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 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.

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.

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.

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.

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.

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.

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.

Desipramine inhibits the growth of a mouse skin squamous cell carcinoma cell line and affects glucocorticoid receptor-mediated transcription.

The purpose of this study was to examine the effect of tricyclic antidepressant desipramine (DMI) on the growth inhibition and translocation of the glucocorticoid receptor (GR) from the cytoplasm to the nucleus in cancerous and noncancerous cell lines and the effect of DMI on GR-mediated transcription. Nontumorigenic, immortalized keratinocytes cell line (3PC), papilloma (MT1/2), and squamous cell carcinoma (Ca3/7) cell lines were initially used to study the cell growth inhibition by DMI. Although, the growth of all three cell lines was suppressed by DMI, it was more effective in Ca3/7 cells. Therefore, we next examined the effect of DMI on Ca3/7 cells, resistant to growth inhibition by the synthetic glucocorticoid fluocinolone acetonide (FA). DMI inhibited cell proliferation in a time-dependent manner. The translocation of GR was induced by FA alone, DMI alone, and combination of both agents. FA induced GR-mediated transcription in Ca3/7 cells transfected with a luciferase reporter gene under the control of glucocorticoid response element (GRE), but DMI alone did not affect GR-mediated transcription. However, DMI inhibited FA-induced, GR-mediated transcription when both agents were given together. Pretreatment with DMI followed by combination of DMI and FA decreased GR-mediated transcription more than pretreatment with FA. The expression of metallothionein-1 (Mt-1) gene, which is regulated by GR, was induced significantly by the combination of DMI and FA, and enhanced significantly by pretreatment with FA but not DMI. DMI is suggested to inhibit the growth of Ca3/7 cells and to affect GR-mediated transcription.

Development of gastro-lymphatic fistula during chemoradiotherapy for advanced esophageal cancer: a case report.

This is a case report of a gastro-lymphatic fistula which appeared during chemoradiotherapy for advanced esophageal cancer. A 60-year-old male was referred to the University of the Ryukyus Hospital because of a 10 kg monthly weight loss and dysphagia. Computed tomography (CT) scans indicated thickened esophageal wall at the lower thoracic esophagus and a swollen lymph node attached to the lesser curvature of the stomach. Histological analysis of the biopsy specimen revealed poorly differentiated squamous cell carcinoma and the diagnosis was of advanced esophageal cancer. A combination of chemotherapy (nedaplatin and 5-fluorouracil) and radiotherapy was initiated. After radiotherapy (20 Gy), CT scans revealed that the swollen lymph node penetrated the gastric wall resulting in a gastro-lymphatic fistula. Although gastrostomy and intestinal fistula repair were performed for gastric decompression and tube feeding, respectively, the patient's general status did not improve and he died two months after interruption of his chemoradiotherapy. The results indicate that there may be some risks of gastro-lymphatic fistula in patients treated with concurrent chemoradiotherapy for advanced esophageal cancer when there are possible signs of involvement by CT scans.

[Concurrent chemoradiotherapy for squamous cell carcinoma of the anal canal-report of four cases].

We have treated four Japanese patients with squamous cell carcinoma of the anal canal using concurrent chemoradiotherapy. The chemotherapy consisted of one or two cycles of mitomycin C 10 mg/m(2)/day (intravenous bolus injection) on day 1, and 5-fluorouracil 700 or 1,000 mg/m(2)/day (continuous intravenous infusion) on days 2-5 during radiotherapy. The total radiation dose was 40-54 Gy to the primary lesion. Acute grade 4 hematological toxicity was observed in one patient. These four patients have been alive and free of disease (follow-ups of 55, 14, 7 and 5 months, respectively), with excellent function of the anal sphincter after treatment. These results suggest that concurrent chemoradiotherapy is safe and effective for Japanese patients with squamous cell carcinoma of the anal canal.

[Case of esophageal cancer successfully performed in early response evaluation for preoperative chemotherapy by FDG-PET].

We present a case of esophageal cancer with multiple lymph node metastases successfully performed early response evaluation for preoperative chemotherapy by FDG-PET. The decrease of SUV from baseline to 11 days after initiation of low-dose FP chemotherapy were 32.8% in the primary lesion, 60.4% in the cervical lymph node and 13.5% in the abdominal lymph node. He underwent extended radical esophagectomy 4 weeks after the end of chemotherapy. The histopathologic response was Grade 1 in the primary lesion, Grade 3 in the cervical lymph node and Grade 0 in the abdominal lymph node. The early response evaluation by FDG-PET in each lesions were consistent with histopathologic response evaluation of after chemotherapy.

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.

Radiation enterocolitis requiring surgery in patients with gynecological malignancies.

PURPOSE: To identify the characteristics, risk factors, and clinical outcomes of radiation enterocolitis requiring surgery in patients with gynecologic malignancies. METHODS AND MATERIALS: The records of 1,349 patients treated with pelvic radiotherapy were retrospectively reviewed. The majority of the patients (88%) were treated with 50 Gy or 50.4 Gy pelvic irradiation in conventional fractionations with anteroposterior fields. RESULTS: Forty-eight patients (3.6%) developed radiation enterocolitis requiring surgery. Terminal ileum was the most frequent site (50%) and most of the lesions had stenosis or perforation. On univariate analysis, previous abdominopelvic surgery, diabetes mellitus (DM), smoking and primary site had an impact on the complications, and on multivariate analysis, abdominopelvic surgery, DM, and smoking were independent predictors of the complications requiring surgery. After the surgical intervention, the frequency of Grade 2 or more bleeding was significantly lower in patients treated with intestinal resection in addition to decompression than those treated with intestinal decompression alone. CONCLUSIONS: Severe radiation enterocolitis requiring surgery usually occurred at the terminal ileum and was strongly correlated with previous abdominopelvic surgery, DM, and smoking. Concerning the management, liberal resection of the affected bowel appears to be the preferable therapy.

[A case of advanced gastric cancer with lung metastasis effectively treated by combination chemotherapy using S-1 and CDDP].

We report a case with gastric cancer and lung metastasis,who responded remarkably to combination chemotherapy using S-1 and weekly CDDP. A 59-year-old man was hospitalized for aphagia. Based on upper GI endoscopy and CT,type 3 gastric cancer associated with lung metastases was diagnosed. Cardiac gastrectomy, D 1 dissection, intermittented small intestine were performed. At 18 days postoperatively,the patient was administered 3 courses of S-1 (100 mg/body, on day 1-21) and CDDP (30 mg/body, on day 8, 15, 22) every 5 weeks. The treatment resulted in the metastatic tumors in the lung disappearing after 1 course. No severe adverse effects were observed. This combination chemotherapy proved useful for treating lung metastasis from gastric cancer in this patient.

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.

Reduced expression level of mgmt mRNA and beta-catenin gene mutation in rat colon tumors.

BACKGROUND: O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein and protects DNA from the biological effects of alkylating carcinogens. The purpose of this study was to investigate the association between the mRNA expression level of the Mgmt gene and mutation of the beta-catenin gene in rat colon tumors induced by azoxymethane (AOM) plus dextran sulfate sodium (DSS). MATERIALS AND METHODS: Eleven tumor samples from rat colon treated by AOM plus DSS were examined. Mutation of the beta-catenin gene was identified by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. The expression level of Mgmt mRNA was determined by reverse transcription-PCR (RT-PCR). RESULTS: Four out of five adeno-carcinoma samples bearing beta-catenin gene mutation (5 out of 11, 45%) displayed a decrease in expression levels of Mgmt mRNA (p<0.02). CONCLUSION: These results suggest that the reduced expression of Mgmt mRNA and beta-catenin gene mutation may contribute to the development of rat colon tumors.

Successful treatment for esophageal carcinoma with lung metastasis by induction chemotherapy followed by salvage esophagectomy: report of a case.

We here report a case of a 51-year-old man with lung metastasis from esophageal carcinoma that was initially treated by combination chemotherapy consisting of fluorouracil and nedaplatin. Because metastatic disease disappeared, salvage esophagectomy was performed. Although chest wall recurrence developed at the thoracotomy wound, prolonged survival of 48 mo was achieved by local tumor resection and additional chemotherapy. This combination chemotherapy is regarded as a promising and considerable treatment for metastatic esophageal carcinoma.