[Seven-Year Follow-Up of Advanced Gastric Carcinoma Treated Only with Chemotherapy Considering the Macroscopic Findings].

A 75-year-old woman presented with difficulty in swallowing. Esophagogastroduodenoscopy(EGD)revealed a Borrmann type 3 advanced gastric cardia carcinoma. Computed tomography(CT)revealed three lymph node metastases, and thus, the preoperative diagnosis was cT4aN2M0, cStage ⅢB. However, the patient refused resection, and chemotherapy was initiated. The chemotherapy regimen was sequentially changed based on the macroscopic characteristics of the lesion: S-1 plus CDDP followed by S-1 alone, S-1 plus PTX, and PTX alone. We have continued to follow-upthe lesion using EGD and CT, and have observed the macroscopic characteristics of the advanced gastric carcinoma treated without resection for 7 years.

Postoperative pneumatosis intestinalis (PI) and portal venous gas (PVG) may indicate bowel necrosis: a 52-case study.

BACKGROUND: The significance of pneumatosis intestinalis (PI) and portal venous gas (PVG) is controversial. This retrospective study evaluated the risk factors for bowel necrosis in patients with PI and/or PVG. METHODS: Between 2002 and 2015, 52 patients were diagnosed with PI and/or PVG and were included in this study. The patients were classified according to the presence or absence of bowel necrosis in surgical findings or at autopsy. Patient characteristics and clinical findings related to bowel necrosis were investigated. RESULTS: Bowel necrosis was diagnosed in 17 (32.7 %) patients. Amongst these 17, 10 patients received salvage surgical intervention, and seven of those diagnosed with bowel necrosis survived after the operation. The remaining 35 patients received conservative treatment with or without exploratory laparotomy. Between patients with and without bowel necrosis, laboratory data revealed significant differences in the levels of C-reactive protein (P = 0.0038), creatinine (P = 0.0054), and lactate (P = 0.045); clinical findings showed differences in abdominal pain (P = 0.019) and peritoneal irritation signs (P = 0.016); computed tomography detected ascites (P = 0.011) and changes of bowel wall enhancement (P = 0.03) that were significantly higher in patients with bowel necrosis. The rate of PI and/or PVG detected in patients postoperatively was significantly higher in patients with bowel necrosis (P < 0.0001). Multivariate analysis showed that bowel necrosis was significantly more likely when PI or PVG was detected in postoperative patients than in patients who had not had surgery (P = 0.003). CONCLUSIONS: PI and/or PVG, alone, are not automatically indicative of bowel necrosis. However, when these conditions occur postoperatively, they indicate bowel necrosis requiring reoperation.

F-18 FDG PET/CT imaging of bulky myxofibrosarcoma in chest wall.

Myxofibrosarcoma (MFS) has a spectrum of malignant fibroblastic lesions with variably myxoid stroma and pleomorphism. A 67-year-old man with a bulky mass on his chest wall was diagnosed with MFS. He underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography for detection of metastasis. FDG positron emission tomography /computed tomography showed inhomogeneous high FDG uptake (max standardized uptake value, 10.1) in the bulky tumor with no evidence of metastasis, and the tumor was successfully resected. FDG uptake seemed to be reflected by the broad spectrum of pathologic heterogeneity. And MFS should be considered when making a diagnosis of inhomogeneous FDG-avid lesions in the bulky masses of soft tissue.

[Two cases of cancer in the reconstructed gastric tube after resection of esophageal cancer -An analysis of 7 cases in our hospital-].

We review 7 cases of cancer in the reconstructed gastric tube after resection for esophageal cancer in our hospital. From this experience, we report 2 cases which were resected curatively by endoscopic or open surgery. Case 1, a 61-year-old man received a subtotal esophagectomy reconstructed by a gastric tube, retromediastinally. 85 months after operation, cancer in the gastric tube was detected endoscopically, and partial resection was performed. Case 2, a 75-year-old man received subtotal esophagectomy reconstructed by a gastric tube via a retro-mediastinal route. After 104 months, early cancer in the gastric tube was diagnosed and we performed endoscopic mucosal dissection (ESD). Long-term follow-up by regular endoscopy is necessary in patients after esophageal surgery to screen for cancer in the reconstructed gastric tube.

BRAF and K-ras gene mutations in human pancreatic cancers.

We investigated the frequency of BRAF mutations in human pancreatic cancer specimens to determine its role in the development of pancreatic cancer. Nine pancreatic cancer samples without a K-ras codon 12 mutation and 19 with a K-ras mutation were included in the study. Analyses of the BRAF sequence revealed mutations in exon 15 (V599E) in two cases, both of which also exhibited a K-ras codon 12 mutation. No BRAF mutation was found in cases without a K-ras mutation. The BRAF V599E mutation was not found to be a major mutation in pancreatic cancers that had no K-ras codon 12 mutation.

Problems in the N-classification of the new 1997 UICC TNM stage classification for gastric cancer: an analysis of over 10 years' outcome of Japanese patients.

BACKGROUND: One of the major changes in the new TNM classification (5th edition, 1997) for gastric cancer was made in the classification of N category: the 5th edition employs the number of involved nodes and a minimum of 15 examined nodes is required for N0 classification. The validity of the new TNM classification was assessed by comparing the survivals according to the number of nodal involvement and especially the cut-off point of number of involved nodes and the problems in N0 classification in T1 were focused. PATIENTS AND METHODS: Between 1982 and 1999, a total of 641 patients underwent gastrectomy for gastric cancer in our department. The stage and the degree of subcategories were classified according to the pathological assessment after surgery, and the survival and its correlation with clinicopathological factors were statistically analyzed. RESULTS: pT classification included 325 pT1, 103 pT2, 102 pT3 and 111 pT4 cases, while pN classification included 448 pN-classifiable cases (223 pNO, 149 pN1, 52 pN2 and 24 pN3); 193 were unclassifiable (pNx), 123 of which were classified pNx due to the examined lymph nodes being less than 15. In 448 pTNM-classifiable cases the pN2 and pN3 groups showed almost the same survivals, while the pN1 included subgroups with a significant difference in prognosis. The pN1 category should be classified into two categories: pN1a, 1-3 involved nodes and pN1b, 4-6 involved nodes. Furthermore, out of 325 pT1 cases, 151 (46.5%) were pN-unclassifiable (pNx): 123 were due to the examined number being less than 15 for pN0 classification and 28 where the number of examined nodes were not reported. Although the mean number of examined nodes in pT1 was 24.7 for pN0 and 8.3 for pNx, there were no differences in survival rates between the pT1pN0 group and the pT1pNx group. This suggests the over-requirement of the number of examined nodes for pN0 classification in pT1 cases. We propose that pN0 classification in pT1 should be required for a minimum of 6 examined nodes. CONCLUSION: The pN1 category should be subclassified into pN1a and pN1b. Furthermore, pN0 classification in pT1 should be required for a minimum of 6 examined nodes.

p53 alteration is not an independent prognostic indicator, but affects the efficacy of adjuvant chemotherapy in human pancreatic cancer.

BACKGROUND AND OBJECTIVES: Mutations in the p53 gene are found in more than 50% of human cancers and are observed in 60-80% of pancreatic cancers. The clinicopathologic implications of p53 abnormalities and their effects on the efficacy of the adjuvant chemotherapy for pancreatic cancer remain controversial. METHODS: We investigated the p53 status in core exon-4 to -9 (codon 33-331) by direct DNA sequencing in a series of 72 pancreatic cancers and analyzed the effects of p53 abnormalities on the patients' survival and the efficacy of adjuvant chemotherapy. RESULTS: p53 mutations were found in 62.5% (45/72) of cases, including 38 point mutations and 7 frameshift mutations. The subtypes of p53 mutations included 68.9% (31/45) transitions and 15.6% (7/45) transversions. 39.5% (15/38) of point mutations were CGT (Arg) to CAT (His) mutation at codon-273 of exon-8. 34.2% (13/38) of point mutations were CGG (Arg) to TGG (Trp) mutation at codon-248 of exon-7. Of seven frameshift mutations, four were seen at exon-4, two at exon-5, and one at exon-6. Of overall cases, p53 abnormalities were not associated with a poorly differentiated grade and an advanced stage. The relationship of adjuvant chemotherapy to survival is approaching statistical significance. Univariate analysis showed that in the p53 mutation group, the patients who received adjuvant chemotherapy had a better survival ratio than that of patients who did not do. Multivariate analysis indicated that in the group with p53 mutations, the significant factors for survival were adjuvant chemotherapy, histologic grade, and clinical stage. However, in the group with a wild-type p53 gene, only histologic grade was a significant factor. In addition, 34.7% (25/72) of the cases harbor p53 polymorphism mutation only at codon-72 of exon-4, which did not show any significant effect on the pathology, prognosis, and efficacy of adjuvant chemotherapy of the pancreatic cancers. CONCLUSIONS: A p53 abnormality was not an independent factor for evaluating the prognosis of patients with pancreatic cancer, but was a beneficial indicator for selecting a reasonable strategy of adjuvant chemotherapy against pancreatic cancer.

Clinicopathological significance of abnormalities in Gadd45 expression and its relationship to p53 in human pancreatic cancer.

PURPOSE: The growth arrest and DNA damage-inducible 45 gene (GADD45a) is one of the downstream mediators of the p53 gene that stimulates DNA excision repair. The present study was designed to assess the clinicopathological significance of GADD45a and p53 in resectable invasive ductal carcinomas (IDCs) of the pancreas. EXPERIMENTAL DESIGN: This study included 72 pancreatic IDC patients who received surgery between 1982 and 2001. Point mutations in exons 1 and 4 of GADD45a and the expression of the GADD45a gene product (Gadd45) and p53 protein were analyzed by direct DNA sequencing and immunohistochemistry. RESULTS: Point mutations were found in exon 4 of GADD45a in eight cases (13.6%). Gadd45 and p53 were expressed in 54.2% (39 of 72) and 47.2% (34 of 72) of the patients. The expression of Gadd45 did not necessarily correlate with that of p53. However, Gadd45 expression correlated significantly with the grade of the pT factor of the tumors. Coexpression analysis of Gadd45 and p53 indicated that in patients with p53(+) IDC, the Gadd45(+) group had a significantly lower survival rate than the Gadd45(-) group. Furthermore, Gadd45 expression had no effect on the efficacy of the adjuvant chemotherapy. Multivariate analysis indicated that pTNM (tumor-node-metastasis) stage, grade, and adjuvant chemotherapy were significant variables for survival. Furthermore, in the p53(-) group, there were no significant variables. In contrast, in the p53(+) group, pTNM stage, histological grade, and Gadd45 expression were significant variables. CONCLUSIONS: The frequency of GADD45a mutation is appreciable in human pancreatic IDC, and the expression of Gadd45, combined with that of p53, significantly affects the survival of patients with resectable IDCs of the pancreas.

Implication of thymidylate synthase in the outcome of patients with invasive ductal carcinoma of the pancreas and efficacy of adjuvant chemotherapy using 5-fluorouracil or its derivatives.

Thymidine synthase (TS) is a key enzyme in the synthesis of pyrimidine in the de novo pathway of DNA synthesis and a major target of 5-fluorouracil (5-FU), but the implications of TS regarding human pancreatic cancer have not been reported. We assessed the expression of TS in invasive ductal carcinoma (IDC) of the pancreas by immunostaining and evaluated its clinicopathological significance, especially its implications regarding the efficacy of chemotherapy with 5-FU or its derivatives. The expression of TS in the nuclei of pancreatic cancer cells in 72 primary lesions of resectable IDC and 30 distant metastases of unresectable IDC was examined by immunostaining using anti-TS polyclonal antibody and immunoreactivity was classified into three categories: negative (-), low (+) and high (2+). High TS immunoreactivity was detected in 43% (31 of 72) of the primary lesions of the resectable IDCs and in 47% (18 of 38) of the metastatic lesions of the unresectable IDCs. The high TS in primary lesions showed a significantly inverse correlation with the level of nodal involvement. High TS immunoreactivity had a significant influence on the outcome of patients with resectable IDC and the rate of survival of the high TS immunoreactivity group was significantly higher than that of the negative or low reactivity groups, although high TS immunoreactivity did not have a significant influence on survival of the patients with unresectable IDC. The implications of TS immunoreactivity regarding the efficacy of 5-FU-based adjuvant chemotherapy (ACT) was also assessed. The high TS immunoreactivity group showed significantly better survival in both the patients who received ACT and those who were treated by surgery alone, in the resectable IDC among patients with resectable IDC. In cases of unresectable IDC, there were no differences in survival between the high and low TS groups among the patients who received ACT and those who were treated by surgery. In conclusion, high TS immunoreactivity was found to be cogent in predicting the prognosis of patients with pancreatic IDC, but its implications regarding the efficacy of 5-FU-based ACT are still unclear.

Oral UFT (uracil plus futrafur) for neoadjuvant chemotherapy of gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy has become one of the topics of interest in chemotherapy of gastric cancer; the present study assessed the clinical benefits of neoadjuvant chemotherapy with oral uracil and futrafur (UFT) for gastric cancer.METHODS: Between 1991 and 1997, 82 patients with gastric cancer (36 with early and 46 with advanced cancers) received UFT at 300-600 mg/day orally for 1-6 weeks before surgery. Objective responses, histological effects, and postsurgical survival rates were assessed.RESULTS: In 69 of the 82 patients, the objective responses of the primary lesions were assessed by endoscopy or upper gastrointestinal series examination, and 2 complete responses (CR)s, 25 partial responses (PRs), and 42 no changes (NCs) were seen (39.1% response). Histological effects were evaluated in 82 patients, and 2 grade 3, 11 grade 2, 11 grade 1b, 27 grade 1a, and 31 grade 0 effects were seen. A longer period of UFT administration was associated with a CR or PR. However, the objective responses did not correlate with the histological effects. All the patients underwent gastrectomy, and during the median follow-up period of 41 months, 3-year survival rates were 97.1% for pTNM stage 1, 75% for stage 2, 86.7% for stage 3, and 41.6% for stage 4. The survival rates of stage 3 and stage 4 patients were higher than those of the historical controls in our department. However, CR or PR did not correlate with the improvement in survival. Side effects before surgery were not serious; they included slight myelotoxicity, liver dysfunction, and anorexia; however, 3 patients (3.7%) had suture insufficiency, 3 patients (3.7%) had methicillin-resistant Staphylococcus aureus (MRSA) enteritis, and 7 patients (8.5%) had liver dysfunction.CONCLUSIONS: Preoperative chemotherapy for gastric cancer with oral UFT was safe and resulted in a good local response (macro- and microscopically) which may indicate the possibility of improved survival with neoadjuvant chemotherapy with UFT. Furthermore, preoperative chemotherapy with oral UFT is easy and patients can receive this treatment on an outpatient basis.