Robotic versus laparoscopic distal gastrectomy in patients with gastric cancer: a propensity score-matched analysis.

BACKGROUND: Robotic distal gastrectomy (RDG) has been increasingly used for the treatment of gastric cancer (GC). However, whether RDG has a clinical advantage over laparoscopic distal gastrectomy (LDG) is yet to be determined. Thus, this study aimed to assess the feasibility and safety of RDG for the treatment of GC as compared with LDG. METHODS: In total, 157 patients were enrolled between February 2018 and August 2020 in this retrospective study. We then compared the surgical outcomes between RDG and LDG using propensity score-matching (PSM) analysis to reduce the confounding differences. RESULTS: After PSM, a clinicopathologically well-balanced cohort of 100 patients (50 in each group) was analyzed. The operation time for the RDG group (350.1 ± 58.1 min) was determined to be significantly longer than that for the LDG group (257.5 ± 63.7 min; P < 0.0001). Of interest, there was a decreased incidence of pancreatic fistulas and severe complications after RDG as compared with LDG (P = 0.092 and P = 0.061, respectively). In addition, postoperative hospital stay was statistically slightly shorter in the RDG group as compared with the LDG group (12.0 ± 5.6 vs. 13.0 ± 12.3 days; P = 0.038). CONCLUSIONS: Our study confirmed that RDG is a feasible and safe procedure for GC in terms of short-term surgical outcomes. A surgical robot might reduce postoperative severe complications and length of hospital stay.

Comparison of Postoperative Quality of Life among Three Different Reconstruction Methods After Proximal Gastrectomy: Insights From the PGSAS Study.

BACKGROUND: Proximal gastrectomy (PG) has become an increasingly preferred procedure for early cancer in the upper third of the stomach, owing to reportedly superior quality of life (QOL) after PG when compared with total gastrectomy. However, various methods of reconstruction have currently been proposed. We compared the postoperative QOL among the three different reconstruction methods after PG using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45) questionnaire. METHODS: Post Gastrectomy Syndrome Assessment Study (PGSAS), a nationwide multi-institutional survey, was conducted to evaluate QOL using the PGSAS-45 among various types of gastrectomy. Of the 2,368 eligible data from the PGSAS survey, data from 193 patients who underwent PG were retrieved and used in the current study. The PGSAS-45 consists of 45 items including 22 original gastrectomy specific items in addition to the SF-8 and GSRS. These were consolidated into 19 main outcome measures pertaining postgastrectomy symptoms, amount of food ingested, quality of ingestion, work, and level of satisfaction for daily work, and the three reconstruction methods (n = 193; 115 esophago-gastrostomy [PGEG], 34 jejunal interposition [PGJI], and 44 jejunal pouch interposition [PGJPI]) were compared using PGSAS-45. RESULTS: Size of the remnant stomach was significantly larger in PGEG, and significantly smaller in PGJI and PGJPI (P < 0.05). There was no difference in other patient background factors among the groups. EGJPI tended to be superior to PGEG in several of the 19 main outcome with marginal significance (P = 0.047-0.076). CONCLUSION: PGJPI appears to be the most favorable of the three reconstruction methods after PG especially when the size of remnant stomach is rather small. TRIAL REGISTRATION NUMBER: UMIN-CTR #000002116 entitled as "A study to observe correlation between resection and reconstruction procedures employed for gastric neoplasms and development of postgastrectomy syndrome".

Expression of CD133 in the cytoplasm is associated with cancer progression and poor prognosis in gastric cancer.

BACKGROUND: CD133 is one of the most important stem cell markers in solid cancers. Some recent reports have described a possible relationship between CD133 and hypoxia-inducing factor-1-alpha (HIF-1α). The aim of this study was to clarify the clinical role of CD133 expression in gastric cancer and to investigate the correlation between CD133 expression and HIF-1α expression. METHODS: We studied 189 gastric cancer patients who underwent gastrectomy at Kurume University Hospital. CD133 and HIF-1α expression was examined using immunohistochemical staining. Fifty-six cases were CD133 positive, and they were divided into two expression types: luminal expression of the gland and cytoplasmic expression. We investigated the relationship among CD133 expression types, clinicopathological variables, prognosis, and HIF-1α expression. RESULTS: When comparing clinicopathological variables, expression of CD133 in the cytoplasm was related to metastasis and tumor progression. However, this relationship was not observed with luminal expression of the gland type. The survival rate in patients with cytoplasmic CD133 expression was significantly worse than that in the CD133-negative group. This relationship was observed in the survival rate of the adjuvant chemotherapy group and the curative resection group. Multivariate analysis revealed that the expression of CD133 in the cytoplasm was an independent prognostic factor in gastric cancer. Regarding the correlation between CD133 expression and HIF-1α expression, the HIF-1α positive rate was lower in patients with CD133 luminal expression of the gland type and higher in patients with cytoplasmic expression of CD133. CONCLUSION: Gastric cancer cells with CD133 expression in the cytoplasm were cells with high potential for malignancy, and this phenotype was associated with cancer progression, chemotherapy resistance, recurrence, and poor prognosis. Cytoplasmic expression of CD133 may be a useful prognostic marker in gastric cancer. Significant correlation was observed between HIF-1α expression and the immunohistochemical staining pattern of CD133.

Factors Associated with Perioperative Edema in Patients with Stage I Gastric Cancer Using a Body Composition Analyzer.

PURPOSE: Assessment of nutritional status and nutritional interventions is important in gastric cancer patients. We investigated the factors associated with perioperative edema in patients with stage I gastric cancer using a body composition analyzer. METHODS: The study included 106 patients with stage I gastric cancer who underwent distal gastrectomy. The body composition of each patient was evaluated by bioelectrical impedance analysis (BIA) using an InBody 720 body composition analyzer. Patients with an extracellular water to total body water ratio of ≥ 0.4 before and 1 week after gastrectomy were considered to have edema, the cause of which was determined retrospectively. RESULTS: Patients with preoperative edema were significantly older, had a significantly higher lymph node metastasis rate and disease stage, and had a significantly poorer Controlling Nutritional Status (CONUT) score, and Prognostic Nutritional Index (PNI) compared with patients without preoperative edema. The group with postoperative edema had significantly higher proportions of elderly and female patients as well as a higher rate of Billroth-II reconstruction compared with the group without postoperative edema. The group with postoperative edema also had significantly lower intracellular water content, total body water content, protein content, skeletal muscle mass, and PNI. CONCLUSIONS: Preoperative edema occurs in elderly patients with poor nutritional status, and postoperative edema occurs in elderly patients with a shorter operative time. Perioperative edema status assessed by BIA is thought to be related to perioperative nutritional status.

Clinicopathological significance of hypoxia-inducible factor-1 alpha (HIF-1α) expression in gastric cancer.

BACKGROUND: Hypoxia is a common feature of rapidly growing solid tumors. Therefore, cellular adaptation to hypoxia and altered glucose metabolism are fundamental to the biology of cancer cells. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor for more than 60 genes recognized to control the delivery of oxygen and nutrients through the induction of angiogenesis and glycolysis under hypoxic conditions. Therefore, inhibition of the expression of HIF-1α can be expected to be potentially tumor-specific molecular target-based therapy. In this study, we evaluated the significance of HIF-1α expression in relationship to clinicopathological factors, prognosis, vascular endothelial growth factor (VEGF) expression, and microvessel density (MVD). METHODS: Paraffin-embedded tumor specimens from 128 patients who underwent gastrectomy at Kurume University from 2004 to 2005 were used to assess the clinical significance of HIF-1α expression. We used the ABC method to perform an immunohistochemical analysis of the HIF-1α and VEGF expression. RESULTS: Eighty-four (65.6%) of gastric cancer specimens were positive for HIF-1α expression. Multivariate analysis showed that histology, depth of invasion, VEGF expression, and MVD were significantly associated with HIF-1α expression. On relapse-free and overall survival curves, the HIF-1α-negative group was significantly higher than the HIF-1α-positive group. Moreover, HIF-1α(+)/VEGF(+) patients had the worst prognosis. HIF-1α expression was identified as a significant predictor of relapse-free survival and overall survival by multivariate Cox's proportional hazard analyses. CONCLUSION: Overexpression of HIF-1α was found to be an indicator of poor prognosis for patients with gastric cancer and was significantly correlated with histology, depth of invasion, VEGF, and MVD.

Expression of p27Kip1 protein in gastric carcinoma.

BACKGROUND/AIMS: p27 protein resulted in the accumulation of cyclin E/cyclin dependent kinase 2/p27 ternary complexes inhibits gap1 to synthesis phase transition. Here, we have investigated the correlations, if any, between the expressions of p27 and p53, and proliferation cell nuclear antigen. METHODOLOGY: A retrospective study was performed on 75 cases of gastric cancer that had undergone surgical resection. Immunohistochemical staining was performed using the avidin-biotin-peroxidase complex technique method, with anti-p27 antibody, anti-p53 antibody and anti-proliferation cell nuclear antigen antibody. RESULTS: The rate of lymph node metastasis in the p27 negative cases was significantly higher than that in the p27 positive cases.The rate of tumor limited to the gastric wall in the p27 positive cases was significantly higher than-that in the p27 negative cases.The mean proliferation cell nuclear antigen index of the p27 negative cases was significantly higher than that of the p27 positive cases. The survival rate of the p27 positive cases was significantly higher than that of the p27 negative cases. In Stage III cases, the survival rate of the p53 negative p27 positive or p53 negative p27 negative cases was significantly higher than that of p53 positive p27 negative cases. CONCLUSIONS: p27 was correlated with lymph node metastasis, depth of invasion, and proliferative activity of gastric cancer. Immunoreactivity of combination of p53 and p27 was a useful predictive marker of prognosis of gastric cancer.

[Neoadjuvant chemotherapy with combined S-1 plus weekly low-dose cisplatin followed by surgical resection for advanced gastric cancer].

We retrospectively examined patients with advanced gastric cancer who underwent gastrectomy following neoadjuvant chemotherapy (NAC) with S-1 plus weekly low-dose cisplatin (CDDP). Between 2007 and 2009, 27 patients with advanced gastric cancer not amenable to curative surgery were enrolled. One course of NAC comprised S-1 (80 mg/m2/day) for 21 consecutive days and CDDP (20 mg/m2) on days 1, 8, and 15; this was followed by a 2-week rest after the end of S-1 administration. Grade 3 side effects were observed in 5 patients: 3 experienced neutropenia and 2 experienced digestive symptoms. The outpatient completion rate was 81.5% (22/27); there was no incidence of renal dysfunction. During pretherapy diagnosis, depth of invasion was classified as T4 in all cases. Postoperative pathologic results showed that the depth of invasion was T3 or lower in 4 patients. In addition, the number of patients with N0 and M0 classification increased and downstaging was observed in 12 patients (44.4%). A comprehensive assessment revealed that a partial response (PR) was observed in 13 patients and stable disease (SD) was observed in 12 patients, resulting in a response rate of 48.1%. The median survival time was 580 days, and the 1-year survival rate was 72%. NAC with S-1 plus weekly low-dose CDDP can also be administered on an outpatient basis, and it is a potential regimen for the treatment of advanced gastric cancer associated with a poor prognosis.

Impact of Skeletal Muscle Mass Reduction on Long-term Survival After Radical Resection of Gastric Cancer.

BACKGROUND/AIM: This study aimed to investigate the effect of preoperative skeletal muscle mass and muscle mass loss after surgery on overall survival in patients with gastric cancer who underwent radical resection. We also examined factors involved in postoperative skeletal muscle loss. PATIENTS AND METHODS: One hundred fifty gastric cancer patients who underwent radical resection were retrospectively examined. Skeletal muscle index (SMI) was measured using computed tomography before surgery and 1 year after. Degree of muscle reduction (MR) was calculated. Patients were stratified according to preoperative SMI (high/low) and MR (high/low) for analysis. In addition, patients were grouped according to SMI and MR stratification as follows: group A, low SMI/high MR; group B, low SMI/low MR; group C, high SMI/high MR; and group D, high SMI/low MR. RESULTS: In multivariate analysis, preoperative SMI and MR were independent predictors of overall survival. Overall survival significantly differed among groups A, B, C, and D (p<0.0001). The list of groups in order of worsening overall survival was as follows: group D, group C, group B, and group A. In multivariate analysis, patient group according to SMI and MR stratification was an independent predictor of overall survival. MR was affected by operation time (>430 min) and surgical procedure (total gastrectomy). CONCLUSION: Preoperative SMI and reduction in skeletal muscle mass after gastric cancer surgery were significantly associated with overall survival. Long-term management of these patients should focus on maintenance of postoperative skeletal muscle mass.

Initial Experience with Robotic Gastrectomy in Patients with Gastric Cancer: An Assessment of Short-Term Surgical Outcomes.

Robotic gastrectomy (RG) is an alternative minimally invasive surgical technique that has gradually come into use for the treatment of gastric cancer (GC). This study aimed to assess the feasibility and safety of RG for the treatment of GC. We retrospectively reviewed the use of RG in 47 patients with GC, and clinicopathological features and surgical outcomes were evaluated. The median age and body mass index of the patients were 68 years and 21.9 kg/m2, respectively. Distal gastrectomy, total gastrectomy, and proximal gastrectomy were performed in 39 (83.0%), 5 (10.6%), and 3 (6.4%) patients, respectively. The median operative time was 354 (256- 603) min. None of the operations were converted to open or laparoscopic procedures. The median blood loss was 15 (2-350) ml. None of the patients required blood transfusion. The mean number of resected lymph nodes was 43 (7-93). The median duration of postoperative hospital stay was 13 (9-37) days. Approximately 4.3% and 2.1% of the patients had anastomotic leakage and pancreatic fistula, respectively. One (2.1%) patient had Clavien-Dindo classification grade IIIa surgical complication (anastomotic leakage). No treatment-related deaths were observed. These findings suggest that RG might be a safe and feasible procedure for the treatment of GC.

Significance of Intraperitoneal-free KRT20 and CEACAM6 mRNA Expression for Peritoneal Recurrence of Gastric Cancer.

BACKGROUND/AIM: Peritoneal lavage cytology is widely used to predict peritoneal recurrence after surgery, but cases of peritoneal recurrence are often recognized in patients with peritoneal lavage cytology negativity (CY0) who underwent no residual tumour (R0) surgery. We used peritoneal lavage fluid before and after gastric cancer surgery to detect cytokeratin 20 (KRT20) and carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) mRNA by RT-PCR. MATERIALS AND METHODS: We collected peritoneal lavage fluid before and after surgery from 58 patients who underwent gastrectomy. RNA was extracted from these samples and RT-PCR was performed. RNA expression was defined as positive and negative in cases with values higher or lower than the median value. We investigated the relationship between mRNA expression and clinicopathological and surgical factors and prognosis. RESULTS: Tumour invasion to the sub-serosa (T3) or penetration of the serosa (T4a), lymph node metastasis, and more than 150 ml intraoperative bleeding were significantly correlated with KRT20 mRNA expression. Multivariate analysis of its relationship with peritoneal recurrence showed that the odds ratio of CEACAM6 mRNA for recurrence was high (odds ratio=24.753; 95%CI=0.883-694.06; p=0.0592). All cases with peritoneal recurrence were CEACAM6-positive at pre- or post-surgery. The prognosis of peritoneal recurrence for both KRT20- and CEACAM6-positive cases was significantly poorer than that of other cases. The recurrence-free survival of the CEACAM6-positive group was significantly poorer than that of the CEACAM6-negative group. CONCLUSION: Measurement of CEACAM6 mRNA in peritoneal lavage fluid at pre- and post-surgery may be useful as a predictor of peritoneal recurrence.

Suppressive effect of bevacizumab on peritoneal dissemination from gastric cancer in a peritoneal metastasis model.

PURPOSE: Vascular endothelial growth factor (VEGF) has been reported to enhance vascular permeability and angiogenesis in the abdominal wall, thereby contributing to peritoneal dissemination with malignant ascites. We conducted this experimental study to find out if bevacizumab, a humanized monoclonal antibody against VEGF, had a suppressive effect on peritoneal dissemination from gastric cancer, in an experimental nude mouse model of peritoneal metastasis. METHODS: Each mouse was treated with a single intraperitoneal (i.p.) injection of bevacizumab. Five mice were killed, and we measured their body weight, the mean number of tumor nodules, and the volume of ascites. We also extracted retroperitoneal tissues for histological examination, to count the frequency of mitosis, and to calculate the mitotic index. Another five mice were monitored until death, and their mean survival duration was calculated. RESULTS: The volume of ascites and the mitotic index were significantly lower in the therapy group than in the nontherapy group (P = 0.042 and P < 0.01, respectively). The survival curve of the therapy group was significantly higher than that of the nontherapy group (P = 0.005). CONCLUSION: Bevacizumab may suppress peritoneal dissemination from gastric cancer.

Evaluation of the expression of bone marrow-derived mesenchymal stem cells and cancer-associated fibroblasts in the stroma of gastric cancer tissue.

AIM: Cancer-associated fibroblasts (CAFs) generated by bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in cancer progression. In this study, we investigated the relationships of BM-MSCs and CAFs in resected gastric cancers with the clinicopathological factors of patients. METHODS: We analyzed 120 gastric cancer patients who underwent gastrectomy. Immunostaining was performed with an anti-CD271 antibody (BM-MSCs) and anti-α-smooth muscle actin (αSMA) antibody (CAFs). Staining intensity was used to divide patients into low and high expression groups. Observation sites in cancer tissues were invasive, central, and whole portions. RESULTS: Expression of αSMA was significantly related to depth of tumor invasion (T), lymph node metastasis (N), lymphatic invasion (ly), venous invasion (v), and stage. Expression of CD271 was significantly related to v, stage, stromal volume, and tumor infiltration pattern (INF). Overall survival (OS) of the high expression group was significantly lower than that of the low expression group for both αSMA and CD271. Multivariate analysis showed that N, αSMA (whole), and CD271 (invasive) were independent prognostic factors. CONCLUSIONS: Cancer-associated fibroblasts and BM-MSCs are related to the progression, invasion, and prognosis of gastric cancer and may be therapeutic targets of gastric cancer.

Malignant potential of gastrointestinal stromal tumor of the stomach.

Here, we report the Ki-67 Labeling Index, the expression of c-kit, p53, bcl-2, and apoptosis in 11 gastrointestinal stromal tumors (GISTs). The Ki-67 Labeling Index in the malignant GIST group was higher than that in the benign group. The Ki-67 Labeling Index in the p53-positive cases was higher than that in the p53-negative cases. The Ki-67 Labeling Index in the C-kit-positive group was higher than that in the C-kit-negative group. The bcl-2 expression was not correlated with potential malignancy. The apoptotic count in the bcl-2-positive cases was higher than that in the bcl-2-negative cases. The Ki-67 Labeling Index, the p53 overexpression, and the C-kit expression were useful in predicting the potential malignancy.

Quality of life after total vs distal gastrectomy with Roux-en-Y reconstruction: Use of the Postgastrectomy Syndrome Assessment Scale-45.

AIM: To investigate the detrimental impact of loss of reservoir capacity by comparing total gastrectomy (TGRY) and distal gastrectomy with the same Roux-en-Y (DGRY) reconstruction. The study was conducted using an integrated questionnaire, the Postgastrectomy Syndrome Assessment Scale (PGSAS)-45, recently developed by the Japan Postgastrectomy Syndrome Working Party. METHODS: The PGSAS-45 comprises 8 items from the Short Form-8, 15 from the Gastrointestinal Symptom Rating Scale, and 22 newly selected items. Uni- and multivariate analysis was performed on 868 questionnaires completed by patients who underwent either TGRY (n = 393) or DGRY (n = 475) for stage I gastric cancer (52 institutions). Multivariate analysis weighed of six explanatory variables, including the type of gastrectomy (TGRY/DGRY), interval after surgery, age, gender, surgical approach (laparoscopic/open), and whether the celiac branch of the vagus nerve was preserved/divided on the quality of life (QOL). RESULTS: The patients who underwent TGRY experienced the poorer QOL compared to DGRY in the 15 of 19 main outcome measures of PGSAS-45. Moreover, multiple regression analysis indicated that the type of gastrectomy, TGRY, most strongly and broadly impaired the postoperative QOL among six explanatory variables. CONCLUSION: The results of the present study suggested that TGRY had a certain detrimental impact on the postoperative QOL, and the loss of reservoir capacity could be a major cause.

A Case of Gastric Cancer with Neuroendocrine Carcinoma, Signet Ring Cell Carcinoma Components, and Intramural Metastases.

BACKGROUND: Many neuroendocrine carcinomas exhibit medullary infiltration and expanded proliferation. Differentiated tubular adenocarcinoma is frequently seen in the superficial region in many neuroendocrine carcinoma cases. However, the present case showed non-medullary infiltration and signet ring cell carcinoma in the superficial region, with intramural metastases distributed throughout the whole of the stomach. CASE REPORT: A 67-year-old man was referred to our institution for treatment of gastric cancer. Type IIc-like advanced gastric cancer was detected in the greater curvature of the middle body of the stomach. The patient underwent total gastrectomy, splenectomy with D2 lymph node dissection, and Roux-en-Y reconstruction with curative resection. The tumor was diagnosed as a large-cell endocrine carcinoma of the stomach. A solid growth of signet ring cells was seen in the mucosa and submucosa. Intramural metastases were observed in many other depressed lesions. Large-cell carcinoma invaded the submucosa, mainly in the intramural metastatic site. Metastasis to one lesser curvature lymph node was also seen on histological examination. The final diagnosis was a gastric cancer of type 0-IIc (T4a) [M] (with intramural metastases) at T4aN1H0P0M0 Stage IIIA. This patient has remained alive without recurrence for 72 months after surgery. CONCLUSIONS: We recommend close preoperative examination of neuroendocrine carcinoma, taking intramural metastases into consideration.

Long-term survival of a patient with small cell carcinoma of the stomach with metachronous lung metastases treated by multimodal therapy: a case report.

A 69-year-old man was referred to our institution for treatment of gastric cancer. Type 2 gastric cancer was found on the anterior wall of the lower body of the stomach.The patient underwent distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction with curative resection. The tumor was diagnosed as a small cell carcinoma of the stomach. Recurrence occurred in the lung after surgery. The patient underwent several chemoradiation therapy regimens, including cisplatin + irinotecan + radiation, S-1 + paclitaxel, amrubicin, carboplatin + etoposide, nogitecan, and docetaxel for lung metastases and radiation for brain and bone metastases for 43 months. He finally died of brain metastases 74 months after surgery (47 months after recognition of the lung metastases). Long continuous multimodal treatment including surgery, regimens for small cell lung cancer, S-1, taxanes, and radiation was thought to prolong the survival of this man with small cell carcinoma of the stomach.

Characteristics and prognosis of mucinous gastric carcinoma.

Mucinous gastric carcinoma (MGC) is a rare histological subtype of undifferentiated gastric carcinoma, accounting for ~2.6-6.6% of all gastric cancer cases. The clinicopathological characteristics and prognosis of MGC are controversial. The present study aimed to determine the clinicopathological characteristics and prognosis of patients with MGC. We retrospectively compared the characteristics and postoperative survival of 70 patients with MGC and 2,492 non-MGC (NMGC) cases who underwent surgical resection between 1990 and 2010. MGC was characterised by larger tumor size, macroscopic Borrmann type 2 and 3, T4 invasion of the gastric wall, positive N2 and N3 lymph node metastasis, positive lymphatic vessel invasion, positive venous invasion, peritoneal metastasis and advanced tumor stage III and IV. The prognosis of MGC patients was worse compared to that of NMGC patients, as the former group consisted of more advanced-stage cases. When patients with similar disease stages were compared, the incidence of peritoneal metastasis was significantly higher among MGC patients. However, hepatic metastasis was found significantly more often in NMGC patients. Otherwise, the prognosis of MGC and NMGC patients with similar disease stages was not significantly different. Therefore, our findings indicated that, although MGC is more rare and mostly detected at an advanced stage, the diagnosis of the mucinous histological subtype was not an independent prognostic factor.

A Patient with Advanced Gastric Cancer and Situs Inversus Totalis: Report of a Case.

Situs inversus totalis (SIT) is a rare congenital anomaly in which the positions of the abdominal and thoracic cavity structures are reversed. The reported incidence of SIT is one in 10,000 to 50,000 live births. There are few reports of gastric cancer in individuals with SIT or of the potential complications of surgical intervention in such cases. We report the case of a 79-year-old woman with SIT who underwent surgical treatment for advanced gastric cancer at our hospital and review the pertinent literature. Prior to surgery, abdominal computed topography angiography with 3-dimensional reconstruction was performed to uncover any variations and to verify the exact structures and locations of vessels. Total gastrectomy with D2 lymphadenectomy and cholecystectomy were performed safely and with careful consideration of the mirror-image anatomy.

The expression of proliferating cell nuclear antigen, p53, p21, and apoptosis in primary gastric lymphoma.

BACKGROUND: We have investigated the correlations among the expression of proliferating cell nuclear antigen (PCNA), p53, p21, and the prognosis of primary gastric lymphoma, and we have investigated apoptosis by using transferase-mediated deoxyuridine triphosphate nick-end labeling staining. METHODS: A retrospective study was performed on 33 cases of primary gastric lymphoma that were surgically resected. Histopathologic examination was undertaken according to the Working Formulation classification. Immunohistochemical staining was performed by using the avidin-biotin-peroxidase complex method, with anti-PCNA antibody, anti-p53 antibody, and anti-p21 antibody. Apoptosis was quantified in situ from paraffin-embedded specimens by using an in situ apoptosis detection kit. RESULTS: On histologic grade, the survival rate of high-grade type was significantly lower than that of low-grade type and than that of intermediate-grade type. The PCNA index of low-grade type was significantly lower than that of intermediate-grade type and than that of high-grade type. Those patients who experienced recurrence were both p53(+) and p21(-). Two of these patients were receiving postoperative chemotherapy but nevertheless experienced recurrence at 18 months and at 5 months after surgery. The PCNA index of p53(+) p21(-) cases was significantly higher than that of p53(-) p21(+) cases. The apoptotic count of p53(-) p21(+) cases was significantly higher than that of p53(+) p21(-) cases. CONCLUSIONS: The Working Formulation classification and the PCNA index were each significant factors predicting the prognosis of primary gastric lymphoma. The prognosis of p53(+) p21(-) cases was poor, and the apoptotic count of p53(+) p21(-) cases was low. Accordingly, the effect of combined chemotherapy for those cases was thought to be poor.

The expression of p53, p21 and TGF beta 1 in gastric carcinoma.

The aim of the present study was to examine the significance of the p21 expression in gastric cancer. We examined the expression of p53, p21, TGF beta 1 and PCNA in 75 cases of gastric cancer using immunohistochemical examinations and the expression of p21 RNA by in situ hybridization (ISH). The combination of p53 and p21 expression was related to depth of invasion, lymph node metastasis, and stage grouping. The survival curves of the p53 negative-Group and the p21-positive Group were significantly higher than those of the p53-positive and the p21-negative Group, the p53-and-p21-both-positive Group, and the p53-and-p21-both-negative Group (each p < 0.01). The average PCNA Labelling Index (LI) of the p53-negative-and-p21-positive Group was significantly lower than that of either the p53-positive-and-p21-negative Group or the p53-and-p21-both-positive Group or the p53-and-p21-both-negative Group (p < 0.01, p < 0.05, p < 0.05, respectively). All of the p53-and-p21-both-positive cases were TGF beta 1 positive, and the rate of the TGF beta 1 positive cases in the p53-and-p21-both-positive Group was significantly higher than that of the p53-positive-and-p21-negative Group, and than the rate in the p53-and-p21-both-negative Group (each p < 0.01). The survival curves of the cases with expression of p21 RNA were higher than that of cases without p21 RNA (p < 0.05). Many of the p53-positive-and-p21-negative cases were advanced cancer with very poor prognosis, but many of the p53-negative-and-p21-positive cases were early cancer with good prognosis. These results suggest that p21 suppressed synthesis of DNA via PCNA, and TGF beta 1 is a regulation factor for the expression of p21, and that the combination of p53 and p21 expression is concluded to be a useful prognostic marker of gastric carcinoma.