Intramural Metastasis Research Articles

Esophageal squamous cell carcinoma with intramural metastasis presenting as a pendiculated polyp

Esophageal squamous cell carcinoma with intramural metastasis presenting as a pendiculated polyp

Radiation therapy for gastric wall metastasis from esophageal carcinoma

An 86-year-old man with dysphagia underwent gastrointestinal fiberscopy (GIF) and was found to have a circumferential type 3 advanced carcinoma in the upper thoracic esophagus and a type 2 tumor in the posterior wall of the gastric body. Microscopic examination of biopsy specimens of both tumors demonstrated moderately differentiated squamous cell carcinoma. He was diagnosed as having stage IVb (T3N0M1b) esophageal carcinoma with gastric wall metastasis. A total of 60 Gy in 30 fractions of three-dimensional conformal radiation therapy (3D-CRT) was first administered to the esophageal carcinoma, next to the gastric wall metastasis. Concurrent chemotherapy was not given because of the patient's refusal. No subjective morbidity was observed during the treatment. In the GIF study immediately after 3D-CRT, both esophageal and gastric wall tumors had attained a complete response. The dysphagia dissolved as the esophageal tumor shrunk. The patient has been doing well for 17 months after the start of 3D-CRT. No local recurrence was observed in either the esophagus or the stomach during follow-up GIF. Considering the dismal prognosis of esophageal carcinoma patients with intramural metastasis to the stomach, a watchful follow-up is needed.

Esophageal Stricture Due to Intramural Metastases of Lobular Breast Carcinoma

Esophageal Stricture Due to Intramural Metastases of Lobular Breast Carcinoma

Intramural Metastasis of Esophageal Carcinoma to the Reconstructed Gastric Tube Detected by FDG PET/CT

Intramural Metastasis of Esophageal Carcinoma to the Reconstructed Gastric Tube Detected by FDG PET/CT

Transglutaminase 3 as a prognostic biomarker in esophageal cancer revealed by proteomics

To develop a prognostic biomarker for esophageal squamous cell carcinoma (ESCC), we examined the proteomic profile of ESCC using two-dimensional difference gel electrophoresis (2D-DIGE), and identified proteins associated with prognosis by mass spectrometry. The prognostic performance of the identified proteins was examined by immunohistochemistry in additional cases. We identified 22 protein spots whose intensity was statistically different between ESCC cases with good (N = 9; survived more than 5 years without evidence of recurrence) and poor (N = 24; died within 2 years postsurgery) prognosis, within the patient group that had two or more lymph node metastases. Mass spectrometric protein identification resulted in 18 distinct gene products from the 22 protein spots. Transglutaminase 3 (TGM3) was inversely correlated with shorter patient survival. The prognostic performance of TGM3 was further examined by immunohistochemistry in 76 ESCC cases. The 5-year disease-specific survival rate was 64.5% and 32.1% for patients with TGM3-positive and TGM3-negative tumors, respectively (p = 0.0033). Univariate and multivariate analyses revealed that TGM3 expression was an independent prognostic factor among the clinicopathologic variables examined. It is noteworthy that the prognostic value of TGM3 was shown to be higher than those of the lymph node metastasis, intramural metastasis and vascular invasion status. These results establish TGM3 as a novel prognostic biomarker for ESCC for the first time. Examination of TGM3 expression may provide novel therapeutic strategies to prevent recurrence of ESCC.

Multiple and metachronous esophageal intramural metastases from a gastric adenocarcinoma

Esophageal squamous cell carcinoma is often accompanied by intramural metastases, and it has been reported to carry a poor prognosis. Intramural metastasis from gastric cancer to the esophageal wall, however, has rarely been reported. We herein report a rare case of a 46-year-old man with an elevated esophageal lesion, resembling a 0-IIa-type esophageal cancer, which was discovered 13 months after a total gastrectomy performed for gastric cancer. The esophageal tumor, resected by endoscopic mucosal resection (EMR), was an adenocarcinoma with the same histology as the previously resected primary gastric cancer, and it showed massive lymphatic permeation. Soon after the EMR, other similar lesions emerged on the esophageal wall. We therefore considered the esophageal tumor to be a systemic expansion of the primary gastric cancer, and we administered the anticancer drug, S-1. Esophageal intramural metastases from a gastric cancer imply a systemic expansion of the gastric cancer, and portend a poor prognosis.

下部直腸扁平上皮癌が上部直腸に同時性壁内転移をきたした１切除例

症例は60歳女性，粘血便を主訴に大腸内視鏡検査，注腸造影検査を施行したところ上部直腸-直腸S状部(Ra-Rs）に1型腫瘍を認め，肛門管にかかる下部直腸(Rb-P）に2型腫瘍を認めた．生検結果はともに扁平上皮癌であった．以上よりRb-Pの約2cmの2型腫瘍，Ra-Rsの約6cmの1型腫瘍に対し，平成17年8月腹会陰式直腸切断術を施行した．病理検査結果ではRb-P腫瘍は低分化型扁平上皮癌，mp, ly2, v2であった．Ra病変は主座が粘膜下にあり，粘膜面には陰窩が残存して比較的保たれていること，これら組織が類似していることから下部直腸扁平上皮癌の上部直腸への壁内転移と判断した．われわれは下部直腸扁平上皮癌が上部直腸に同時性壁内転移をきたし，切除しえた稀な症例を経験したので報告する．

Have Surgical Outcomes of Pathologic T4 Esophageal Squamous Cell Carcinoma Really Improved? Analysis of 268 Cases During 45 Years of Experience

Because invasion to an adjacent organ (T4) indicates highly advanced disease, and most surgeons avoid esophagectomy, the prognostic impact of clinicopathologic factors for survival of these patients after esophagectomy has rarely been analyzed. From 1960 to 2005, a total of 268 patients with esophageal squamous cell carcinoma underwent esophagectomy for pathologic T4 disease (pT4). The impact of clinicopathologic factors on survival was evaluated by univariate and multivariate analysis. Changes in surgical outcomes and longterm survival between the earlier period (1960 to 1989) and the later period (1990 to 2005) were analyzed. Overall survival rates of all patients were 25% at 1 year, 10% at 3 years, and 5% at 5 years. The survival curve of the later group was significantly better than that of the earlier group (p < 0.01). Multivariate analysis indicated that venous invasion (hazards ratio, 1.76; 95% CI, 1.33 to 2.33, p < 0.01) and presence of a postoperative complication (hazards ratio, 2.62; 95% CI, 1.96 to 3.51, p < 0.01) were independent risk factors for poor overall survival. Presence of residual cancer was also an independent risk factor for poor cause-specific survival (hazards ratio, 2.40; 95% CI, 1.23 to 4.69, p=0.01). Venous invasion and intramural metastasis were risk factors for residual cancer. A total of 38 (14%) patients, 15 in the early period and 23 in the later period, underwent complete resection (R0). Although overall survival after R0 resection in the later period improved slightly, cancer-related survival rates were similar in both periods. Although overall survival of patients with pT4 improved after 1990, this improvement might be mainly dependent on curability of the resection.

Extranodal Spreading of Esophageal Squamous Cell Carcinoma: Clinicopathological Characteristics and Prognostic Impact

Microscopic cancer spreading to extranodal connective tissues (extranodal spreading: ENS) is occasionally found in resected specimens from patients with esophageal squamous cell carcinoma (SCC), but the prognostic impact of ENS remains unclear. The aims of this study were to elucidate the prognostic impact of ENS to help determine the most suitable management for the patients with ENS. We histologically re-evaluated 7,349 lymph nodes obtained from 171 patients with SCC of the thoracic esophagus who underwent potentially curable resection between 1992 and 2003. We defined ENS as microscopic penetration of tumor cells from metastatic lymph nodes or tumor cell dissemination into extranodal connective tissues. Extranodal spreading was found in 37 (21.6%) patients, and it had a significant relationship with diameter and depth of the tumor, lymphatic and venous invasion, intramural metastasis, and number of metastatic nodes. Patients who were ENS positive were at higher risk of recurrence, and their overall survival rate was lower than that for ENS-negative patients. Furthermore, recurrent risk was higher and overall survival rate was lower in ENS-positive patients than in ENS-negative patients when they had 1-3 metastatic nodes, but recurrent risk and overall survival rate of the patients with 4 or more metastatic nodes were very similar in ENS-positive and ENS-negative patients. The present findings suggest that in SCC of the thoracic esophagus, the presence of ENS increases recurrent risk and reduces the overall survival of the patients with 1-3 metastatic nodes. Patients showing ENS should be managed in the same way as patients with 4 or more metastatic nodes.

Lymph Node Metastasis Density and Growth Pattern as Independent Prognostic Factors in Advanced Esophageal Squamous Cell Carcinoma

Esophageal cancer is one of the leading types of cancer, and it is a particularly deadly form of malignancy. TNM classification is the most common staging system, but it has been reported that prognosis is not reflected adequately by this classification. The purpose of this study was to clarify independent prognostic factors in esophageal squamous cell carcinoma (ESCC), a dominant type of esophageal cancer in Japan, to broaden the staging system to improve its predictive value. Thus staging could be expanded to make the prognosis a valuable clinical tool, and to improve knowledge of the biological traits of advanced ESCC. The present study included 121 patients with advanced ESCC (stage II to IVA) treated by esophagectomy between 1990 and 2003 at the Kitasato University Higashi Hospital. Univariate prognostic analysis of the disease-specific survival revealed that TNM stage (p < 0.0001), lymph node metastasis density over 10% (ND10; p < 0.0001), R-category (p = 0.003), intramural metastasis within the esophagus (IM; p = 0.009), growth pattern (p = 0.01), and size of tumor (p = 0.02) were significantly associated with a poor outcome in advanced ESCC. Multivariate analysis confirmed that growth pattern (p = 0.02, HR = 3.1) and ND10 (p = 0.02, HR = 2.0) were finally remnant prognostic factors independent of TNM stage. Growth pattern was prominent in stage II, whereas ND10 was directly proportional to stage progression and characteristics to stage IV disease. Interestingly, ND20, the most malignant phenotype of ESCC, was the only prognostic determinant, even in stage IV disease. From the present study, we concluded that progression of lymph node density is characteristic of a life-threatening phenotype of advanced ESCC, and it should be employed as a therapeutic target to improve patient survival. Growth pattern is an alternative target characteristic of less advanced ESCC. Both of these parameters may be applied as useful clinical tools in the management of patients with advanced esophageal cancer.

壁内進展巣が直腸粘膜脱症候群様病理像を呈した直腸Ｓ状部癌の１症例

患者は50歳代の男性. 近医にて直腸S状部進行癌と, 下部直腸前壁の壁不整を指摘され当科紹介となった. 内視鏡的には二つの病変間は3.5cmあり, 下部直腸病変はII型pitを呈し, 生検にてfibromuscular obliterationが検出された. 癌性狭窄による排便困難からいきみを誘発し, 二次的に生じた粘膜脱症候群を疑った. しかし, 当院での生検では下部直腸病変の一部にGroup 5が検出された. 下部直腸病変が癌である場合には直腸切断術を考慮する必要がある. 確定診断を得るためにEMRを行った. EMRの組織像では粘膜下層を中心に中分化腺癌が検出され, 直腸S状部癌の肛門側壁内進展と診断した. このため直腸切断術を行い, 病巣を遺残させることなく切除した.本症例はMPS様を呈した直腸S状部癌壁内進展巣を術前診断し, 適切な手術術式を選択しえた貴重な症例であった.

Intestinal metastases in a squamous cell carcinoma arising in mature cystic teratoma of the ovary: a case report

Metastatic spread to the intestines by squamous cell carcinoma (SCC) arising in mature cystic teratoma (MCT) or dermoid cyst is a very rare event. A case of a 40-year-old cachectic woman is presented with an MCT of the left ovary found at autopsy. Focal mural thickening of the cyst wall harbored a moderately differentiated SCC with single cell keratinization. Intramural metastases were noted in the jejunum, ileum, colon transversum, and left colonic flexure. In addition, liver metastases were detected. The tumor was staged as FIGO IV. The peritoneum was covered diffusely by fibrinous and suppurative exudate. In this unusual case, metastasizing SCC of the ovary arising in an MCT led to suppurative peritonitis and consequently to death of the patient. Follow-up procedures regarding intestinal spread could be useful in patients with SCC in MCT.

Esophageal carcinosarcoma with intramural metastasis

A case of esophageal carcinosarcoma is described herein. A 58-year-old man presented with dysphagia and was admitted to our hospital. Imaging studies revealed a type 3 tumor in the upper intrathoracic esophagus with direct invasion to the left main bronchus. Analysis of a biopsy specimen revealed carcinosarcoma. The patient underwent esophageal bypass and chemoradiotherapy. Eight months after surgery, he died of esophago-bronchial fistula. Autopsy examination revealed liver metastasis, peritoneal dissemination and intramural metastasis. The sarcomatous component was predominant in the intramural and liver metastatic lesions.

Coexistence of esophageal superficial carcinoma and multiple leiomyomas: A case report

Leiomyomas are the most common benign tumors of the esophagus. They usually occur as a single lesion or as two or three nodules. Only two cases of esophageal multiple leiomyomas comprising more than 10 nodules have been reported previously. Moreover, there have been few reports of esophageal squamous cell carcinoma overlying submucosal tumors. We describe a 71-year-old man who was diagnosed as having a superficial esophageal cancer coexisting with two or three leiomyoma nodules. During surgery, 10 or more nodules that had not been evident preoperatively were palpable in the submucosal and muscular layers throughout the esophagus. As intramural metastasis of the esophageal cancer was suspected, we considered additional lymphadenectomy, but had to rule out this option because of the patient's severe anoxemia. Microscopic examination revealed that all the nodules were leiomyomas (20 lesions, up to 3 cm in diameter), and that invasion of the carcinoma cells was limited to the submucosal layer overlying a relatively large leiomyoma. This is the first report of superficial esophageal cancer coexisting with numerous solitary leiomyomas. Multiple minute leiomyomas are often misdiagnosed as intramural metastasis, and a leiomyoma at the base of a carcinoma lesion can also be misdiagnosed as tumor invasion. The present case shows that accurate diagnosis is required for the management of patients with coexisting superficial esophageal cancer and multiple leiomyomas.

Gastric involvement of oesophageal squamous cell carcinoma.

Among 402 patients with squamous cell carcinoma of the oesophagus, gastric wall involvement was evident in 32 (8.0 per cent). These could be grouped into four types according to the pattern of involvement: group 1 included six patients with gastric involvement via metastases in perigastric lymph nodes; group 2 consisted of 11 patients with gastric intramural metastasis; group 3 contained 12 with direct invasion of the gastric wall by the oesophageal squamous cell carcinoma; and group 4 three patients with intraepithelial spread of oesophageal cancer to the gastric epithelium. Prognosis was poor, all patients dying except for one in each of groups 3 and 4. The mean survival time was 5.6, 8.6, 14.8 and 18.7 months in groups 1, 2, 3 and 4, respectively. Gastric involvement via metastases to lymph nodes and by intramural metastasis therefore indicates an extremely poor prognosis, while the prognosis in groups 3 and 4 was influenced by the depth of invasion and lymph node metastasis of the oesophageal cancer. Histological examination of tissues from group 4 patients demonstrated that malignant squamous cells proliferated and invaded the gastric epithelial layer, that is, there was intraepithelial spread of the oesophageal cancer.

Efficacy and toxicity of fluorouracil, doxorubicin, and cisplatin/nedaplatin treatment as neoadjuvant chemotherapy for advanced esophageal carcinoma

Objective. Patients with advanced esophageal carcinoma including clinical T4 tumor, extensive lymph node metastasis, or intramural metastasis have a dismal prognosis, despite recent multimodality treatments. The aim of this study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy using fluorouracil, doxorubicin, and cisplatin or nedaplatin (FAP/N) in these patients. Material and methods. Twenty-six patients were enrolled in this study. The first 9 patients received 600 mg/m2 fluorouracil on days 1–7 and days 29–35, and 30 mg/m2 doxorubicin and 60 mg/m2 cisplatin on days 1 and 29 (FAP). The next 17 patients received modified FAP, in which 50 mg/m2 nedaplatin was given instead of cisplatin (FAN). Results. Grade 3 or 4 toxicities developed in 6 patients (23.1%) during chemotherapy, but there was no discontinuation of treatment. The clinical response rate was 46.2%. Twenty-one patients (80.8%) underwent esophagectomy, and R0 resection was achieved in 16 patients (61.5%). The 1-year survival rates of 26 patients, 21 patients with resectable tumor, 16 with R0 resection, and 12 clinical responders, were 31.3%, 32.1%, 33.3%, and 45.5%, respectively, each with a median survival time of 9 months. The median progression-free survival time of 26 patients was 6 months; in 16 patients with R0 resection progression-free survival was 6.5 months. There was no correlation between the recurrence pattern and tumor spread before treatment. Conclusions. FAP/N was found to have acceptable toxicities and the ability to control locoregional tumors, but made little contribution to patient survival. The efficacy of this treatment for patients with advanced esophageal carcinoma, however, may not yet be apparent.

Thirteen cases with intramural metastasis to the stomach in 1259 patients with oesophageal squamous cell carcinoma

Among a total of 1259 patients with oesophageal cancer who underwent surgical resection, intramural metastasis (IMM) was verified in 93 patients (7.4%), of which IMM to the stomach (IMMS) constituted 13 patients (1.0%). In all 13 cases, the primary cancer was located in the middle or lower thoracic oesophagus and all had lymph nodes metastasis, while 12 of the 13 (92.3%) had lymphatic invasion. In our series, as the depth of invasion advanced, the number of patients with IMM or IMMS increased, although even superficial IMMS was revealed. The gross appearance of the metastatic tumours in the stomach resembled submucosal tumours. The possibility exists that metastasis via a lymphatic duct allows expansive growth in the gastric submucosae. These findings suggest that oesophageal cancer metastasizes to the stomach via a lymph duct. In conclusion, oesophageal cancer with lymphatic invasion may lead to IMM and IMMS. Therefore, careful examination for the existence of IMM, including the stomach, is required.

P53 mutation profiling of multiple esophageal carcinoma using laser capture microdissection to demonstrate field carcinogenesis.

Inactivation of the p53 tumor suppressor gene is one of the most frequent genetic alterations observed in human esophageal carcinomas. In patients with esophageal carcinoma, one of the significant pathological features of the tumor is the presence of multiple lesions within the esophagus. However, the molecular mechanisms involved in the occurrence of multiple lesions have remained elusive. To characterize p53 alterations in multiple esophageal carcinomas and to study their roles in carcinogenesis, we performed p53 immunohistochemical and p53 mutation analyses using laser capture microdissection on surgically resected human esophageal carcinomas from 11 patients: 9 patients with multiple esophageal carcinomas, 1 with an intramural metastasis lesion within the esophagus and 1 with an intraepithelial carcinoma lesion contiguous to the main lesion. In each of the patients with multiple esophageal carcinomas, we examined samples from 1 main lesion and 1 representative concomitant lesion. Molecular analyses of samples from fresh-frozen normal tissues and tumor tissues of the main lesion (whole tumor) were also performed by the same method. p53 protein accumulation was observed in 16 (72.7%) of 22 lesions from the 11 cases. No p53 mutation was found in normal esophageal tissues. In the 9 cases of multiple esophageal carcinomas, point mutations were detected in the whole tumor in 1 (11.1%) case, in the microdissected tumor samples of main lesions in 3 (33.3%) cases and in the microdissected tumor samples of concomitant lesions in 3 (33.3%) cases. For the microdissected tumor samples, there was a 54.5% (12/22) concordance rate between the results of immunostaining and molecular analysis. In the 8 cases of whole tumors in which a p53 mutation was not observed, 2 cases revealed p53 mutation in the microdissected tumor samples of the main lesion. All 6 cases of multiple esophageal carcinomas that showed a p53 mutation in the microdissected tumor sample had a discordant p53 mutational status between the main and concomitant lesions. In contrast, both the intramural metastasis lesion and the intraepithelial carcinoma contiguous to the main lesion showed p53 mutational patterns identical to those of the main lesions. In conclusion, the analysis of microdissected DNA by laser capture microdissection is useful for characterizing the heterogeneity of the p53 gene mutation in multiple carcinoma lesions that cannot be accurately analyzed in whole esophageal tumor DNA. The finding of different p53 gene mutations among multiple esophageal carcinoma lesions suggest further evidence of multicentric or field carcinogenesis of the human esophagus.

Esophageal intramural metastasis from adenocarcinoma of the gastroesophageal junction.

Among a total of 143 patients examined for diagnosis of adenocarcinoma of the cardia, intramural esophageal metastases were verified in six patients (4.19 %). In each case the diagnosis was confirmed by histological examination. The histological structure of the primary tumors and metastases was the same. Metastases were detected by endoscopic ultrasound examination in three cases. All the cardia tumors proved to be well advanced. As well as endoscopic identification of the primary tumor, thorough examination of the proximal part of the esophagus is of great importance.

Clinicopathologic characteristics of superficial spreading type squamous cell carcinoma of the esophagus

Intraepithelial carcinoma concomitant with the main tumor is a conspicuous feature in squamous cell carcinoma (SCC) of the esophagus. The aim of the current study was to clarify the clinicopathologic features of superficial spreading type SCC of the esophagus. Ninety-seven patients with esophageal squamous cell carcinoma, whose main carcinoma is invading the mucosa or submucosa, were investigated in the current study. The clinicopathologic features were compared between 13 cases demonstrating a superficial spreading type carcinoma in which the spreading size of the tumor was 5 cm or more in length and 84 cases with the size less than 5 cm. Although no significant difference was observed regarding lymphatic invasion, venous invasion, intramural metastasis and lymph node metastasis, the survival rate of patients with superficial spreading type carcinoma was much better than that of patients with ordinary superficial carcinoma of the esophagus. Coexistence of superficial spreading type carcinoma may be correlated with a favorable prognosis of patients with superficial esophageal SCC.