by the findings that the incidence of cholelithiasis was significantly higher in totally-gastrectomized patients and patients with upper stomach cancer. Comparison of the perioperative status revealed a significantly higher rate of complications in the gallstone patients. Analysis of the changes in liver function showed significantly higher values of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase at time points of 1 and 3 months after surgery in the gallstone patients. The results suggest that the postoperative development of liver dysfunction and complications is associated with the formation of gallstones.

Preoperative radio/chemo-radiotherapy in combination with intraoperative radiotherapy for T3-4Nx rectal cancer.

AIMS: To analyse the results of a single institution experience of combined preoperative radio/chemo-radiotherapy and intraoperative electron-radiation therapy (IORT) for locally advanced rectal cancer and to compare the results with surgery alone retrospectively. METHODS: The study cohort comprised 99 patients with clinical T3-4NxM0 adenocarcinoma of the rectum who had received preoperative radio/chemo-radiotherapy, radical surgery, and IORT [Group I]. Until 1998, 67 patients were treated with radiation only [Group Ia], and after 1999, 32 patients were concurrently given tegafur and uracil (UFT) [Group Ib]. 68 patients with clinical T3-4NxM0 rectal cancer were treated with surgery alone [Group II]. RESULTS: The median follow-up was 67 months in Group I and 83 months in Group II. Local recurrence rate was 2% in Group I, which was significantly lower than 16% in Group II (p=0.002) Both disease-free survival and overall survival in Group I were significantly better than those in Group II (p=0.04, p=0.02, respectively). Sphincter preservation was possible in 78% in Group Ib, which was significantly more than 42% in Group Ia (p=0.002). CONCLUSIONS: The combined preoperative radio/chemo-radiotherapy and IORT for clinical T3-4Nx rectal cancer significantly reduces local recurrence and improves prognosis. Combination of preoperative radiotherapy and oral UFT improves the feasibility of sphincter-preservation.