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Biomedical subjects

T Tsujinaka

Publications and source records attributed to T Tsujinaka.

At least 19 recordsLinked to original sources

Stage migration caused by D2 dissection with para-aortic lymphadenectomy for gastric cancer from the results of a prospective randomized controlled trial.

BACKGROUND: Extended lymphadenectomy (D2) provides accurate nodal staging of gastric cancer. The aim of this study was to clarify the degree of stage migration seen with D2 combined with para-aortic lymph node dissection for gastric cancer invading the subserosa, the serosa and adjacent structures (T2ss-4) in patients considered not to have distant metastases (M0). METHODS: Between July 1995 and April 2001, 523 patients were recruited and randomized in a prospective phase III trial comparing D2 with D2 and para-aortic nodal dissection for T2ss-4 gastric cancer without macroscopic para-aortic nodal metastases. Stage migration was evaluated by Japanese Gastric Cancer Association staging in 260 patients who underwent D2 with para-aortic dissection by analysing pathological information from the dissected lymph nodes. RESULTS: Node (N)-stage migration was observed in 1 per cent (1 of 82) of patients with N1 disease, 20 per cent (12 of 59) with N2, 43 per cent (10 of 23) with N3 and 8.8 per cent (23 of 260) of all patients. Final stage migration occurred in 9 per cent (5 of 58) of patients with stage IIIa, 19 per cent (8 of 42) with stage IIIb, 56 per cent (9 of 16) with stage IVa and 8.5 per cent (22 of 260) of all patients. Metastasis to N4 nodes was found in 4 per cent (four of 95) of tumours invading the subserosa and 17.4 per cent (19 of 109) of tumours penetrating the serosa. The overall incidence of N4 involvement was 8.8 per cent (23 of 260). CONCLUSION: Extended para-aortic lymphadenectomy for gastric cancer provides accurate nodal staging and results in stage migration, which may improve stage-specific survival regardless of overall survival benefit.

Humans↗

Expression and mutation of SMAD4 in poorly differentiated carcinoma and signet-ring cell carcinoma of the colorectum.

Poorly differentiated adenocarcinoma (Por) and signet-ring cell carcinoma (Sig) are rare but highly malignant types of colorectal cancer. To explore their genetic backgrounds we investigated TGF-beta type II receptor (TGF-beta RII) and SMAD4 in the TGF-beta signaling pathway, and to identify their mutator phenotype we examined microsatellite instability (MSI) status. Loss of SMAD4 expression was significantly more frequent in Por (12 of 38; 31%) and Sig (4 of 5; 80%) tumors than in well (Well) and moderately differentiated (Mod) carcinomas (p = 0.04, 0.003, respectively). Mutation of the SMAD4 gene was detected in 2 of 26 Por tumors. MSI was positive in 14 of the 38 Por tumors and in 1 of the 5 Sig tumors, but in none of the Well or Mod tumors examined. We also found mutation of TGF-beta RII, a putative target of MSI, in 10 of 35 Por tumors (28.6%), but in none of 3 Sig tumors. As a whole, about 50% of the Por tumors and 80% of the Sig tumors showed abnormalities of either TGF-beta RII or SMAD4 expression. This suggests that disruption of the TGF-beta signaling pathway may play a central role in the pathogenesis of Por and Sig tumors of the colorectum.

Adenocarcinoma↗

Phase I study of the combination of nedaplatin, adriamycin and 5-fluorouracil for treatment of advanced esophageal cancer.

This trial was conducted to determine the maximum-tolerated dose, principal toxicity, and recommended dose (RD) for the phase II study of the combination of nedaplatin (NED), adriamycin (ADM), and 5-fluorouracil (5-FU) in patients with advanced esophageal cancer. Patients with previously untreated esophageal cancer were eligible if they had performance status 0-1, were 75 years or younger and had adequate organ function. The dose of NED, the key anticancer platinum complex drug, was increased from 60 to 70, and 80 mg/m(2) on day 1. ADM and 5-FU were administered at fixed doses (30 mg/m(2) on day 1, and 700 mg/m(2) on days 1-5). The dose-limiting toxicities of NED were neutropenia and severe diarrhea, and its maximum-tolerated dose and RD were 70 mg/m(2) and 60 mg/m(2), respectively. There were four responders among the six patients administered the RD. The present study thus revealed combination chemotherapy with NED, ADM, and 5-FU to be active and well-tolerated and to warrant phase II study.

Aged↗

Detection of peritoneal micrometastases of gastric carcinoma with green fluorescent protein and carcinoembryonic antigen promoter.

The aim of this study was to specifically visualize micrometastases in the peritoneal cavity, which cannot be detected by conventional methods, by using enhanced Green Fluorescent Protein (EGFP) containing carcinoembryonic antigen (CEA) promoter in an upstream position. In in vitro experiments, two cell lines from human gastric cancer, MKN45 and MKN1, and a cell line from human fibrosarcoma, HT1080, were transduced with pCEA-EGFP, which contains the CEA promoter region. MKN45 and MKN1, which expressed CEA mRNA, showed positive fluorescence after transduction of pCEA-EGFP, whereas HT1080 did not. In in vivo experiments, 7 days after 10(7) MKN45 had been injected into the peritoneal cavity of BALB/c nude mice, pCEA-EGFP was transduced in the peritoneal cavity using a fusogenic liposome with the envelope protein of Hemagglutinating Virus of Japan on the surface. On the peritoneum of the abdominal wall, fluorescent nodules were detected by fluorescence stereomicroscopy. These nodules had a minimal size of approximately 0.15 mm and could not be detected by conventional stereomicroscopy or macroscopy. They were histologically confirmed to be cancer cells by H&E staining. The results suggest that visualization of peritoneal micrometastasis of gastric cancer using CEA promoter and EGFP can offer a new strategy for diagnosis of micrometastasis.

Animals↗

New technique of laparoscopic-assisted excision of a cholecystocolic fistula: report of a case.

Cholecystocolic fistula is a rare complication of gallstone disease that is most commonly diagnosed at the time of surgery. It is generally considered to be a contraindication to laparoscopic cholecystectomy because of the difficulties involved in its management intraoperatively. Laparoscopic stapling or suturing techniques have been reported as feasible and safe methods for repairing such fistulas; however, these procedures are not always able to be performed due to technical difficulties. We exteriorized a cholecystocolic fistula through an umbilical incision, whereby it was repaired safely and easily. This report describes our new technique for managing a cholecystocolic fistula found incidentally during a laparoscopic cholecystectomy.

Cholecystectomy, Laparoscopic↗

Synchronous rectal and esophageal cancer associated with prurigo chronica multiformis: report of a case.

The skin lesions that appear in association with internal malignancies are called dermadromes or paraneoplastic cutaneous disorders. These skin changes characteristically develop with progression of the internal malignancy. A 75-year-old Japanese man who had been diagnosed as having prurigo chronica multiformis, a form of dermadrome, 5 years previously was referred to our hospital for further investigation. On admission, numerous itchy red papules were present on the right side of the abdomen and the inner aspect of both thighs. Intensive screening for internal malignancies revealed advanced rectal cancer and early esophageal cancer. After surgical resection, the skin lesions improved without any treatment. To the best of our knowledge, this is the first case of synchronous double cancers associated with prurigo chronica multiformis.

Aged↗

Lymph node metastasis along the recurrent nerve chain is an indication for cervical lymph node dissection in thoracic esophageal cancer.

This study examined whether recurrent nerve chain node metastasis serves as an indicative factor for cervical lymph node dissection in thoracic esophageal cancer. The association of recurrent nerve chain lymph node metastasis and cervical node metastasis was analyzed for 91 patients with thoracic esophageal cancer who had undergone three-field lymph node dissection. In patients with upper thoracic esophageal cancer, the incidence of cervical lymph node metastasis was similar regardless of recurrent nerve chain node metastasis. On the other hand, in patients with middle or lower esophageal cancer, the incidence was significantly higher in recurrent nerve-positive (16/31, 51.6%) than in recurrent nerve-negative (5/43, 11.6%) patients. The prognosis of patients with recurrent nerve chain node metastasis was significantly better in the three-field dissection group than in the two-field dissection group, while in patients with no recurrent nerve chain node metastasis, survival was similar between the two groups. In conclusion, cervical lymphadenectomy can be omitted for recurrent nerve chain node-negative patients with middle and lower thoracic esophageal cancer.

Abdomen↗

[Clinical results of concurrent chemoradiation therapy for primary highly advanced esophageal cancer].

Clinical results after non-curative resection of highly advanced esophageal cancer are extremely poor. We administered concurrent chemoradiation therapy (CRT) as a multidisciplinary therapy in cases of highly advanced esophageal cancer for which non-curative resection is expected. The efficacy rate of the therapy was 59.4%, and the 3-year-survival rate 10.2%. A life-prolonging effect (the 3-year survival being 17.9%) was observed in the effective cases. Our future aim is to establish a safer, more reliable and cost-effective therapy by estimating the degree of efficacy before administration of CRT and then selecting cases suitable for CRT.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of hepatocellular carcinoma responding to hepatic arterial infusion chemotherapy with low-dose cisplatin and 5-fluorouracil].

A 74-year-old man had multiple liver recurrence of hepatocellular carcinoma (HCC) after extended left hepatectomy. He was treated by continuous hepatic arterial infusion (HAI) chemotherapy with low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) via an implanted reservoir. A catheter was inserted percutaneously into the hepatic artery using the Seldinger technique. The patient was administered 10 mg of CDDP on day 1 and 500 mg/day of 5-FU for 4 days as one course. Four courses were administered and the PIVKA-II level decreased from 427 to 216 mAU/ml. However, infusion port problems led to interruption of chemotherapy and PIVKA-II increased to 798 mAU/ml. His chemotherapy was changed to 10 mg of CDDP on day 1 and 750 mg/day of 5-FU for 2 days. After five courses were administered, PIVKA-II decreased to 540 mAU/ml. This patient is still alive 15 months after the start of therapy. This case suggests that HAI with low-dose CDDP and 5-FU might be useful for prolonging the survival of HCC patients with a good quality of life.

Aged↗

[Efficacy of continuous hepatic arterial infusion of high-dose 5-FU for liver metastases of gastric cancer].

We studied the efficacy of continuous hepatic arterial infusion of high-dose 5-FU (high-dose CHAI) in two patients with multiple (five or more) bilobar liver metastases of gastric cancer. 5-FU was given continuously via the hepatic artery at 1 g/day for 3 days, followed by one day off therapy and repetition of the initial treatment as one course. Case 1 was a 67-year-old man with Borrmann type 2 gastric cancer who had undergone total gastrectomy. Metachronous multiple liver metastases (maximum diameter: 3.5 cm) were detected at 11 months after surgery. One month later, we started high-dose CHAI and gave two courses with a 4-day interval between them. After that, 5-FU was given twice by hepatic arterial infusion (HAI) at dose of 1.5 g/week. The tumor diameter had decreased by 50% at 3 months after high-dose CHAI. Case 2 was a 64-year-old man with Borrmann type 3 gastric cancer who had synchronous multiple liver metastases (maximum diameter: 9 cm) and liver dysfunction. One month after distal gastrectomy, we started high-dose CHAI and finished one course. After that, liver function returned to normal and 5-FU was given by HAI at dose of 1 g/week on an outpatient basis. The tumor diameter decreased to 1/3 of the initial size at four months after high-dose CHAI. High-dose CHAI using 5-FU may be safe and effective for liver metastases from gastric cancer.

Aged↗

Optimal management of the axilla in patients with breast cancer.

BACKGROUND: Although most surgeons perform some form of axillary lymph node dissection (ALND) as part of locoregional management of operable breast cancer, the extent of dissection remains controversial. PATIENTS AND METHODS: Observation of the axilla trial (protocol I) and partial dissection trial (protocol I) began in January 1996. Between January 1996 and May 2000, 45 post-menopausal and 207 women with clinically node-negative breast cancer were enrolled into protocol I and protocol II respectively. RESULTS: The 4-year cumulative incidence rate of axillary recurrence was 7% in patients with untreated the axilla. The 4-year overall survival rate was 98% in patients with untreated the axilla. The 4-year disease-free and overall survival rates were 96% and 98% respectively in patients treated with partial dissection. CONCLUSION: Total axillary dissection seems to be unnecessary in Japanese breast cancer patients with relatively small tumors.

Adult↗

Preoperative intranasal mupirocin ointment significantly reduces postoperative infection with Staphylococcus aureus in patients undergoing upper gastrointestinal surgery.

Nasal carriage of Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) is associated with an increased risk for postoperative staphylococcal infection. This study was conducted to investigate the effect of preoperative nasal mupirocin treatment on the postoperative infections in patients undergoing upper gastrointestinal surgery. The intervention group consisted of 141 consecutive patients who underwent upper gastrointestinal surgery between March 1, 1997, and February 28, 1998. The patients in the intervention group were treated with intranasal mupirocin three times a day for 3 consecutive days before surgery. The incidence of postoperative staphylococcal infections in the intervention group was then compared with that of the historical control group. The control group consisted of 128 consecutive patients who underwent upper gastrointestinal surgery without mupirocin treatment between January 1, 1996 and December 31, 1996. The postoperative staphylococcal infection rate in the control group (11.7%) was significantly higher (P < 0.001) than in the intervention group (0.71%). The postoperative MRSA infection rate was significantly reduced by the intervention (control group 7.0% and intervention group 0%; P < 0.01). These results suggest that preoperative nasal eradication of S. aureus with mupirocin thus appears to be an effective measure to prevent postoperative staphylococcal infection in patients undergoing upper gastrointestinal surgery.

Administration, Intranasal↗

Appraisal of treatment strategy by staging laparoscopy for locally advanced gastric cancer.

More accurate preoperative staging is necessary to determine the treatment strategy for locally advanced gastric cancer. Thirty-two patients with T3 or T4 gastric cancer expected to undergo curative resection based on conventional examinations underwent staging laparoscopy. The disease stages determined were compared with those obtained by conventional methods. The discrepancy rate of disease staging was 16 of 32 (50.0%), with down-staging in 5 of 32 (15.6%) and up-staging in 11 of 32 (34.4%). Of the 32 patients, 13 (40.6%) were found to have unsuspected peritoneal dissemination. The positive predictive value for peritoneal metastasis by staging laparoscopy was 100%, whereas the negative predictive value was 89% (17/19). The accuracy rate was 94%. After laparoscopy, 15 of the 32 (46.9%) were diagnosed as candidates for curative resection. Of these 15 patients who underwent surgery, 13 (86.7%) underwent curative resection (1 R0 and 12 R1); the remaining two underwent R2 resection because of peritoneal metastasis that was undetected by staging laparoscopy. Patients with tumors judged noncurable by laparoscopy (n = 11) received neoadjuvant chemotherapy. In 7 of the 11 cases, salvage surgery was done (one R0, three R1, three R2 resections). A second staging laparoscopy was performed in four cases to determine the indication for salvage surgery. Three of the four were judged to be curable and underwent curative resection. Staging laparoscopy is an effective tool for detecting unsuspected peritoneal metastasis, and it can increase the curative resection rate and decrease unnecessary laparotomy for advanced gastric cancer. Second-look laparoscopy enables accurate assessment of the chemotherapeutic response, which can help in decisions about salvage surgery.

Adenocarcinoma↗

Squamous cell carcinoma of the esophagus infiltrating the respiratory tract is less sensitive to preoperative concurrent radiation and chemotherapy.

BACKGROUND: The prognosis of upper thoracic esophageal cancer is poor when compared with middle and lower thoracic esophageal cancer because the tumor easily infiltrates the respiratory tract and surgical en-bloc resection is difficult. Recently, preoperative chemoradiation therapy has been shown to lead to down-staging of the disease and improve prognosis. But the benefit of this therapy for tumors infiltrating the respiratory tract remains unknown. STUDY DESIGN: Fifty-six patients with thoracic esophageal cancer infiltrating neighboring organs, but with no hematogeneous metastasis, were given preoperative concurrent chemotherapy (5-fluorouracil and cisplatin) and radiation (40 Gy) therapy. When a clinical response was observed, making a curative resection potentially possible, patients were scheduled for esophagectomy with extended lymphadenectomy. Patient prognosis with respect to the organs infiltrated by the tumors was estimated by calculating survival curves using the Kaplan-Meier method and comparing the curves by the log-rank test. RESULTS: The prognosis was significantly poorer for patients with tumors infiltrating the respiratory tract (T) or aorta plus respiratory tract (A + T) than for patients with tumors infiltrating the aorta alone (A) or other organs (Oth) (p < 0.05 for Oth versus T; p < 0.05 for Oth versus A + T; p < 0.0001 for A versus T; p < 0.0001 for A versus A + T by log-rank test). Patients positive for respiratory tract invasion (T, T + A), compared with those negative for respiratory tract invasion (A, Oth), showed a poorer clinical response to chemoradiation (3.0%, 45.5%, 39.4%, and 9.1% versus 4.3%, 82.6%, 4.3%, and 8.7% in complete response (CR), partial response (PR), nonresponse (NC) and progressive disease (PD), respectively, p = 0.0156) and surgical resectability (36.4% vs. 87.0%, p = 0.0003). Histologic effectiveness (8.3%, 50.0%, and 41.7% versus 25.0%, 70.0%, and 5.0% in grade 3, grade 2, and grade 1, respectively, for patients with respiratory tract invasion versus those without it, p = 0.0189) and histologic stages (8.3%, 8.3%, 8.3%, 8.3%, 25.0%, and 41.7% versus 20.0%, 0%, 15.0%, 25.0%, 40.0%, and 0% in pathologic CR, stage I, stage IIA, stage IIB, stage III, and stage IV, respectively, for patients with respiratory tract invasion versus those without it, p = 0.0496) were significantly better in patients negative for respiratory tract invasion; the percentages of patients with lymph node metastasis did not differ significantly between the two groups. Comparison of the recurrence patterns showed that local failure was most common in patients with respiratory tract invasion, and distant failure was the leading cause of recurrence in patients without it. CONCLUSIONS: Because the prognosis of patients with thoracic esophageal cancer infiltrating the respiratory tract is extremely poor, partially because of the low local effectiveness of preoperative concurrent chemotherapy and radiation therapy, caution is needed when deciding on salvage surgery.

Adult↗

Larynx preservation in surgical treatment of cervical esophageal cancer--combined procedure of laryngeal suspension and cricopharyngeal myotomy.

From July 1994 to July 1998, a larynx-preserving procedure was performed on 10 out of 22 (45%) patients in the surgical treatment of hypopharyngeal and cervical esophageal cancer. At first, all 10 patients were treated with concurrent radiochemotherapy with cisplatin (10 mg/m2/day), 5-fluorouracil (500 mg/m2/day) and radiation (2 Gy/day) five times per week for 4 weeks. After preoperative radiochemotherapy, the larynx-preserving procedure, combining laryngeal suspension and cricopharyngeal myotomy, was performed. The operative and hospital mortality rate was 0%. The incidence of post-operative morbidity with minor complications was 70% in the present study. Laryngeal speech and oral food intake were preserved in all patients after this procedure. The new larynx-preserving procedure combining laryngeal suspension and cricopharyngeal myotomy for cervical esophageal cancer is a favorable operative method for retaining intelligible laryngeal speech and good food intake.

Adult↗

Loss of p27(KIP1) expression predicts poor prognosis in patients with esophageal squamous cell carcinoma.

Immunohistochemical studies of cell cycle-regulating proteins were conducted on tissue samples from 106 patients with esophageal squamous cell carcinoma. Reduction of p27(KIP1) was observed in 41 (39%) cases and was significantly associated with a poor prognosis by univariate and multivariate analyses (p = 0.015). In contrast, p16(INK4) expression was reduced in 55 (52%) of the cases and was not correlated with prognosis. p27(KIP1) was not correlated with the PCNA index, while p16(INK4) expression was inversely correlated with the PCNA index (p = 0.01). The expression of these two proteins was not correlated with the clinicopathological parameters of the patients. Nodal status was shown by univariate analysis (p = 0.01) to be a prognostic factor, and poorly differentiated tumors were significantly associated with a poor prognosis by multivariate analysis (p = 0.027). Thus, reduction of p27(KIP1) plays an important role in the progression of esophageal squamous cell carcinomas and is considered to be an independent prognostic indicator of this disease.

Adult↗

Cyclin D1 overexpression in esophageal dysplasia: a possible biomarker for carcinogenesis of esophageal squamous cell carcinoma.

There is controversy as to whether esophageal squamous dysplasia is a pre-cancerous lesion or a non-cancerous lesion. In this study, we conducted an immunohistochemical investigation of cyclin D1, retinoblastoma (Rb), p16INK4 and p27KIP1 expression in 36 squamous dysplasias and 34 early squamous cell carcinomas of the esophagus. The frequency of cyclin D1 overexpression was similar in dysplasias and early cancers (30% vs. 35%). Loss of p16INK4 and p27KIP1 expression was less frequent in dysplasias than in early cancers (p=0.005 and 0.001, respectively). Loss of Rb protein expression was not detected in dysplasia and rarely observed in early cancer (7%). The proliferation cell nuclear antigen index increased from moderate dysplasia to mucosal invasive carcinoma and was correlated significantly with the expression of cyclin D1, p16INK4 and p27KIP1 (p=0.0001, 0.003, and 0.007, respectively). Thus, this study found that cyclin D1 overexpression starts early in dysplasia and could be a useful marker for its malignant potentiality while reduction of p16INK4 and p27KIP1 occurs during the transformation from dysplasia to cancer. These findings suggest that esophageal dysplasia should be treated as a precancerous lesion.

Biomarkers, Tumor↗