[Locally Advanced Gastric Cancer Treated with Curative Gastrectomy and Showing Pathological Complete Response after Chemotherapy with S-1].

A 77-year-old man presented with epigastralgia. Gastrointestinal endoscopic examination showed advanced gastric cancer, type 3, in the distal antrum. The patient refused surgery and preferred chemotherapy. The regimen consisted of 80 mg/body/day of S-1, continuously administered from day 1-14, followed by discontinuation for 2 weeks. After 2 courses, the patient experienced fatigue and recurrent vomiting. Laboratory studies revealed severe anemia; the hemoglobin level was 5.5 g/dL. An upper gastrointestinal endoscopy revealed pyloric stenosis and significant tumor reduction. Therefore, distal gastrectomy was performed. Histological examination did not reveal any viable cancer cells in the stomach and lymph nodes. Thus, a Grade 3 postchemotherapeutic effect was revealed.

Endosonographic detection of mediastinal lymph node metastasis in superficial carcinoma of the esophagus: assessment by type classification and histogram.

BACKGROUND: Endoscopic ultrasonography (EUS) has been shown to be useful for detecting lymph node metastasis in esophageal cancer. The evaluation of nodal metastasis requires both objective and subjective analyses. In the present study, mediastinal lymph nodes in superficial esophageal carcinoma (SEC) were examined by both EUS appearance and histography, using NIH image software. METHODS: One hundred and seventy-one lymph nodes of 56 patients with SEC were detected by EUS. These lymph nodes were diagnosed by type classification, based on boundary and internal echo, and by the construction of internal echo histograms using NIH image software. The results were compared with the histological findings. RESULTS: . The sensitivity, specificity, and accuracy in assessing mediastinal lymph node metastasis by type classification were 83.3%, 88.2%, and 87.7%, respectively. The mean and SD of the histogram correlated well with histological findings and type classification ( P < 0.0001). All lymph nodes with a mean value of less than 185 of the histogram were negative nodes. When positive nodes by type classification were reevaluated according to the threshold value of 185 using the histogram, the sensitivity, specificity, and accuracy improved to 83.3%, 100%, and 98.2%, respectively. CONCLUSIONS: Type classification assisted by histography improved the diagnostic accuracy of mediastinal lymph node metastasis in SEC.

Esophageal cancer associated with the right aortic arch: a case study.

A case of esophageal cancer associated with the right aortic arch in a 62-year-old Japanese male is described herein. Endoscopy performed after an initial complaint of dysphagia revealed cancer at the upper third of the esophagus. The right aortic arch was located by routine chest X-ray and an irregularly-shaped tumor defect and a shadow defect due to right aortic arch were detected on the right side of the thoracic esophagus by barium study. Computed tomography and magnetic resonance imaging offered useful information for surgical procedure. The patient underwent a subtotal esophagectomy and regional lymphadenectomy though a left thoracotomy. The clinical features of cases previously reported in Japan are reviewed following the presentation of this case.

Significant host- and tumor-related factors for predicting prognosis in patients with esophageal carcinoma.

OBJECTIVE: To identify clinically useful parameters obtainable before treatment of predicting clinical outcomes in patients with esophageal carcinoma. SUMMARY BACKGROUND DATA: Various factors regarding the biologic state of tumors or the nutritional state of patients have been individually reported to correlate with prognosis. Reliable estimates of life expectancy before treatment are important, and consideration needs to be given not only to tumor-related but also to host-related factors in patients with esophageal carcinoma. METHODS: The following clinicopathological factors were retrospectively analyzed in 356 consecutive patients with surgical treatment: sex; age; serum C-reactive protein (CRP); proportion of lymphocytes; body weight changes; serum albumin; clinical TNM staging; tumor location; serum squamous cell-related antigen; serum carcinoembryonic antigen; and histology. Factors related to prognosis were evaluated by using univariate and multivariate analyses. RESULTS: According to univariate analysis, significant differences in survival were found for sex, serum CRP, proportion of lymphocytes, body weight change, serum albumin, serum squamous cell-related antigen, and clinical TNM staging. Multivariate analysis demonstrated that CRP levels (P = 0.0285), body weight change (P = 0.0165), and clinical TNM staging (P = 0.0008) displayed independent correlations to prognosis. When serum CRP elevation, body weight loss, and clinical TNM staging III and IV were scored as a combined index, the total score (prognostic index for esophageal cancer, PIEC) demonstrated a good stratification value for prognosis. Moreover, PIEC was superior to the conventional clinical TNM staging by the likelihood ratio test. CONCLUSIONS: PIEC based on serum CRP, body weight change, and clinical TNM staging before treatment offers a very simple and informative method for predicting the prognosis of patients with esophageal carcinoma.

Clinical significance of circulating tumor cells in blood by molecular detection and tumor markers in esophageal cancer.

BACKGROUND: The clinical significance of circulating tumor cells in the blood during surgery has not been elucidated in esophageal squamous cell carcinoma (ESCC). We evaluated the relationship between circulating tumor cells and clinicopathologic findings, compared with that of serum squamous cell carcinoma (SCC) antigen and carcinoembryonic antigen (CEA), in ESCC. METHODS: Blood samples from 54 consecutive patients were obtained from the peripheral artery and the superior vena cava at three points in time: immediately before surgery, and before and after tumor resection. CEA-specific reverse transcriptase-polymerase chain reaction (RT-PCR), which can quantify circulating tumor cells in blood, was performed. The preoperative values of serum SCC antigen and CEA were also obtained for all patients. RESULTS: CEA messenger RNA (CEA mRNA) was detected in the blood of 31 out of 54 patients (57.4%). CEA mRNA positivity was detected most frequently after tumor resection and correlated with nodal status and stage grouping. The incidence of total recurrence and blood-borne recurrence was significantly greater in patients with CEA mRNA positivity than in those with CEA mRNA negativity (P =.036 and.0026, respectively). Preoperative serum levels of SCC antigen and CEA did not correlate with clinicopathologic findings and tumor recurrence. CONCLUSIONS: CEA mRNA detected by RT-PCR was more predictive of tumor recurrence than serum tumor markers. Effective adjuvant therapy is recommended for patients with CEA mRNA positive expression.

Anterior chest wall approach for video-assisted thyroidectomy using a modified neck skin lifting method.

Neck endoscopic surgery is likely to prove less invasive and more cosmetically advantageous than conventional methods. The surgical procedure used for 42 consecutive patients undergoing video-assisted thyroidectomy by the anterior chest wall approach is described herein. A 3-4 cm incision was made at the anterior chest wall 2 cm below the clavicle on the tumor side. Two Kirshner wires connected to a winching device were horizontally inserted beneath the skin in order to lift the neck skin. Specially made retractors were passed through the chest wall wound to the lateral neck bilaterally. Strap muscle on the tumor side was retracted laterally and the thyroid tumor was retracted medially. A suitable working space was thus created using this modified neck lifting method without gas insufflation. All patients underwent video-assisted thyroidectomy utilizing an anterior chest wall approach without conversion to open thyroidectomy. Mean operative time from incision to removal of the tumor was 145 min. Mean tumor size was 4.1 cm (range: 2.0-7.5 cm). The advantage of our approach is that the scar below the clavicle is invisible under normal clothing. In addition, conventional instruments for open thyroidectomy can be used. In our method, the thyroid tumor and trachea are palpable and some parts of the operation can be conducted under direct visualization if the assistant retracts the anterior chest wall wound upward. Video-assisted thyroidectomy utilizing an anterior chest wall approach is cosmetically less invasive, particularly for women who are frequently nervous about operative scars on the neck.

Biologic and imaging diagnosis of lymph node metastasis in esophageal carcinoma.

BACKGROUND AND OBJECTIVES: Few reports have described the combined use of biologic and imaging techniques in the diagnosis of lymph node metastasis. We prospectively evaluated lymph node metastasis diagnosed by biologic and imaging means in patients with esophageal carcinoma. METHODS: Preoperative ultrasound and endoscopic ultrasound (EUS) examination were performed in 80 patients. Biopsy specimens were immunohistochemically examined using cyclin D1 (CD1) and desmoglein 1 (DG1) antibodies, and tumors were classified into three grades. RESULTS: The sensitivity, specificity, and accuracy values of ultrasound examination were 88.2, 58.6, and 77.5%, respectively. The incidence of nodal involvement was 0% (0/10) in patients with grade 1 tumors, 57.1% (16/28) in those with grade 2 tumors, and 83.3% (35/42) in those with grade 3 tumors. Of the 57 patients with lymph node metastasis determined sonographically, 50 had grade 2 or 3 tumors that were histologically confirmed. The remaining seven patients with grade 1 tumors did not have involved nodes. Of the 23 patients without lymph node metastasis according to ultrasound examination, the incidence of lymph node metastasis in patients with grade 1, 2, and 3 tumors was 0, 16.7, and 50.0%, respectively. CONCLUSIONS: When used together, imaging and molecular procedures may offer improved identification of lymph node metastasis in patients with squamous cell carcinoma of the esophagus.

Smad4 and transforming growth factor beta1 expression in patients with squamous cell carcinoma of the esophagus.

PURPOSE: The members of the Smad family play key rolesin regulating gene expression in the transforming growth factor (TGF)-beta1 signaling pathways. Activation of Smads causes their translocation from the cytoplasm to the nucleus, where they function as transcription factors. The present study analyzed the expression and clinicopathological significance of Smad4 and TGF-beta1 in squamous cell carcinoma of the esophagus. EXPERIMENTAL DESIGN: Immunohistochemistry was used to investigate the expression of Smad4 and TGF-beta1 proteins in 258 patients with squamous cell carcinoma of the esophagus. The relationship between expression of these proteins and clinicopathological factors was analyzed, and the usefulness of Smad4 in disease prognosis was evaluated in relation to TGF-beta1 expression. RESULTS: Smad4 expression was preserved in 32.2% of tumors, and TGF-beta1 expression was identified in 42.6% of tumors. Patients with preserved expression of Smad4 had a higher rate of early-stage carcinoma (P < 0.01) and fewer lymph node metastases (P < 0.01) than those with reduced Smad4 expression. The expression of TGF-beta1 was not associated with any of the clinicopathological factors. Postoperative survival analysis indicated that patients with a tumor in which Smad4 expression was reduced had worse clinical outcomes than those with preserved expression (P = 0.01). In patients with TGF-beta1-negative tumors, the survival rate was significantly higher in patients with a preserved level of Smad4 expression than in those with reduced Smad4 expression (P = 0.02). However, according to multivariate analysis, Smad4 expression could not be used as an independent prognostic factor. CONCLUSIONS: Although Smad4 expression could not be used as a prognostic factor, its expression reflected tumor progression such as tumor depth and lymph node metastasis.

Distribution of lymph node micrometastasis in pN0 well-differentiated thyroid carcinoma.

BACKGROUND: The role of lymph node dissection in the treatment of differentiated thyroid carcinoma remains controversial, and the benefit of therapy is debatable. This study was designed to identify the precise localization of lymph node micrometastases (LNMM) and map their cervical involvement in relation with the tumor location within the thyroid gland. METHODS: A total of 2551 cervical lymph nodes were obtained from 80 patients with well-differentiated thyroid cancer. They were diagnosed as clear lymph nodes by hematoxylin and eosin stain and then examined immunohistochemically with cytokeratins (AE1/AE3) for evidence of micrometastases. RESULTS: Forty-two patients out of 80 (53%) had LNMM. Forty-eight patients (60%) had the tumor confined to only one third of 1 of the 2 lobes of the thyroid gland or isthmus. The frequencies and locations of LNMM in patients were 50% (3/6) in the deep upper cervical nodes, with tumors localized in the upper third; 31% (5/16) in the paraglandular nodes, with tumors affecting the middle third; 63% (12/19) in the paratracheal nodes, with tumors affecting the lower third of the thyroid lobe; and 71% (5/7) in the pretracheal nodes in the isthmus-located tumor. All the LNMM occurred on the ipsilateral side of the tumor. CONCLUSIONS: When thyroid carcinoma is located in the upper third of the thyroid lobe, the LNMM are found in the direction of upward lymphatic flow. When the tumor is located in the lower third or isthmus, LNMM are directed downward. In addition, early thyroid carcinoma micrometastases do not cross the midline but remain on the ipsilateral side of the tumor.

Influence of exogenous fat emulsion on pulmonary gas exchange after major surgery.

The use of fat emulsion in total parenteral nutrition (TPN) is closely related to changes in respiratory function. The aim of this study was to evaluate the influence of exogenous fat emulsion on pulmonary gas exchange in the early period after major surgery. Total parenteral nutrition was administered to 18 patients for 6 days after esophagectomy for carcinoma. Half of the patients received glucose (glucose group), and the other half received glucose and fat (fat group). The fat emulsion was continuously infused for 24 hours over 6 days. Glucose utilization was significantly higher in the glucose group than in the fat group. Fat utilization was significantly higher in the fat group than in the glucose group. Carbon dioxide (CO2) production and respiratory quotient were significantly decreased in the fat group compared to the glucose group. There were no differences in the pulmonary vascular resistance index or alveolar-arterial difference in oxygen tension between the two groups. Although exogenous fat emulsion utilized as energy substrate decreases CO2 production after major surgery, it does not clinically influence the pulmonary hemodynamics or diffusion capacity.

Biological properties of biopsy specimens are useful for predicting lymph node micrometastasis in esophageal carcinoma.

BACKGROUND: Some studies have reported on lymph node micrometastasis (MM) by RT-PCR. We attempted to predict MM by biological means using preoperative biopsy specimens. MATERIALS AND METHODS: Lymph nodes from 60 patients with esophageal carcinoma were examined by routine histological examination and CEA-specific RT-PCR. The biopsy specimens were immunohistochemically examined using p53, cyclin D1 (CD1) and desmoglein 1 (DG1) antibodies. RESULTS: Of 659 lymph nodes, 53 (8.0%) nodes were positive according to histological examination and 158 (24.0%) had MM by RT-PCR. The percentage of patients with lymph node metastasis according to histological examination and RT-PCR was 65.0% and 81.7%, respectively. CD1 and DG1 expression correlated with MM, whereas p53 expression did not. MM was frequently detected in the tumors with CD1-positive, DG1-negative or reduced expression. CONCLUSION: The expression of CD1 and DG1 in biopsy specimens may offer useful information on lymph node metastasis, including MM in esophageal carcinoma.

Histological differences in the invasion of advanced esophageal and gastric carcinoma beyond the esophago-gastric junction.

BACKGROUND: The esophago-gastric junction (EGJ) has several unique anatomical and histological features. We investigated the histological differences between esophageal squamous cell carcinoma with invasion of the gastric wall (esophageal group of patients) and gastric carcinoma with invasion of the esophageal wall (gastric group of patients).METHODS: Thirty-six patients in the esophageal group and 83 patients in the gastric group were histologically examined in regard to the mode of invasion. The pattern of tumor invasion beyond the EGJ was classified as continuous or discontinuous.RESULTS: The discontinuous pattern was more frequently seen in the esophageal group than in the gastric group. In the gastric group, however, the distance invaded beyond the EGJ was significantly greater in tumors with the discontinuous pattern than in those with the continuous pattern ( P < 0.01). Gastric mucosal invasion at the EGJ was not seen in 36% of the esophageal group, whereas tumor infiltration into the esophageal mucosal layer at the tip beyond the EGJ was found in 60% of the gastric group. The incidence of invasion deeper than the muscularis propria in the gastric and esophageal groups was 18% and 58%, respectively ( P < 0.0001).CONCLUSION: The histological characteristics of esophageal or gastric carcinoma beyond the EGJ should be taken into consideration in diagnosis and surgical procedures.

Paraaortic lymph node micrometastasis and tumor cell microinvolvement in advanced gastric carcinoma.

BACKGROUND: Paraaortic lymph node dissection in advanced gastric carcinoma is controversial. The purpose of this study was to investigate the incidence and significance of micrometastasis (MM) or tumor cell microinvolvement (TCM) in these critical lymph nodes.METHODS: A total of 2339 lymph nodes, including 390 paraaortic nodes, obtained from 47 patients with advanced gastric carcinoma were examined immunohistochemically, using cytokeratin antibody.RESULTS: Lymph node metastasis was found in 95 of the 390 paraaortic nodes of 14 patients by routine histological examination. MM or TCM was immunohistochemically detected in 45 of the 295 negative paraaortic lymph nodes from 15 of 33 patients (MM, n = 5; TCM, n = 10). The 5-year-survival rate in the paraaortic node-negative group and cytokeratin-positive group was significantly higher that that of the hematoxilin and eosin-positive group. The total number of lymph node metastases by hematoxylin and eosin staining and the pathological lymph node compartments, by cytokeratin-positive nodes, were prognostic factors by multivariate analysis.CONCLUSIONS: We demonstrated a high rate of MM or TCM in the paraaortic lymph nodes and suggest that such harbored metastases are related to the prognosis of patients with advanced gastric carcinoma. On the basis of this study, a multi-institutional study should be considered.

Role of cyclin E and p53 expression in progression of early gastric cancer.

BACKGROUND: To elucidate the role that cyclin E overexpression plays in the progression of early gastric cancer, we examined the expression of cyclin E and p53, as abnormal p53 expression is linked with cyclin E overexpression in exerting adverse affects on the cell cycle.METHODS: Specimens from 108 early gastric cancers were stained by an immunohistochemical method, using anti-cyclin E and anti- p53 antibodies.RESULTS: The positivity rate of cyclin E expression in early gastric cancer was 33% (36/108). Cyclin E-positive tumors invaded more deeply ( P < 0.05), infiltrated lymphatic vessels more frequently ( P < 0.01), showed a higher incidence of differentiated cancer ( P < 0.01), and more often expressed p53 ( P < 0.01) than cyclin E-negative tumors. Differentiated cancers showing coexpression of cyclin E and p53 were more likely to metastasize to the lymph nodes.CONCLUSIONS: Overexpression of cyclin E may promote the progression of early gastric cancer.