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Biomedical subjects

D M Ota

Publications and source records attributed to D M Ota.

At least 37 records · Page 2Linked to original sources

Patterns of residual disease after preoperative chemoradiation in ultrasound T3 rectal carcinoma.

BACKGROUND: Rectal carcinoma tends to recur locally, with invasion of adjacent organs and significant pelvic pain. Both radiation therapy alone and combined chemoradiation have been used in an attempt to decrease the local recurrence rate and thereby improve survival. Although preoperative chemoradiation can clinically downstage rectal tumors, the pathologic extent of the residual disease has not been studied. METHODS: Thirty-seven patients with T3 rectal cancer diagnosed by transrectal ultrasonography (uT3) received 45 Gy with continuous infusion 5-fluorouracil (300 mg/m2/day). Proctoscopy with mucosal/submucosal biopsy was performed in patients (16 of 37) posttreatment and before definitive surgery. RESULTS: Microscopic evaluation of the 37 resected specimens showed a 30% (11 patients) pathologic complete remission rate. The pattern of residual disease in the remaining 26 patients showed that nine (25%) had microscopic residual tumor without evidence of mucosal involvement. Of the 14 patients with a negative proctoscopic evaluation and biopsy only, five (36%) had no residual tumor on final pathology. CONCLUSIONS: After chemoradiation, the pathologic presentation of rectal cancer may be altered, making endoscopic procedures and mucosal/submucosal biopsies unreliable in detection of residual disease. Despite the relatively good pathologic complete remission rate noted in this study, all patients undergoing chemoradiation for uT3 rectal carcinomas need definitive surgical resection to confirm a complete clinical remission.

Adenocarcinoma↗

MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma.

BACKGROUND/AIMS: The MUC1 mucin distributes among a variety of epithelial tissues (except the intestinal epithelia) and is often detectable in colorectal carcinoma tissues and cell lines. This study aimed to elucidate whether MUC1 mucin expression correlated to the progression of colorectal carcinomas. METHODS: We collected 113 tissue specimens, including primary colorectal carcinoma, normal mucosa, liver metastases, lymph node metastases, and normal livers from 58 patients with colorectal carcinoma. Immunohistochemical staining and Western blotting analysis with mature MUC1 mucin-specific monoclonal antibodies were performed. RESULTS: The levels of mature MUC1 mucins were significantly higher in carcinoma tissues than those in normal colonic mucosa (P < 0.001). Furthermore, the levels of mature MUC1 mucins were significantly higher in primary tumors from patients having metastasis or metastatic tumors than in primary tumors from patients without metastasis (P < 0.001). In the primary sites, mature MUC1 mucin levels apparently increased according to progression of the stages (P < 0.001). CONCLUSIONS: These results strongly suggest that mature MUC1 mucins become ectopically expressed in colorectal carcinoma progressed to the metastatic stages and that mature MUC1 mucins may be a useful marker for advanced colorectal carcinoma.

Adult↗

Laparoscopic-assisted segmental colectomy: surgical techniques.

OBJECTIVE: To describe our surgical techniques for successful completion of laparoscopic-assisted segmental colectomy. DESIGN: We reviewed the important preoperative, operative, and postoperative factors that should be considered for laparoscopic resection of the right, left, and sigmoid colon. RESULTS: The current indications for laparoscopic-assisted colectomy include most benign colonic conditions (such as colorectal polyps, rectal prolapse, diverticular disease, and colonic lipomas). Laparoscopic procedures for malignant disease, however, are currently reserved for prospective trials and palliation of patients with stage IV colonic cancer because the adequacy of staging and lymphatic resection remains questionable. Patients who are appropriate candidates for laparoscopic-assisted colectomy should be counseled about the potential benefits, risks, and possible need for conversion to an open surgical procedure--a decision that should be considered application of sound surgical judgment rather than a failure. For laparoscopic-assisted colectomy, we prefer to use the closed technique for establishing a pneumoperitoneum. We use a two-surgeon, four-cannula approach for resections of the right and left colon and a three-surgeon, five-cannula technique for resections of the sigmoid colon. Laparoscopic techniques are used to mobilize the bowel and divide the principal blood supply; the resection and anastomosis are performed extracorporeally, with use of a small incision. CONCLUSION: The associated morbidity and mortality rates are comparable to those for conventional open procedures. Despite a shortened period of ileus and fewer hospital days, the total costs for laparoscopic colectomy have been equivalent to those for standard colectomy. This result has generally been due to longer operative times, which should decrease with additional experience.

Colectomy↗

Controversies regarding laparoscopic colectomy for malignant diseases.

Surgical investigators have shown that a hemicolectomy can be done laparoscopically. This minimally invasive approach to treat colon cancer potentially reduces hospitalization time, hastens return to normal activity, and reduces health care costs. Hopefully, all of these favorable outcomes can be achieved without compromising cancer control. At present, however, the issues regarding laparoscopic colectomy are not clear, and prospective studies are necessary to validate that this new procedure is superior to open colectomy. Because cancer control might be compromised by this new procedure, laparoscopic colectomy should not be accepted by the surgical community because of the allure of new technology or the hope that it is equivalent to open colectomy in controlling a curable disease. Rather, a randomized trial of laparoscopic colectomy compared with open colectomy is needed to prove that cancer control is not different and that laparoscopic colectomy is cost-effective.

Colectomy↗

Pharmacologic intervention can reestablish baseline hemodynamic parameters during laparoscopy.

BACKGROUND: Several studies in both animal models and human beings have shown that CO2 abdominal insufflation for laparoscopy can cause a variety of alterations in hemodynamic and pulmonary physiology. These physiologic changes could potentially have deleterious effects in patients with underlying cardiopulmonary disease. METHODS: We prospectively evaluated 15 patients with preexisting heart and/or lung disease to determine whether the use of invasive monitoring would allow early identification and treatment of these physiologic alterations and thus enable laparoscopy to be performed safely in this group of patients. RESULTS: CO2 abdominal insufflation caused statistically significant increases in systemic vascular resistance, mean arterial pressure, left ventricular stroke work index, and pulmonary capillary wedge pressure along with a concomitant decrease in cardiac index and oxygen delivery in these patients. The use of intravenous nitroglycerin resulted in a rapid return of the systemic vascular resistance, mean arterial pressure, pulmonary capillary wedge pressure, and cardiac index to baseline levels. No significant intraoperative or postoperative cardiac or pulmonary complications were noted. CONCLUSIONS: These results suggest that laparoscopy with CO2 pneumoperitoneum can be safely performed in high-risk patients if appropriate monitoring and pharmacologic interventions are used.

Aged↗

Laparoscopic intracorporeal harvest of jejunal tissue for autologous transplantation.

Our goal in this study was to assess the feasibility and safety of performing an intracorporeal laparoscopic jejunal harvest. The initial technique was developed and refined in a pig and then a dog model. In the animal studies, careful dissection of the jejunal flap with its feeding vessel was accomplished along with an intracorporeal anastomosis. The laparoscopic dissection was facilitated by temporarily anchoring the jejunal flap to the anterior abdominal wall and transilluminating the mesentery. We present the first case report of a patient who underwent a laparoscopic jejunal harvest, intracorporeal small bowel anastomosis, and a microvascular anastomosis in the neck for reconstruction of the laryngopharynx.

Adult↗

Preoperative and postoperative combination chemotherapy for potentially resectable gastric carcinoma.

BACKGROUND: Median survival of patients with local-regional gastric carcinoma is 10 months. Resection of the primary tumor and regional lymph nodes, with tumor-free margins (curative resection), has been the most effective treatment for local-regional gastric carcinoma. However, median survival of patients with curative resection of gastric carcinoma is 24 months, and the 5-year survival rate is about 20%. A single institution pilot study has established the feasibility of administering two courses of chemotherapy preoperatively and three courses postoperatively. In another study, a 15% pathologically documented complete response (pathologic complete response) has been reported in unresectable gastric carcinoma treated with etoposide, doxorubicin, and cisplatin. PURPOSE: Our purpose was to increase the curative resection rate in potentially resectable gastric carcinoma and to delay or eliminate micrometastases and thus improve survival. We also evaluated clinical and pathologic response to chemotherapy. METHODS: Forty-eight previously untreated patients with potentially resectable gastric carcinoma received a chemotherapy regimen (EAP) consisting of etoposide (120 mg/m2 intravenously over a 2-hour period on days 4, 5, and 6), doxorubicin (20 mg/m2 as a 10-minute intravenous infusion on days 1 and 7), and cisplatin (40 mg/m2 as a 1-hour intravenous infusion on days 2 and 8). Patients received three courses of chemotherapy before resection, and responding patients received two courses postoperatively. Clinical and pathologic response rates, toxicity, patterns of treatment failure, and survival times were assessed. RESULTS: A median of three courses (range, 1-5) of preoperative therapy was administered; six (12%) of the 48 patients had clinical complete response, and nine (19%) had partial response. Forty-one (85%) underwent surgery; 37 (90%) of these 41 (77% of the 48 patients) had a curative resection. There were no pathologic complete responses. Median survival for all patients is 15.5 months (range, 2-29+ months). Therapy was discontinued because of the toxic effects in one patient before surgery and in six patients after surgery. Doses were reduced in 37 patients (77%), mainly because of hematologic toxicity. Nineteen (40%) were hospitalized because of toxic effects, including 15 patients who developed fever with neutropenia. Grade 3 or 4 nausea and vomiting occurred in 15 patients and grade 3 or 4 diarrhea in seven patients. One death was directly related to chemotherapy. CONCLUSIONS: These data support that administration of preoperative and postoperative chemotherapy for local-regional gastric carcinoma is feasible in a multi-institutional setting. Our findings demonstrate that this EAP regimen is modestly active but is associated with substantial toxicity. IMPLICATIONS: Use of preoperative chemotherapy in resectable gastric carcinoma merits further evaluation, but more effective drug regimens will be required before a controlled trial is initiated.

Adenocarcinoma↗

Preoperative chemotherapy and radiation therapy for locally advanced primary and recurrent rectal carcinoma. A report of surgical morbidity.

BACKGROUND: Complete surgical resection of locally advanced primary and recurrent rectal cancer is often incomplete. Improved tumor downstaging may improve resection rates and local control if postoperative morbidity is not increased. METHODS: The clinical and pathologic records of 119 patients with locally advanced primary and recurrent rectal carcinoma were reviewed to determine the effect of preoperative chemoradiation on postoperative morbidity compared with a control group treated with external beam radiation therapy alone. Group I (56 patients) was treated with 45 Gy of external beam radiation therapy. Group II (63 patients) received 45 Gy of external beam radiation therapy with continuous-infusion cisplatin, 5-fluorouracil, or both. RESULTS: Forty-one patients (73.2%) in Group I and 48 in Group II (76.1%) underwent surgical resection. Anal-sparing procedures were performed more frequently in Group II (25%) than in Group I (5.3%, P < 0.05). The overall complication rate for Group I was 51% versus 44% for Group II (P < 0.05) or 1.17 complications per patient in Group I and 0.58 complications per patient in Group II. One patient in each group died of treatment-related septic complications. CONCLUSIONS: It was concluded that the addition of chemotherapy to radiation to treat rectal carcinoma does not result in an increased operative morbidity and may contribute to a higher proportion of patients being treated with anal-rectal-conserving surgical procedures.

Antineoplastic Combined Chemotherapy Protocols↗

Glutamine stability in biological tissues evaluated by fluorometric analysis.

Although glutamine has been considered unstable during storage and therefore difficult to quantitate, recent results suggest this amino acid is stable at low pH ranges. We evaluated the stability of glutamine in plasma and tissue extracts, using fluorometric analysis. The measured concentration of glutamine detected varied linearly up to 0.8 mmol/L for the aqueous solution (r2 = 98.7, P = 0.0001) with a mean (+/- SD) coefficient of variation of 2.41% +/- 0.79%. When glutamine was dissolved in 50 g/L trichloroacetic acid (TCA), the values were essentially unaltered. Glutamine in an aqueous solution and stored at -70 degrees C was stable for at least 16 days; glutamine in TCA was stable for 6-8 days, then decreased to a concentration significantly lower than that of the aqueous solution. The expected and observed concentrations in plasma were equal (r2 = 0.99975) for increasing amounts of added glutamine. Glutamine concentrations in plasma were stable for > 1 year when stored at -70 degrees C. The glutamine of a transplantable rat sarcoma and a normal rat liver could be extracted with 50 g/L TCA with high efficiency (88.6% +/- 1.9% and 90.2% +/- 0.04%, respectively); the extracted glutamine is stable in TCA for at least 7 days without neutralization when stored at -70 degrees C. Fluorometric analysis of glutamine required only a small quantity of plasma (25 microL) or tissue (200 mg) and is a convenient method for quantifying this important amino acid.

Drug Stability↗

13-cis-retinoic acid and interferon alpha-2a: effective combination therapy for advanced squamous cell carcinoma of the skin.

BACKGROUND: Retinoids (vitamin A derivatives) and interferon-alpha (IFN-alpha) are potent regulators of malignant cell differentiation and proliferation, and both have immunomodulatory and antiangiogenesis activity. A large body of preclinical and clinical data supports the use of combination therapy with 13-cis-retinoic acid (13-cRA) and IFN-alpha in patients with squamous cell carcinoma of the skin. This carcinoma is an extremely common and frequently severely disfiguring cancer, for which about 10% of patients remain uncured following standard local therapy. PURPOSE: Our purpose was to test whether a 20% or greater complete response rate could be achieved using a combination of these two agents in patients with advanced squamous cell carcinoma of the skin in whom local therapy had failed or was unfeasible or who had regional and/or distant metastases. METHODS: Thirty-two patients with heavily pretreated, advanced inoperable cutaneous squamous cell carcinoma of the skin were given a combination of oral 13-cRA (1 mg/kg per day) and subcutaneous recombinant human IFN alpha-2a (3 million units per day) for at least 2 months, unless disease progressed earlier, in a phase II trial. RESULTS: Nineteen (68%) of the 28 assessable patients responded, seven (25%) of whom had complete responses. Response rates were 93% (13 of 14) in patients with advanced local disease (six complete responses), 67% (four of six) in patients with regional disease (no complete responses), and 25% (two of eight) in patients with distant metastases (one complete response). The relationship between decreased response rate and increased extent of disease was highly statistically significant (P less than .005, chi-square test). The median response duration was greater than 5 months. No life-threatening toxic effects occurred in assessable patients treated with this combination, although dose reductions were required in 18 patients. The major limiting side effect in this elderly patient population (median age, 67 years) was cumulative fatigue. CONCLUSION: These results indicate that combined systemic therapy with 13-cRA and IFN alpha-2a is highly effective in patients with advanced squamous cell carcinoma of the skin.

Aged↗

Substituting ornithine for arginine in total parenteral nutrition eliminates enhanced tumor growth.

Total parenteral nutrition (TPN) may enhance the growth of some tumors: this enhanced growth is associated with an increase in the erythrocyte polyamine levels. The effect of arginine in TPN on tumor growth was compared with ornithine using rats with a transplantable Ward colon tumor. The relationship of circulating arginine, ornithine, glutamine, and polyamines with tumor growth was investigated. For rats fed chow ad libitum, increasing tumor weights were associated with a linear decrease in the plasma arginine levels which was consistently lower than that of age-matched non-tumor bearing (NTB) rats; ornithine and lysine levels were not affected. Subsequent experiments suggest that plasma glutamine levels were also lower in tumor bearing rats. Pair-fed NTB rats had reduced arginine but not glutamine levels in plasma. TPN regimens with arginine or with ornithine substituted for arginine at two levels (equimolar [Orn-Em] or isonitrogenous [Orn-IN]) were given to colon tumor bearing rats for 8 days. The final tumor weight of rats which received the arginine-containing regimen (19.8 +/- 5.7 g, n = 4) (P less than 0.05) was significantly greater than the tumor weight of rats fed chow ad libitum (12.1 +/- 3.3 g, n = 6). The final tumor weights of Orn-EM (11.2 +/- 2.6 g, n = 4) or Orn-IN (11.6 +/- 0.8 g, n = 6) were similar to the chow-fed controls. The plasma arginine levels were elevated, compared with the control, when arginine was present in the regimen. The plasma arginine levels of rats which received Orn-EM or Orn-IN were lower than the controls. The plasma ornithine levels were not affected by arginine in the regimen but were elevated with increasing levels of ornithine in TPN. Plasma glutamine levels were decreased when arginine was present in the regimen but were elevated when ornithine was substituted for arginine. Erythrocyte putrescine was increased when either arginine or ornithine was included in the TPN regimens. These results demonstrate that while arginine in a parenteral regimen stimulates tumor growth, substituting ornithine for arginine in TPN does not enhance the growth of a transplantable colon tumor.

Amino Acids↗

Complications associated with indwelling catheters.

Between 1983 and 1985, 170 consecutive patients received doxorubicin-containing adjuvant chemotherapy through central venous catheters, and four via a long indwelling catheter in the antecubital fossa. The objective of this retrospective study is to determine the acute and chronic complications associated with indwelling catheters. Ninety-four (56%) patients did not experience any complications. The incidence of acute complications was 2%, which included three pneumothorax. Twenty-nine (17%) patients experienced chronic complications. Of those, 20 (12%) developed infectious complications, and 9 (19%) developed thrombus. In addition, 12 (7%) developed multiple complications, and 32 (19%) patients had other local complications at the catheter site, which included allergic reactions and catheter breakage. Each of these complications was resolved with appropriate treatment. None of the patients died from complications of the indwelling catheter.

Bacterial Infections↗

Extramammary Paget's disease of the perineal skin: role of radiotherapy.

We have reviewed our treatment results in 65 patients with extramammary Paget's disease arising in the vulva, perianal area, or scrotum. In 30 patients with primary disease, positive surgical margins were found in 53%, and there was an actuarial local recurrence rate of 40% within 5 years. The median follow-up period for primary extramammary Paget's disease patients treated with surgery alone was 198 months, and none died of this disease. Three patients treated with definitive radiotherapy were without recurrence at 12, 21, and 60 months after 56 Gy of supervoltage x-rays. In 22 patients with extramammary Paget's disease and associated adnexal or rectal adenocarcinoma, nine treated with surgery alone had a 75% local control rate. Three patients treated with surgery and adjuvant radiotherapy all had local control; of two patients treated with radiotherapy alone, one had persistent adenocarcinoma. The median survival for all patients with extramammary Paget's disease and adenocarcinoma was 22 months. We conclude that patients with extramammary Paget's disease have excellent survival but that local recurrence and morbidity from surgery, especially in the elderly, can be high. Radiotherapy greater than 50 Gy as primary treatment for extramammary Paget's disease in those medically unfit for surgery, or as an alternative to further surgery for recurrence after surgery and for anyone wishing to avoid mutilating surgery, is indicated. For those with adenocarcinoma and extramammary Paget's disease, the use of adjuvant postoperative radiotherapy in doses greater than 55 Gy is indicated because of the high risk of local recurrence after surgery alone.

Adenocarcinoma↗

Laparoscopic feeding jejunostomy tube in oncology patients.

Laparoscopic-guided feeding jejunostomy tubes are being utilized in two specific groups of patients: (i) patients with resectable or locally advanced adenocarcinoma of the pancreas treated on a protocol of preoperative chemoradiation, who may require nutritional support, and (ii) patients with metastatic or obstructing foregut tumours who require a route for delivery of fluid and medication. The technique, rationale and results for our first 17 patients who underwent laparoscopic placement of a tube jejunostomy are described. Laparoscopic feeding tube placement is a safe and cost-effective method to gain enteral access and stage the oncology patient's disease. This procedure is less invasive than standard surgery for tumour staging and feeding tube placement, and facilitates formula advancement and the patient's early hospital release without morbidity or mortality.

Aged↗

Human colonic sulfomucin identified by a specific monoclonal antibody.

Since the 1960s, the loss of sulfomucin from colonic epithelium has been considered to be an indicator of an early stage of carcinogenesis; yet, the biochemical basis for this phenomenon has never been elucidated. We recently prepared a monoclonal antibody (mAb) 91.9H that immunoprecipitates the normal colonic mucins metabolically incorporating [35S]-sulfate. This mouse IgG1 antibody did not cross-react with colon carcinoma mucins that lack sulfate groups. Using normal colonic epithelia unlabeled or radiolabeled with [35S]sulfate and [3H]glucosamine, we purified a high molecular weight glycoprotein that reacts with mAb 91.9H. This was achieved by a combination of DEAE-cellulose anion-exchange chromatography, consecutive treatments with chondroitinase ABC plus heparitinase and with sodium dodecyl sulfate plus 2-mercaptoethanol, and gel filtration on Sepharose CL-2B in the presence of 8 M urea. Antibody reactivity was found in acidic but not neutral high molecular weight glycoproteins. After Sepharose CL-2B fractionation, the mAb 91.9H-reactive fractions consisted of a component with an approximate molecular weight of 500,000-900,000. A purified sulfomucin contained protein, neutral sugar, amino sugar, sialic acid, and sulfate in an approximate ratio of 2.5:1.0:1.1:0.4:0.5. The polypeptide portion was rich in hydrophilic amino acids, particularly threonine. Binding of mAb 91.9H in solid-phase assays was inhibited to 50% by purified normal colon acidic mucin at doses of 5-50 micrograms/ml, depending on different preparations. Various glycosaminoglycans or sulfatides did not show inhibitory activity. Sulfomucin reactivity with mAb 91.9H, as determined by solid-phase-binding inhibition and by dot blot assays, was significantly reduced by chemical desulfation of sulfomucins with anhydrous hydrochloric acid, suggesting that sulfate groups served as a portion of the immunochemical determinant for this antibody. Sulfate residues were apparently linked to alkaline-sensitive carbohydrate chains, but alkaline-released carbohydrate chains did not react with mAb 91.9H. Immunohistochemical examinations showed that mAb 91.9H bound normal colonic epithelial cells, which also stained with high-iron diamine, more strongly than it bound colon carcinoma cells.

Antibodies, Monoclonal↗

Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy.

Patients with locoregional gastric carcinoma often die because of the low rates of curative resection and frequent appearance of distant metastases (mainly peritoneal and hepatic). To evaluate the feasibility of preoperative and postoperative chemotherapy, 25 consecutive previously untreated patients with potentially resectable locoregional gastric carcinoma received two preoperative and three postoperative courses of etoposide, 5-fluorouracil, and cisplatin (EFP). Ninety-eight courses (median, five courses; range, two to five courses) were administered. Six patients had major responses to EFP. Eighteen patients (72%) had curative resections, and three specimens (12%) contained only microscopic carcinoma. At a median follow-up of 25 months, the median survival of 25 patients was 15 months (range, 4 to 32+ months). Peritoneal carcinomatosis was the most common indication of failure. One patient died of postoperative complications, but there were no deaths due to chemotherapy. EFP-induced toxic reactions were moderate. Preoperative and postoperative chemotherapy for locoregional gastric carcinoma is feasible, and additional studies to develop regimens that could result in 5% to 10% complete pathologic responses may be warranted.

Adenocarcinoma↗

Lactose-binding lectin expression in human colorectal carcinomas. Relation to tumor progression.

Lactose-binding lectins having Mr values of approximately 14,000 (L-14.5) and approximately 35,000 Da have been found in a variety of vertebrate tissues, including normal intestine and colon, and in several types of tumors such as colon carcinomas. To determine the clinical relevance of such lectins in human colon cancer, specimens from 46 patients with colorectal carcinoma of identified Dukes' stages were selected and analyzed for the presence and amount of lactose-binding lectins by immunoblotting using a polyclonal, rabbit anti-lectin antibody followed by binding of 125I-labeled anti-rabbit IgG. The amount of a lectin having an Mr value of approximately 31,000 Da (L-31) varied among the specimens. The levels of L-31 lectin in colorectal cancer specimens from primary tumors of patients with distant metastases (Dukes' stage D) were significantly higher than were those from patients without detectable metastases (Dukes' stages B1 and B2). In contrast, among the various specimens the variation in the level of the L-14.5 lectin was smaller, and there was no correlation between the amount of this lectin and cancer stage. Immunohistochemical staining of thin sections of colorectal tumor specimens using antibodies specific for either L-31 or L-14.5 lectin revealed that the two were located at different places, the L-31 lectin primarily within the cytoplasm of carcinoma cells, and the L-14.5 lectin associated with secreted material. These results indicated that the relative amount of the L-31 lectin increases as the colorectal cancer progresses to a more malignant stage.

Colorectal Neoplasms↗