Occult lung cancer incidentally found during surgery for esophageal and gastric cancer: a case report.

A 70-year-old male was admitted to our hospital because of advanced esophageal squamous cell carcinoma and early gastric adenocarcinoma. A esophagectomy and partial gastrectomy with three-field lymph node dissection (neck, mediastinum and abdomen) was performed. Both tumors had lymph node metastases. In addition, three mediastinal lymph nodes (two subcarinal lymph nodes and a middle thoracic paraesophageal lymph node) were involved with adenocarcinoma. To elucidate whether they were metastases from the gastric cancer, an immunohistochemical analysis was performed. The cancer cells in these lymph nodes were positive for cytokeratin (CK) 7 and negative for CK 20, thus suggesting metastasis from a nondigestive organ. Interestingly, they were positive for thyroid transcription factor 1 (TTF-1), indicating metastasis from a lung cancer. Since the preoperative computed tomographic scan showed no evidence of lung cancer, a diagnosis of metastases from an occult lung cancer was finally recorded. Ten months after surgery, the patient was alive without a recurrence or the appearance of a lung cancer.

Surgical treatment of intractable cutaneous fistula with osteomyelitis in the neck developed after esophagectomy.

A case of intractable cutaneous fistula in an esophagogastrostomized region complicated by osteomyelitis is reported. A three-stage operation was performed, and gratifying results were obtained. The patient was a 74-year-old man who received a subtotal esophagectomy and a cervical esophagogastrostomy through a retrosternal approach for advanced esophageal cancer. Following subsequent radiotherapy, the anastomosed region in the neck was found to have been stenosed. Endoscopic balloon dilatation was then performed and perforation of the stenosed region occurred to form an intractable fistula. A chest computed tomography scan revealed osteolysis of the sternum, clavicular head and left first rib. Treatment comprised an initial control of the infective foci including osteomyelitis and, after achieving stabilization of the wounds, the subsequent step of reconstruction. The patient's postoperative course was satisfactory without involvement of any leakage or stenosis of the anastomosed regions, or wound infection. It is considered feasible to cure even a cutaneous fistula in the neck complicated by osteomyelitis, as in the present case, by sufficient control of infection and procedural contrivance.

Collision carcinoma of the residual cervical esophagus 27 years after esophageal cancer surgery.

A case of collision carcinoma (squamous cell carcinoma and Barrett's adenocarcinoma) in the residual cervical esophagus of a 68-year-old woman at 27 years after subtotal esophagectomy for thoracic esophageal carcinoma is reported. The patient initially noticed cervical dysphagia in 2002, but did not seek treatment. In April 2004, the patient was referred to our department by a local physician with the diagnosis of carcinoma of the cervical esophagus. In September 2004, the patient underwent resection of the cervical esophagus and partial resection of the gastric tube combined with cervical lymph node dissection under a diagnosis of double cancer (i.e., metachronous cervical esophageal carcinoma and carcinoma of the gastric tube). Esophagogastric continuity was restored by transplantation of a free jejunal graft with vascular anastomosis. Pathological examination showed squamous cell carcinoma on the esophageal side of the esophagogastric anastomosis and columnar epithelium with a tongue-shaped extension across the anastomotic line that included Barrett's epithelium, as well as adenocarcinoma, on the gastric tube side. The squamous cell carcinoma and adenocarcinoma were contiguous, but there was a distinct border between them and no morphological transition. Immunohistochemical staining showed positivity for p53 in the squamous carcinoma cells, while it was negative in the adenocarcinoma cells. In contrast, HER2 (c-erb-2) was strongly positive in the adenocarcinoma cells, but negative in the squamous carcinoma. Based on these findings, it was concluded that two separate carcinomas had arisen at different sites and grown independently until they collided and merged to form a collision carcinoma.

Chemoradiotherapy with and without esophagectomy for advanced esophageal cancer.

BACKGROUND/AIMS: To evaluate the impact of surgery on survival after chemoradiotherapy, we analyzed the long-term outcome of patients with advanced esophageal cancer. METHODOLOGY: Data on 92 consecutive patients with T3 or T4 esophageal cancer who were initially treated by chemoradiotherapy were reviewed retrospectively. Of 82 patients who completed the planned schedule, 35 patients underwent esophagectomy (CRT+E Group) and 47 patients received definitive chemoradiotherapy (CRT Group). RESULTS: A response to chemoradiotherapy was obtained in 71% of all 92 patients. The 1- and 3-year survival rates in the patients with T3M0 were 87 and 44 percent respectively, while these in the patients with T4 and/or M1(Lymph) disease were 47 and 20 percent. Although there was no difference in overall survival between the CRT+E Group and the CRT Group, the survival of responders in the CRT+E Group was significantly higher than that of those in the CRT Group (P=0.0448). The locoregional recurrence rate of responders in the CRT Group was higher than that in the CRT+E Group. Multivariate analysis showed that the independent prognostic factors were response, M(Lymph), and esophagectomy. CONCLUSIONS: Although this study was retrospective and nonrandomized, esophagectomy after chemoradiotherapy might improve the survival of responders for locoregional control.

Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study--JCOG9204.

PURPOSE: We performed a multicenter randomized controlled trial to determine whether postoperative adjuvant chemotherapy improves outcome in patients with esophageal squamous cell carcinoma undergoing radical surgery. PATIENTS AND METHODS: Patients undergoing transthoracic esophagectomy with lymphadenectomy between July 1992 and January 1997 at 17 institutions were randomly assigned to receive surgery alone or surgery plus chemotherapy including two courses of cisplatin (80 mg/m2 of body-surface area x 1 day) and fluorouracil (800 mg/m2 x 5 days) within 2 months after surgery. Adaptive stratification factors were institution and lymph node status (pN0 versus pN1). The primary end point was disease-free survival. RESULTS: Of the 242 patients, 122 were assigned to surgery alone, and 120 to surgery plus chemotherapy. In the surgery plus chemotherapy group, 91 patients (75%) received both full courses of chemotherapy; grade 3 or 4 hematologic or nonhematologic toxicities were limited. The 5-year disease-free survival rate was 45% with surgery alone, and 55% with surgery plus chemotherapy (one-sided log-rank, P =.037). The 5-year overall survival rate was 52% and 61%, respectively (P =.13). Risk reduction by postoperative chemotherapy was remarkable in the subgroup with lymph node metastasis. CONCLUSION: Postoperative adjuvant chemotherapy with cisplatin and fluorouracil is better able to prevent relapse in patients with esophageal cancer than surgery alone.

Comparison of extended esophagectomy through mini-thoracotomy/laparotomy with conventional thoracotomy/laparotomy for esophageal cancer.

OBJECTIVE: In order to assess the usefulness of esophagectomy through mini-thoracotomy/laparotomy as a minimally invasive surgical procedure for esophageal cancer, we compared the results to those of conventional right thoracotomy/laparotomy. METHODS: From 1998 to 2002, 40 patients with thoracic esophageal cancer were prospectively assigned to two groups. Twenty patients underwent esophagectomy through mini-thoracotomy/laparotomy (M-group), while the other 20 had conventional thoracotomy/laparotomy (C-group). Surgical complications, the duration of the systemic inflammatory response syndrome (SIRS), postoperative pain, cytokine responses, and respiratory function were compared between the two groups. RESULTS: There was no difference of morbidity between the M- and C-groups after surgery. There were also no differences between the two groups with respect to the operating time, bleeding, and number of dissected lymph nodes. The duration of SIRS was shorter in the M-group than in the C-group (p = 0.055). Use of morphine was lower in the M-group than in the C-group with patient-controlled anesthesia (p = 0.002). The interleukin-6 level of the M-group was lower than that of the C-group at 3, 6 hours, and 3 days after the operation. Recovery of vital capacity by the M-group was better than by the C-group after the operation. Postoperative hospital stay of the M-group was significantly shorter than that of the C-group (p = 0.014). Long-term survival was not different in the two groups. CONCLUSION: Mini-thoracotomy/laparotomy reduces invasiveness and pain compared with conventional thoracotomy/laparotomy for esophagectomy without causing any differences of morbidity or long-term survival.

Detection of bone marrow micrometastasis in esophageal cancer patients by immunomagnetic separation.

Detection of micrometastasis to the bone marrow can predict widespread disease and a poor prognosis of cancer patients. The purpose of this study was to evaluate the clinical significance of detecting micrometastasis in the bone marrow of esophageal cancer patients. Bone marrow and peripheral blood samples were obtained from 52 squamous esophageal cancer patients at the time of surgery. These samples were enriched by immunomagnetic separation and immunostained with an anti-cytokeratin antibody. Expression of vascular endothelial growth factor (VEGF) and cyclin D1 was examined in the primary tumors. Cytokeratin-positive cancer cells were observed in the bone marrow of 13 (25%) out of 52 patients. Among them, three patients also had cancer cells in the peripheral blood. The presence of bone marrow micrometastasis was correlated with lymph node metastasis (pN) but not associated with depth of tumors (pT). Detection of bone marrow micrometastasis was significantly correlated with VEGF expression of the primary tumors. Cumulative survival of patients with bone marrow micrometastasis was significantly lower than that of patients without it (p=0.0008). Hematogenous recurrence was more frequent in patients with bone marrow micrometastasis than in those without it (p=0.0004). Three patients who had local or dissemination recurrence did not have bone marrow micrometastasis. Detection of cancer cells in the bone marrow might be an indicator of early hematogenous metastasis in esophageal cancer patients. Intensive postoperative chemotherapy seems to be indicated for these patients.

Case report: a young woman with advanced esophageal cancer showing pathological complete response to neoadjuvant chemotherapy (CDDP, 5-FU and ADM).

A 32-year-old woman was admitted to our hospital with dysphagia. An upper gastrointestinal series revealed Borrmann type 2 esophageal cancer in the lower thoracic esophagus. Because direct invasion of the thoracic aorta was suspected, FAP therapy (CDDP, 5-FU and ADM) was given as neoadjuvant chemotherapy. After completion of two courses, her dysphagia resolved and the tumor shrank by over 90%, so radical surgery was performed. No lesions were found when the resected specimen was examined macroscopically. The only histological change was hyperplasia of collagen fibers in the submucosa, lamina propria and adventitia of the esophagus. No cancer cells and no metastases to the lymph nodes were observed. Because the tumor had completely disappeared, the histological effect of chemotherapy was classified as grade 3, i.e., pathological complete response (PCR). The response to FAP therapy was excellent and no serious adverse events occurred. Therefore, this is one of the treatments that should be actively applied in patients who have advanced esophageal cancer with suspected lymph node metastasis and invasion of other organs.

Salvage esophagectomy after definitive chemotherapy and radiotherapy for advanced esophageal cancer.

BACKGROUND: Although local recurrence of advanced esophageal cancer is frequent after definitive chemoradiotherapy (CRT), the clinical benefit of salvage esophagectomy has not been elucidated. METHODS: We reviewed 27 patients with squamous-cell cancer who underwent esophagectomy after definitive CRT (> or = 50 Gy) (salvage group) and 28 patients who underwent planned esophagectomy after neoadjuvant CRT (30 to 45 Gy) (neoadjuvant group). RESULTS: The preoperative albumin level and vital capacity were significantly lower in the salvage group than in the neoadjuvant group. Two patients (7.4%) from the salvage group who underwent extended esophagectomy with three-field lymphadenectomy died of postoperative complications, but no deaths occurred after less-invasive surgery. There was no difference of overall postoperative survival between the salvage and neoadjuvant groups. CONCLUSIONS: The outcome of salvage esophagectomy after definitive CRT was similar to that of planned esophagectomy after neoadjuvant CRT. Less-invasive procedures might be better for salvage esophagectomy because of the high operative risk.

Concomitant analysis of p16/INK4, cyclin D1, and retinoblastoma protein expression in esophageal squamous cell carcinoma.

BACKGROUND/AIMS: Cyclin D1 expression is one of the important biologic factors and its close association with p16/INK4 and retinoblastoma protein expression has been proven in patients with esophageal squamous cell carcinoma, however, the clinical implication of these associations is still unknown. The objective of this study is to clarify its clinical significance. METHODOLOGY: We studied p16, cyclin D1, and pRB expression using immunohistochemistry in the resected specimens of 156 patients who underwent curative esophagectomy. RESULTS: Alteration of p16 expression, positive cyclin D1 expression and loss of pRB expression were demonstrated in 108 (69%) patients, 47 (30%) patients, and 48 (31%) patients, respectively. An inverse correlation was found between p16 expression and pRB expression (P < 0.0001). Of 47 cyclin D1-positive tumors, 39 (83%) tumor exhibited alteration of p16 and 43 (92%) tumors were positive for pRB. Based on p16, cyclin D1, and pRB expression, 138 (88%) patients were divided into the following three groups: p16-/cyclin D1+/pRB+ (n = 44), p16+/cyclin D1-/pRB- (n = 38), p16-/cyclin D1-/pRB+ (n = 56). The three groups were the most influential prognostic factors in a Cox's proportional regression model. The p16-/cyclin D1+/pRB+ group had frequent hematogenous recurrence, while the other groups had frequent lymph node recurrence. CONCLUSIONS: Assessment of p16, cyclin D1, and pRB expression may be helpful for determining postoperative therapeutic strategies in patients with esophageal squamous cell carcinoma.

Preoperative evaluation of lymph node metastasis in esophageal cancer.

Lymph node metastasis (LMN) in esophageal cancer occurs from the superficial cancer and spreads wildly from the neck to the abdomen. Hence precise determination of LMN is essential when adequate treatments are employed. There are several reports about ultrasonic features of malignant lymph nodes (LNs), and in summary, reports of endoscopic ultrasonography (EUS) findings of malignant LNs showed they were more than 5-10 mm in diameter, with a distinct border, hypoechoic internal echo and round shape. Sensitivity, specificity and accuracies for the diagnosis of malignant LNs by EUS were 49-99%, 33-99% and 71-96%. The rates widely varied, because the accuracy of EUS's ability to determine malignancy were based on the evaluation of various echo features of LNs, and were dependent on the judgement of subjective observers. Therefore histological analysis is necessary for adequate treatments. Endoscopic ultrasonography guided fine-needle aspiration cytology (EUS-FNA) has been performed for the diagnosis of malignant LNs since 10 years. Results of those reports were sensitivity 81-97%, specificity 83-100% and accuracy 83-97%. EUS-FNA staging was better than EUS staging. Also clinically obvious complications by EUS-FNA have not been reported. Therefore published evidence showed that EUS-FNA is safe and useful for confirmation of malignant LNs.

[Malignant melanoma of the alimentary tract].

We reviewed case reports of malignant melanoma in the alimentary tract and discussed the diagnosis and treatment. Cases of malignant melanoma in the alimentary tract have mostly originated from the esophagus and an anorectal lesion. Metastatic tumors occurred mainly in the stomach and the small intestine. Although resection with lymph node dissection was performed, the prognosis of these patients was worse than that of patients with carcinoma. Malignant melanoma of the alimentary tract might be more aggressive than that of the skin. A combined modality treatment including progressive chemotherapy and biotherapy is expected to improve the prognosis of these patients.

[Nedaplatin and 5-fluorouracil combined with radiotherapy for advanced esophageal cancer].

We conducted a pilot study of nedaplatin + 5-fluorouracil (5-FU) combined with radiotherapy for 29 patients with primary advanced (stage IV) esophageal cancer. A complete remission (CR) was obtained in 4 (14%) and a partial response in 13 patients (response rate: 59%). The median survival time and one-year survival rate were 238 days and 34.5%, respectively. Of the 29 patients, 24 (83%) completed the treatment schedule and toxicity of stomatitis and the like was infrequent. In conclusion, these results suggest that the efficacy of nedaplatin + 5-FU combined with radiotherapy might not differ from that of cisplatin + 5-FU combined with radiotherapy. Clearly, the usefulness of this combined therapy needs to be assessed in multicenter phase III trials.

[Radical surgery with mini-thoracolaparotomy for esophageal cancer].

In our institute, radical esophagectomy through mini-thoracolaparotomy has been performed as a less-invasive surgery for esophageal cancer since 1996. We describe the indications for and operative procedures of mini-thoracolaparotomy. Next we report the preliminary results of a prospective randomized trial that compared mini-thoracolaparotomy with conventional thoracolaparotomy in 30 patients without neoadjuvant therapy. There were no differences between the two groups in operative time, bleeding volume, and number of dissected lymph nodes. Thoracolaparotomy was effective in decreasing the quantity of morphinerequired in the ICU and shortening hospitalization after surgery. Thoracolaparotomy was effective in preventing a decrease in and early recovery of postoperative vital capacity. In clinical data on radical esophagectomy performed through a right thoracotomy and reconstruction with a stomach tube from 1996 to 2000, the 5-year survival rate of 63 patients in the thoracolaparotomy group (67.6%) did not differ from that of 124 patients in the conventional surgery group (49.9%).

Neural correlate of human reciprocity in social interactions.

Reciprocity plays a key role maintaining cooperation in society. However, little is known about the neural process that underpins human reciprocity during social interactions. Our neuroimaging study manipulated partner identity (computer, human) and strategy (random, tit-for-tat) in repeated prisoner's dilemma games and investigated the neural correlate of reciprocal interaction with humans. Reciprocal cooperation with humans but exploitation of computers by defection was associated with activation in the left amygdala. Amygdala activation was also positively and negatively correlated with a preference change for human partners following tit-for-tat and random strategies, respectively. The correlated activation represented the intensity of positive feeling toward reciprocal and negative feeling toward non-reciprocal partners, and so reflected reciprocity in social interaction. Reciprocity in social interaction, however, might plausibly be misinterpreted and so we also examined the neural coding of insight into the reciprocity of partners. Those with and without insight revealed differential brain activation across the reward-related circuitry (i.e., the right middle dorsolateral prefrontal cortex and dorsal caudate) and theory of mind (ToM) regions [i.e., ventromedial prefrontal cortex (VMPFC) and precuneus]. Among differential activations, activation in the precuneus, which accompanied deactivation of the VMPFC, was specific to those without insight into human partners who were engaged in a tit-for-tat strategy. This asymmetric (de)activation might involve specific contributions of ToM regions to the human search for reciprocity. Consequently, the intensity of emotion attached to human reciprocity was represented in the amygdala, whereas insight into the reciprocity of others was reflected in activation across the reward-related and ToM regions. This suggests the critical role of mentalizing, which was not equated with reward expectation during social interactions.

A case of esophageal cancer with multiple lymph node metastases which responded to neoadjuvant chemotherapy (DCF therapy).

It is difficult to perform radical surgery for esophageal cancer with multiple lymph node metastases. Therefore, effective neoadjuvant adjuvant treatment is necessary to achieve successful radical resection. The use of neoadjuvant chemotherapy of docetaxel, cisplatin (CDOP) and 5-fluorouracil (5-FU) (DCF) in an advanced case is reported. The patient (a 67-year-old female) was diagnosed with esophageal cancer, T3, N4, M0, stage IVa with a large number of lymph node metastases in the mediastinum and in the abdominal cavity. Neoadjuvant DCF chemotherapy was initiated in August 2006. Adverse events were mild. A complete response of the lymph node metastases in the abdominal cavity and a partial response of the esophageal lesion were achieved. The surgical procedure included a right thoracolaparotomy followed by a subtotal excision of the esophagus and two-field lymph node dissection. The cancer was diagnosed to be moderately differentiated squamous cell cancer, pT2, pN4(3c) and pstage IVa. The histological efficacy of the chemotherapy was determined to be grade 1a. Two additional courses of DCF therapy were administered followed by postoperative adjuvant chemotherapy.

Neural correlates of attitude change following positive and negative advertisements.

Understanding changes in attitudes towards others is critical to understanding human behaviour. Neuropolitical studies have found that the activation of emotion-related areas in the brain is linked to resilient political preferences, and neuroeconomic research has analysed the neural correlates of social preferences that favour or oppose consideration of intrinsic rewards. This study aims to identify the neural correlates in the prefrontal cortices of changes in political attitudes toward others that are linked to social cognition. Functional magnetic resonance imaging (fMRI) experiments have presented videos from previous electoral campaigns and television commercials for major cola brands and then used the subjects' self-rated affinity toward political candidates as behavioural indicators. After viewing negative campaign videos, subjects showing stronger fMRI activation in the dorsolateral prefrontal cortex lowered their ratings of the candidate they originally supported more than did those with smaller fMRI signal changes in the same region. Subjects showing stronger activation in the medial prefrontal cortex tended to increase their ratings more than did those with less activation. The same regions were not activated by viewing negative advertisements for cola. Correlations between the self-rated values and the neural signal changes underscore the metric representation of observed decisions (i.e., whether to support or not) in the brain. This indicates that neurometric analysis may contribute to the exploration of the neural correlates of daily social behaviour.

Phase II study of cisplatin and 5-fluorouracil with concurrent radiotherapy in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group trial (JCOG9516).

BACKGROUND: In Japan, concurrent chemoradiotherapy is the standard treatment for unresectable esophageal cancer. The optimal combination of chemotherapeutic agents and radiotherapy dose remains controversial. The present study consists of a phase II trial of a cisplatin (CDDP)/5-fluorouracil (5-FU) infusion with concurrent radiotherapy in patients with unresectable, advanced esophageal cancer. METHODS: Between March 13, 1996, and April 28, 1998, 60 patients with advanced squamous cell carcinoma of the thoracic esophagus having either T4 tumor or distant lymph node metastasis (M1 Lym) were enrolled in this study. CDDP 70 mg/m(2) was administered on days 1 and 29, and 5-FU 700 mg/m(2)/day was administered on days 1-4 and 29-32. Fractionated radiotherapy was performed on days 1-21 and 29-49; a total dose of 60 Gy was delivered at the rate of 2 Gy per fraction. RESULTS: The overall response rate of all the 60 registered patients was 68.3% (41/60), and the complete response rate was 15% (9/60). The median survival time was 305.5 days, and the 2-year survival rate was 31.5%. One toxicity-related death occurred. The major form of toxicity exceeding grade 2 was found to be myelosuppression; grade 4 toxicity was observed in five patients. CONCLUSION: Based on the overall response rate, the results obtained from the present trial do not appear to be promising. However, it is currently suitable for the treatment of patients with unresectable, advanced esophageal cancer because of certain clinical advantages, a higher CR rate and a lower incidence of fistula formation. A phase II/III trial will be started in order to compare low-dose continual CDDP/5-FU infusion and concurrent radiotherapy with the results obtained in this study.