[Examination of stent treatment and bypass surgery for unresectable advanced gastric cancer].

This study was conducted to analyze the outcomes of endoscopic stent placement (n=9) and bypass surgery (n=9) with regard to perioperative complications and dietary intake conditions in patients with unresectable advanced gastric cancer with stenosis. Regarding perioperative complications, 1 patient in the stent group experienced a stent failure and 1 patient in the bypass group developed an adhesive ileus. Dietary intake began from the first day in the stent group and from the fourth day in the bypass group, and it was continued for 55 and 113 days, respectively. There was no difference in the introduction of chemotherapy or length of treatment between the groups, and the survival period for the patients in the stent and bypass groups was 83 and 127 days, respectively. Endoscopic stent placement for unresectable advanced gastric cancer with stenosis is a safe and effective method for improving the quality of life( QOL) of patients.

A case of esophageal cancer with multiple lymph node metastases which responded to neoadjuvant chemotherapy (DCF therapy).

It is difficult to perform radical surgery for esophageal cancer with multiple lymph node metastases. Therefore, effective neoadjuvant adjuvant treatment is necessary to achieve successful radical resection. The use of neoadjuvant chemotherapy of docetaxel, cisplatin (CDOP) and 5-fluorouracil (5-FU) (DCF) in an advanced case is reported. The patient (a 67-year-old female) was diagnosed with esophageal cancer, T3, N4, M0, stage IVa with a large number of lymph node metastases in the mediastinum and in the abdominal cavity. Neoadjuvant DCF chemotherapy was initiated in August 2006. Adverse events were mild. A complete response of the lymph node metastases in the abdominal cavity and a partial response of the esophageal lesion were achieved. The surgical procedure included a right thoracolaparotomy followed by a subtotal excision of the esophagus and two-field lymph node dissection. The cancer was diagnosed to be moderately differentiated squamous cell cancer, pT2, pN4(3c) and pstage IVa. The histological efficacy of the chemotherapy was determined to be grade 1a. Two additional courses of DCF therapy were administered followed by postoperative adjuvant chemotherapy.

The efficacy of endoscopic submucosal dissection compared with modified endoscopic aspiration mucosectomy by assessing the short-term therapeutic results for differentiated mucosal gastric cancer.

BACKGROUND: We developed a modified method of endoscopic aspiration mucosectomy (m-EAM) which includes the pre-cutting of the peripheral mucosa before aspiration, and which has been employed in this department since 1998. An endoscopic submucosal dissection (ESD), which enables the resection of a larger area of the lesion using newly-developed surgical devices, has also been employed here since March 2003. This study was performed to investigate the efficacy of ESD at the present time by assessing the short-term therapeutic results for the procedure in patients with a preoperative diagnosis of early-stage differentiated gastric mucosal cancer, by tumor diameter, as well as by comparing these results with those obtained previously with m-EAM. PATIENTS AND METHODS: The study included 110 patients with a preoperative diagnosis of early-stage differentiated gastric mucosal cancer (57 underwent m-EAM and 53 received ESD). A comparison was made between these two groups regarding the short-term therapeutic response (en bloc resection rate, curability, complications, and days of postoperative hospitalization) by the tumor diameter. RESULTS: The en bloc resection rate was significantly higher for patients with a tumor measuring 21 mm or larger who underwent ESD in comparison to that for those with a similar tumor size who underwent m-EAM (p<0.05). Complications were reported significantly more frequently in patients treated with ESD for a tumor measuring 11 mm or larger (p<0.05) in comparison those treated with m-EAM. There was no significant difference between the two groups with regard to the curability and the days of postoperative hospitalization. CONCLUSION: This study confirmed the efficacy of the ESD procedure which enables surgeons to perform a more reliable en bloc tumor resection.

[The significance of Onodera's prognostic nutritional index for the treatment of gastrointestinal cancer].

BACKGROUND: We evaluated the role of the prognostic nutritional index reported by Onodera (Onodera's PNI) in patients with gastrointestinal cancer regarding the occurrence of postoperative complications. METHOD: Subjects were 324 patients (42 with esophageal cancer, 107 with gastric cancer, and 175 with colon cancer). We classified them into the high risk group (< or = 40) and the non-high risk group (> 40) according to Onodera's PNI. We evaluated the rate of the occurrence of postoperative complications between the high risk group and the non-high risk group. RESULT: The rate of postoperative complications occurring in the high risk group was higher than that of the non-high risk group (p=0.04). CONCLUSION: Onodera's PNI is useful for patients with gastrointestinal cancer regarding the occurrence of postoperative complications.

Neoadjuvant chemotherapy (FAP) for advanced esophageal cancer.

This study was performed to assess the usefulness and safety of neoadjuvant chemotherapy utilizing the FAP regimen consisting of 5-fluorouracil, cisplatin and adriamycin for the treatment of highly advanced esophageal cancer. Twenty-seven patients with Stage III or more advanced esophageal cancer were enrolled in the study. The patients generally received two cycles of FAP. The response rate was as high as 55.6% and the resectability rate as high as 85.2%. All adverse events reported were mild in intensity. The histological effect was assessed as follows: Grade 1 in 18 patients, Grade 2 in 3 patients and Grade 3 (a pathological complete response) in 2 patients. All patients with nonresectable tumors died within 6 months, whereas of the 5 patients who responded with Grade 2 or better histological effects, all survived without recurrence for a follow-up period up to 60 months. The results of this study therefore showed the usefulness and safety of FAP therapy, which is considered to be a treatment method worth aggressively trying for highly advanced esophageal cancer in which a curative resection can hardly be expected.

Surgical treatment for superficial esophageal cancer with liver cirrhosis and esophageal varices: report of a case.

Surgical treatment of esophageal cancer is substantially invasive and often entails some postoperative complications. Perioperative management for patients with liver cirrhosis involves great difficulties. Recently, we conducted an esophagectomy for the treatment of superficial esophageal cancer in a 52-year-old male patient with liver cirrhosis and esophageal varices, with gratifying results. Although the hepatic function was impaired, as indicated by a reduced indocyanine green R15 value of 27.4%, the patient was assessed as capable of tolerating operative procedures. The procedures comprised a subtotal esophagectomy through a transhiatal approach, an anastomosis of the cervical esophagus with a gastric tube via the posterior mediastinal route, and super drainage of the short gastric vein of the gastric tube. The patient had an uneventful postoperative course without any complications such as anastomotic leakage or pneumonia. It is considered practicable to accomplish an esophagectomy by careful appraisal of liver function and planning of the operative procedure and perioperative management even in patients with liver cirrhosis.

Surgical treatment of intractable cutaneous fistula with osteomyelitis in the neck developed after esophagectomy.

A case of intractable cutaneous fistula in an esophagogastrostomized region complicated by osteomyelitis is reported. A three-stage operation was performed, and gratifying results were obtained. The patient was a 74-year-old man who received a subtotal esophagectomy and a cervical esophagogastrostomy through a retrosternal approach for advanced esophageal cancer. Following subsequent radiotherapy, the anastomosed region in the neck was found to have been stenosed. Endoscopic balloon dilatation was then performed and perforation of the stenosed region occurred to form an intractable fistula. A chest computed tomography scan revealed osteolysis of the sternum, clavicular head and left first rib. Treatment comprised an initial control of the infective foci including osteomyelitis and, after achieving stabilization of the wounds, the subsequent step of reconstruction. The patient's postoperative course was satisfactory without involvement of any leakage or stenosis of the anastomosed regions, or wound infection. It is considered feasible to cure even a cutaneous fistula in the neck complicated by osteomyelitis, as in the present case, by sufficient control of infection and procedural contrivance.

[A short-term outcome of endoscopic submucosal dissection (ESD) for early gastric cancer].

In this study, we investigated a short-term outcome of 56 cases of ESD for early gastric cancer performed in our department concerning the tumor diameter within or over 20 mm. Seventeen lesions were larger than 21 mm (large group), and 39 lesions were within 20 mm (indication group). There was no significant difference in the background factors between the two groups. The mean operating time and median of post operative hospital stay of the large group were longer than those of the indication group, and those differences were statistically significant. On the other hand, no significant difference was seen in the rate of one-piece resection, the incidence of complications and curability. With a further improvement of our skills, an ESD application in a case where the tumor diameter is larger than 21 mm may be extended.

Modification of the procedure for esophageal reconstruction after resection of esophageal cancer.

BACKGROUND/AIMS: Reconstruction after esophagectomy is still associated with the highest risk of anastomotic leakage among all of the gastrointestinal anastomoses. In 1994, the reconstruction phase of our procedure was modified aiming to reduce the risk of anastomotic leakage. We evaluated usefulness of our modified procedure. METHODOLOGY: 32 patients before the modification of reconstruction were included in Group A, whereas Group B included 80 patients after the modification. In Group A, a thin gastric tube was constructed along the greater curvature. In Group B, the gastric tube was made thinner and longer. We were able to preserve a vessel feeding the terminal segment of the gastric tube that secured ample blood supply to this segment. The cut end of the cervical esophagus was anastomosed to the posterior wall of the gastric tube near the greater curvature, where adequate blood supply is available, and the anastomotic line was covered with omentum. RESULTS: In Group A, anastomotic leakage occurred in 15.6%. In Group B, minor leaks occurred 2.5%, indicating a marked decrease. CONCLUSIONS: The method of esophageal reconstruction currently performed at our department does not require special techniques, but the occurrence of anastomotic leakage is very low.

Clinical usefulness of the angiotensin II receptor antagonist losartan in patients with portal hypertensive gastropathy.

BACKGROUND/AIMS: An elevated portal vein pressure is an important factor in the onset of portal hypertensive gastropathy associated with liver cirrhosis, and propranolol or vasopressin (drugs with a portal hypotensive effect) are used to treat this problem. It has been reported that angiotensin II receptor antagonists, which were developed as antihypertensive agents, also have a portal hypotensive effect, but their usefulness for portal hypertensive gastropathy is unclear. In this study, the angiotensin II receptor antagonist losartan was administered to 16 portal hypertensive gastropathy patients, and its clinical usefulness was examined. METHODOLOGY: Losartan was administered once a day after breakfast at a dose of 25mg or 50mg. The effect on portal hypertensive gastropathy was evaluated from the endoscopic findings at baseline and after 4 weeks of administration. And changes of portal hemodynamics were monitored by pulse Doppler ultrasonography at baseline and after 4 weeks of administration. RESULTS: Portal hypertensive gastropathy was found to have improved in nine out of 16 patients for an efficacy rate of 56%. The efficacy rate in the 50mg group (n=6) was 83%, and was higher than the rate of 40% in the 25mg group (n = 10). The mean portal vein blood flow velocity was found to increase significantly, while the congestion index decreased significantly, supporting evidence of a decrease in portal pressure. CONCLUSIONS: Losartan may become one of the effective treatments for portal hypertensive gastropathy in the future.

Platelet factor 4 gene transfection into tumor cells inhibits angiogenesis, tumor growth and metastasis.

Tumor growth and metastasis depend on angiogenesis, which is triggered by a chemical signal from the tumor cells to resting endothelial cells which then enter into a phase of rapid growth. Platelet Factor 4 (PF4) inhibits endothelial proliferation in vitro and angiogenesis in vivo. PF4 also inhibits tumor growth, however, as with other angiogenesis inhibitors, sustained tumor growth inhibition requires prolonged exposure to the recombinant protein. In this study, Lewis lung carcinoma (LLH) cells were transfected with the human PF4 via mammalian expression vectors and the ability of the transfected cells to form tumors and metastasis in vivo was evaluated. To evaluate the tumor growth rate of PF4-transfected (LLH/PF4) or control (LLH/neo) cells in vivo, we injected LLH/PF4 or LLH/neo cells subcutaneously (s.c.) or intravenously (i.v.). In the s.c. assay, LLH/PF4 had no significant effect on tumor growth. Conversely, in the i.v. assay, PF4 significantly reduced the number of lung metastasis (p=0.019) and weight (p=0.056). The inhibition of lung metastasis suggests that PF4 may inhibit tumor-associated neovascularization, and may prevent the affinity of tumor cells for the normal lung tissue.

[A case of gastric cancer with paraaortic lymph node metastasis responding to TS-1/CDDP combination therapy].

A 53-year-old man had consulted another physician regarding his epigastralgia and anorexia. Since gastric cancer was detected, he was referred to our department. An upper gastrointestinal endoscopy revealed a type-2 gastric cancer at the upper portion of the lesser curvature of the stomach, and an abdominal CT scan showed marked swelling of periaortic lymph nodes. Since a radical resection appeared impossible, we used preoperative chemotherapy with a combination of TS-1 and CDDP. The patient was administered TS-1 for 3 weeks at 120 mg/ day, received an intravenous drip infusion of 90 mg/body of CDDP on day 8, and then discontinued chemotherapy for 2 weeks, which was regarded as one course. After 2 courses of the chemotherapy, an upper gastrointestinal endoscopy showed that the primary tumor was reduced in size, the periphery of the tumor almost flattened, and an abdominal CT scan confirmed the loss of swelling in the periaortic lymph nodes. The responsive rate was evaluated as PR. Since a radical resection was considered possible, we performed a total gastrectomy with complete D3 extirpation combined with a splenectomy. Histological efficacy was evaluated as grade 2 in primary cancer, and grade 3 in lymph nodes. Regrettably, the patient died one year and 7 months postoperatively. However, we consider the TS-1 and CDDP in combination useful as preoperative chemotherapy for advanced gastric cancer with periaortic lymph node involvement.

Perforated duodenal ulcer at seven years after heart-renal transplantation: a case report.

We experienced a rare case of perforated duodenal ulcer that occurred at seven years after heart-kidney transplantation. This patient is reported here together with a discussion of the etiology, the selection of treatment, and perioperative management. The patient was a 46-year-old man who presented with precordial pain. In 1995, he had undergone simultaneous heart and kidney transplantation in the United States and had been on long-term immunosuppressive and corticosteroid therapy. His precordial pain started from May 24, 2002. He was examined at our hospital on May 27 and underwent emergency surgery with a diagnosis of upper gastrointestinal perforation. A 4-mm perforation was observed on the anterior wall of the duodenal bulb and panperitonitis was also present. Patch closure of the perforation was performed by pulling the omentum over the defect. Perioperative management consisted of his usual immunosuppressants together with antacid therapy. The postoperative course was good and he was discharged on hospital day 15. In this patient, the mechanism of perforation was assumed to involve sudden irritation combined with poor circulation in the duodenum and tissue ischemia, as well as a decrease of mucosal protective factors based on long-term corticosteroid therapy. Perforated duodenal ulcer is a rare problem after heart transplantation. Because the time that elapses after perforation is an important determinant of the prognosis, early diagnosis and appropriate surgical repair are essential.

Clinical experience of transjugular intrahepatic portosystemic shunt (TIPS) and its effects on systemic hemodynamics.

We performed TIPS (transjugular intrahepatic portosystemic shunt) in patients with intractable esophageal varices accompanied by repeated hematemesis or with refractory ascites for the purpose of portal venous decompression, and successfully obtained complete elimination of esophageal varices or a marked decrease in ascites. While TIPS caused no particular variations in mean blood pressure or heart rate, cardiac output increased markedly on the 2nd and 3rd postoperative days before declining on the 5th postoperative day. Along with this, right atrial pressure, pulmonary arterial pressure and pulmonary capillary wedge pressure also increased transiently. TIPS has the potential to become an established effectual therapy for intractable esophageal varices and refractory ascites. However, careful attention should be paid to its hemodynamic effects, including the occurrence of cardiac failure.

Expression of twist and wnt in human breast cancer.

Twist, a transcription factor of the basic helix-loop-helix class, has been suggested to have oncogenic properties. We reported Twist expression was regulated by Wnt/beta-catenin signaling and that both Wnt-1 and Twist could contribute to mammary tumorigenesis. The aim of this study was to demonstrate the expression of Twist, Wnt-1 and Wnt-2 in human breast cancer tissue. We examined the expression in patients with breast cancer by RT-PCR and immunohistochemistry. RT-PCR of twenty-three pairs of cancer and normal breast tissue revealed that Twist was up-regulated in 69.6% (16/23) of the cancer lesions and 21.7% (5/23) of the normal breast tissues. Wnt-2 was up-regulated in all of the cancer lesions and 13.0% (3/23) of the normal breast tissues, whereas Wnt-1 was expressed in both the cancer and normal breast tissues of the five cases examined. Immunohistochemical analyses revealed that Twist was positively expressed in 52.2% (12/23) of the cancer lesions and 34.8% (8/23) of the normal breast tissues. Twist and Wnt-2 are highly expressed in breast cancer tissue, suggesting that both molecules could play important roles in mammary carcinogenesis.

Mutation analysis of copper-transporting P-type adenosine triphosphatase (ATP7B) in human solid carcinomas.

A major obstacle in the treatment of human solid carcinomas is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphatase (ATP7B) has been reported to be associated with cisplatin resistance in vitro. ATP7B is overexpressed in human solid carcinomas such as breast, gastric and oral squamous cell carcinomas. ATP7B expression has an influential effect on some subsets of patients with cisplatin-treated carcinomas. ATP7B mutation is well-known as a cause of Wilson's disease. In addition, the six copper-binding domain and ATP-binding domain of ATP7B are important for the transportation of metals. Therefore, we performed the mutation analysis at the six copper-binding domain and ATP-binding domain of ATP7B. No mutation at the six copper-binding domain and ATP-binding domain was observed in breast, gastric and oral squameous cell carcinomas. These results indicate that the analysis of the ATP7B gene and/or protein will be helpful for the choice of chemotherapy in patients with human solid carcinomas.

Expression of copper-transporting P-type adenosine triphosphatase in human esophageal carcinoma.

A major obstacle in the treatment of esophageal carcinoma is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphatase (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the clinical significance of this transporter has not previously been addressed. Our goal was to investigate if ATP7B is expressed in esophageal carcinoma and whether its expression correlates with reduced responsiveness to cisplatin treatment. We retrospectively examined the expression of ATP7B in primary esophageal carcinoma and its association with chemotherapeutic effect. Tissues were surgically removed from 17 esophageal carcinoma patients. Twelve of them received cisplatin-based chemotherapy before surgery. We performed immunohistochemical analysis of ATP7B using a monoclonal antibody against ATP7B in 17 esophageal carcinomas. A variable degree of cytoplasmic staining of tumor cells was observed in 76.5% (13/17 cases) of the analyzed carcinomas. ATP7B expression was not observed in adjacent non-neoplastic tissues. ATP7B positivity was not significant in gender, age, histopathological grading or TNM categories. Patients with ATP7B-positive tumors tended to have an inferior response to chemotherapy compared with the patients with ATP7B-negative tumors. These findings suggest that overexpression of ATP7B in esophageal carcinoma could be associated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. Therefore, ATP7B gene expression might be considered as a chemoresistance marker for cisplatin in the patients of esophageal carcinoma and provider of important information on the strategy against esophageal carcinoma.

Copper-transporting P-type adenosine triphosphatase (ATP7B) is expressed in human gastric carcinoma.

This study describes the first report that a copper-transporting P-type adenosine triphosphatase, ATP7B, is expressed in human gastric carcinomas. Herein, we investigated the hypothesis that ATP7B, which was shown to be associated with cisplatin resistance in vitro, is expressed in certain gastric carcinomas. To test this hypothesis, ATP7B expression level was examined in 51 gastric carcinomas by immunohistochemistry. ATP7B protein could be detected in 41.2% (21/51) of gastric carcinoma by immunohistochemical analysis. In ATP7B-positive tumors, adjacent non-neoplastic tissue was similarly analyzed, revealing that ATP7B is upregulated in gastric carcinoma. ATP7B expression in poorly differentiated/undifferentiated carcinoma was significantly higher than that in well/moderately-differentiated carcinoma (P=0.0278). These findings suggested that ATP7B expression might be a chemoresistance marker against cisplatin in some patients with poorly differentiated/undifferentiated gastric carcinoma.

Thymidine phosphorylase expression in gastric carcinoma as a marker for metastasis.

BACKGROUND: Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECCF) and has a function of angiogenesis in vitro and in several types of human carcinoma tissues. We have reported that expression of dThdPase was an independent prognostic factor in 116 gastric carcinomas by immunohistochemical analysis. MATERIALS AND METHODS: In the present study, we updated the analysis of recurrence in 116 patients with gastric carcinomas to find how dThdPase plays an important role in progression of gastric carcinoma. RESULTS: Expression of dThdPase was significantly involved in the progression and metastasis of gastric carcinoma. Further, the proportion of recurrence of the patients with dThdPase-positive gastric carcinoma (23 out of 50, 46.0%) was significantly higher than that with -negative gastric carcinoma (5 out of 66, 7.6%) (p < 0.05). Interestingly, the proportion of hematogenous metastasis (liver, lung) of the patients with dThdPase-positive gastric carcinoma (8 out of 8, 100%) was significantly higher than that with -negative gastric carcinoma (0 out of 8, 0%)) (p < 0.05). The proportion of peritoneal metastasis of the patients with dThdPase-positive gastric carcinoma (10/13, 76.9%) was also significantly higher than that with -negative gastric carcinoma (3 out of 13, 23.1%)) (p < 0.05). CONCLUSION: These findings suggested that dThdPase promotes hematogenous and peritoneal metastases in gastric carcinoma. Inhibition of dThdPase may suppress hematogenous and peritoneal metastases in gastric carcinoma and improve prognosis of patients with gastric carcinoma.

Modification of endoscopic aspiration mucosectomy (EAM) for early gastric cancer: EAM with pre-cutting.

BACKGROUND/AIMS: We have performed endoscopic aspiration mucosectomy for early gastric cancer since June 1993. In order to increase the complete resection rate, it is necessary to place the cancer in the center of the resection field. To facilitate complete resection, a circular incision to guide aspiration mucosectomy was made with a cutting knife (pre-cutting) before endoscopic aspiration mucosectomy, a procedure that we call endoscopic aspiration mucosectomy, with pre-cutting. METHODOLOGY: Eleven patients who had undergone endoscopic aspiration mucosectomy with pre-cutting for early gastric cancer at our department were included in this study. All resected specimens were examined macroscopically and histopathologically to assess the curative potential of this modified method of mucosectomy. RESULTS: The resected specimens ranged from 22 to 28 mm (mean: 25 mm) in maximum diameter, while the tumors ranged from 10 to 18 mm (mean: 12 mm) in size. Each resected specimen had the tumor at its center. The resection rating was EA in 10 (90.9%) of the 11 lesions and EC in 1 lesion (9.1%). CONCLUSIONS: For curative endoscopic surgery, there is no dispute that complete resection is essential. Thus, endoscopic aspiration mucosectomy with pre-cutting should contribute to the cure of early gastric cancer.