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.

Sentinel node mapping for gastric cancer: a prospective multicenter trial in Japan.

PURPOSE: Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique. PATIENTS AND METHODS: Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using a standardized dual tracer endoscopic injection technique. Following biopsy of the identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines. RESULTS: Among 433 patients who gave preoperative consent, 397 were deemed eligible on the basis of surgical findings. SN biopsy was performed in all patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of 57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99% (383 of 387). Only four false-negative SN biopsies were observed, and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure. CONCLUSION: The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.

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 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.

Postoperative long-term evaluation of interposition reconstruction compared with Roux-en-Y after total gastrectomy in gastric cancer: prospective randomized controlled trial.

BACKGROUND: The postoperative clinical superiority of the interposition of jejunum reconstruction (INT) to Roux-en-Y reconstruction (RY) after total gastrectomy has not been clarified. Postoperative quality of life (QOL) was evaluated between the 2 methods by a multi-institutional prospective randomized trial. METHODS: A total of 103 patients with gastric cancer were prospectively randomly divided into groups for RY (n = 51) or INT reconstruction (n = 52) after total gastrectomy. They were stratified by sex, age, institute, histology, and degree of lymph node dissection. Postoperatively, body mass index (BMI) and nutritional conditions were measured serially, and QOL and postoperative squalor scores were evaluated at 3, 12, and 60 months and compared between the 2 groups. RESULTS: After removing patients who did not complete the follow-up survey or censured cases, 24 patients in the RY group and 18 patients in the INT group were clinically available and their postoperative status was assessed. QOL scores were increased and complication scores were improved in the postoperative periods (P < .01). Postoperative BMI significantly deteriorated compared with preoperative BMI in each group. The postoperative QOL and complication scores at 60 months after surgery were significantly better than those at 3 months after surgery in each group (P < .01). However, there was no significant difference of QOL scores and postoperative complication scores between the 2 reconstruction groups. The nutritional condition in the INT group was nearly the same as that in the RY group. CONCLUSIONS: Although our patient sample was small and patients who did not complete the follow-up survey were present, we could not identify any clinical difference between INT and RY after total gastrectomy 60 months after surgery. The safer and simpler RY method may be a more suitable reconstruction method than INT after total gastrectomy.

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.

Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas.

A number of studies have reported the presence of human papillomavirus (HPV) in lung carcinoma. Interestingly, its detection rate appears to differ histologically and geographically. The present study examined 30 adenocarcinomas and 27 squamous cell carcinomas of the lung in a southern area of Japan, and detected high-risk HPV genome in 9 (30%) adenocarcinomas and 2 (7%) squamous cell carcinomas, using PCR with SPF10 primers and INNO-LiPA HPV genotyping assay. The difference of HPV detection rates in adenocarcinomas and squamous cell carcinomas was statistically significant (P=0.044, Fisher's exact test). HPV-16 was the most prevalent HPV genotype, and was detected in 27% (8/30) of adenocarcinomas and in 7% (2/27) of squamous cell carcinomas. High-risk-HPV positive carcinomas had decreased proportions of pRb (P=0.107) and significantly increased proportions of p16INK4a expressing cells (P=0.031) when compared to HPV-negative lung carcinomas. All HPV-16-positive cases were considered to have an integrated form of HPV-16 but its viral load was low (geometric mean = 0.02 copy per cell). In 20 additional adenocarcinomas treated with gefitinib, a tyrosine kinase inhibitor specific for epidermal growth factor receptor, the presence of HPV was examined. Note that East Asian ethnicity is a predictive factor of gefitinib response. High-risk HPV genome was found in 75% (6/8) of adenocarcinomas with complete or partial response to gefitinib but was not found in the remaining 12, which did not respond to gefitinib. In conclusion, the present study suggests that high-risk HPV may be more strongly related to adenocarcinomas, particularly gefitinib-responsive adenocarcinomas, when compared to squamous cell carcinomas. However, its low viral load makes it difficult to determine the etiological significance of these findings.

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.

Significance of Twist expression and its association with E-cadherin in esophageal squamous cell carcinoma.

BACKGROUND: Twist is a basic helix-loop-helix (bHLH) transcriptional factor that has been identified to play an important role in epithelial-mesenchymal transition (EMT)-mediated metastasis through the regulation of E-cadherin expression. However, few authors have examined the expression of Twist and E-cadherin and their prognostic value in patients with esophageal squamous cell carcinoma (ESCC). The purpose of this study is to evaluate the clinical significance of Twist and E-cadherin expression in ESCC. METHODS: We immunohistochemically investigated the relationship between their expression and clinicopathological factors including prognosis in surgical specimens of primary tumors in 166 patients with ESCC. RESULTS: The expression rate of high Twist was 42.0% and that of preserved E-cadherin was 40.4%. The expression of high Twist and reduced E-cadherin was significantly associated with depth of tumor invasion, lymph node metastasis, distant nodal metastasis, stage and lymphatic invasion, and poor prognosis. High Twist expression significantly correlated with reduced E-cadherin expression. In the preserved E-cadherin group, the 5-year survival rate was better for patients who were low for Twist expression than for those who were high for Twist expression. Multivariate analysis indicated that the combination of low Twist and preserved E-cadherin expression was an independent prognostic factor along with tumor depth, distant nodal metastasis and E-cadherin expression. CONCLUSIONS: Evaluation of Twist and E-cadherin expressions should be useful for determining tumor properties, including prognosis, in patients with ESCC.

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.

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.

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.

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.

Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial.

PURPOSE: Although the outcome of surgery for locally advanced pancreatic cancer remains poor, it is improving, with 5-year survival up to about 10% in Japan. The preliminary results of our multi-institutional randomized controlled trial revealed better survival after surgery than after radiochemotherapy. We report the final results of this study after 5 years of follow-up. METHODS: Patients with preoperative findings of pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric or common hepatic arteries, or distant metastasis, were included in this randomized controlled trial, with their consent. If the laparotomy findings were consistent with these criteria, the patient was randomized to a surgery group or a radiochemotherapy group (5-fluorouracil 200 mg/m2/day and 5040 Gy radiotherapy). We compared the mean survival time, 3-and 5-year survival rates, and hazard ratio. RESULTS: The surgery and radiochemotherapy groups comprised 20 and 22 patients, respectively. Patients were followed up for 5 years or longer, or until an event occurred to preclude this. The surgery group had significantly better survival than the radiochemotherapy group (P<0.03). Surgery increased the survival time and 3-year survival rate by an average of 11.8 months and 20%, respectively, and it halved the instantaneous mortality (hazard) rate. CONCLUSION: Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

Efficacy of anatomic resection vs nonanatomic resection for small nodular hepatocellular carcinoma based on gross classification.

BACKGROUND/PURPOSE: It has been reported that anatomic resection may be preferable to nonanatomic resection for small hepatocellular carcinomas (HCCs), by reducing so-called "micrometastases" (portal venous tumor extension and intrahepatic metastases). Nonanatomic resection or ablation has also been used as therapy for small HCCs. We studied the effectiveness of anatomic resection for small nodular HCCs, especially from the viewpoints of tumor size and gross classification. METHODS: A retrospective cohort study was performed in 116 consecutive patients who underwent curative hepatic resection for HCCs 3 cm or smaller and with three or fewer nodules. The outcome of anatomic resection (including segmentectomy, sectoriectomy, and hemihepatectomy) was compared to that of nonanatomic partial hepatectomy. RESULTS: The group that underwent anatomic resection (n = 52) had relatively better overall survival and significantly better recurrence-free survival than those with nonanatomic resection (n = 64). On Cox multivariate analysis, however, liver function was more closely associated with survival. The effect of anatomic resection was more prominent in the subgroup with the nonboundary type nodules (single nodular type with extranodular growth, confluent multinodular type, and invasive type) than in the subgroup with the boundary type (vaguely nodular and single nodular type). Micrometastases in the nonboundary type were found further from the main tumor (9.5 +/- 6.2 mm) than those in the boundary type (within 3.1 +-1.4 mm). CONCLUSIONS: In patients with HCC nodules equal to or less than 3 cm and with the nonboundary type, anatomic resection should be employed to the extent that liver function allows, because this procedure would be more favorable than nonanatomic resection in eradicating micrometastases that have extended away from the tumor's margin.

Homeostatic mass control in gastric non-neoplastic epithelia under infection of Helicobacter pylori: an immunohistochemical analysis of cell growth, stem cells and programmed cell death.

We evaluated homeostatic mass control in non-neoplastic gastric epithelia under Helicobacter pylori (HP) infection in the macroscopically normal-appearing mucosa resected from the stomach with gastric cancer, immunohistochemically analyzing the proliferation, kinetics of stem cells and programmed cell death occurring in them. Ki67 antigen-positive proliferating cells were found dominantly in the elongated neck portion, sparsely in the fundic areas and sporadically in the stroma with chronic infiltrates. CD117 could monitor the kinetics of gastric stem cells and showed its expression in two stages of gastric epithelial differentiation, namely, in transient cells from the gastric epithelial stem cells to the foveolar and glandular cells in the neck portion and in what are apparently progenitor cells from the gastric stem cells in the stroma among the infiltrates. Most of the nuclei were positive for ssDNA in the almost normal mucosa, suggesting DNA damage. Cleaved caspase-3-positive foveolar cells were noted under the surface, suggesting the suppression of apoptosis in the surface foveolar cells. Besides such apoptosis of the foveolar cells, in the severely inflamed mucosa apoptotic cells were found in the neck portion where most of the cells were Ki67 antigen-positive proliferating cells. Beclin-1 was recognized in the cytoplasm and in a few nuclei of the fundic glandular cells, suggesting their autophagic cell death and mutated beclin-1 in the nuclei. Taken together, the direct and indirect effects of HP infection on the gastric epithelial proliferation, differentiation and programmed cell death suggested the in-situ occurrence of gastric cancer under HP infection.

[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.

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.