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Biomedical subjects

M Kiyabu

Publications and source records attributed to M Kiyabu.

15 recordsLinked to original sources
PubMed2001

Retinoic acid receptor-alpha messenger RNA expression is increased and retinoic acid receptor-gamma expression is decreased in Barrett's intestinal metaplasia, dysplasia, adenocarcinoma sequence.

BACKGROUND: Expression levels of the retinoic acid receptors (RAR-alpha, RAR-beta, and RAR-gamma) are significantly different in neoplastic tissues compared with non-neoplastic tissues for some tumors. This study investigated whether retinoic acid receptor messenger RNA (mRNA) expression levels are altered in Barrett's esophagus and Barrett's adenocarcinoma tissues. METHODS: Relative mRNA expression levels of the RARs were quantified by using the ABI 7700 Sequence Detector (Taqman) system in Barrett's intestinal metaplasia (n = 15), dysplasia (n = 6), adenocarcinoma (n = 17), and matching normal esophagus tissues (n = 36). RESULTS: RAR-alpha expression was significantly increased, and RAR-gamma expression was significantly decreased, at higher stages in the Barrett's sequence. There was almost complete loss of RAR-gamma expression (relative expression level < or = 1) in a majority (70%) of the dysplasia and adenocarcinoma tissues. There were significant differences in RAR-alpha and RAR-gamma expression in histopathologically normal tissues in patients with cancer versus patients without cancer. RAR-beta expression levels were significantly elevated in adenocarcinoma versus normal esophagus tissues. The RAR expression profile was similar for cancers arising within the esophagus and for cancers arising at the gastroesophageal junction. CONCLUSIONS: RAR mRNA expression levels are significantly different in Barrett's tissues compared with normal esophagus tissues, and these levels are significantly different in Barrett's dysplasia and adenocarcinoma tissues compared with nondysplastic tissues. These results suggest that RAR mRNA levels may be useful biomarkers for this disease and that gastroesophageal junction adenocarcinomas are genetically similar to esophageal adenocarcinomas. These results also suggest that a cancer field is present in the esophagus in patients with cancer and that genetic alterations can precede histopathologic alterations in this disease.

Adenocarcinoma↗
PubMed2001

Use of fibrin sealant for prosthetic mesh fixation in laparoscopic extraperitoneal inguinal hernia repair.

OBJECTIVE: To evaluate the efficacy of mesh fixation with fibrin sealant (FS) in laparoscopic preperitoneal inguinal hernia repair and to compare it with stapled fixation. SUMMARY BACKGROUND DATA: Laparoscopic hernia repair involves the fixation of the prosthetic mesh in the preperitoneal space with staples to avoid displacement leading to recurrence. The use of staples is associated with a small but significant number of complications, mainly nerve injury and hematomas. FS (Tisseel) is a biodegradable adhesive obtained by a combination of human-derived fibrinogen and thrombin, duplicating the last step of the coagulation cascade. It can be used as an alternative method of fixation. METHODS: A prosthetic mesh was placed laparoscopically into the preperitoneal space in both groins in 25 female pigs and fixed with either FS or staples or left without fixation. The method of fixation was chosen by randomization. The pigs were killed after 12 days to assess early graft incorporation. The following outcome measures were evaluated: macroscopic findings, including graft alignment and motion, tensile strength between the grafts and surrounding tissues, and histologic findings (fibrous reaction and inflammatory response). RESULTS: The procedures were completed laparoscopically in 49 sites. Eighteen grafts were fixed with FS and 16 with staples; 15 were not fixed. There was no significant difference in graft motion between the FS and stapled groups, but the nonfixed mesh had significantly more graft motion than in either of the fixed groups. There was no significant difference in median tensile strength between the FS and stapled groups. The tensile strength in the nonfixed group was significantly lower than the other two groups. FS triggered a significantly stronger fibrous reaction and inflammatory response than in the stapled and control groups. No infection related to method of fixation was observed in any group. CONCLUSION: An adequate mesh fixation in the extraperitoneal inguinal area can be accomplished using FS. This method is mechanically equivalent to the fixation achieved by staples and superior to nonfixed grafts. Biologic soft fixation with FS will prevent early graft migration and will avoid the complications associated with staple use.

Animals↗
PubMed1999

Node status in transmural esophageal adenocarcinoma and outcome after en bloc esophagectomy.

OBJECTIVE: Adenocarcinoma has replaced squamous cell as the most common esophageal cancer in the United States. The purpose of this study was to determine the prevalence and location of lymph node metastases, the feasibility of performing an R0 resection, and disease recurrence and survival in patients with transmural adenocarcinoma of the lower esophagus and gastroesophageal junction. METHODS: Forty-four patients with transmural adenocarcinoma underwent en bloc esophagectomy with systematic thoracic and abdominal lymphadenectomy. They were followed up for a median of 23 months. RESULTS: Actuarial survival for the entire group was 26% at 5 years. The most important predictors of the likelihood of recurrent disease and 5-year survival were the presence and number of lymph node metastases and the ratio of involved to total removed nodes. Seven patients (16%) were found to have no lymph node metastases and had an 85% 5-year survival. In contrast, patients with more than 4 involved nodes or a node ratio greater than 0.1 had a high likelihood of recurrence and death. Location of involved lymph nodes did not predict the likelihood of recurrence or death. Despite all patients having transmural tumors, recurrence within the field of the en bloc resection occurred in only 1 patient (2%). CONCLUSIONS: En bloc esophagectomy in patients with transmural esophageal adenocarcinoma is required to obtain the survival benefit of an R0 resection, to adequately assess lymphatic tumor burden, and to be able to predict the likelihood of recurrence and death and thereby guide the use of postoperative adjuvant therapy.

Abdomen↗
PubMed1999

Prevalence and location of nodal metastases in distal esophageal adenocarcinoma confined to the wall: implications for therapy.

OBJECTIVE: The purpose of this study was to characterize the prevalence and location of regional lymph node metastases in adenocarcinoma confined to the esophagal wall, to determine the extent of dissection required, and to investigate the applicability of nonoperative therapy. METHODS: Histologic evaluation of the resected specimens after en bloc esophagogastrectomy with mediastinal and abdominal lymphadenectomy was performed on 37 patients with adenocarcinoma confined to the esophageal wall. Follow-up was complete in all patients (median 24 months). RESULTS: Fifteen patients (41%) had intramucosal tumors. Twelve (32%) had submucosal tumors and 10 (27%) had muscular invasion. The prevalence of regional lymph node metastases (15/37 patients, 41%) increased progressively with depth of tumor invasion, with involved nodes identified in 80% of patients with muscular invasion. Lymph node metastases were also more common at distant node stations in intramuscular tumors (5/10, 50%). Actuarial survival for the entire group was 63% at 5 years. Recurrence was identified in 6 of the 37 patients (16%), with the risk of recurrence correlating with tumor depth. CONCLUSIONS: Tumor depth is a strong predictor of the probabilities of regional lymph node metastases, the likelihood of involvement of distant node groups, and the risk of recurrence. Patients with invasion of the muscular wall are at particularly high risk. En bloc esophagectomy with mediastinal and abdominal lymphadenectomy has the highest likelihood of achieving an R0 resection. The long-term survival and low recurrence rate achieved with an en bloc esophagectomy emphasizes the importance of an aggressive lymph node dissection to remove all potentially involved nodes.

Adenocarcinoma↗
PubMed1999

Occult esophageal adenocarcinoma: extent of disease and implications for effective therapy.

OBJECTIVE: The need for esophagectomy in patients with Barrett's esophagus, with no endoscopically visible lesion, and a biopsy showing high-grade dysplasia or adenocarcinoma has been questioned. Recently, endoscopic techniques to ablate the neoplastic mucosa have been encouraged. The aim of this study was to determine the extent of disease present in patients with clinically occult esophageal adenocarcinoma to define the magnitude of therapy required to achieve cure. METHODS: Thirty-three patients with high-grade dysplasia (23 patients) or adenocarcinoma (10 patients) and no endoscopically visible lesion underwent repeat endoscopy and systematic biopsy followed by esophagectomy. The surgical specimens were analyzed to determine the biopsy error rate in detecting occult adenocarcinoma. In those with cancer, the depth of wall penetration and the presence of lymph node metastases on conventional histology and immunohistochemistry staining was determined. The findings were compared with those in 12 patients (1 with high-grade dysplasia, 11 with adenocarcinoma) who had visible lesions on endoscopy. RESULTS: The biopsy error rate for detecting occult adenocarcinoma was 43%. Of 25 patients with cancer and no visible lesion, the cancer was limited to the mucosa in 22 (88%) and to the submucosa in 3 (12%). After en bloc esophagectomy, one patient without a visible lesion had a single node metastasis on conventional histology. No additional node metastases were identified on immunohistochemistry. The 5-year survival rate after esophagectomy was 90%. Patients with endoscopically visible lesions were significantly more likely to have invasion beyond the mucosa (9/12 vs. 3/25, p = 0.01) and involvement of lymph nodes (5/9 vs. 1/10, p = 0.057). CONCLUSIONS: Endoscopy with systematic biopsy cannot reliably exclude the presence of occult adenocarcinoma in Barrett's esophagus. The lack of an endoscopically visible lesion does not preclude cancer invasion beyond the muscularis mucosae, cautioning against the use of mucosal ablative procedures. The rarity of lymph node metastases in these patients encourages a more limited resection with greater emphasis on improved alimentary function (esophageal stripping with vagal nerve preservation) to provide a quality of life compatible with the excellent 5-year survival rate of 90%.

Adenocarcinoma↗
PubMed1994

Selection of patients for curative or palliative resection of esophageal cancer based on preoperative endoscopic ultrasonography.

OBJECTIVE: To assess the accuracy of pretreatment staging and the potential of using endosonographic findings to select patients for curative or palliative resection by comparing the preoperative endosonographic and computed tomographic (CT) findings with the histology of the surgical specimen. METHODS: Forty-two patients referred to our clinic with esophageal carcinoma underwent preoperative upper endoscopy with biopsy, endosonography, thoracic CT, and abdominal CT. Based on endoscopic ultrasonographic findings, patients with early-stage disease underwent en-bloc esophagogastrectomy, whereas those with advanced disease had a palliative transhiatal esophagectomy. Exceptions included patients with poor physiologic reserve who were treated by the transhiatal route. RESULTS: In eight patients, we were unable to pass the ultrasonographic endoscope. Seven of these eight had transmural tumors with nodal involvement on histologic study. Tumor length, based on endosonographic measurements, was correctly predicted in 34 patients (85%). Extent of wall penetration was accurately predicted in 26 (76%) of the 34, and regional lymph node status was accurately predicted in 28 (82%) of the 34. Of the patients with sonographic wall penetration, 80% had histologic evidence of one or more positive nodes. Using the WNM staging system, endoscopic ultrasonography correctly staged the cancer in 68% of the patients. Three patients were treated with an inappropriate procedure. CONCLUSION: Endosonography is a reliable method for the preoperative staging and selection of patients for curative or palliative resection. Endosonographic wall penetration appears to be a critical factor in determining tumor spread.

Adult↗
PubMed1994

Is Barrett's metaplasia the source of adenocarcinomas of the cardia?

OBJECTIVE: To investigate the prevalence of Barrett's esophagus in patients with adenocarcinomas located at the gastroesophageal junction. DESIGN: A case series of patients who underwent esophagogastrectomy for adenocarcinoma was retrospectively reviewed. Tumors were grouped by location as esophageal, cardiac, and subcardiac, and the prevalence of specialized intestinal metaplasia in the histological specimens was determined. SETTING: A university department of surgery that specializes in esophageal diseases. PATIENTS: One hundred patients with adenocarcinoma of the esophagus, cardia, or proximal stomach. MAIN OUTCOME: Cardiac adenocarcinomas were associated with Barrett's esophagus in 42% of the patients. RESULTS: Specialized intestinal metaplasia was identified in the histological sections from the resected specimen in 42% (13/31) of cardiac adenocarcinomas and in 79% (38/48) of esophageal adenocarcinomas but in only 5% (1/21) of subcardiac adenocarcinomas. The preoperative endoscopic biopsy results concurred with the final diagnosis of Barrett's esophagus in 33 of the 38 esophageal tumors, six of the 13 cardiac tumors, and the one subcardiac tumor but failed to detect specialized intestinal metaplasia in 54% (7/13) of cardiac tumors. Cardiac tumors were associated with shorter lengths of Barrett's mucosa than esophageal tumors (2.7 +/- 1.8 cm vs 7.4 +/- 3.4 cm, P < .01). The Barrett's metaplasia was dysplastic in 36 of the 38 esophageal tumors, 10 of the 13 cardiac tumors, but not in the subcardiac tumor. CONCLUSIONS: Adenocarcinomas located at the gastroesophageal junction were associated with Barrett's metaplasia in nearly one half of the patients. The length of the Barrett segment tends to be short and may be missed during endoscopy. The presence of high-grade dysplasia within Barrett's mucosa supports a barrett's origin for half of the adenocarcinomas arising at this location.

Adenocarcinoma↗
PubMed1994

Fulminant amebic colitis. A morphologic study of four cases.

PURPOSE: The morphologic features of fulminant amebic colitis are poorly documented. In this report, we describe the clinical and pathologic findings in four of these cases. METHODS: The surgical pathology reports and accompanying histologic slides were examined from four patients who underwent surgical resections for fulminant amebic colitis. Clinical information was obtained from the patients' medical records. RESULTS: Large, geographic mucosal ulcers were typically present and were accompanied by yellow-green pseudomembranes. The muscularis externa was usually attenuated and necrotic, imparting a "wet blotting paper" consistency. Large numbers of amebic trophozoites were present within the inflammatory exudates. The mucosa adjacent to and undermined by the ulcers was often hemorrhagic or inflamed, resembling ischemic colitis or idiopathic inflammatory bowel disease, respectively. Two patients died within four weeks of their surgery. A third patient died one year later as a result of AIDS-related complications. The remaining patient has been lost to follow-up. CONCLUSION: An uncommon but life-threatening manifestation of intestinal amebiasis is a fulminant colitis. Early surgical intervention and intensive antiamebic chemotherapy are essential for efficacious management.

AIDS-Related Opportunistic Infections↗
PubMed1994

Metastatic renal cell carcinoma to the contralateral ureter.

Renal cell carcinoma uncommonly metastasizes to the ureter, with only rare reports of metastatic lesions developing in the contralateral side. Recently at our institution, two patients presented with contralateral ureteral metastases from a primary renal adenocarcinoma; one was synchronous and the second metachronous. Following extensive metastatic evaluations, both lesions were believed to be solitary metastases. The involved ureters were managed with total ureterectomy and construction of an ileal ureter. We report these two cases and review the literature.

Aged↗
PubMed1993

Granulomatous response to Pneumocystis carinii in patients infected with HIV.

Pneumocystis carinii is the most frequent manifestation of the acquired immune deficiency syndrome. Typical histologic findings include foamy, acellular eosinophilic intra-alveolar exudate in which the cysts of the organisms are readily demonstrated with silver stains. Granuloma formation is rare. Only nine such cases have been described in the English literature. We reviewed 400 transbronchial biopsies done in patients suspected of having pneumocystis pneumonia at our institution between the period of 1987-1990. Of the 320 biopsy specimens with Pneumocystis carinii identified, 17 cases had granulomatous inflammation with or without Pneumocystis carinii present. All cultures for tuberculosis and fungi were negative during initial admission and follow up in fifteen cases. One was later found to have tuberculosis and another about 6 months later histoplasmosis, when rebronchoscoped for suspicion of recurrent Pneumocystis infection. None of our patients had clinical evidence for sarcoidosis or hypersensitivity pneumonitis. We believe that granulomatous pneumonitis should be included in the list of pulmonary complications associated with Pneumocystis carinii pneumonia. Clinical significance and immunologic nature remains unexplained.

AIDS-Related Opportunistic Infections↗
PubMed1993

Intestinal perforation due to Mycobacterium tuberculosis in HIV-infected individuals: report of two cases.

Intestinal perforation is an extremely uncommon complication of Mycobacterium tuberculosis (MTB) infection. We describe two cases of multiple intestinal perforations secondary to MTB in individuals infected with the human immunodeficiency virus (HIV) presenting at the Los Angeles County-University of Southern California Medical Center over a 2-month period. For each case, this was the first presentation of AIDS. One of the two patients had concurrent pulmonary involvement. One patient died, and the other responded to therapy and was discharged in stable condition. The most striking finding in both cases was the extremely large number of acid-fast bacteria seen transmurally on the pathological specimens. This might be related to impaired T-cell function. The resurgence of MTB infection in North America, in the presence of the AIDS epidemic, may result in an increasing frequency of unusual presentations, such as intestinal perforation. Intestinal perforation due to MTB should be considered in HIV-infected patients presenting with an acute abdomen.

AIDS-Related Opportunistic Infections↗
PubMed1992

Effects of preoperative chemotherapy on gastric adenocarcinomas. A morphologic study of 25 cases.

BACKGROUND: Surgical neoadjuvant therapy for gastric adenocarcinoma affords the opportunity to evaluate critically the histologic effects of preoperative chemotherapy. METHODS: Morphologic alterations in gastric adenocarcinomas were examined in the surgical-resection specimens from 25 patients after 6 weeks of preoperative chemotherapy. The group included 1 patient with a complete response; 4, with subtotal responses; 4, with partial responses; and 16, with no response to preoperative chemotherapy. RESULTS: Histologic manifestations of preoperative chemotherapy included mucosal edema, aggregates of histiocytes in the submucosa and muscularis externa, and stromal fibrosis of the submucosa and muscularis externa. Cytologic manifestations were uncommon and included a single case of signet ring cell carcinoma with diminution of the cytoplasmic vacuoles after preoperative chemotherapy. Clinical follow-up was limited, but 3 of the 25 patients died within 5-8 months after the diagnosis of gastric adenocarcinoma. The gastric-resection specimens from these three patients did not show any histologic manifestations of preoperative chemotherapy. CONCLUSION: As in tumors at other sites, the efficacy of surgical neoadjuvant therapy for gastric adenocarcinoma can be assessed, based on the histologic response of the resected tumor to preoperative chemotherapy.

Adenocarcinoma↗
PubMed1992

Multiple granular cell tumors of the gastrointestinal tract with subsequent development of esophageal squamous carcinoma.

A 52-year-old woman initially presented to our medical center with synchronous, submucosal tumors of the esophagus, stomach, and transverse colon. The gastric and colonic tumors were resected, and both displayed infiltrating sheets of polygonal cells with coarsely granular cytoplasm and small vesicular nuclei. The neoplastic cells of both tumors were immunoreactive for S-100 protein. Ultrastructural studies revealed the lysosomal nature of the cytoplasmic granules. Although the esophageal mass was not resected, it was felt that this represented another focus of granular cell tumor of the gastrointestinal tract. Two years later, she presented with disseminated squamous carcinoma of the esophagus. At autopsy, a submucosal granular cell tumor was found adjacent to the squamous carcinoma of the esophagus. To our knowledge, this is the first reported case of synchronous granular cell tumors that involved multiple segments of the gastrointestinal tract, one of which was later associated with a squamous carcinoma of the esophagus.

Carcinoma, Squamous Cell↗
PubMed1992

Preoperative systemic chemotherapy followed by adjuvant postoperative intraperitoneal therapy for gastric cancer: a University of Southern California pilot program.

PURPOSE: A clinical trial for patients with gastric cancer amenable to curative resection was undertaken to determine feasibility and response to preoperative systemic chemotherapy followed by postoperative intraperitoneal (IP) chemotherapy. METHODS AND MATERIALS: Thirty-eight patients with resectable gastric tumor received two cycles of protracted intravenous (IV)-infusion fluorouracil (5FU), 200 mg/m2/d, for 3 weeks with weekly IV leucovorin 20 mg/m2 and IV cisplatin 100 mg/m2 days 1 and 29. Resection of the gastric tumor followed within 3 weeks of completion of systemic chemotherapy. Those who had all visible tumor removed with clear margins received two cycles of IP floxuridine 3,000 mg (total dose) per day for 3 days and IP cisplatin 200 mg/m2 with IV sodium thiosulfate on the fourth day of IP therapy. RESULTS: Thirty-seven of 38 patients (97%) received two cycles of systemic chemotherapy. Thirty-five of 38 patients (92%) underwent laparotomy for gastric tumor resection. Thirty-three patients (87%) had gastric resections performed; 29 (76%) had all visible tumor removed with microscopically negative margins. No operative mortality was encountered. Twenty-six patients (68%) received IP treatment. IV neoadjuvant treatment was well tolerated and resulted in 68% of the patients reporting improvement in abdominal pain, 45% objective remissions by computed tomography (CT), 38% objective remissions by gastroscopy and biopsy, and 8% had complete surgical pathologic response. Neutropenic sepsis during the IP treatment phase contributed to the only treatment-related death. Four of 29 completely resected patients (14%) have had tumor recurrence. The median follow-up time of patients remaining alive is now 19 months. The median survival for 38 patients entered onto this protocol has not been reached at 17+ months. CONCLUSION: This novel approach to the treatment of adenocarcinoma of the stomach is feasible. The neoadjuvant systemic therapy results in significant primary tumor regression. The determination of whether systemic or IP components of the program contribute to decreased recurrence or increased survival awaits a prospectively randomized clinical trial.

Adenocarcinoma↗