Use of indocyanine green fluorescence imaging to determine the area of bowel resection in non-occlusive mesenteric ischemia: A case report.

INTRODUCTION: Non-occlusive mesenteric ischemia (NOMI) is a type of acute intestinal ischemia, and its associated mortality is very high. In laparotomy of NOMI, we often have difficulty determining the area of bowel resection. We herein describe a case in which we detected the area of bowel resection using indocyanine green (ICG) fluorescence imaging. PRESENTATION OF THE CASE: An 89-year-old man diagnosed as having advanced gastric cancer underwent distal gastrectomy. On the night of postoperative day 4, he strongly complained of distention of the abdomen. The laboratory data indicated severe metabolic acidosis and dehydration. The abdominal computed tomography scan showed a dilated small bowel, but there were no specific signs suggestive of bowel necrosis. We suspected NOMI and decided to perform emergency laparotomy because we could not exclude the possibility of bowel necrosis. During the operation, we could not detect the necrotic bowel macroscopically. After injecting 2.5 mg of ICG, the ischemic area of the bowel became visible as a region with poor fluorescence emission using the Photodynamic Eye™ (Hamamatsu Photonics K.K.). We resected the ischemic bowel and performed anastomosis. We confirmed that he was alive at 4 months after the operation of NOMI. CONCLUSION: Intraoperative ICG fluorescence imaging makes it possible to detect necrotic intestine that cannot be found with the naked eye. By using this method, planned reoperation to find any newly developed necrotic intestine might be unnecessary. Intraoperative ICG fluorescence imaging is useful for defining the area of ischemic bowel in a patient with NOMI.

Spatial relationships of the bronchial arteries to the left recurrent laryngeal nerve in the sub-aortic arch area.

PURPOSE: To safely perform lymphadenectomy in the sub-aortic arch area during esophagectomy for esophageal cancer, we investigated the spatial relationships between the bronchial arteries (BAs) and the left recurrent laryngeal nerve (LRLN). METHODS: For this macro-anatomical study, 72 cadavers were used. RESULTS: Of the 195 dissected BAs, 15 (7.7%) arteries ran dorsally across the LRLN. Such a running pattern of the BA was found in 15 (20.8%) of the 72 cadavers. Fourteen (93.3%) of the 15 arteries ran anteriorly along the left side of the esophagus, and 13 (86.7%) passed further to the lateral side of the left main bronchus to reach the ventral surface of the tracheobronchus; we named this running pattern "Type III". Of the 51 arteries with the Type III pattern, 25.5% ran across the dorsal side of the LRLN. CONCLUSION: Approximately 20% of the cadavers had BAs running dorsally to the LRLN in the sub-aortic arch area. Most of these arteries had the Type III pattern. One-quarter of the BAs with the Type III pattern showed this running pattern. Care must be practiced to safely perform lymphadenectomy for esophageal cancer in patients with Type III BAs.

A case of HER2-positive male occult breast carcinoma with skin and lymph node metastases that exhibited complete response to trastuzumab monotherapy.

Metastatic male occult HER2-positive breast cancer can be successfully treated with trastuzumab monotherapy.

A new anatomical classification of the bronchial arteries based on the spatial relationships to the esophagus and the tracheobronchus.

PURPOSE: To reveal the patterns of the mediastinal course of the bronchial arteries (BAs). METHODS: The BAs were dissected to determine the positional relationships of their mediastinal courses with the tracheobronchus and the esophagus in 72 adult cadavers. RESULTS: The mediastinal courses of the 227 BAs found in this study were classified into 4 types. There were 61 and 163 BAs passing the right side (Type I) and the left side (Type II reaching dorsal surface (n = 98), or Type III reaching ventral surface (n = 65) of the tracheobronchus) of the esophagus, respectively. Three BAs originated from the subclavian artery (Type IV). All Type I BAs were right BAs, whereas 91.8% of the Type II BAs were left BAs. However, 43.1 and 56.9% of the Type III BAs were the right and left BAs, respectively. CONCLUSION: The classification of the mediastinal course of the BAs determined by the spatial relationships to the tracheobronchus and the esophagus may be clinically useful, because each category of this classification can be determined during esophagectomy and indicates whether the BA is a right or left BA.

Surgical treatment of liver metastasis of gastric cancer: a retrospective multicenter cohort study (KSCC1302).

BACKGROUND: The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. PATIENTS AND METHODS: We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria. RESULTS: Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3- and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3- and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapse-free survival. CONCLUSIONS: To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.

Silver Nanoscale Hexagonal Column Chips for Detecting Cell-free DNA and Circulating Nucleosomes in Cancer Patients.

Blood tests, which are commonly used for cancer screening, generally have low sensitivity. Here, we developed a novel rapid and simple method to generate silver nanoscale hexagonal columns (NHCs) for use in surface-enhanced Raman scattering (SERS). We reported that the intensity of SERS spectra of clinical serum samples obtained from gastrointestinal cancer patients is was significantly higher than that of SERS spectra of clinical serum samples obtained from non-cancer patients. We estimated the combined constituents on silver NHCs by using a field emission-type scanning electron microscope, Raman microscopes, and a 3D laser scanning confocal microscope. We obtained the Raman scattering spectra of samples of physically fractured cells and clinical serum. No spectra were obtained for chemically lysed cultured cells and DNA, RNA, and protein extracted from cultured cells. We believe that our method, which uses SERS with silver NHCs to detect circulating nucleosomes bound by methylated cell-free DNA, may be successfully implemented in blood tests for cancer screening.

Clinicopathological factors predicting R0 resection and long-term survival after esophagectomy in patients with T4 esophageal cancer undergoing induction chemotherapy or chemoradiotherapy.

PURPOSE: To identify clinicopathological factors predicting R0 resection and long-term survival after esophagectomy in patients with T4 esophageal cancer following induction chemotherapy or chemoradiotherapy. METHODS: Of 48 patients with T4 esophageal cancer who underwent induction treatment, 30 underwent R0 esophagectomy. The factors predicting R0 resection and prognostic indicators were assessed in the 48 and 30 patients, respectively, using univariate and multivariate analyses. RESULTS: In the univariate analyses, the primary tumor response, improvement of dysphagia, the post-induction therapy Glasgow Prognostic Score, an early tumor response and the post-induction therapy serum albumin and C-reactive protein levels were significantly correlated with R0 resection. Multivariate logistic regression analyses revealed that the response status and improvement of dysphagia were independent predictors of R0 resection. The univariate analyses identified a yp-T classification (yp-T0/1 vs. yp-T2/3/4), yp-nodal status and the number of pathologically positive nodes post-therapy (≤ 1 vs. ≥ 2) as significant prognostic factors. The multivariate analysis revealed that the number of pathologically positive nodes was the only significant independent prognostic indicator. CONCLUSION: Patients showing an early tumor response to induction treatment and improvement of dysphagia may be appropriate candidates for esophagectomy, and individualized postoperative management strategies should be developed for patients with initially unresectable T4 esophageal cancer who have ≥ 2 positive nodes post-treatment.

Prognostic significance of simultaneous presence of histological and immunohistochemical metastasis to lymph nodes in patients with esophageal cancer.

PURPOSE: Presence of simultaneous pathological and immunohistochemical nodal metastasis (pNM and iNM, respectively) and/or other clinical factors may be reliable prognostic predictors of survival in esophageal cancer patients who have undergone multidisciplinary treatment. METHODS: Univariate and multivariate analysis of the data collected from 77 patients who had undergone R0 esophagectomy was performed to determine the significance of presence of iNM or pNM, presence of simultaneous pNM, and other clinical factors as prognostic indicators in patients who had (n = 40) and had not (n = 37) undergone preoperative treatment. RESULTS: Presence of pNM was found to be a significant prognostic predictor in patients who had undergone preoperative treatment, presence of iNM in patients who had not undergone preoperative treatment, and presence of simultaneous pNM and iNM in both patient groups. Multivariate analysis indicated that the sole prognostic predictor for patients who had undergone preoperative treatment was presence of simultaneous pNM and iNM while that of patients who had not undergone preoperative treatment was clinical T category. CONCLUSION: Assessment of simultaneous presence of pNM and iNM may facilitate highly accurate prediction of survival in esophageal cancer patients undergoing R0 esophagectomy, regardless of whether they have undergone preoperative treatment.

Acute phlegmonous esophagitis as a rare but threatening complication of chemoradiotherapy: report of a case.

Phlegmonous infection involving the digestive tract has been reported to have a poor prognosis. However, the pathogenesis and clinical features of acute phlegmonous esophagitis have remained unclear due to the rarity of the disease. We herein report a case of acute phlegmonous esophagitis that showed a fulminant course during chemoradiotherapy for uterine cancer. The patient developed septic shock 10 h after postprandial nausea and vomiting, and a computed tomographic scan showed diffuse thickening of the esophageal wall. Severe leukopenia that was refractory to the administration of granulocyte colony-stimulating factor persisted during the first few days. The patient fortunately survived after intensive treatment. The acute phlegmonous esophagitis of the present case might have been evoked and worsened by chemoradiotherapy due to its emetic and myelosuppressive adverse effects, respectively. Although its incidence is extremely rare, acute phlegmonous esophagitis may occur as a life-threatening complication of chemoradiotherapy.

Clinical and oncological effects of triplet chemotherapy followed by radical esophagectomy for resectable esophageal cancer associated with unfavorable prognostic factors.

PURPOSES: The purpose of this study was to evaluate the hypothesis that the survival of patients undergoing R0 resection after triplet chemotherapy for resectable esophageal cancer with unfavorable prognostic factors (Category 3) would be similar to that of patients undergoing esophagectomy for esophageal cancer without such factors (Category 1). METHODS: Patients with Category 3 tumors were assigned to receive triplet chemotherapy consisting of 5-fluorouracil, doxorubicin and nedaplatin (FAN) followed by radical esophagectomy. The outcomes of the bimodality treatment for Category 3 patients (n = 25) were compared with those of Category 1 patients (n = 41) in a prospective cohort study. RESULTS: Grade 3 or higher toxicity developed during chemotherapy in 32 % of the Category 3 patients, with no treatment-related deaths. No significant difference was detected in the surgery-related mortality and morbidity rates between the two groups. The recurrence-free survival was significantly worse in Category 3 than in Category 1 patients (p = 0.002), although the overall survival was not significantly different (p = 0.085) between the two groups in cases of R0 resection (5-year survival rates: 34.4 vs. 66.5 %). CONCLUSIONS: Although FAN chemotherapy followed by radical esophagectomy can be safely performed, this treatment modality may not have sufficient power to cure Category 3 disease.

Induction chemotherapy or chemoradiotherapy followed by radical esophagectomy for T4 esophageal cancer: results of a prospective cohort study.

BACKGROUND: We hypothesized that the survival rate of patients undergoing R0 esophagectomy after induction chemotherapy or chemoradiotherapy for unresectable T4 esophageal cancer (URT4) would be similar to that of patients undergoing esophagectomy for immediately resectable esophageal cancer with no unfavorable prognostic factors (RNU). METHODS: Between April 2002 and June 2012, 87 of 283 patients with esophageal cancer who presented at the University Hospital of the Ryukyus were enrolled in this prospective cohort study. Tumors were classified as RNU and URT4 in 44 and 43 of the 87 patients, respectively. Outcomes of treatment for URT4 patients were compared with those of RNU patients. RESULTS: The R0 resection rate (61 %) and in-hospital mortality rate (20 %) of URT4 patients were significantly poorer than those of RNU patients (98 and 2.3 %, respectively), although the morbidity rate was similar in the two groups (63 and 52 %, respectively). The 5-year survival rate (35 %) of URT4 patients was significantly poorer than that of RNU patients (67 %) in the intention-to-treat analysis. However, no significant difference was noted between the two survival curves for cases of R0 resection (5-year survival rate, 60 % vs. 69 %). Multivariate analysis revealed R status as the only significant independent prognostic factor for URT4 patients (P < 0.001; hazard ratio = 8.279). CONCLUSIONS: Satisfactory survival rates can be achieved if R0 resection is performed after induction treatment in patients with T4 esophageal cancer, although secondary radical esophagectomy is associated with a higher risk of in-hospital mortality.

Phase II trial of alternating mFOLFOX6 and FOLFIRI regimens in the first-line treatment for unresectable or metastatic colorectal cancer (KSCC0701).

OBJECTIVE: This phase II study examined the efficacy and safety of alternating regimens of mFOLFOX6 and FOLFIRI as a first-line treatment for unresectable or metastatic colorectal cancer. PATIENTS AND METHODS: Forty-eight patients were enrolled in this study. Patients received an alternating regimen of 4 cycles of mFOLFOX6 followed by 4 cycles of FOLFIRI. RESULTS: The characteristics of the study population were as follows: males/females 34/12, median age 66 years (range 43-75) and Eastern Cooperative Oncology Group performance status 0/1/2 in 37/9/0 patients. The overall response rate was 58.7% [95% confidence interval (CI) 43.9-73.5]. The median progression-free survival was 10.3 months (95% CI 7.5-11.9), and the median overall survival was 28.4 months (95% CI 22.5-35.7). Among the 47 patients evaluated for toxicity, the most common grade 3-4 adverse events were leukopenia (26%), neutropenia (55%), anemia (4%), neurotoxicity (0%), diarrhea (2%), febrile neutropenia (4%), nausea (4%), vomiting (2%), and hypersensitivity (0%). CONCLUSIONS: The results of this phase II study indicate that this alternating schedule is effective and well tolerated as a first-line treatment for unresectable or metastatic colorectal cancer. The low rate of grade 3 neurotoxicity is also promising.

Tuberculous lymphadenopathy mimicking pancreatic neoplasm.

Abdominal tuberculosis (TB) is the sixth most common location of extrapulmonary TB involvement. Because its symptoms and signs are often nonspecific, laboratory and imaging findings mimic other diseases including carcinoma. Therefore, the diagnosis of abdominal TB is challenging. We herein report a case of 74-year-old woman who presented with abdominal pain, anorexia, and weight loss. She had been given a diagnosis of pancreatic head carcinoma. Laboratory data was unremarkable except for elevated erythrocyte sedimentation rate, CA125, and sIL-2R. CT scan revealed multiple enlarged peripancreatic lymph nodes and concentric thickening of the ileocecal wall. Colonoscopy demonstrated deformed ileocecal valve and erosions. Histological examination showed epithelioid granulomas. Laparoscopy revealed numerous white tubercles diffusely covering the parietal peritoneum. Histopathological images of peripancreatic lymph node revealed large multiple caseating granulomas surrounded by Langhans_giant cells and epithelioid cells. Polymerase chain reaction and culture of the specimens were positive for Mycobacterium tuberculosis. Tuberculous lymphadenopathy, colitis, and peritonitis were finally diagnosed. She responded well to the antitubercular treatment.

Radical radiotherapy for superficial esophageal cancer: impact of clinical N stage on survival.

AIM: To retrospectively analyze the results of radical radiotherapy for patients with superficial esophageal cancer (SEC). PATIENTS AND METHODS: Forty-eight patients with SEC were reviewed. The median dose of external beam radiotherapy was 66 Gy (range, 30 to 70 Gy). Intraluminal brachytherapy was used in 10 patients, and 15 patients (31%) underwent chemotherapy. The median follow-up period was 28 months (range, 4 to 116 months). RESULTS: Sixteen patients had recurrence (11 patients: in-field local recurrence; 3 patients: regional lymph node recurrence; 2 patients: distant metastasis), and the 5-year local control (LC) rate was 74.2%. The 5-year overall survival and disease-free survival (DFS) rates were 44.5% and 48.6%, respectively. Patients with clinical N1 disease (5-year DFS: 0%) had significantly poorer DFS than patients with clinical N0 disease (5-year DFS: 51%, p=0.019). CONCLUSION: Radical radiotherapy yielded relatively favorable LC rates in patients with SEC, and clinical N stage was a significant prognostic factor for DFS.

Interleukin-17A is involved in enhancement of tumor progression in murine intestine.

Interleukin (IL)-17A is a cytokine involved in neutrophilic inflammation but the role of IL-17A in anti-tumor immunity is controversial because both pro- and anti-tumor activities of IL-17A have been reported. We hypothesized that constitutive expression of IL-17A in intestinal environment modifies tumor growth. To address the issue, mice were inoculated into subserosa of cecum (i.c.) with murine EL4 lymphoma expressing a model tumor antigen, and tumor growth was monitored. IL-17A-producing cells were detected both in tumor mass and in normal intestinal tissue of i.c. tumor-bearing wild type mice. Tumor size in the wild-type mice was significantly higher than that in the cecum of IL-17A gene-knockout mice. Furthermore, anti-IL-17A monoclonal antibody treatment of wild-type mice resulted in decreased tumor size in the cecum. Model tumor-antigen-specific interferon-γ production was not modified in draining mesenteric lymph node cells in the absence or after neutralization of IL-17A. All the results suggest that constitutive expression of IL-17A in intestine enhances tumor growth, and anti-IL-17A antibody treatment is a candidate of a new anti-tumor immunotherapy against intestinal tumors.

Identification of preneoplastic lesions as mucin-depleted foci in patients with sporadic colorectal cancer.

In experimental models, mucin-depleted foci (MDF), formed by dysplastic crypts devoid of mucin production have been recognized to be correlated with colorectal carcinogenesis and to serve as preneoplastic lesions of colorectal cancer (CRC). In humans, there is only one report of identification of MDF in patients with familial adenomatous polyposis and CRC; however, the histological characteristics of human MDF are not discussed extensively in the report. In the present study, colonic samples from 53 patients with sporadic CRC were stained with Alcian blue and examined for the presence of MDF. Subsequently, the samples were examined for the presence of aberrant crypt foci (ACF) by methylene blue staining. We classified MDF into two categories: flat-MDF and protruded-MDF (having the characteristics of both ACF and MDF). We found a total of 354, 41 and 19 colonic mucosal lesions with a mean multiplicity of 44, 38.9 and 66.9 crypts (ACF, flat-MDF and protruded-MDF, respectively). The density of MDF was 0.0082 lesions/cm(2) . The ACF identified in sporadic CRC patients corresponded to hyperplastic or non-dysplasic lesions. However, MDF identified in these patients corresponded to low-grade dysplasia. In addition, we found that Paneth cell metaplasia and inflammatory cell infiltration were specific histological features of MDF. These histological characteristics are reported to be associated with the development of CRC. Therefore, our results indicate that MDF might represent preneoplastic lesions in human colorectal carcinogenesis.

Severe late complications in patients with uterine cancer treated with postoperative radiotherapy.

AIM: Severe late complications, particularly radiation enterocolitis and leg edema, remain major problems in patients with uterine cancer, who have undergone hysterectomy and postoperative external beam radiotherapy (EBRT). We carried out this retrospective analysis to identify the incidence of risk factors for such complications. PATIENTS AND METHODS: The records of 228 patients, who underwent radical hysterectomy and postoperative EBRT (uterine cervix: 149 patients; uterine corpus: 79 patients) were reviewed retrospectively. The majority of the patients (90.8%) were treated with 50 to 50.4 Gy EBRT in conventional fractionations with anteroposterior fields. Intracavitary brachytherapy (ICBT) was administered to 9 patients (3.9%), and 35 patients (15.2%) received chemotherapy. The median follow-up for all 228 patients was 81.7 months (range, 1-273 months). RESULTS: Nineteen patients (8.3%) developed severe radiation enterocolitis with a median latency of 12.6 months, and the ileum was the most frequently affected site. On multivariate analysis, smoking was an independent predictor of severe radiation enterocolitis. Nineteen patients (8.3%) developed severe leg edema with a median latency of 32.7 months. The degree of leg edema did not improve in any of the 19 patients despite intensive treatment. On multivariate analysis, addition of ICBT was an independent predictor of severe leg edema. CONCLUSION: Severe radiation enterocolitis and severe leg edema were each observed in approximately 8% of patients with uterine cancer, who underwent postoperative radiotherapy. Severe radiation enterocolitis correlated strongly with smoking, and severe leg edema correlated strongly with addition of ICBT. These factors should be considered before administering postoperative radiotherapy to uterine cancer patients.

Clinical significance of HIF-1alpha expression in patients with esophageal cancer treated with concurrent chemoradiotherapy.

AIM: We investigated whether hypoxia-inducible factor-1α (HIF-1 α) expression in pretreatment biopsies of esophageal cancer is predictive of clinical outcome in patients with esophageal cancer undergoing concurrent chemoradiotherapy (CRT). PATIENTS AND METHODS: A total of 25 patients were reviewed. Radiotherapy was administered to total doses of 40-66.6 Gy (median: 66.6 Gy) with a single fraction of 1.8-2 Gy. Cisplatin (80 mg/m2 on day 1) and 5-fluorouracil (800 mg/m2 on days 2-6) were administered concurrently with radiotherapy, every 3-4 weeks to a total of 1-2 courses. Tissue samples from esophageal cancer were obtained from all 25 patients by biopsy before concurrent CRT, and semiquantitative analyses of HIF-1α expression were performed using immunohistochemical staining. RESULTS: High HIF-1α expression was observed in 11 out of 25 patients (42.7%), and HIF-1α expression was significantly correlated with initial response to CRT (p=0.0027). Patients with high HIF-1α expression had significantly poorer local control (LC) (5-year LC: 42.7%) than those with low expression (5-year LC: 72.5%; p=0.0322). Patients with high HIF-1α expression also had significantly lower recurrence-free survival (RFS) (5-year RFS: 18.2%) compared to those with low HIF-1α expression (5-year RFS: 39.8%; p=0.0009), and on multivariate analysis, HIF-1α (p=0.001) and number of chemotherapy courses (p=0.010) were independent prognostic factors for RFS. CONCLUSION: HIF-1α expression is significantly correlated with initial response to concurrent CRT, and is predictive of RFS for patients with esophageal cancer receiving concurrent CRT.

Clinical significance of GLUT-1 expression in patients with esophageal cancer treated with concurrent chemoradiotherapy.

This study aimed to investigate whether glucose transporter-1 (GLUT-1) expression in a pretreatment esophageal cancer biopsy was predictive of clinical outcomes in patients with esophageal cancer undergoing concurrent chemoradiotherapy (CRT). A total of 25 patients with esophageal cancer treated with concurrent CRT were reviewed. Radiotherapy was administered up to total doses of 40-66.6 Gy (median 66.6 Gy) with a single fraction of 1.8-2 Gy. Regarding chemotherapy, cisplatin (80 mg/m(2) on day 1) and 5-fluorouracil (800 mg/m(2) on days 2-6) were used concurrently with radiotherapy, every 3-4 weeks for a total of 1-2 courses. Tissue samples from esophageal carcinoma were obtained from the 25 patients by biopsy prior to concurrent CRT, and a semiquantitative analysis of GLUT-1 expression was performed using immunohistochemical staining. High GLUT-1 expression was observed in 7 of 25 (28%) patients, and GLUT-1 expression was significantly correlated with clinical T stage (p=0.0454), clinical N stage (p=0.0324) and initial response to CRT (p=0.0185). Patients with a high GLUT-1 expression had significantly poorer local control (LC) (5-year LC 28.6%) than those with a low expression (5-year LC 73.4%, p<005). Multivariate analysis revealed that GLUT-1 and the number of chemotherapy courses were independent prognostic factors for LC. Patients with a high GLUT-1 expression had significantly lower recurrence-free survival (RFS) compared to those with a low GLUT-1 expression (p=0.0405). Multivariate analysis revealed that GLUT-1, the number of chemotherapy courses and clinical M stage were independent prognostic factors for RFS. GLUT-1 expression was significantly correlated with clinical T stage, clinical N stage and initial response to concurrent CRT, and was predictive of LC and RFS for patients with esophageal cancer treated with concurrent CRT.