Outcome and status of microsatellite stability in Japanese atomic bomb survivors with early gastric carcinoma.

BACKGROUND: In the decade after the 1945 atomic bombing of Hiroshima, a high incidence of leukemia was observed among atomic bomb survivors. However, the incidence of other cancers gradually increased, while that of leukemia decreased after this period. We evaluated the clinical outcome of early gastric cancer and microsatellite stability over a long-term period in atomic bomb survivors. METHODS: The results of surgical treatment for early gastric cancer were reviewed for 117 atomic bomb survivors and 394 control patients between 1995 and 2006. In addition, immunohistochemical staining for hMSH2 and hMLH1 expression was performed to evaluate the status of microsatellite stability in 57 atomic bomb survivors and 82 control patients. RESULTS: The long-term survival rate for early gastric cancer in atomic bomb survivors was significantly lower than that in control patients (p < 0.01). Multivariable analysis revealed that age and sex were significant and independent prognostic factors for early gastric cancer. Defective hMSH2 and/or hMLH1 expression was also significantly higher in survivors than in control patients (p < 0.001). Logistic regression analysis revealed that atomic bomb survivorship was related to defective hMSH2 and/or hMLH1 expression. CONCLUSIONS: The prognosis of early gastric cancer in atomic bomb survivors was poor and was related to age and sex, rather than to being an atomic bomb survivor. Furthermore, a higher rate of defective hMSH2 and/or hMLH1 expression was observed in the survivors.

Surgery after preoperative chemotherapy for patients with unresectable advanced gastric cancer.

OBJECTIVE: The study aimed to evaluate the efficacy of surgery after preoperative chemotherapy for unresectable advanced gastric cancer. METHOD: Twenty patients with disappeared peritoneal dissemination or decreased lymph node metastasis by systemic chemotherapy underwent surgery (group S), while 14 with peritoneal dissemination or lymph nodes >N2 (group C) received continuous systemic chemotherapy. Among group S patients, 15 underwent a curative resection (group R0), while the other 5 did not microscopically undergo a curative resection (group R1). RESULTS: The median survival time for all patients was 535 days. Survival time was significantly dependent on the chemotherapy response (p < 0.002). The survival period in group S was significantly longer than that in group C (median survival time 747 vs. 476 days; p < 0.02). The relapse-free survival was 299 days in group S. In particular, the survival period of patients who underwent R0 surgery by preoperative chemotherapy was significantly longer than that of group R1 patients (median survival time 794 vs. 485 days; p < 0.02). Multivariate analysis revealed that R0 surgery was a significant and independent prognostic factor. CONCLUSION: Surgery was effective for advanced gastric cancer patients when performed as R0 resection following the disappearance of non-curative factors by preoperative chemotherapy.

The clinicopathological impact of gross classification on solitary small hepatocellular carcinoma.

BACKGROUND/AIMS: The aim of this retrospective study was to determine the effect of gross classification on the outcome of hepatic resection for small solitary hepatocellular carcinoma (HCC). METHODOLOGY: This study consisted of 179 consecutive primary HCC patients who were not preoperatively diagnosed with vascular invasion or intrahepatic metastasis. The clinicopathological impact of gross classification was compared. Patients were classified into four groups, vaguely nodular (VN) type, single nodular (SN) type, single nodular type with extranodular growth (SNEG), and confluent multinodular (CMN) type, according to the gross classification of resected specimens. RESULTS: The SNEG and CMN types showed a significantly higher rate of MVI and intrahepatic metastasis than VN and SN type. Multivariate analysis showed SNEG and CMN type is independent predictor of MVI. The survival rates and the disease free survival rates of four groups were equal after curative hepatectomy. CONCLUSIONS: This study demonstrated that the gross classifications were correlated significantly with the prevalence of MVI or intrahepatic metastasis, and that aggressive tumor spread in the SNEG type and in the CMN type was observed even in patients with small solitary HCC.

Plasma D-dimer level as a mortality predictor in patients with advanced or recurrent colorectal cancer.

OBJECTIVE: Plasma D-dimer levels are elevated in patients with a variety of solid tumors. Recently, it has been reported that the level before curative surgery is a prognostic factor for colorectal cancer (CRC). We investigated whether the plasma D-dimer level before systemic chemotherapies is a predictor for advanced or recurrent unresectable CRC. METHODS: This study included 42 patients treated with systemic chemotherapies for advanced or recurrent unresectable CRC. Variables including clinicopathological factors, plasma D-dimer levels and the modified Glasgow Prognostic Factor Score (mGPS) were evaluated. RESULTS: The plasma D-dimer level was closely related to the mGPS. Survival was shorter for patients with plasma D-dimer levels >5 µg/ml than for those with lower levels. Compared with an mGPS of 0 or 1, an mGPS of 2 was predictive of poor prognosis (p < 0.0001). Old age, advanced stage, plasma D-dimer level and mGPS were significantly associated with mortality, but plasma D-dimer level was the only independent risk factor in multivariate analysis, and was significant related to the clinical response to chemotherapy (p < 0.05). CONCLUSIONS: Survival was significantly shorter in patients with elevated plasma D-dimer levels having advanced or recurrent CRC. The plasma D-dimer level before systemic chemotherapies was an independent mortality predictor.

Subcuticular absorbable suture with subcutaneous drainage system prevents incisional SSI after hepatectomy for hepatocellular carcinoma.

BACKGROUND: The effectiveness of subcuticular absorbable suture with subcutaneous drainage to decrease the risk of postoperative incisional surgical site infection (SSI) in hepatocellular carcinoma (HCC) patients was evaluated. METHODS: A total of 149 patients with HCC who underwent hepatectomy (Hx) were retrospectively investigated. Patients were divided into two groups: the patients with subcuticular suture combined with subcutaneous drainage (the drainage group; 61 patients) and the patients with nylon suture without subcutaneous drainage (the nylon group; 88 patients). After the operations, the complication rate of postoperative incisional SSI was analyzed and compared between the two groups. RESULTS: In the drainage group the rate of incisional SSI was significantly lower compared to the nylon group: 14-3 % (p = 0.033), respectively. Patients with incisional SSI needed significantly longer postoperative hospital care than the patients without incisional SSI: 28 versus 15 days (p < 0.005). Multivariate analysis revealed that subcuticular absorbable suture with subcutaneous drainage significantly reduced the occurrence of incisional SSI (odds ratio; 0.15; p = 0.034). CONCLUSIONS: We have demonstrated that the subcuticular suture with subcutaneous drainage is effective in preventing incisional SSI in patients undergoing Hx for HCC.

Outcome of hepatectomy in hepatocellular carcinoma patients aged 80 years and older.

BACKGROUND/AIMS: The aim of this retrospective study was to determine the effect of age on the outcome of hepatic resection in octogenarian patients with hepatocellular carcinoma (HCC). METHODOLOGY: Data of 408 consecutive primary HCC patients who underwent curative hepatectomy were studied. The surgical results of the younger group (<80 years of age) and the elderly group (≥80 years of age) were compared. RESULTS: Preoperative parameters, such as comorbid conditions and liver function tests, of the younger group (n=385) were comparable with those of the elderly group (n=23). Surgical data and the prevalence of postoperative complications did not differ significantly between the two groups. The long-term prognosis of the elderly group patients was almost identical to that of the younger group patients. Overall 3-year survival rates for the elderly group and the younger group were 95.7% vs. 84.8%, respectively (p=0.56). Disease-free three-year survival rates for the elderly group and the younger group were 47.2% vs. 47.7%, respectively (p=0.65). CONCLUSIONS: Hepatectomy is a viable treatment alternative with satisfactory surgical outcome for HCC even in patients aged 80 years or older.

Laparoscopy-assisted resection for Mesenteric Castleman's disease: Report of a case.

A 65-year-old female patient was diagnosed with breast cancer in 1995. An abdominal mass was detected by computed tomography and the patient was preoperatively diagnosed with a gastrointestinal stromal tumor. Laparoscopy-assisted surgical resection revealed a mesenteric Castleman's tumor of the hyaline vascular type. Mesenteric Castleman's disease is rare, and there have been only 42 cases reported in the English literature. We herein discuss the clinical findings of these cases.

Gastric carcinoma with protein-losing gastroenteropathy: report of a case.

This report describes the successful treatment of a case of true gastric cancer presenting as protein-losing gastroenteropathy. A 58-year-old Japanese male presented gastric carcinoma. His serum albumin and total protein levels were 1.8 and 4.2 g/dl, respectively. He was diagnosed with gastric cancer with protein-losing gastroenteropathy based on (99m)Tc-human serum albumin scintigraphy. The patient underwent a total gastrectomy following neoadjuvant chemotherapy. There are 23 detailed case reports of gastric carcinoma with protein-losing gastroenteropathy. Most of these cases had large villous or cauliflower-like gastric tumors that were defined as papillary or well differentiated adenocarcinoma. Gastric cancer with protein-losing gastroenteropathy is extremely rare, but it can easily be diagnosed if the villous or cauliflower-like features are well defined.

The long-term outcome of atomic bomb survivors with gastric carcinoma.

OBJECTIVE: During the decade following the 1945 atomic bombing of Hiroshima, a high incidence of leukemia was observed among atomic bomb survivors. Subsequently, the incidence of other cancers gradually increased while that of leukemia decreased. We examined the long-term clinical outcome of gastric cancer and second primary cancer in atomic bomb survivors. METHODS: Results of surgical treatment of gastric cancer were reviewed in 231 atomic bomb survivors and 759 control patients between 1995 and 2006. RESULTS: Long-term prognosis of gastric cancer in atomic bomb survivors was significantly poorer than that in control patients (P < 0.05). In a multivariate analysis, age, depth of tumor invasion, lymph node metastases, and curability were found to be significant and independent prognostic factors for gastric cancer. The incidence of second primary cancer after gastric cancer was significantly higher in survivors than in control patients (P < 0.01), because the number of elderly patients in the survivors was higher. CONCLUSIONS: Gastric cancer in survivors had a significantly poorer prognosis. Although the frequency of second primary cancer after gastric cancer in survivors was higher than that in control patients, it did not influence the prognosis.

Prognostic re-evaluation of peritoneal lavage cytology in Japanese patients with gastric carcinoma.

BACKGROUND/AIMS: The aim of the present study was to re-evaluate CY(+) with gastric carcinoma in Japanese patients to identify the characteristics that might distinguish patients with a poor prognosis from those with an intermediate prognosis among CY(+) patients. METHODOLOGY: CY(+) was found in 56 of 566 patients (9.9%) who had undergone surgery for gastric carcinoma between January 2000 and December 2006. The 56 patients with CY(+) were classified into four groups: group A, P(-)CY(+) (n = 10); group B, P1CY (+) (n = 10); group C, P2,3CY(+) (n = 18); group D, other (n = 18). RESULTS: The 5-year survival of all patients with CY(+) was 12%. A multivariate analysis demonstrated serosal invasion, lymph node metastasis, and CY(+) to be independent prognostic factors. However, the 5-year survival in group A was 30%. The prognosis of group A patients was significantly better than that of patients in any other group (Groups B, C, D; p < 0.02). Sites of the recurrence in group A were located only in the peritoneum but the lymph nodes, etc. CONCLUSIONS: Gastric carcinoma with CY(+) has a poor prognosis because it is associated with non-curative factors, peritoneal dissemination, and liver or lymph nodes metastases. However, a small subpopulation of patients with P(-)CY(+) showed an intermediate prognosis.

High dorsal resection for recurrent hepatocellular carcinoma originating in the caudate lobe.

Standards that enable surgeons to balance radical operative procedures with functional preservation for recurrent hepatocellular carcinoma (HCC) in the caudate lobe have not yet been established. A 54-year-old man with recurrent HCC originating in the caudate lobe was readmitted to our hospital. The combined resection of the adjacent hepatic parenchyma may have carried a risk of postoperative liver failure. The anterior transhepatic approach may have caused massive bleeding due to the presence of scarring from the previous hepatectomy. Therefore, we performed an isolated total caudate lobectomy, i.e., a "high dorsal resection" as a second hepatectomy. The postoperative course of the patient was uneventful, and there has been no local recurrence 1 year after the repeat hepatectomy. Indeed a "high dorsal resection" is rarely required, but it is still ingenious, and this surgical modality can balance the curability with the hepatic functional reserve even for recurrent caudate HCC in patients with liver cirrhosis.

Impact of obesity on the surgical outcome following repeat hepatic resection in Japanese patients with recurrent hepatocellular carcinoma.

AIM: To evaluate the impact of obesity on the posto-perative outcome after hepatic resection in patients with hepatocellular carcinoma (HCC). METHODS: Data from 328 consecutive patients with primary HCC and 60 patients with recurrent HCC were studied. We compared the surgical outcomes between the non-obese group (body mass index: BMI < 25 kg/m(2)) and the obese group (BMI > or = 25 kg/m(2)). RESULTS: Following curative hepatectomy in patients with primary HCC, the incidence of postoperative complications and the long-term prognosis in the non-obese group (n = 240) were comparable to those in the obese group (n = 88). Among patients with recurrent HCC, the incidence of postoperative complications after repeat hepatectomy was not significantly different between the non-obese group (n = 44) and the obese group (n = 16). However, patients in the obese group showed a significantly poorer long-term prognosis than those in the non-obese group (P < 0.05, five-year survival rate; 51.9% and 92.0%, respectively). CONCLUSION: Obesity alone may not have an adverse effect on the surgical outcomes of patients with primary HCC. However, greater caution seems to be required when planning a repeat hepatectomy for obese patients with recurrent HCC.

Leiomyosarcoma originating from the superior mesenteric vein: a case report and review of the literature.

We describe a rare case of leiomyosarcoma originating from the superior mesenteric vein with concomitant liver metastases in a 62-year-old woman. She underwent a tumor resection and venous reconstruction, right hemicolectomy, and right hepatic lobectomy. Since the tumor was weakly positive for c-kit, she was treated with imatinib mesylate for the recurrent liver tumors. She has survived for about 3 years after undergoing the surgical procedures.

[Present status and prospects for chemotherapy for advanced or recurrent gastric cancer in our hospital].

Since S-1 was approved in 1999, the response rate and the disease control rate of the chemotherapy for advanced or recurrent gastric cancer have improved. It is important to perform chemotherapy using key drugs and to plan the chemotherapy for each case. Of the 32 patients in our hospital, the median survival time (MST) was 21 months for chemotherapy in advanced or recurrent gastric cancer during 2003-2006. MST for patients who had up to second- or third-line treatment was longer than for patients with up to first-line treatment. In addition, it there was no difference in prognosis for patients using CPT-11 or taxane at second-line after using S-1 at first-line treatment. The first-line chemotherapy for advanced or recurrent gastric cancer should be decided by the disease condition of each patient and the characteristics of each anti-cancer drug. In addition, the prognosis of patients will improve if second- or third-line chemotherapy can be performed.

[Long- and short-term survivors after chemotherapy among patients with advanced or recurrent gastric cancer in our hospital].

Since S-1 was approved in 1999, the response rate and the disease control rate of this chemotherapy for advanced or recurrent gastric cancer has been improved. Aa a result, we can plan for chemotherapy in patients with advanced or recurrent gastric cancer, because the median survival time (MST) with advanced or recurrent gastric cancer was over 20 months. We examined the characteristic findings of long- and short-term survivors in chemotherapy patients with advanced or recurrent gastric cancer. The prognosis for advanced gastric cancer is better than that for recurrent gastric cancer (p <0.02). In patients with only recurrent gastric cancer, the interval from surgery to recurrence is a significant prognostic factor. We thus show the results of chemotherapy for advanced or recurrent gastric cancer in our hospital and the characteristic findings in long- and short-term survivors for chemotherapy, and discuss effective planning of chemotherapy for each patient with advanced or recurrent gastric cancer.

[A case of advanced gastric cancer with Schnitzler's metastases effectively treated by the combination of paclitaxel and S-1].

The patient was a 70-year-old woman who underwent combined chemotherapy of paclitaxel (PTX) and S-1 after diagnosis of non-resectable advanced gastric cancer with Schnitzler's metastases. The administration schedule was as follows: 120 mg/m(2) of PTX on days 1 and 15 intravenously and 80 mg/m(2) of S-1 on days 1-14 orally. One course lasted for 4 weeks. The abdominal pain and appetite loss improved after the first course of chemotherapy, and therapeutic efficacy was rated PR. At present, there is no evidence of relapse or adverse reactions that require intervention after 4 courses. PTX and S-1 combination treatment promises good therapeutic efficacy and improves QOL in patients with advanced gastric cancer associated with Schnitzler's metastases.

Undifferentiated carcinoma of the liver: a case report with immunohistochemical analysis.

BACKGROUND: Undifferentiated carcinoma (UC) of the liver is extremely rare, and its clinicopathological characteristics have not been fully elucidated. CASE PRESENTATION: The present study reports the case of a 56-year-old male with UC of the liver. At 16 days post-admission, the patient suddenly succumbed due to intra-abdominal bleeding resulting from a ruptured liver. Macroscopic examination revealed that the hepatic parenchyma was almost completely replaced by innumerable minute nodules. Microscopically, the tumor demonstrated a diffuse proliferation of anaplastic cells that were positive for epithelial membrane antigen and neuron-specific enolase, suggesting neuroendocrine differentiation. Grimelius and Fontana-Masson staining were negative. Neuroendocrine markers were also negative, including chromogranin A, synaptophysin, and S-100 protein. Cytokeratin markers and mesenchymal markers were all negative. Tumor markers, such as α-fetoprotein and carcinoembryonic antigen, were also negative. CONCLUSIONS: Although larger studies involving more patients are required to establish a therapeutic strategy, appropriate chemotherapy following an early diagnosis may be important to UC of the liver because the tumor behaves in an aggressive way.

Diagnostic laparoscopy for pneumatosis intestinalis in a very elderly patient: A case report.

INTRODUCTION: Pneumatosis intestinalis is rare but may be associated with life-threatening intra-abdominal conditions such as intestinal ischemia or perforation. However, it can be difficult, particularly in the very elderly, to identify candidates for immediate surgical intervention. PRESENTATION OF CASE: A 94-year-old man with abdominal distension underwent abdominal computed tomography, which demonstrated accumulation of air bubbles within the intestinal wall and some free intraperitoneal air, suggestive of pneumatosis intestinalis. His vital signs showed evidence of systemic inflammatory response syndrome, and laboratory examination revealed inflammation and hypoxia. As the patient was frail, with his age and concomitant conditions which may have masked the symptoms and severity of his illness, immediate diagnostic laparoscopy was performed, which confirmed the diagnosis of pneumatosis intestinalis, with multiple gas-filled cysts seen within the subserosa of the small intestine. No additional surgical procedure was performed. His symptoms improved postoperatively. DISCUSSION: Optimal management of pneumatosis intestinalis in a timely manner requires a comprehensive evaluation of factors in each individual. In patients with severe symptoms, PI might be a sign of a life-threatening intra-abdominal emergency. Despite the contrast-enhanced CT and prediction markers in previous reports, it considered to be difficult to completely rule out these fatal conditions without surgery, especially in very elderly patients with poor performance status. CONCLUSION: Diagnostic laparoscopy may be a useful option for definitively ruling out the lethal conditions associated with pneumatosis intestinalis in frail elderly patients with severe conditions in the emergency setting.

Allele loss and promoter hypermethylation of VHL, RAR-beta, RASSF1A, and FHIT tumor suppressor genes on chromosome 3p in esophageal squamous cell carcinoma.

Promoter hypermethylation is an alternative way to inactivate tumor suppressor genes in cancer. Alterations of chromosome 3p are frequently involved in many types of cancer, including esophageal squamous cell carcinoma. Here, we investigated the methylation status and loss of heterozygosity (LOH) of 3p tumor suppressor genes. We examined the promoter methylation status of von Hippel-Lindau disease (VHL), retinoic acid receptor beta (RAR-beta), RAS association domain family 1A (RASSF1A), and fragile histidine triad (FHIT) genes in 22 esophageal squamous cell carcinoma cell lines and 47 primary tumors and corresponding noncancerous tissues by a methylation-specific PCR. In addition, we analyzed 47 paired samples for LOH at eight loci on chromosome 3p. Hypermethylation in VHL, RAR-beta, RASSF1A, and FHIT was detected in 36, 73, 73, and 50% of tumor cell lines, respectively. In primary tumors, hypermethylation in VHL, RAR-beta, RASSF1A, and FHIT was detected in 13, 55, 51, and 45%, respectively. In corresponding noncancerous tissues, hypermethylation in RAR-beta and FHIT was frequently detected in 38 and 30%, respectively, whereas no VHL hypermethylation and only 4% of RASSF1A hypermethylation were detected. Furthermore, in clinical stages I and II, hypermethylation in RAR-beta (67%) and FHIT (78%) was frequently detected, whereas no VHL hypermethylation and 11% of RASSF1A hypermethylation were detected. On the other hand, the correlation between FHIT hypermethylation and LOH at FHIT region was statistically significant (P = 0.008). Our findings suggest that hypermethylation of the RAR-beta and FHIT may play an important role in the early stage of esophageal squamous cell carcinogenesis. In addition, FHIT may be inactivated in accordance with the two-hit inactivation model, involving deletion of one allele and hypermethylation of the other.

Allelic loss on chromosome 3p21.3 and promoter hypermethylation of semaphorin 3B in non-small cell lung cancer.

The aim of this study was to evaluate the promoter methylation status and loss of heterozygosity (LOH) of the SEMA3B in non-small cell lung cancers (NSCLCs). We analyzed the methylation status of semaphorin 3B (SEMA3B) promoter and LOH at 3p21.3 in eight NSCLC cell lines and 27 primary tumors. Hypermethylation of SEMA3B was found in 50% of the cell lines and 41% of the primary tumors studied. The presence of hypermethylation was statistically associated with loss of SEMA3B expression in both cell lines (P = 0.02) and primary tumors (P < 0.01). There was no correlation between SEMA3B and tumor stage. On the other hand, the correlation between SEMA3B methylation status and LOH at 3p21.3 was significant (P = 0.02). Notably, 7 of 8 tumors with both hypermethylation and LOH of SEMA3B showed the absence of the expression. Treatment with 5-AZAC restored SEMA3B expression in NSCLC cell line. These results indicate that SEMA3B gene alterations may play a important role in the malignant transformation of NSCLC via a two-hit mechanism, including epigenetic changes and allelic loss, for tumor suppressor gene inactivation.