Sentinel node mapping for post-endoscopic resection gastric cancer: multicenter retrospective cohort study in Japan.

BACKGROUND: Standard gastrectomy with systematic lymphadenectomy as an additional surgery after endoscopic resection (ER) causes a deterioration in long-term quality of life. If the sentinel lymph node (SN) basin concept can be applied in post-ER gastric cancer, minimal surgery can be applied without reducing the curability. This retrospective multicenter cohort study aimed to verify the validity of the SN basin concept in post-ER gastric cancer. PATIENTS AND METHODS: Individual data of 132 patients who underwent SN mapping after ER were collected from 8 university hospitals in Japan from 2001 to 2016. Tracers were injected endoscopically in the submucosal layer at four sites around the post-ER scar. We compared the SN basin distribution of post-ER gastric cancer with that of 275 patients with non-ER gastric cancer. RESULTS: Two cases of SN were unidentified, both involving a single tracer (SN detection rate: 98.5%). Nine cases (6.8%) of lymph node metastasis were found, of which eight had a metastatic lymph node within the SNs and one had a non-SN metastasis within the SN basin. The diagnostic sensitivity of SN mapping for lymph node metastasis was 88.9% in post-ER group and 95.7% in non-ER group (P = 0.490); the accuracy was 99.2% and 99.6% (P = 0.539), respectively. Regarding the SN basin, no significant intergroup differences were found regardless of the primary tumor location. CONCLUSIONS: Our findings clarified the feasibility of SN mapping based on the SN basin concept in patients with gastric cancer who previously underwent ER.

Current status of pylorus-preserving gastrectomy for the treatment of gastric cancer: a questionnaire survey and review of literatures.

PURPOSE: This study was designed to investigate the current status of pylorus-preserving gastrectomy (PPG) for the treatment of gastric cancer by sending a questionnaire to institutions in Japan. METHODS: The questionnaire was prepared and sent to 930 institutions approved by the Japanese Society of Gastroenterological Surgery. Questions were the indications for PPG, preservation of the vagus nerves and the infra-pyloric artery, whether suprapyloric lymph nodes are dissected, distance between the pylorus and the gastrogastrostomy, and the advantages and disadvantages of PPG. RESULTS: Responses were obtained from 345 institutions (37.1%). In 148 institutions, PPG was included in the choices of operations for gastric cancer and indicated for patients with tumors no deeper than the submucosal layer for differentiated-type carcinoma, or for tumors limited to the mucosa even in poorly differentiated types in 105 institutions. The vagus was preserved in 73.5%, the infrapyloric artery was preserved in 49.4%, and the dissection of suprapyloric lymph nodes were partly performed in 56.2%. The distance between gastrogastrostomy and the pyloric ring was 3-3.9 cm in 43.4% and 2-2.9 cm in 39%. Layer-to-layer anastomosis was the most representative technique for gastrogastrostomy. The advantages of PPG with decreased incidence of dumping syndrome and remnant gastritis were quoted in 130 and 82 institutions, respectively. Delayed gastric emptying was considered as the most frequent disadvantage of PPG, as quoted by 111 institutions. CONCLUSIONS: These results indicate that standard technique in PPG includes the preservation of the vagus and infrapyloric artery, in part dissection of suprapyloric lymph nodes, and layer-to-layer anastomosis for reconstruction. The optimal length of the antral cuff is still controversial.

Questionnaire survey regarding the current status and controversial issues concerning reconstruction after gastrectomy in Japan.

The Japanese Society for the Study of Postoperative Morbidity after Gastrectomy conducted a nationwide questionnaire survey to clarify the current status of reconstruction after gastrectomy. One hundred and forty-five institutions (66%) responded to the survey. The questionnaire dealt with the reconstruction after a distal gastrectomy, pylorus-preserving gastrectomy (PPG), total gastrectomy, and proximal gastrectomy. The most common method of reconstruction after distal gastrectomy was Billroth I in 112 institutions (74%), and Roux-en-Y (RY) in 30 (21%). Seventy-seven institutions (53%) responded to the PPG questions. The lengths of the antral cuff were widely distributed among the institutions. Segmental gastrectomy was performed by 23 institutions for limited cases. The most common method of reconstruction after total gastrectomy was RY in 138 institutions (95%). Reconstruction with a pouch after total gastrectomy was done in 26 institutions (18%). The most common reconstructions after proximal gastrectomy were esophagogastrostomy in 69 institutions (48%), jejunal interposition in 41 (28%), double tract in 19 (13%) and pouch reconstruction in 6 (7%). Although most Japanese surgeons are concerned about the revised methods of reconstruction and quality of life after gastrectomy, surgeons have not yet reached a full consensus on these issues.

Current state of gastric stump carcinoma in Japan: based on the results of a nationwide survey.

BACKGROUND: Carcinoma of the gastric remnant after partial gastrectomy for benign disease or cancer is unusual but an important cancer model. The Japanese Society for the Study of Postoperative Morbidity after Gastrectomy (JSSPMG) performed a nationwide questionnaire survey to understand the current state of gastric stump carcinoma in Japan. METHODS: In the questionnaire survey of November 2008, gastric stump carcinoma was defined as an adenocarcinoma of the stomach occurring 10 years or more after Billroth I or Billroth II gastrectomy for benign condition or cancer disease. The survey was conducted at the request of reports on five or more patients with gastric stump carcinoma for each institution. Items for the survey included gender, age, methods of reconstruction in an original gastrectomy, original diseases, time interval between original gastrectomy and first detection of stump carcinomas, locations of stump carcinomas, tumor histology, tumor depth, and extent of lymph node metastasis. The questionnaire was sent to 163 surgical institutions in the JSSPMG. RESULTS: Ninety-five institutions (58.3%) responded to the survey, and the data of 887 patients satisfied the required conditions for the survey. A total of 887 patients were composed of 368 patients who received Billroth I distal gastrectomy and 519 who received Billroth II. The Billroth II group has a significantly higher number of original benign lesions than the Billroth I group (P < 0.001). This study confirmed the following issues: (1) The remnant stomach after gastrectomy for cancer disease had a higher prevalence to develop stump carcinomas occurring in a shorter time interval since original gastrectomy; (2) Patients with Billroth II gastrectomy had stump carcinomas most frequently in the anastomotic area, but not in the non-stump area as in Billroth I gastrectomy; (3) Tumor histology of 72.4% of 304 stump carcinomas at an early stage was intestinal type adenocarcinoma, i.e., well or moderately differentiated adenocarcinoma, whereas it decreased to 42.2% at the locally advanced stage of 521 stump carcinomas (P = 0.0015), suggesting that stump carcinoma mostly may develop from intestinal type and change to diffuse type during the evolution to advanced stage cancers. CONCLUSIONS: This large series of surveys suggest that there are two distinct biological plausibilities in the development of gastric stump carcinoma: (1) it develops in a shorter time interval of 10 years or less since the original gastrectomy, may come from a higher risk of gastric mucosa after gastrectomy for cancer diseases that highly predisposes to cancer, and (2) it develops during a longer time interval of 20 years or more, may come from gastrectomy-relating mechanisms after gastrectomy for original benign diseases.

Roux-en-Y reconstruction with stapled distal jejunal pouch after total gastrectomy.

Roux-en-Y reconstruction after total gastrectomy is a simple and safe procedure; however, it eliminates the gastric reservoir function and markedly changes the postoperative digestive physiology. The patients therefore suffer from insufficient food intake and malabsorption. It has been reported that jejunal pouch reconstruction increases food intake and improves the nutritional status. We established a novel Roux-en-Y reconstruction with stapled distal jejunal pouch after total gastrectomy. A jejunal pouch, 8 cm in size, was attached at the jejunojejunostomy. We performed this novel reconstruction for 20 gastric cancer patients after total gastrectomy with lymph node dissection as a feasible study. One year after operation, the average percentage weight was maintained in more than 90 per cent and 17 (85%) of these patients were in the normal range of the body mass index. This procedure may improve postoperative malnutrition after total gastrectomy according to our feasible study. A multicenter randomized trial of this approach comparing with Roux-en-Y reconstruction without a pouch is ongoing.

Asymptomatic somatostatinoma of the pancreatic head: Report of a case.

A 44-year-old man was attending routine follow-up 5 years after colon cancer resection, when ultrasonography detected a pancreatic tumor with a low echoic area. He had no symptoms. Computed tomography (CT) showed a protruding-type tumor, 4 cm in diameter, in the pancreatic head with central necrosis. Angiography revealed that the tumor was hypervascular. The serum somatostatin level was elevated, at 27 pg/ml (normal range, 1.0-12 pg/ml). As somatostatinoma of the pancreas was suspected, we performed pylorus-preserving pancreaticoduodenectomy. Histological and immunohistochemical staining confirmed somatostatinoma of the pancreas without nodal metastasis. Thus, if an endocrine tumor of the pancreas is suspected in a patient with a hypervascular tumor, the possibility of somatostatinoma should be included in the differential diagnosis.

CCR7 and CXCR4 expression predicts lymph node status including micrometastasis in gastric cancer.

The chemokine receptors CCR7 and CXCR4 play a major role in the mechanism of lymph node metastasis from primary tumor cells. We postulated that their expression in gastric tumor cells could predict lymph node status including lymph node micrometastasis (LNMM). We assessed CCR7 and CXCR4 expression in 93 resected gastric tumor specimens by immunohistochemistry. Dissected lymph nodes were examined by reverse transcription-polymerase chain reaction and immunohistochemistry using cytokeratin monoclonal antibody to detect LNMM in addition to hematoxylin-eosin (H&E) staining. Levels of CCR7 and CXCR4 expression were high in 26.9% (25/93) and in 32.3% (30/93), respectively of tumor cells and the levels significantly correlated with lymph node metastasis according to H&E staining (P=0.0212 and P=0.0115, respectively). We identified LNMM in 25 of 83 (30.1%) node-negative patients. Both CCR7 and CXCR4 expression significantly correlated with lymph node status including LNMM (P=0.0092 and P=0.0075, respectively). Furthermore, levels of combined CCR7 and CXCR4 expression significantly correlated with lymph node metastatic status (P=0.0021). Assessment of CCR7 and CXCR4 expression in gastric cancer is a useful tool for predicting lymph node metastatic status including LNMM.

The utility of rapid diagnosis of lymph node metastasis in gastric cancer using a multiplex real-time reverse transcription polymerase chain reaction assay.

BACKGROUND: Lymph node metastasis is the most important prognostic factor in gastric cancer. However, diagnosis by hematoxylin and eosin staining or immunohistochemistry is not always sufficient for the detection of cancer cells because only representative number of slices are examined. Cancer cells may, therefore, be missed by traditional histological methods. Recently, reverse transcription polymerase chain reaction (RT-PCR) methods have been introduced for improved detection of cancer cells. The purpose of this study was to evaluate the utility of a prototype RT-PCR assay run on the Cepheid SmartCycler system compared to conventional RT-PCR using the LightCycler system. PATIENTS AND METHODS: Forty-seven overt metastatic lymph nodes from 8 patients with advanced gastric cancer and 22 benign lymph nodes from patients without malignant tumor who received surgery were obtained with informed consent. We examined the lymph nodes by RT-PCR, using markers for CEA and CK19 and the LightCycler and SmartCycler systems. RESULTS: In the singlex assay, the sensitivity of CEA and CK19 was 91.5 and 70.2% in the LightCycler system, and 97.9 and 95.7% in the SmartCycler system, respectively. In the multiplex assay, the sensitivity was 91.5% in the LightCycler system and 100% in the SmartCycler system, respectively. CONCLUSION: In this study, rapid diagnosis using RT-PCR by the SmartCycler system had higher accuracy for detecting lymph node metastasis than the conventional LightCycler system. The SmartCycler system is more effective for the diagnosis of lymph node metastasis in gastric cancer when run with the prototype assay.

Vascular endothelial growth factor-C and -D expression correlates with lymph node micrometastasis in pN0 early gastric cancer.

BACKGROUND AND OBJECTIVES: Vascular endothelial growth factors (VEGF)-C and -D play an important role in lymphangiogenesis, and the expressions of these factors are related to lymphatic invasion and lymph node metastasis in various malignant neoplasms. The present study investigates the expression of VEGF-C and -D in early gastric cancer and analyzes its relationship to lymph node micrometastasis determined by reverse transcription-polymerase chain reaction (RT-PCR). METHODS: We examined 1,828 lymph nodes obtained from 80 patients with node-negative early gastric cancer. All dissected lymph nodes were examined by RT-PCR for CEA mRNA in addition to hematoxylin-eosin staining. The resected primary specimens were immunostained using anti-VEGF-C and -D polyclonal antibodies. RESULTS: The incidence of lymph node micrometastasis determined by RT-PCR was 23.8% (19/80). The high expression of VEGF-C and -D was found in 27.5% (22/80) and in 21.3% (17/80), respectively. The expression of VEGF-C and -D was closely related to lymph node micrometastasis (P = 0.0390 and 0.0213, respectively). CONCLUSIONS: We demonstrated a close relationship between micrometastasis and VEGF-C and -D expression of the primary tumor. Thus, levels of VEGF-C and -D expression might be useful for predicting micrometastasis in patients with early gastric cancer.

Expression of CXCL12 and its receptor CXCR4 in esophageal squamous cell carcinoma.

The chemokine CXCL12, also known as stromal cell-derived factor-1 and its receptor CXCR4 have been shown to play prominent roles in regulating the directional migration and proliferation of various types of cancer cells during the metastatic process. However, few researchers have examined the expression of CXCL12 and CXCR4 and their prognostic value in patients with esophageal squamous cell carcinoma (ESCC). We investigated immunohistochemically the relationship between CXCL12 and CXCR4 expression and clinicopathological factors including prognosis in surgical specimens of primary tumors in 214 patients with ESCC. The positive expression rate of CXCL12 was 53.7% and that of CXCR4 was 84.6%. Positive CXCL12 expression was significantly correlated with lymph node metastasis, tumor stage, gender and lymphatic invasion. The overall and disease-free survival rate was significantly lower in patients with positive CXCL12 expression than in those with negative CXCL12 expression. The expression of CXCR4 had no correlation with clinicopathological variables and prognosis. We showed that positive CXCL12 expression was related to a greater degree to tumor development, compared with CXCR4 expression. Evaluation of CXCL12 expression is useful for determining tumor properties, including nodal metastasis and prognosis in patients with ESCC.

Copper-transporting P-type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer.

We and others have shown that the copper transporters ATP7A and ATP7B play a role in cellular resistance to cis-diaminedichloroplatinum (II) (CDDP). In this study, we found that ATP7A transfection of Chinese hamster ovary cells (CHO-K1) and fibroblasts isolated from Menkes disease patients enhanced resistance not only to CDDP but also to various anticancer drugs, such as vincristine, paclitaxel, 7-ethyl-10-hydroxy-camptothecin (SN-38), etoposide, doxorubicin, mitoxantron, and 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11). ATP7A preferentially localized doxorubicin fluorescence to the Golgi apparatus in contrast to the more intense nuclear staining of doxorubicin in the parental cells. Brefeldin A partially and monensin completely altered the distribution of doxorubicin to the nuclei in the ATP7A-expressing cells. ATP7A expression also enhanced the efflux rates of doxorubicin and SN-38 from cells and increased the uptake of SN-38 in membrane vesicles. These findings strongly suggested that ATP7A confers multidrug resistance to the cells by compartmentalizing drugs in the Golgi apparatus and by enhancing efflux of these drugs, and the trans-Golgi network has an important role of ATP7A-related drug resistance. ATP7A was expressed in 8 of 34 (23.5%) clinical colon cancer specimens but not in the adjacent normal epithelium. Using the histoculture drug response assay that is useful for the prediction of drug sensitivity of clinical cancers, ATP7A-expressing colon cancer cells were significantly more resistant to SN-38 than ATP7A-negative cells. Thus, ATP7A confers resistance to various anticancer agents on cancer cells and might be a good index of drug resistance in clinical colon cancers.

Morphological distribution of metastatic foci in sentinel lymph nodes with gastric cancer.

BACKGROUND: The TNM classification defines micrometastasis (MM) and isolated tumor cells (ITC) in lymph nodes (LN). Sentinel node (SN) navigation surgery has been introduced in gastrointestinal cancer. Few reports have examined the morphological distribution of MM and ITC of SN in gastric cancer. The purpose of this study was to clarify the clinical significance of the morphological distribution of cancer cells in SNs according to metastasis (MA), MM, and ITC. METHODS: All dissected LNs obtained from 160 consecutive patients with mapped SNs arising from cT1-2 N0 tumors were examined. Metastasis in these LNs was examined by histology and cytokeratin staining. The distribution of MA, MM, and ITC was classified as marginal sinus (MS), intermediate sinus (IS), parenchymal (PA), and diffuse types (DF). RESULTS: Nodal metastases were detected in 65 SNs from 30 patients and MA, MM, and ITC accounted for 53.9%, 21.5%, and 24.6%, respectively. MS, IS, PA, and DF accounted for 57%, 6%, 17%, and 20.0%, respectively. Patients with metastasis of non-MS had more nodal metastasis in non-SNs (P = .025) and had nodal metastasis in second tier (P = .009), compared with the patients with metastasis of MS. The incidence of metastasis in non-MS was higher in tumors larger than 40 mm than those smaller than 40 mm (P = .011). CONCLUSION: When performing SN navigation surgery in gastric cancer, we should keep in mind that the patients with tumor larger than 40 mm in size and nodal metastasis of non-MS may have non-SN metastasis and nodal metastasis in second tier.

A novel function of the receptor for advanced glycation end-products (RAGE) in association with tumorigenesis and tumor differentiation of HCC.

BACKGROUND: The expression of the receptor for advanced glycation end products (RAGE) has an impact on the mechanisms giving rise to characteristic features of various cancer cells. The purpose of this study was to elucidate the clinicopathological relevance of the level of RAGE expression in patients with hepatocellular carcinoma (HCC) and to explore the effect of RAGE expression on the characteristic features of HCC. METHODS: The expression of RAGE was assessed in paired cancer and noncancerous tissues with HCC, using reverse-transcription polymerase chain reaction (RT-PCR), and immunohistochemistry. The quantitative RT-PCR data were analyzed in association with the clinicopathological factors of the patients with HCC. In in vitro experiments, the survival of RAGE-transfected Cos7 and mock-transfected Cos7 cells was compared under hypoxic conditions. In addition, after reducing RAGE levels in RAGE-transfected Cos7 cells by siRNA, similar experiments were performed. RESULTS: The expression of RAGE mRNA was lower in normal liver than in hepatitis and highest in HCC. Furthermore, in HCC, it was high in well- and moderately differentiated tumors but declined as tumors dedifferentiated to poorly differentiated HCC. Furthermore, HCC lines resistant to hypoxia were found to have higher levels of RAGE expression, and RAGE transfectant also showed significantly prolonged survival under hypoxia. CONCLUSIONS: Our results suggest that HCC during the early stage of tumorigenesis with less blood supply may acquire resistance to stringent hypoxic milieu by hypoxia-induced RAGE expression.

Detection of micrometastases in sentinel node navigation surgery for gastric cancer.

Although lymph node metastasis is one of the important prognostic factors for patients with gastric cancer, the clinical significance of micrometastasis remains controversial. In the 6th edition of the TMN classification, micrometastases were classified as micrometastasis (MM) and isolated tumor cells (ITC) according to its greatest dimension. The accurate diagnosis of micrometastases is required when considering less invasive surgery, especially in early stage of gastric cancer. Since generating useful information about micrometastases by conventional RT-PCR is time-consuming, this procedure is not useful for rapid diagnosis during surgery. Recently some new methods of genetic diagnosis have reduced the amount of time required to obtain information about micrometastases in lymph nodes to 30-40 min. Such methodology can be clinically applied during less invasive surgery. The sentinel node (SN) concept has recently been applied to gastric cancer and SN navigation surgery (SNNS) is ideal for reduction of lymphadenectomy in patients with early gastric cancer. However, we should think about some conditions to establish SN concept for gastric cancer: the particle size of radioisotope, relationship between metastatic area and RI uptake, and the diagnosis of micrometastases by various method such as histological examination, immunostaining and RT-PCR. Here, we described the current status of MM and ITC in the lymph nodes and the SN concept in gastric cancer.

Carcinoembryonic antigen messenger RNA expression in blood can predict relapse in gastric cancer.

PURPOSE: To clarify the clinical implications of intraoperative carcinoembryonic antigen (CEA) mRNA copy number in peripheral blood samples from gastric cancer patients. METHODS: Blood samples were obtained from 67 gastric cancer patients immediately after curative gastrectomy. mRNA in blood samples was extracted and amplified for CEA mRNA detection. CEA mRNA levels were examined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay targeting CEA mRNA. RESULTS: Thirty-three of 67 patients (49%) were positive for CEA mRNA expression. Positivity for CEA mRNA was not correlated with clinical stage, or presence or absence of postoperative relapse. CEA mRNA copy number was not correlated with serum levels of CEA. However, CEA mRNA copy number was correlated with presence or absence of tumor recurrence (P < 0.01). When confined to 21 gastric cancer patients with relapsed disease, CEA mRNA copy number was significantly and negatively correlated with postoperative period before recurrence discovery (r = 0.52, P = 0.007). Outcomes in patients with high CEA mRNA copy number and high serum CEA levels were significantly poorer than those in patients with normal CEA mRNA copy number and normal serum CEA levels (P < 0.01). CONCLUSION: CEA mRNA copy number, not positivity, was significantly associated with postoperative term of recurrent disease. Copy number of CEA mRNA, as detected by real-time quantitative PCR, appears to be a promising marker to evaluate the risk and period of postoperative tumor spread.

Analysis of T-helper type 1 and 2 cells and T-cytotoxic type 1 and 2 cells of sentinel lymph nodes in breast cancer.

The immune suppression of sentinel lymph node (SN) is directly influenced by primary tumors. It has been reported that the T-helper type 1 (Th1) to T-helper type 2 (Th2) ratio or T-cytotoxic type 1 (Tc1) to T-cytotoxic type 2 (Tc2) ratio of lymph node lymphocytes could be used to evaluate direct immunological circumstances. We attempted to evaluate the Th1 to Th2 cell and Tc1 to Tc2 cell balance in SN and non-SN and to clarify the immunological status of sentinel nodes in breast cancer. To evaluate this balance, SN and non-SN were identified by radioguided methods and lymph node lymphocytes were collected, and prepared for flow cytometry. The Th1 to Th2 and Tc1 to Tc2 ratio were calculated by 3-color flow cytometry. The ratio of SN and non-SN was compared. The results demonstrated that SN was detected in 24 out of 24 patients (100%). As regards the correlation between SN and non-SN in the same patients, the Th1 to Th2 ratio in SN was significantly lower than that in non-SN for all patients (p<0.05). Among clinicopathological factors, a larger tumor diameter, histology and nodal involvement affected the decreased Th1 to Th2 ratio in SN significantly (p<0.05). We reached the conclusion that the increasing immunosuppressive conditions derived from the tumor may deteriorate the Th1 to Th2 ratio of SN in an earlier stage as compared with non-SN. According to the tumor extension and nodal involvement, the Th1 to Th2 ratio in SN was significantly suppressed. The current result supports that mainly helper T-cell paralysis occurred first in SN and this seems to be a favorable condition in forming lymph node metastases in SN. Moreover, the immunologic interaction between the primary site and regional lymph nodes may serve as useful criteria for identifying sentinel nodes.

Ultrasound examination is useful for prediction of histologic type in invasive ductal carcinoma of the breast.

The aim of this study was to estimate the histologic type of invasive ductal carcinoma of the breast according to the ultrasound (US) criteria and to identify the high-risk patients for lymph node metastases. An acceptable preoperative diagnosis of lymph node metastasis is essential when performing the reduction of lymphadenectomy. The positive relationship between histology and prognosis has been reported in breast cancer. However, few reports have examined the relationship between preoperative US findings and histology. Ultrasound examination was performed in 252 patients with invasive ductal carcinoma (91 papillotubular, 54 solid-tubular and 107 scirrhous carcinoma). Risk factors for nodal metastasis were analyzed in clinicopathological findings. After nine criteria were defined based on US findings, all tumors were classified into US histologic type. According to the multivariate analysis, lymph node metastases was significantly associated with tumor size (p < 0.001), histology (p < 0.001) and age (p = 0.038). Histology was an important risk factor for nodal metastasis, especially in scirrhous carcinoma. When comparing the US classification and histology, the accuracy rate of US for papillotubular, solid-tubular and scirrhous type was 75%, 78% and 75%, respectively. To predict the scirrhous carcinoma with frequent nodal metastasis, US criteria such as the larger ratio of depth-to-width, boundary echo and attenuation of the back echo was important. It is important to preoperatively estimate the histologic type by tumor property using US. Our US classifications may be useful to pick up high-risk patients for nodal metastasis in invasive breast cancer.

Survival benefit of pancreaticoduodenectomy in a Japanese fashion for a limited group of patients with pancreatic head cancer.

BACKGROUND/AIMS: To evaluate the clinical benefit of pancreaticoduodenectomy in a Japanese fashion for patients with pancreatic head cancer. METHODOLOGY: One hundred and one patients underwent pancreatectomy for pancreatic head cancer between 1980 and 2001. Of these, 40 patients in the extended resection (ER) group had an extended lymphadenectomy and neural plexus dissection as a Japanese fashion, while 61 patients in the conventional resection (CR) group. Tumor status, morbidity, mortality, survival and pattern of recurrence were retrospectively studied. RESULTS: The incidence of R0 operations in the ER group was higher than that in the CR group (p<0.01). The actuarial 5-year survival rate (30.6%) of patients with pStage IIA or IIB in the ER group was significantly higher than that (8.2%) in the CR group (p=0.04) because local recurrence (47%) in the CR group was higher than that (25%) in the ER group (p=0.02). In an immunohistochemical study of isolated tumor cells (ITCs), 13 patients (57%) with lymph node ITCs were included in the 23 pN0 patients. CONCLUSIONS: Pancreaticoduodenectomy in a Japanese fashion with an adequate extended resection might bring a survival benefit for patients with pStage IIA or IIB pancreatic head cancer.

[A case of advanced gastric cancer with multiple liver metastases completely responding to combination of paclitaxel and S-1].

A 46-year-old female was admitted to Kagoshima University Hospital with a complaint of epigastralgia and dysphasia. Gastrointestinal scopy revealed advanced gastric cancer in the upper third of the stomach. Pathological diagnosis of the biopsy specimen was moderately-differentiated adenocarcinoma. Abdominal CT suggested multiple liver metastases, so a combination of biweekly paclitaxel(PTX)and S-1 was started. After five courses of this regimen, the liver metastases and primary tumor were remarkably regressed. PTX was discontinued because of a grade 3 adverse effect of numbness. Nevertheless S-1 monotherapy for liver metastases resulted in a complete response. She has been well without tumor re-growth for 4 years. The combination of PTX and S-1 may be an effective regimen for gastric cancer with liver metastases.

Clinical implication of CXCL12 expression in gastric cancer.

PURPOSE: Recent research has revealed that tumor cells expressing chemokine receptors have a crucial impact on patient survival. However, there is no information regarding chemokine expression in gastro-intestinal cancer. This study immunohistochemically investigated CXCL12 expression in gastric cancer and evaluated its association with clinical factors, including patient prognosis. METHOD: A total of 185 gastric cancer patients receiving curative gastrectomy were assessed. CXCL12 expression was evaluated by immunohistochemical analysis. Tumors with CXCL12-positive cancer cells were regarded as CXCL12 positive, and according to the degree of CXCL12 expression, patients were divided into three groups (weak, 31 cases; moderate, 27 cases; strong, 20 cases). Correlations between CXCL12 expression and clinical factors in gastric cancer were then determined. RESULTS: CXCL12 was found in the cellular membrane of cancer cells. Seventy-four of 185 patients were classified into the CXCL12-positive group. Patients were divided into three groups according to the positivity of CXCL12 expression. Significant associations between CXCL12 and lymph node metastases (p < 0.05), depth of invasion (p < 0.01), lymphatic invasion (p < 0.01), tumor diameter (p < 0.05), and clinical stage (p < 0.01) were seen. Univariate analysis revealed that the CXCL12-positive group had significantly poorer surgical outcome than the CXCL12-negative group (p < 0.01). Multivariate analysis revealed CXCL12 to be an independent prognostic factor in gastric cancer (p = 0.02). CONCLUSION: Cancerous CXCL12 positivity was determined to be an independent prognostic factor in gastric cancer, with CXCL12-positive gastric cancer showing more-aggressive behavior. Autocrine CXCL12 secretion from tumor cells may activate CXCR-4 on the tumor cells, which may be related to of the viability of distant metastases.