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Biomedical subjects

W A Kokal

Publications and source records attributed to W A Kokal.

At least 19 recordsLinked to original sources

The value of symptom directed evaluation in the surveillance for recurrence of carcinoma of the breast.

Specific postoperative tests used to diagnose recurrent carcinoma of the breast were evaluated for their ability to have an impact on the over-all course of the disease. Sixty-four patients with recurrent or new contralateral primary disease were divided into two groups based on the method of diagnosis. Those patients with a new complaint at an interval between scheduled follow-up visits and who went on to have tests to document a recurrence were categorized as interval follow-up. Those who were seen at a prearranged regular follow-up period and received tests as recommended by the attending physician or surgeon and had a documented recurrence were classified as routine follow-up. Thirteen patients presented with new contralateral primary disease and 51 with metastatic disease (16, bone; 13, lung; 11, local; three, liver, and eight, multiple). The median time to discovery of recurrence from the primary treatment was 29 and 28 months for the interval and routine groups, respectively. Ninety per cent of the failures occurred by 53 months. The survival time after recurrence was significantly greater in those patients diagnosed routinely (p = 0.003). However, the over-all survival time (from primary therapy to death) was only significantly improved for the routine group when the contralateral new primary diseases were included (p = 0.009). The method of diagnosis of a contralateral primary carcinoma was physical examination and mammogram. Strong recommendations for follow-up testing can be limited to mammogram and physical examination.

Breast Neoplasms↗

Sialosyl-Tn. A novel mucin antigen associated with prognosis in colorectal cancer patients.

Colon cancers typically produce mucin. However, it is not known whether tumor mucin plays a biological role in cancer cell behavior. To address this issue, the expression of a mucin-associated antigen, sialosyl-Tn, was examined by immunohistochemical study in 128 primary colorectal carcinoma specimens from 137 patients who underwent curative surgical resection. Antigen expression was correlated with disease-free and overall 5-year survival. Sialosyl-Tn antigen expression occurred in 112 (87.5%) tumors, and was independent of age, gender, tumor location, Dukes' stage, depth of invasion, degree of differentiation, and ploidy status. Survival at 5 years for patients with sialosyl-Tn-negative versus sialosyl-Tn-positive tumors was 100% versus 73% (P less than 0.05) and disease-free survival was 94% versus 73%, respectively (P = 0.12). Although more advanced Dukes' stage, deeper invasion, and aneuploidy were all associated with poorer overall 5-year survival, antigen-negative tumors within each of these groups had much better prognoses than antigen-positive tumors. Multivariate regression analysis revealed that tumor ploidy (P less than 0.001) and sialosyl-Tn expression (P less than 0.05) were the two variables of most importance for predicting both disease-free and overall survival. The authors conclude that sialosyl-Tn expression is an independent predictor of poor prognosis in colon cancer, and therefore suggest that qualitative mucin alterations may reflect important differences in the biological behavior of these neoplasms.

Aged↗

A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver.

Over a 4-year period (1982 to 1986), 91 patients with solitary or multiple metastases from colorectal cancer were stratified, based on findings at laparotomy, to one of three groups and then prospectively randomized to one of two treatment arms within each group. Group A patients had solitary resectable metastases, group B patients had multiple, resectable metastases, and group C patients had multiple, unresectable metastases. Patients were randomized to one of two treatment arms within a group: group A-arm A1: resection only, arm A2: resection and continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUdR); group B-arm B1: resection and CHAI, arm B2: CHAI only; group C-arm C1: CHAI, arm C2: systemic fluorouracil followed by CHAI. Median time to failure (TTF) was 31.8, 11.1, and 8.8 months for groups A, B, and C, respectively. Arm A2 had an improved TTF when compared with arm A1 (P = .03). Median survival correlated with extent of disease and was 37.3, 22.4, and 13.8 months for groups A, B, and C, respectively. Survival was not changed by treatment variation (arms) within each group. Two- and 5-year cumulative survivals for groups A, B, and C were 72.7% and 45.4%; 45.8% and 16.7%; and 31.7% and 3.2%, respectively. In patients with multiple metastases (groups B and C), those patients whose original tumor was a Dukes' B had a significantly improved TTF and survival over those patients whose tumor was a Dukes' C (P less than or equal to .02).

Adult↗

A prospective, randomized double-blind study of the use of antibiotics at the time of mastectomy.

The ability of perioperative cefazolin to reduce the incidence of postoperative wound infection in patients undergoing ablative surgical treatment for carcinoma of the breast was tested in this prospective, randomized, double-blinded study. From May 1983 until December 1985, 118 women were divided into two groups at random. Group 1 consisted of 59 patients and received cefazolin and group 2 was made up of 59 patients who received a placebo. The groups were similar with respect to age, operative procedure, operative time and time to discharge after operation. Three infections occurred among those in group 1 and five among those in group 2 (p = 0.72). The time to onset of infection was delayed in the patients in group 1 versus those in group 2 (17.7 days versus 9.6 days, p = 0.04). Six of eight infections occurred in patients in whom an interval between biopsy and definitive surgical treatment was present. Prophylactic antibiotics in mammary operations did not reduce postoperative wound infections in this study.

Breast Neoplasms↗

Evaluation of a short-stay program for patients undergoing mastectomy.

Two hundred twenty-eight patients were included in a retrospective study to evaluate the morbidity and feasibility of early discharge after mastectomy. Group I (early discharge, n = 75) patients were given pre- and postoperative instruction related to wound and drain care. Group II (concurrent control, n = 44) was given similar postoperative instruction, but received no preoperative teaching. Group III (historical controls, n = 109) underwent surgery during a period of more liberal hospitalization and discharge policies. The groups were similar in age, cultural background, operations performed, and pathologic diagnosis. Length of stay for groups I, II, and III was 5.5 +/- 0.4, 3.5 +/- 0.2, and 8.6 +/- 0.3 days, respectively. Groups I and II had a significantly shorter stay than group III. There was no difference among the groups for the presence of wound erythema, rate of primary healing, seroma formation, or wound infection. The practice of same-day admission and early discharge to limit length of stay for patients undergoing mastectomy is safe and effective.

Breast Neoplasms↗

Natural history and treatment of mucosal melanoma.

Forty-three patients with primary mucosal melanomas seen between 1960 and 1987 were reviewed. There were 17 patients with tumors arising from the head and neck, 17 from the vulva and/or vagina, 8 from the anorectum, and 1 from the esophagus. Twenty-one patients were resected with curative intent. In patients with head and neck tumors, local recurrence was the initial cause of failure in the majority of cases, whereas with tumors arising from the anorectum, vulva, and vagina, systemic recurrence was more common. There were four long-term survivors, and three of these had melanomas less than 1 mm thick with negative regional lymph nodes; no patients with mucosal melanoma less than 1 mm thick developed recurrent disease. Overall, actuarial survival was 64% after 1 year and 23% after 5 years. Mucosal melanoma has a poor prognosis, and adequate resectional surgery affords the only chance of long-term survival.

Actuarial Analysis↗

Tumor DNA content in resectable, primary colorectal carcinoma.

Tumor DNA content was measured in patients with colorectal carcinoma in order to determine whether tumor ploidy was a prognostic indicator independent of standard clinical and pathologic characteristics. One hundred forty-seven patients were analyzed who had their primary resectable colorectal carcinomas resected with curative intent from 1974 to 1981. Aneuploid colorectal cancers (i.e., tumors with abnormal DNA content) tended to be less well-differentiated, to invade the serosa or extend beyond, and to have lymph node metastases rather than diploid tumors (i.e., tumors with normal DNA content). A significantly increased rate of recurrent disease was demonstrated in patients with aneuploid tumors as opposed to those with diploid tumors (46.7% vs. 4.8%, respectively [p less than 0.001]). In addition, patients with aneuploid tumors exhibited a significantly decreased disease-free and overall survival in comparison with patients with diploid colorectal carcinomas. A Cox regression analysis demonstrated that tumor DNA content was the single most important factor in predicting recurrence or death from colorectal carcinoma.

Aged↗

Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial.

A prospective randomized trial was performed in patients with advanced squamous cell carcinomas (SCC) of the oral cavity, larynx, and pharynx to examine the effect of adjuvant postoperative radiation therapy on locoregional recurrence and survival following "curative" resection. Fifty-one patients with stage III or IV SCC treated from 1981 through 1984 were randomized to receive either surgery alone (n = 27) or surgery with postoperative radiation (n = 24). Five patients were excluded from the study after randomization because of ineligibility or protocol violations. Overall recurrence rates of 55.6% and 36.8% were noted in the surgery and surgery with adjuvant radiotherapy arms, respectively (p = NS). This trend towards a higher recurrence rate in the surgery only arm was in part due to the development of lymph node metastases in the contralateral, nonoperated neck. Thus far, no significant differences in either locoregional or overall survival have been noted between the two treatment arms. In this preliminary analysis, adjuvant postoperative radiotherapy does not appear to improve disease-free or overall survival.

Adult↗

Radiographic evaluation for pulmonary metastases in sarcoma patients.

The records of 130 patients with soft tissue and bone sarcomas were retrospectively analyzed to identify the subgroups of patients that would benefit from tomographic studies for pulmonary metastasis. Sixty-six of 96 patients with a normal conventional chest roentgenogram (CXR) had tomography to diagnose pulmonary metastasis. Of the 53 patients who had primary disease and a normal CXR followed by tomography, only 1 (1.9%) had metastases identified on tomograms. Of the 13 patients who had locally recurrent sarcoma and a CXR plus tomographic studies, 2 (15%) had metastases detected on tomogram only. Tomographic studies detected significantly more sarcoma patients with pulmonary metastasis in the group with locally recurrent disease than in the group with primary disease (P less than 0.05).

Adult↗

Predicting the need for prolonged enteral supplementation in the patient with head and neck cancer.

Nutritional support is an important consideration in the management of the head and neck cancer patient. In our series, characteristics significantly associated with the need for long-term postoperative nutritional support included stage IV cancers, primary pharyngeal tumors, combined treatment utilizing surgery and radiotherapy, and preoperative weight loss of more than 10 pounds. In planning nutritional support, nasogastric tube feeding is appropriate for short-term use. In contrast, gastrostomy tube feeding is preferable for those head and neck cancer patients with a high probability of requiring long-term nutritional support postoperatively.

Body Weight↗

Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the head and neck region.

Our purpose in this study was to determine whether tumor DNA content is a prognostic factor independent of other standard clinical and histologic parameters in squamous cell carcinoma (SCC) of the head and neck region. Tumor DNA content was determined in 76 patients with primary resectable SCC of the oral cavity, larynx, or pharynx who were treated from 1978 to 1984 at the City of Hope. In addition, we measured various clinical and pathologic parameters in all patients. In comparison to patients with diploid SCC, those with aneuploid SCC had significantly decreased relapse-free and overall survival rates (p less than 0.001 for both). A Cox regression analysis demonstrated that tumor DNA content was a prognostic factor independent of all clinicopathologic features examined. By regression analysis, it was the single most important prognostic factor in determining relapse and death from SCC (p less than 0.001 for both).

Aged↗

The inferior trapezius musculocutaneous flap in head and neck reconstruction.

The trapezius musculocutaneous flap based on the descending branch of the transverse cervical vessels has been used to reconstruct a variety of large and complex defects in the head and neck region. Forty-three flaps were performed in 41 patients over a period of 26 months. Excellent reconstruction was achieved in 37 patients. Six total and nine partial flap failures were noted. There were 8 deaths during this time, 2 attributable directly to flap failure. Patient positioning during surgery and the tedious dissection are disadvantageous. The advantages of this flap are its thinness, long reach, and a posterior donor defect. These attributes are ideally suited for certain complex reconstructive endeavors in the head and neck.

Adolescent↗

Transhiatal esophagectomy.

Thirty-six patients underwent resection of the thoracic esophagus without a thoracotomy for the management of cancer of the cervical esophagus (2 patients), middle third and lower third of the esophagus (4 patients and 23 patients, respectively), and the gastroesophageal junction (17 patients). In addition to a total esophagectomy, two patients required a laryngectomy and seven patients had a total gastrectomy. Intraoperative bleeding occurred in three patients. Postoperative complications included subphrenic abscess (Candida) (2 patients), diaphragmatic hernia (1 patient), and salivary fistula (11 patients). Three patients died in the postoperative period from necrosis of interposed colon, pneumonia, and liver failure due to liver metastasis. The average blood loss was 1,300 ml, the duration of surgical procedure was 5.3 hours, and the hospital stay was 21 days. The survival rates at 1, 2, and 3 years were 80 percent, 50 percent, and 33 percent, respectively. Transhiatal esophagectomy can be considered a sound alternative to transthoracic esophagectomy in the management of tumors involving the cervical and lower esophagus. Small lesions of the middle third should also be considered for this procedure, however, bulky lesions of the upper esophagus are better removed by thoracotomy.

Adenocarcinoma↗

Tube feeding enteral nutritional support in patients receiving radiation therapy for advanced head and neck cancer.

A retrospective study evaluated the role of tube feeding enteral nutritional support in patients receiving radiation therapy (RT) for Stage III and IV squamous cell carcinoma of the head and neck. Tube feeding (TF) by either nasogastric, cervical esophagostomy, or gastrostomy route was based on individual physician preference and patient acceptance. TF feeding starting before and continuing through RT (planned TF) was completed in 17 patients, whereas 9 patients did not receive TF until they lost weight during RT (interventional TF). No tube feeding was performed in 63 patients. By the end of RT, the planned TF group lost an average of 4.8% of initial body weight, compared to 7.1% in the no TF group and 9.4% in the interventional TF group. At the end of RT, only 6% of the planned TF group had lost over 10% of initial body weight, compared to 24% of the no TF group and 44% of the interventional group. Excluding patients who continued to lose weight after the end of RT due to rapidly recurrent tumor, 49% of the no TF group had a post-RT nadir weight loss over 10% of initial body weight, compared to 0% of the planned RT group. However, failure to receive the full RT dose and/or lengthy rest periods during RT were just as likely to occur in the planned TF group as in the no TF group. This retrospective review also could not demonstrate improved survival in the planned TF group. Complications, including peptic ulcer disease, aspiration pneumonia, cervical stoma abscess, and hepatic encephalopathy, occurred in 7 of the 26 patients (27%) receiving either planned or interventional TF. We conclude that TF will help minimize weight loss due to side effects of RT for head and neck cancer, particularly when TF is instituted before the onset of significant weight loss due to RT side effects. Survival differences, however, were not apparent.

Body Weight↗

Results of a prospective randomized trial of continuous regional chemotherapy and hepatic resection as treatment of hepatic metastases from colorectal primaries.

One hundred patients were entered on a randomized prospective protocol to evaluate the effectiveness of hepatic resection of single as well as multiple hepatic metastases from colorectal primaries in combination with continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUDR) via the implantable pump (Infusaid, Intermedics Infusaid Inc., Norwood, MA). The eight patients with single metastases were randomized to hepatic resection alone (three patients) or hepatic resection plus CHAI (five patients). The 22 patients with resectable multiple metastases were randomized between receiving CHAI only (12) or CHAI after resection of all metastases (10). Patients who had positive portal lymph nodes (14) were all treated with CHAI. Patients with unresectable metastases (31) were randomized between intravenous 5-fluorouracil or CHAI of FUDR. FUDR was alternately infused every 2 weeks at a dose of 0.1 mg/kg/24 hour escalated to .3 mg/kg/24 hour with heparinized saline as the alternative infusate. The median follow-up of all patients was 20 months. All patients with multiple resectable metastases had at least a partial response (PR) to the CHAI (PR defined as greater than or equal to 50% decrease of the sum of the products of the diameters of the lesions measured on computerized axial tomography scans), and four patients given CHAI only had no metastases in the liver on relaparotomy. Patients with resection and CHAI had a better survival than patients with CHAI only; however, the difference was not significant. Patients with positive portal nodes and CHAI had a lower PR (36%) than patients with unresectable disease treated with CHAI (52%). Patients with positive portal nodes or metastatic disease outside of the liver did significantly worse than patients with unresectable disease treated with CHAI.

Clinical Trials as Topic↗

Tumor DNA content in primary and metastatic colorectal carcinoma.

We performed this study to determine if tumor DNA content was an independent prognostic indicator in patients with primary tumors or hepatic metastases from colorectal cancer. We analyzed tumor DNA content by flow cytometry from paraffin-embedded specimens in 133 patients. In the 77 patients with primary colorectal cancer who had had "curative" resection, DNA content of the tumor was an independent prognostic indicator in predicting both relapse-free and overall survival. Logistics regression analysis demonstrated that aneuploidy, ie, tumors that exhibited a population of cells with an "abnormal" DNA content, was the single most important variable in predicting both recurrence and death from disease, even more important than stage. However, in 56 patients with hepatic metastases from colorectal cancer, the DNA content of the liver metastases bore no relationship to the patients' survival or their response to therapy. These data suggest that tumor DNA content is an important prognostic indicator in patients with primary colorectal carcinoma but does not reflect the natural history of patients with liver metastases.

Colonic Neoplasms↗

Continuous hepatic artery infusion with an implantable pump: problems with hepatic artery anomalies.

The implantable pump for continuous hepatic artery chemotherapy requires even distribution of the chemotherapy to the whole liver for maximum efficacy. The hepatic arterial supply and its anomalies must be understood to achieve this. We reviewed the arteriograms of 100 patients who were potentially arterial perfusion candidates. Fifty percent had normal hepatic arterial anatomy. Twenty percent had a replaced or accessory right hepatic artery and 17% had an accessory or replaced left hepatic artery. The methods used to implant the pump catheters in these anomalous situations were reviewed. The use of dual catheter pumps for arterial anomalies has necessitated extended operative time and increased the risk of uneven hepatic perfusion. Catheterization of the portal vein, which is technically simpler, deserves consideration as an alternative in the presence of an aberrant arterial system.

Antineoplastic Agents↗

The efficacy of total parenteral nutrition in malnourished tumor-bearing rats.

The current study was designed to compare the efficacy of total parenteral nutrition (TPN), provided either before or after tumor removal, in replenishing protein stores in the malnourished tumor-bearing (TB) host. Fisher 344 rats bearing a transplantable methylcholanthrene (MCA)-induced sarcoma were used. After the animals were cachectic from their tumor, a central venous catheter was inserted. At the time of catheter insertion, the animals were randomized into two groups. Group I rats had the TB hindlimb amputated whereas Group II rats had the nontumor bearing (NTB) hindlimb amputated. After amputation, all animals were given TPN for 10 days then sacrificed. The results demonstrated that TB rats (Group II) had a significantly decreased tumor-free carcass weight in contrast to nontumor bearing rats (Group I). Furthermore, the TB animals had a significantly increased body weight gain after completion of TPN. This difference in body weight proved to be due almost entirely to the weight of the growing tumor. Compositional analysis revealed a significantly decreased protein stores and significantly increased fat stores of both the carcass and liver of the TB animals compared to those which the tumor had been resected. The results of the data suggest that TPN given to the sarcoma-bearing animal after tumor removal is better utilized for replenishing protein stores than when it is provided before removal of the tumor.

Animals↗