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Biomedical subjects

H Nava

Publications and source records attributed to H Nava.

At least 19 recordsLinked to original sources

Expression of genes related to activity of oxaliplatin and 5-fluorouracil in endoscopic biopsies of primary esophageal cancer in patients receiving oxaliplatin, 5-flourouracil and radiation: characterization and exploratory analysis with survival.

With a goal of identifying relations between gene expression and response (mucosal or pathological) or survival in esophageal cancer patients (stages II to IV) receiving oxaliplatin, 5-fluorouracil (5FU) and radiation, we measured in endoscopic primary tumor biopsies from 38 patients, the expression of seven genes (gammaGCS, gammaGT, MRP-2, ERCC-1, XPA, TS and DPD) prior to treatment, 1 week following oxaliplatin alone and at the end of the combined radio-chemotherapy cycle using real time QRT-PCR. A higher pretreatment level of XPA was related to shorter survival with a hazard ratio of 2.43 (90% confidence interval 1.09 to 5.43) using Cox regression modeling. However, multivariate analysis with a Cox model indicated low expression of XPA or TS and combined stages II and III had a higher probability of survival (for XPA: hazard ratio 3.0 and 90% C.I. of 1.3 to 6.9, with adjustment for stage included; for TS: hazard ratio is 1.98 with 90% C.I. of 0.94 to 4.20. The expression of TS, gammaGCS, ERCC-1 and MRP-2 declined from D 1 to the end of the cycle (p<0.05, sign test). A validation and further understanding of the findings need to be carried out in a larger study with a more homogeneous population of patients.

Aged↗

Cardiac function after chemoradiation for esophageal cancer: comparison of heart dose-volume histogram parameters to multiple gated acquisition scan changes.

In this paper we determine if preoperative chemoradiation for locally advanced esophageal cancer leads to changes in cardiac ejection fraction. This is a retrospective review of 20 patients treated at our institution for esophageal cancer between 2000 and 2002. Multiple gated acquisition cardiac scans were obtained before and after platinum-based chemoradiation (50.4 Gy). Dose-volume histograms for heart, left ventricle and left anterior descending artery were analyzed. Outcomes assessed included pre- and postchemoradiation ejection fraction ratio and percentage change in ejection fraction postchemoradiation. A statistically significant difference was found between median prechemoradiation ejection fraction (59%) and postchemoradiation ejection fraction (54%) (P = 0.01), but the magnitude of the difference was not clinically significant. Median percentage volume of heart receiving more than 20, 30 and 40 Gy were 61.5%, 58.5% and 53.5%, respectively. Our data showed a clinically insignificant decline in ejection fraction following chemoradiation for esophageal cancer. We did not observe statistically or clinically significant associations between radiation dose to heart, left ventricle or left anterior descending artery and postchemoradiation ejection fraction.

Aged↗

Should preoperative, post-chemoradiotherapy endoscopy be routine for esophageal cancer patients?

Chemoradiation therapy is used widely for locoregional esophageal cancer. Patients with persistent disease may benefit from surgery. Preoperative esophagoscopy can identify persistent tumor but its accuracy is uncertain. The primary objective of this study is to assess the extent of agreement between esophagoscopy and surgical pathology in patients treated with neoadjuvant chemoradiation. A retrospective chart review of patients who underwent chemoradiation, preoperative endoscopy and surgery from January 1996 to December 2002 was performed. Cohen's kappa statistic was used to measure the degree of agreement between findings at endoscopic biopsy and surgical pathology. Thirty cases were identified. All patients received chemoradiation followed by surgical resection. There was insufficient agreement between tumor size (kappa 0.25, standard error 0.17, P = 0.07) and appearance (kappa 0.19, standard error 0.18, P = 0.14). Preoperative endoscopy revealed atypia/inflammation in 15 cases and dysplasia in eight. Of these 23 cases, 11 were adenocarcinomas at surgery. Only nine patients had concurrence between surgical pathology and endoscopy. The positive and negative predictive values of esophagoscopy for identifying residual tumor were 100% and 11%, respectively. Our data suggests that after chemoradiation, esophagoscopy is unreliable for excluding residual disease. The roles of other modalities need to be explored.

Adenocarcinoma↗

Cystic neoplasms of the pancreas--a review.

Cystic neoplasms of the pancreas are rare entities, representing approximately 5% to 10% of all pancreatic malignancies. Seventy-five percent to 90% of all cystic lesions of the pancreas are pancreatic pseudocysts. Thus cystic neoplasms of the pancreas can be easily misdiagnosed and inappropriately treated by drainage. A persistent cystic lesion in the pancreas may pose a considerable diagnostic and therapeutic dilemma for the practicing clinician. This article reviews the various cystic neoplasms of the pancreas and their distinction from pancreatic pseudocysts.

Cystadenocarcinoma, Mucinous↗

Endoscopic laser treatment for palliation of colorectal adenocarcinoma.

Fifty-three patients were treated for palliation with endoscopic neodymium yttrium aluminum garnet (Nd:YAG) laser for colorectal carcinoma at Roswell Park Cancer Institute. There were 25 females and 28 males. The mean age of the patients was 76 years. Thirty-eight tumours were primary and 15 recurrent. The level of the lesions from the anal verge ranged from 2 to 50 cm, with a mean of 10 cm. Eighty-four percent of the lesions were rectal carcinomas within 15 cm of the anal verge. Lesion length ranged from 1.5 to 12 cm with a mean of 5 cm. The number of laser treatments ranged from 1 to 17 with a mean of 3. The duration of treatments ranged from 25 to 90 min with a mean of 35 min. The mean number of joules per treatment was 5093. Eight patients (15%) developed complications. There were no mortalities. The success rate for treating bleeding, the most frequent presenting symptom, was 93%. The overall success rate of patients improved by laser treatment was 79%. Patients who were improved by therapy had a median survival of 18 months versus those not improved who had a median survival of 3 months (P = 0.01). The use of the Nd:YAG laser for palliative treatment of patients with colorectal carcinoma is safe, effective and associated with no mortality.

Adenocarcinoma↗

Accuracy of colonoscopy for the detection of colorectal polyps.

The findings at colonoscopy were compared with the pathologic findings of the surgical specimen in 235 patients who underwent a colon resection for a primary colorectal neoplasm from January 1980 to December 1987 at Roswell Park Cancer Institute. Seven patients (3 percent) were found to have synchronous primary colon carcinomas, and 100 patients (43 percent) were found to have synchronous adenomatous polyps identified by colonoscopy and/or pathology. In patients with polyps 10 mm or greater in diameter, the findings on colonoscopy agreed with the pathology report 96 percent of the time. When polyps of all sizes were included, with many less than 5 mm in diameter, colonoscopy agreed with the pathology in 89 percent of patients. When only the area of the colon resected was used to determine the ability of colonoscopy to locate polyps, 58 percent of polyps of all sizes were located. The majority of the missed polyps were adjacent to a carcinoma. One cecal carcinoma was not seen by colonoscopy because of technical inabilities to reach the cecum. A second carcinoma (20 mm x 17 mm) was not seen at the splenic flexure.

Colectomy↗

Laser palliation for colorectal carcinoma.

A review was conducted of 27 patients with colorectal carcinoma treated palliatively with endoscopic neodymium:yttrium-aluminium-garnet (Nd:YAG) laser. There were 25 rectal carcinomas and 2 primary invasive sigmoid colon carcinomas. Of the 25 rectal carcinomas, there was 1 carcinoma in situ, 16 primary cancers, and 8 recurrent rectal carcinomas. The level of the lesions from the anal verge ranged from 0 to 25 cm, with a mean of 7.2 cm. The length of the lesions ranged from 1.5 to 8.5 cm, with a mean of 5 cm. The mean number of Nd:YAG laser treatments was three, with a range from one to nine. The duration of the treatments ranged from 30 to 90 minutes, with a mean of 40 minutes. Four of 27 patients (15%) developed complications. The success rate in terms of the relief of symptoms was established in 23 of the 27 patients.

Aged↗

Localization of endogenous beta-galactoside-binding lectin in human cells and tissues.

A rabbit antiserum raised against the 14.5-kilodalton (kDa) subunit of human splenic galaptin was used to probe protein blots of several tissue extracts. For all tissues examined, the only immunoreactive species detected was a 14.5-kDa polypeptide. This antiserum and a rabbit antiserum raised against native lung galaptin were used in immunohistochemical assays to determine the localization of galaptin in selected tissues and cells. In normal colon, galaptin was found prominently in the basement membrane and in the stroma. The cytoplasm of epithelial cells stained lightly for galaptin whereas mucous granules and secreted mucin were uniformly negative for galaptin. Hemagglutination inhibition assays also failed to demonstrate an interaction between galaptin and mucin. Macrophages stained conspicuously for galaptin in colonic and cutaneous tissue as did some capillary walls. In cutaneous tissue, the extracellular matrix and hair follicle cells contained abundant galaptin. Galaptin was absent in basal cell carcinoma and associated stroma. Galaptin was found throughout the cytoplasm of carcinoma cells of gynecologic origin present in effusions. Protein blot analysis of extracts of extracellular matrix synthesized in vitro by endothelial cells confirmed the presence of galaptin in matrix. The results show that: (1) galaptin is variably expressed by different cells and tissues; (2) its cellular location is not restricted to the cell surface; (3) galaptin is not associated with normal mucin; (4) the extracellular matrix is a major site of galaptin deposition, and (5) some malignant tissue may be characterized by a deficiency of galaptin.

Animals↗

A phase II trial of 5-fluorouracil, doxorubicin, mitomycin C, and leucovorin in advanced gastric carcinoma.

To determine the feasibility and toxicity of combining leucovorin (CF) with a 5-fluorouracil (5-FU) combination chemotherapy regimen currently accepted by many as standard treatment for gastric cancer, CF (500 mg/m2) was administered in combination with the Georgetown 5-FU, doxorubicin, and mitomycin C (FAM) regimen. Thirty-two patients with advanced adenocarcinoma of the stomach were evaluable for toxicity and 26 patients with measurable disease were evaluable for response. Fifty-four percent of patients were previously treated with chemotherapy or radiation therapy. The response rate was 38% (95% confidence interval, 21% to 59%). The median duration of response was 6 months (range, 2 to 23+ months). The estimated median survival time was 6.8 months for patients with measurable disease and 11.5 months for all 32 patients. Although diarrhea is dose limiting when 5-FU and CF are administered weekly for 6 of 8 weeks, diarrhea occurred rarely on this combination regimen with 5-FU and CF administered only 4 of every 8 weeks. The dose-limiting toxicity of FAM-CF was cumulative myelosuppression, which also occurs with the standard FAM regimen. As a result, the administered dose intensity of 5-FU decreased as patients continued on study. Thus, a randomized comparison of FAM with FAM-CF would not determine whether CF modulation increases the efficacy of 5-FU when it is administered in optimal doses to patients with gastric cancer.

Adult↗

Endoscopic surveillance of patients following a curative resection for colorectal cancer.

From 1974 to 1985, 161 patients were followed by at least one colonoscopy following a polypectomy for an adenomatous polyp. These patients had had a previous curative resection performed for colorectal carcinoma. The median follow-up time after surgery was 54 months. A polyp within 65 cm from the anal verge or from a permanent colostomy was considered detectable by the flexible sigmoidoscope. Seventy-one patients (44%) were found to have adenomatous polyp(s) within 65 cm during the follow-up period. This incidence was influenced by the type of colorectal resection performed. In 36 of 41 patients (88%) undergoing a right hemicolectomy, the adenomatous polyp(s) was found within 65 cm from the anal verge. This was an incidence statistically and significantly higher than the incidence in patients undergoing other types of surgical resections. There were no differences in age, sex, or Dukes' stages according to the type of surgical resection performed. In summary, the present study demonstrates that there is a role for postoperative surveillance by the 65 cm flexible sigmoidoscope. This surveillance can be performed with great safety especially in patients following a right hemicolectomy; significantly more of these patients have adenomatous polyps within reach of the 65 cm flexible sigmoidoscope.

Adult↗

Follow-up colonoscopy in patients with colorectal adenomatous polyps.

Multiple follow-up colonoscopies were performed in 44 asymptomatic patients after polypectomy of colorectal adenomatous polyps. Twenty-six patients (59%) developed new adenomatous polyps. In 81% the new polyps were located in the same segment of the colon where a previous polyp had been totally removed. Polyps removed during follow-up, compared with the initial polyps, revealed significantly more benign and smaller polyps. The number of initial polyps together with occurrence of atypia were factors determining a short time interval for developing new adenomatous polyps. The mean time for developing a 5-mm or larger polyp was significantly longer than polyps less than 5 mm in diameter.

Adenoma↗

The value of colonoscopic surveillance after curative resection for colorectal cancer or synchronous adenomatous polyps.

Between 1975 and 1984, 270 patients underwent a potentially curative resection for colorectal carcinoma. One hundred eighty-eight patients (70%) underwent preoperative colonoscopy, of which 129 patients (69%) were followed up with at least two postoperative colonoscopies. In 91 patients (70%), preoperative colonoscopy revealed no synchronous adenomatous polyps or cancer. Synchronous adenomatous polyps were found in 35 patients (27%), and three patients (2.3%) had a synchronous invasive cancer. Nineteen (54%) of the 35 patients with synchronous adenomatous polyps developed metachronous adenomatous polyps during the follow-up period compared with 24 (26%) of 91 patients without synchronous adenomatous polyps. The median interval to the development of metachronous adenomatous polyps was 19 months, and all of these polyps were 1 cm or less in size. Patients with synchronous adenomatous polyps less than 30 cm from the primary lesion (68%) developed metachronous polyps more often than did patients whose synchronous adenomatous polyps were more than 30 cm from the primary lesion (37%). Preoperative colonoscopy is important for determining synchronous pathology and identifying patients at risk for metachronous polyps.

Adult↗

Follow-up colonoscopy in patients with colorectal adenomatous polyps.

Forty-four asymptomatic patients with adenomatous colorectal polyps were followed by repeated colonoscopies and subsequent removal of new polyps. The median follow-up time was 34 months (range, 4 to 131 months). Twenty-six patients (59 percent) developed new adenomatous polyps. The recurrence rate was 69 percent in patients with multiple polyps compared with 54 percent in patients with a single polyp. The location of new polyps was in the same colonic segment in 81 percent of the patients, but not at the same site in the colon where a previous polyp had been removed. The histopathology and size of new polyps compared with the initial polyps showed a significant improvement in histopathology toward more benign polyps (P less than 0.02) and smaller polyps (P less than 0.001). In patients who initially had single adenomatous polyps, new polyp(s) were diagnosed after a mean time of 23 months compared with 13.5 months in patients with two or more adenomatous polyps initially. Patients with atypia in initial polyp(s) developed new polyp(s) after a mean time of 11 months compared with 23 months in patients without atypia. The mean time from a colon with no polyps to the diagnosis of a new adenomatous polyp less than 5 mm in size was 11.5 months, which was a statistically significant shorter time than the 19.4 months observed for the development of polyps 5 mm or larger.

Adult↗

Galactoside-binding lectin in human tissues.

Lactose-inhibitable lectin activity has been analyzed by hemagglutination assay in a variety of human tissues and cells obtained at surgery and autopsy. The lectin activity was detected in surgically removed melanoma, sarcoma, colon carcinoma, breast carcinoma, adjacent non-malignant tissues, non-malignant tissues obtained at autopsy and in cells isolated from malignant effusions. Although, on average, malignant tissue had a higher hemagglutinating titer than non-malignant tissue, similar tissues from different individuals varied widely in their apparent lectin content. The lectin was isolated from lung by affinity chromatography and was found to have a native molecular mass of 31,000 daltons and a subunit molecular mass of 14,000 daltons. Utilizing rabbit anti-lung lectin serum in an immunohistochemical assay, the lectin was found to be distributed throughout the cytoplasm of lung epithelial cells. Ouchterlony immunodiffusion analysis confirmed the presence of this lectin in a variety of tissues and in some body fluids. In vitro metabolic radiolabelling experiments showed that the presence of lectin in tissues was most likely due to endogenous synthesis rather than absorption from body fluids. Lectin isolated from several tissues was found to bind to human buffy coat cell receptors.

Electrophoresis, Polyacrylamide Gel↗

A phase II trial of 5-fluorouracil and high-dose intravenous leucovorin in gastric carcinoma.

Twenty-eight patients with advanced measurable gastric carcinoma were treated with leucovorin (dl-CF; folinic acid; dl-5-formyltetrahydrofolic acid) 500 mg/m2 administered as a two-hour infusion and 5-fluorouracil (5-FU) 600 mg/m2 intravenous (IV) push midinfusion. Treatment was administered weekly for 6 weeks followed by a 2-week rest. Twenty-five patients were evaluable for response. Twelve of them had received previous combination chemotherapy that included 5-FU. Median age was 59 years, and median Eastern Cooperative Oncology Group (ECOG) performance status was 2. Three patients had partial responses and two of them had been treated previously with 5-FU. Twelve patients had stable disease. Five of these patients had subjective improvement with improved performance status and/or decreased dysphagia. The 95% confidence interval for response is 3% to 32%. Median survival time for all 28 patients enrolled in the study was 22 weeks. Toxicity was moderate and consisted primarily of diarrhea. Myelosuppression, skin rash, and increased lacrimation also occurred. Plasma concentrations of the active reduced folates, I-CF and 5-methyltetrahydrofolic acid (5-CH3FH4), were greater than the 10 mumol/L levels that potentiate 5-FU activity in in vitro models, for more than four hours in all five patients in whom pharmacokinetics were studied. 5-FU and high-dose dl-CF has activity in patients with gastric carcinoma including patients who had previously progressed on 5-FU-containing combinations. Further study in a larger patient population is necessary to determine the usefulness of this regimen in gastric carcinoma.

Adenocarcinoma↗

Postchemotherapy esophagitis: the endoscopic diagnosis and its impact on survival.

Eighteen cancer patients receiving intensive chemotherapy developed leukopenia, fever, dysphagia, and oropharyngeal soreness. Superficial esophageal ulceration suggestive of esophagitis was demonstrated by radiographic examination in 33% of the patients (5/15). Upper gastrointestinal endoscopy revealed superficial ulceration and white mucosal patches in all patients. There was no morbidity associated with the endoscopic procedures. Sixty-one percent of the patients (11/18) had monilia albicans cultured from the oropharyngeal cavity, and 50% (9/18) had monilia cultured from the esophageal lesions. The evolution of the esophagitis correlated well with the survival of the patients. The monilial esophagitis persisted in six patients who all died within 24 days of systemic moniliasis. After initial improvement five additional patients succumbed; three of them from severe fungal infection. There was resolution of the esophagitis in the remaining seven patients who survived longer. However, two of them had recurrent monilial esophagitis and succumbed to systemic candidiasis. The other five have remained free of esophagitis, their underlying malignancies have remained under control, and so far they have survived an average of one and a half years. Endoscopy is more accurate than radiography in detecting postchemotherapy esophagitis. This complication can be fatal, since it is often followed by systemic candidiasis.

Adult↗

Phase I and pharmacologic studies of intraperitoneal leucovorin and 5-fluorouracil in patients with advanced cancer.

Many patients with gastrointestinal (GI) tumors develop extensive peritoneal and serosal metastasis and/or malignant ascites which respond poorly to available treatments. Twelve patients with tumors confined primarily to the intraabdominal cavity were treated with intraperitoneal (IP) 5-fluorouracil (5-FU) in escalating concentrations (2 to 4 mmol/L) in combination with leucovorin (dl-5-formyltetrahydrofolic acid or folinic acid; dl-CF) in a 2-L volume, either by eight consecutive four-hour dwells or once daily for five days. CF dose was 20.8 or 104 mumol/L. Nine of the patients had pancreatic carcinoma, one had stomach carcinoma, and two had hepatobiliary neoplasms. Median age was 62.5 years and median Eastern Cooperative Oncology Group (ECOG) performance status was 3. Toxicity included mucositis, diarrhea, nausea and vomiting, leucopenia, skin rash, and abdominal pain, and was similar to that previously reported for IP 5-FU used as a single agent. Four episodes of peritonitis occurred, but all patients responded to antibiotics. At the 20.8 mumol/L dose, dl-CF concentration in the peritoneal fluid declined from 10.4 +/- 3.0 3.0 mumol/L at one hour to 4.9 +/- 2.2 mumol/L at four hours, corresponding to a mean absorption half-life of 127 +/- 49 minutes and a mean peritoneal clearance of 13.0 +/- 4.5 mL/min. Decline was biphasic in all but five of the 19 exchanges evaluated. The levels of l-CF (biologically active isomer of dl-CF) were 2.8 +/- 2.5 mumol/L after 60 minutes and 1.2 +/- 0.7 mumol/L after four hours. The peritoneal area under the concentration v time curve (AUC) for 5-FU increased proportionally with dose. For example, the AUC at 2.0 and 3.5 mmol/L was 129 +/- 25 and 201 +/- 23 mmol/L X minute, respectively. However, the maximal peritoneal to plasma AUC ratio was 461 at the 2 mmol/L dose, but decreased with increasing doses as systemic clearance decreased. This regimen was well tolerated in patients with advanced cancer, but must be evaluated further to determine its clinical efficacy.

Abdominal Neoplasms↗