Glucocorticoid receptor and serum- and glucocorticoid-induced kinase-1 in esophageal adenocarcinoma and adjacent Barrett's esophagus.

Barrett's esophagus (BE) is a consequence of gastroesophageal reflux disease and is predisposed to esophageal adenocarcinoma (EAC). EAC is an exemplar model of inflammation-associated cancer. Glucocorticoids suppress inflammation through glucocorticoid receptor (GR) and serum- and glucocorticoid-induced kinase-1 (Sgk1) expressions. Therefore, we immunolocalized GR and Sgk1 in EAC and the adjacent BE tissues and studied their association with clinical disease course in 87 patients with EAC who underwent surgical resection (N = 58) or endoscopic submucosal dissection (N = 29). Low GR and Sgk1 expressions in adjacent BE tissues were associated with adverse clinical outcomes (P = 0.0008 and 0.034, respectively). Patients with low Sgk1 expression in EAC cells exhibited worse overall survival (P = 0.0018). In multivariate Cox regression analysis, low GR expression in the adjacent nonmalignant BE tissues was significantly associated with worse overall survival (P = 0.023). The present study indicated that evaluation of GR and Sgk1 expressions in both the EAC cells and adjacent nonmalignant BE tissues could help to predict clinical outcomes following endoscopic and surgical treatments. In particular, the GR status in BE tissues adjacent to EAC was an independent prognostic factor.

Esophagectomy using a thoracoscopic approach with an open laparotomic or hand-assisted laparoscopic abdominal stage for esophageal cancer: analysis of survival and prognostic factors in 315 patients.

UNLABELLED: Survival and prognostic factors were analyzed in 315 patients with esophageal cancer undergoing thoracoscopic-assisted esophagectomy (TAE). The 5-year survival rate of 57.8% was satisfactory, indicating the oncological feasibility of TAE. Perioperative outcomes affected overall survival in the whole cohort but not in the subgroup treated with 2 endoscopic stages. OBJECTIVE: To estimate the oncological feasibility of thoracoscopic-assisted esophagectomy (TAE) for esophageal cancer and to clarify the prognostic impact of perioperative factors after TAE. BACKGROUND: Favorable perioperative outcomes of TAE versus open surgery have been demonstrated. However, survival data after TAE in a large cohort are limited, and no information on the prognostic influence of perioperative factors after TAE is available. METHODS: Prospectively collected data for 315 patients undergoing TAE for esophageal cancer were analyzed. Survival was compared with the Kaplan-Meier analysis and Cox regression analysis between 2 surgical approaches: thoracoscopic and hand-assisted laparoscopic esophagectomy (THLE) and thoracoscopic and open laparotomic esophagectomy (TOE). Factors affecting overall survival were identified with Cox multivariate regression analysis in the whole cohort and the THLE subgroup. RESULTS: THLE and TOE were performed in 153 and 162 patients, respectively. The overall 5-year survival of the whole cohort was 57.8%, with no difference between the THLE and the TOE group. Multivariate analysis of the 315 patients identified the following prognostic factors: blood loss, blood transfusion, intensive care unit stay, cardiovascular complications, pathological T and N stages, lymphatic invasion, intramural metastasis, and number of metastatic nodes. In the THLE subgroup, cerebral comorbidity, histological subtype, pathological T stage, and number of metastatic nodes were independent prognostic factors. CONCLUSIONS: TAE was oncologically feasible. Perioperative factors affected survival in the whole cohort, but did not in the THLE subgroup. However, the reduced perioperative factor effect in this subgroup would be small because the survival rates of the 2 surgical approaches were equal.

Thoracic duct visualization: combined use of multidetector-row computed tomography and magnetic resonance imaging.

PURPOSE: The objective of the study was to assess the ability of magnetic resonance imaging (MRI) and helical multidetector-row computed tomography (MDCT) to visualize the thoracic duct in esophageal cancer patients. METHODS: Sixty esophageal cancer patients underwent preoperative MDCT and MRI using 3-dimensional balanced turbo-field-echo sequence. The visualization grades by MDCT, MRI, and a combination of MDCT and MRI were scored in 4 segments of the thoracic duct (cervical, upper, middle, and lower). RESULTS: In the cervical, middle, and lower segments, MRI provided significantly higher visualization grades than MDCT. In all segments, combined MDCT and MRI resulted in higher grades than MDCT alone. In addition, combined MDCT and MRI successfully allowed visualization of the cervical, upper, middle, and lower segments of the thoracic duct in 46 (76.7%), 50 (83.3%), 58 (96.7%), and 60 (100%) patients, respectively. CONCLUSIONS: Combination of MDCT and MRI allows noninvasive thoracic duct visualization, providing 3-dimensional information on other thoracic structures.

Bronchial artery anatomy: preoperative 3D simulation with multidetector CT.

PURPOSE: To preoperatively evaluate anatomic variations of the bronchial arteries by obtaining three-dimensional (3D) simulations with multidetector computed tomography (CT). MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained from all participants. Seventy-three consecutive patients with esophageal cancer underwent dynamic multidetector CT. The data were used to generate 3D simulations of the thoracic cavity. These images were then used to evaluate anatomic variations of the bilateral bronchial arteries and the mediastinal course in relation to the esophagus and trachea-bronchi. The preoperative CT findings were correlated with the thoracoscopic findings. RESULTS: CT depicted 118 right bronchial and 105 left bronchial arteries. The right bronchial arteries arose from the intercostal-bronchial trunk (IBT), thoracic aorta, common trunk of both bronchial arteries (CTB), and right subclavian artery in 61, 15, 38, and four cases, respectively, whereas the left bronchial arteries arose from the thoracic aorta, IBT, and CTB in 63, four, and 38 cases, respectively. The right bronchial arteries followed preferential courses through the mediastinum, depending on the parent artery: All 61 right bronchial arteries that arose from the IBT ran along the right side of the esophagus, dorsal to the trachea-main bronchi, whereas the majority of direct-origin and CTB-type right bronchial arteries and all left bronchial arteries ran along the left side of the esophagus. During right thoracoscopy, all bronchial arteries coursing along the right side of the esophagus were identified, whereas those coursing along the left side of the esophagus were frequently out of intraoperative view. Six small right bronchial arteries that were not detected at CT were discovered during surgery. CONCLUSION: Three-dimensional simulation with multidetector CT yields precise preoperative information regarding the anatomy of the bronchial arteries and their variants.

Demonstration of the anatomy of the esophageal artery using multidetector-row helical computed tomography.

OBJECTIVE: To assess the ability of multidetector-row helical computed tomography to depict the esophageal artery. METHODS: Patients with esophageal cancer (n = 88) underwent multidetector-row helical computed tomography. Degree of visualization, branching level, angle, and length of the esophageal artery were investigated. RESULTS: In 79 (89.8%) of 88 patients, a total of 146 esophageal arteries were delineated from the origin to the insertion into the esophagus. Of the 146 arteries, 112 (76.7%) originated from the descending aorta and 34 (23.3%) from the right intercostal artery. Of the 112 aorta-originated arteries, 110 (98.2%) originated at a level between T6 and T11 from the left side of the descending aorta to go into the left wall of the esophagus. Of the 34 intercostal-originated arteries, 27 (79.4%) originated from right intercostal arteries between T5 and T7 to go into the esophagus. CONCLUSIONS: Multi-detector-row helical computed tomography depicted the esophageal artery in a high percentage of the patients.

Penetration of a swallowed fish bone into pulmonary vein: diagnosis and management.

We present a case of a 71-year-old woman who accidently swallowed a large fish bone that penetrated into the pulmonary vein. She visited the hospital the next day with a complaint of mild chest discomfort with slight pain and fever of 37.4 °C. Contrast-enhanced chest computed tomography (CT) scan revealed a large fish bone with a length of 35 mm impacted in the middle esophagus. The bone had penetrated into the pulmonary vein, causing mediastinitis. Blood tests revealed elevation in the white blood cell count and C-reactive protein level. Because intractable bleeding from pulmonary vein after endoscopic removal can be lethal, endoscopic removal of the fish bone in an operating room under general anesthesia with cardiovascular surgical standby for possible emergency surgery was selected. After endoscopic removal, mediastinal hematoma was absent with a follow-up chest CT scan, and the mediastinitis was treated with intravenous antibiotics. The patient shortly became afebrile with normalized blood test findings. After confirming the normal findings on the follow-up chest CT scan and endoscopic inspection in the next week, she was discharged from the hospital 10 days after hospitalization without any complications. When the swallowed bone penetrates into the major pericardial vessels, unprepared endoscopic removal may result in fatal sequelae such as intractable mediastinal hemorrhage. Urgent consultation with cardiovascular or thoracic surgeons for a possible emergent surgery is needed before endoscopic removal is attempted.

Immune microenvironment in Barrett's esophagus adjacent to esophageal adenocarcinoma: possible influence of adjacent mucosa on cancer development and progression.

The immune microenvironment plays a pivotal role in cancer development and progression. Therefore, we studied the status of immune cells in esophageal adenocarcinoma (EAC) and adjacent Barrett's esophagus (BE) and their association with the clinical course of patients. We included 87 patients with EAC who underwent surgical resection or endoscopic submucosal dissection. CD3, CD8, Foxp3, p53, and Ki-67 were immunolocalized in EAC and adjacent BE (N = 87) and BE without EAC (N = 13). BE adjacent to EAC exhibited higher CD3+ lamina propria lymphocyte (LPL) numbers than BE without EAC. Abundant Foxp3+ LPLs in BE were associated with dysplasia and increased Ki-67 labeling index (LI) in BE glandular cells and tended to link to aberrant p53 expression. Abundant CD8+ LPLs in adjacent BE were associated with worse prognosis of EAC patients (P = 0.019). Results of our present study firstly revealed the potential influence of the tissue immune microenvironment of BE adjacent to EAC on cancer development and eventual clinical outcome of EAC patients. T cell infiltration could play pivotal roles in facilitating the dysplasia-adenocarcinoma sequence in BE. The number of Foxp3+ T cells is increased at the early stage of carcinogenesis and could help identify patients harboring dysplastic and highly proliferating cells. CD8+ T cells could reflect unfavorable inflammatory response in adjacent tissue microenvironment and help predict worse prognosis of EAC patients.

[Simulation of thoracoscopic esophagectomy for esophageal cancer by three-dimensional computed tomography and usefulness for preservation of bronchial arteries].

Thoracoscopic esophagectomy for esophageal cancer was simulated preoperatively by 3-dimensional computed tomography (3D-CT). The anatomical structures such as major vessels, bone, trachea and bronchi, esophagus, lymph nodes, and broncial arteries were extracted from multi-detector row CT scanning and integrated to build the virtual operative field by multi-volume fusion. The virtual thoracoscopy was helpful to understand the location of lymph nodes and bronchial arteries in relation to the adjacent anatomical structures. Preservation of bronchial arteries is important to avoid tracheobronchial ischemia which is a fatal complication in salvage esophagectomy after definitive chemoradiotherapy. 3D-CT revealed anatomical variations of bronchial arteries and was useful for identification and preservation of bronchial arteries in thoracoscopic esophagectomy.

Thoracoscopic primary repair with mediastinal drainage is a viable option for patients with Boerhaave's syndrome.

BACKGROUND: Spontaneous esophageal rupture (Boerhaave's syndrome) is an emergency that can cause life-threatening conditions. Various procedures have been used to treat Boerhaave's syndrome. However, a standard surgical procedure has not been established. Herein, we report our experience with primary suture of the ruptured esophagus via a thoracoscopy or laparotomy. METHODS: Between November 2002 and May 2015, 11 patients with Boerhaave's syndrome presented to our department and were managed using one of two surgical procedures based on the surgeon's discretion. Six patients underwent a thoracoscopic primary suture and drainage (group A); 5 patients underwent a primary suture via laparotomy followed by thoracoscopic drainage (group B). Patient medical records were retrospectively reviewed. RESULTS: The mean interval between initial perforation and surgery was 13.7 h (group A) and 17.2 h (group B) (P=0.7307). The mean operative time was 190 min (group A) and 249 min (group B) (P=0.106). Patient baseline characteristics and surgical outcomes were similar for both surgical procedures. One patient in each group experienced postoperative leakage that did not require surgical intervention. CONCLUSIONS: The results suggest that thoracoscopic esophageal repair, as well as suturing via laparotomy, is a good surgical alternative for patients with Boerhaave's syndrome.

Virtual CT thoracoscopy: preoperative simulation for thoracoscopic surgery of esophageal cancer.

Thoracoscopic esophageal surgery is a complex procedure requiring simultaneous dissection of the esophagus and lymph nodes while maintaining the surrounding vessels. Because of the difficulty in obtaining comprehensive views of the operative field, three-dimensional (3-D) images with preoperative information on the vascular system, esophagus, trachea, lungs, lymph nodes, skin, and bones would be extremely helpful in performing the surgery.

Inhibitory effect of succinic acid on epithelial cell proliferation of colonic mucosa in rats.

Microbial breakdown of carbohydrates in the large intestine mainly produces short-chain fatty acids (SCFA). SCFA stimulate epithelial cell proliferation of the digestive tract in vivo. Succinic acid sometimes accumulates in the colonic lumen. However, the effect of succinic acid on colonic epithelial cell proliferation is unknown. Thus, we planned to clarify the influence of succinic acid on colonic epithelial cell proliferation in vivo. We continuously administered infusate with or without succinic acid (100 mM) into the distal colon of rats for 6 d and measured accumulated mitosis per crypt of distal colon of these rats. Succinic acid infused into rat colons significantly inhibited colonic cell proliferation and reduced crypt size. These results clearly indicated the inhibitory effects of succinic acid on colonic epithelial cell proliferation in vivo.

[Simulation of thoracoscopic esophagectomy by three-dimensional computed tomography].

The virtual operative field of thoracoscopic surgery for esophageal cancer was created by three-dimensional (3D) computed tomography (CT) imaging. Major vessels, bone, trachea, bronchi, lung, esophagus, lymph nodes and broncial arteries were constructed by a Zio M900 workstation from multidetector-row CT scanning data. The mediastinal lymph nodes and bilateral bronchial arteries were drawn by a free-hand tool. The static images and fry-through movies by a virtual endoscopy mode were useful for simulation of the endoscopic surgery, which is usually performed in very limited viewing. The location of lymph nodes and bronchial arteries in relation to the adjacent anatomical structures was realized by this virtual vision. The bronchial arteries should be preserved to avoid tracheobronchial ischemia, especially in case of salvage surgery after definitive chemoradiotherapy. The left bronchial arteries had many anatomical variations, so that 3D CT images were helpful to identify and to preserve the left bronchial arteries. In conclusion, the simulation of thoracoscopic esophagectomy by 3D CT is thought to contribute to safty and precise navigation for this kind of surgery.

Thoracoscopic esophagectomy for esophageal cancer with situs inversus totalis: a case report and literature review.

A 63-year-old male visited our hospital, complaining of discomfort when swallowing. Upper gastrointestinal endoscopy revealed a type 2 tumor in the middle thoracic esophagus, which was diagnosed as squamous cell carcinoma by endoscopic biopsy. Computed tomography revealed situs inversus totalis (SIT). We assessed the relationship of the esophagus with neighboring organs using preoperative three-dimensional imaging. We performed thoracoscopic esophagectomy with radical lymph node dissection in the right decubitus position and hand-assisted laparoscopic gastric mobilization in the supine position. The definitive diagnosis was squamous cell carcinoma, pT2N1M0, pStage IIB according to the Union for International Cancer Control. The patient's postoperative course was uneventful, and 5 years post-operation, he is alive without recurrence. In SIT patients, surgical procedures are difficult because of anatomic transposition. Three-dimensional imaging effectively assesses the anatomical structure and contributes to safer thoracoscopic esophagectomy for esophageal cancer patients with SIT. Relevant literature is also discussed and reviewed.

Gaps and fragmentation of the superficial cortex in the abdominal and pelvic lymph nodes of elderly Japanese.

Gaps and fragmentation of the superficial lymph node cortex are considered to provide intranodal shunt flow between the afferent and efferent vessels. Using serial sections of 205 nodes obtained from 27 donated cadavers more than 70 years of age, we examined the histological architecture of the abdominal and pelvic nodes in elderly Japanese. Secondary follicles were rare in the specimens. Cortex gaps were, to a greater or lesser degree, found in all nodes. We classified these nodes into three types according to how often the gap occurred. Type 1 nodes, with a relatively complete shield for the afferent lymph, were most frequently found in gastric nodes, whereas type 3 nodes, with numerous gaps, were often observed in the colic, para-aortic and pelvic nodes. The type 3 nodes showed a specific architecture characterized by a fragmented superficial cortex, three-dimensionally assembled cords and a common sinus between them. Primary follicles were located in the assembled cord structures as well as at the superficial cortex. Irrespective of the type, B and T lymphocyte areas were intermingled in the cortex-like areas. The present results reveal region-specific histological heterogeneity in aged human visceral nodes. Due to increased surface areas, the type 3 architecture seemed to accelerate systemic immunity rather than act as a local barrier in the para-aortic and pelvic nodes, which are located centrally along the lymphatic drainage routes. However, thick trabeculae often seemed to develop in the type 3 sinus to decrease nodal function with aging.

Three-dimensional lymphoscintigraphy using SPECT/CT and 123I-BMIPP for the preoperative detection of anatomical anomalies of the thoracic duct.

PURPOSE: Orally administered I-labeled 15-(4-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP), a fatty acid analog, is absorbed from the intestine and ascends to the venous angle through the thoracic duct (TD). The objective of this study was to evaluate the clinical feasibility of 3-dimensional (3D) TD scintigraphy using SPECT/CT and BMIPP for the detection of anatomical anomalies of TD. PATIENTS AND METHODS: This study included 35 consecutive patients with esophageal cancer who underwent tumor resection after TD scintigraphy. For scintigraphy, 111 MBq of BMIPP was orally administered, and static images and SPECT/CT images were obtained. On the basis of the SPECT/CT fusion images, TD was divided into the following 4 segments: cervical, upper thoracic, middle thoracic, and lower thoracic. The TD visualization was categorized into 5 grades, from grade 1 (poor) to 5 (excellent). In addition, the diagnostic accuracy of 3D TD scintigraphy for the detection of anatomical anomalies of TD was calculated using the intraoperative finding as a criterion standard. RESULTS: The TD visualization grades for the cervical, upper, middle, and lower thoracic segments were 4.4 ± 0.6, 3.7 ± 1.0, 3.1 ± 0.8, and 2.1 ± 0.9, respectively. The TD scintigraphy demonstrated an uncommon accumulation including that in the right- or bilateral-sided mediastinum or venous angle in 6 (17%) of the 35 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 3D TD scintigraphy for the detection of anatomical anomalies of TD were 0.75, 0.90, 0.5, 0.97, and 0.89, respectively. CONCLUSIONS: Three-dimensional TD scintigraphy by BMIPP is a simple and minimally invasive method for imaging the anatomical configuration of the TD and for detecting any anatomical anomalies, except in the lower thoracic segment.

Prospective comparison of surgery alone and chemoradiotherapy with selective surgery in resectable squamous cell carcinoma of the esophagus.

PURPOSE: Esophagectomy remains the mainstay treatment for esophageal cancer, although retrospective studies have suggested that chemoradiotherapy (CRT) is as effective as surgery. To determine whether CRT can substitute for surgery as the primary treatment modality, we performed a prospective direct comparison of outcomes after treatment in patients with resectable esophageal cancer who had received CRT and those who had undergone surgery. METHODS AND MATERIALS: Eligible patients had resectable T1-3N0-1M0 thoracic esophageal cancer. After the surgeon explained the treatments in detail, the patients selected either CRT (CRT group) or surgery (OP group). The CRT course consisted of two cycles of cisplatin and fluorouracil with split-course concurrent radiotherapy of 60Gy in 30 fractions. Patients with progressive disease during CRT and/or with persistent or recurrent disease after CRT underwent salvage resection. RESULTS: Of 99 eligible patients with squamous cell carcinoma registered between January 2001 and December 2005, 51 selected CRT and 48 selected surgery. Of the patients in the CRT group, 13 (25.5%) underwent esophagectomy as salvage therapy. The 3- and 5-year survival rates were 78.3% and 75.7%, respectively, in the CRT group compared with 56.9% and 50.9%, respectively, in the OP group (p = 0.0169). Patients in the OP group had significantly more metastatic recurrence than those in the CRT group. CONCLUSIONS: Treatment outcomes among patients with resectable thoracic esophageal squamous cell carcinoma were comparable or superior after CRT (with salvage therapy if needed) to outcomes after surgery alone.

Gastric or rectal instillation of short-chain fatty acids stimulates epithelial cell proliferation of small and large intestine in rats.

Short-chain fatty acids stimulate gut epithelial cell proliferation in vivo, although the difference between oral and rectal routes is unknown. Accordingly, we examined the effect of oral or rectal administration of these acids. We instilled a mixture of acetic acid, propionic acid, and n-butyric acid (150, 60, and 60 mmol/liter, respectively; pH 6.5) or saline (270 mM, pH 6.5) into the stomach (2 ml) or rectum (1 ml) three times daily for five days in rats fed an elemental diet. We measured crypt cell production rate of the jejunum, ileum, and distal colon of these rats. The crypt cell production rate of these segments was higher in rats with gastric or rectal instillation of short-chain fatty acids than in saline controls. The rectal route was slightly more effective than the gastric route. The above results indicated that the instillation of short-chain fatty acids orally or rectally stimulated gut epithelial cell proliferation.