Biomedical subjects

J P Neifeld

Publications and source records attributed to J P Neifeld.

At least 19 recordsLinked to original sources

PubMed1994

p53 tumor suppressor oncogene expression in squamous cell carcinoma of the hypopharynx.

BACKGROUND: Although abnormalities of the p53 tumor suppressor oncogene system are being detected in many human cancers, the frequency and prognostic significance of such events in squamous cell cancer of the head and neck remain unknown. METHODS: Immunohistochemical studies were performed on archival tumor tissue taken from 43 patients with squamous cell carcinoma of the hypopharynx. Statistical analyses examining potential associations between p53 oncoprotein accumulation and various clinicopathologic parameters (including survival) were conducted. RESULTS: Sixteen (37%) tumors demonstrated strong specific staining for p53. Patients whose tumors stained strongly for p53 were significantly younger, presented at a more advanced clinical disease stage, and tended to have increased expression of epidermal growth factor receptor (P = 0.056). There was no correlation between p53 expression and the incidence of multiple primary cancers, tumor grade, DNA ploidy, or percent of S-phase. Median survival times were 11.6 months and 18.0 months for the p53-positive and p53-negative groups (NS). A Cox regression analysis confirmed the lack of significance of p53 in overall survival. CONCLUSIONS: These data suggest that although abnormalities of the p53 oncoprotein are common in this cancer, this finding is of little clinical significance.

Age Factors↗

PubMed1994

Postoperative radiotherapy improves survival in squamous cell carcinoma of the hypopharynx.

BACKGROUND: Postoperative radiation is considered to be "standard of care" therapy for advanced, resectable squamous cell carcinoma of the head and neck. This approach has been supported by retrospective data but has not been validated in randomized clinical trials. PATIENTS AND METHODS: The present analysis examined the clinical course of 110 patients with squamous cell cancer of the hypopharynx treated with surgery alone (n = 65) and postoperative radiotherapy alone (n = 45) between 1966 and 1990. Staging of patients was performed using the 1988 American Joint Committee on Cancer criteria. Cox regression analyses identified clinical and pathologic factors that were significant for disease-free and overall survival. Crude and adjusted cancer-specific survival rates were calculated. RESULTS: The postoperative radiotherapy group presented with more advanced disease than the surgery alone group (stage III and IV combined, 96% versus 77%, P = 0.015). Crude 5-year cancer-specific survival probabilities were 43% for the postoperative therapy group and 27% for the surgery alone group (P = NS). Adjusted 5-year survival rates, correcting for differences in significant prognostic variables between groups, were 18% and 48%, respectively, for the surgery and postoperative radiotherapy groups (P = 0.029). CONCLUSIONS: The addition of postoperative radiotherapy was associated with improved disease-free and adjusted overall cancer-specific survival in patients with advanced hypopharyngeal squamous cancer. The potential survival benefit of postoperative radiotherapy should be addressed in a randomized clinical trial.

Carcinoma, Squamous Cell↗

PubMed1993

Epidermal growth factor receptor expression in squamous cell carcinoma of the hypopharynx.

Expression of the epidermal growth factor receptor (EGFR) has been demonstrated in normal and malignant squamous epithelia. Its presence has been suggested to be important in the pathophysiology and prognosis of epithelial cancers. Archival tumour specimens from 57 patients with squamous cell carcinoma of the hypopharynx were studied using OM-11-951, a new murine anti-EGFR monoclonal antibody which recognizes the receptor on deparaffinized tissue. By visual inspection, 28 (49%) tumours were EGFR negative; 29 (51%) tumours were EGFR positive. While patients whose tumours were EGFR positive were younger, there was no significant correlation with other clinical or pathological variables (including grade and stage). Patients whose tumours were EGFR negative had a median survival of 21 (95% CI 4.3-37.7) months compared with a median survival of 17 (95% CI 11.4-22) months for patients whose tumours were EGFR positive. The difference was not statistically significant. A multiple regression analysis did not demonstrate EGFR status to be important in predicting survival. These data cast doubt on the prognostic significance of EGFR expression in this neoplasm.

Antibodies, Monoclonal↗

PubMed1992

Incompletely resected advanced squamous cell carcinoma of the head and neck: the effectiveness of adjuvant vs. salvage radiotherapy.

Between 1982 and 1988, 441 patients were treated at the Medical College of Virginia for AJC Stage III and IV squamous cell carcinoma of the head and neck. We report here on 84 patients whose tumors were incompletely resected based on histopathological margins of 1 mm or less. Of these 84 patients, 49 were treated with surgery alone and 35 received immediate postoperative irradiation to doses of 50-70 Gy. The two patient groups are comparable with respect to stage of disease, age, male/female and racial ratios. This retrospective analysis, based on follow-up of 24-110 months, gives actuarial locoregional tumor control and survival data. The local control and disease-free survival rates in the combined modality group are significantly superior at the p = 0.0006 and p = 0.0003 levels, respectively, relative to the group treated with surgery alone. Patients in the combined modality group also experienced a significantly improved adjusted and overall survival, p = 0.005 and p = 0.01, respectively. The administration of postoperative irradiation was not associated with an increased rate of complications. The benefit of radiotherapy on survival was only seen when given as postoperative treatment but was lost in patients treated for salvage after tumor recurrence.

Adult↗

PubMed1992

Formal hepatic resection of colorectal liver metastases. Ploidy and prognosis.

Fifty consecutive patients who underwent 52 formal hepatic resections (excluding isolated wedge resections) for metastatic colorectal cancer were analyzed to determine whether DNA content was of prognostic significance. The Dukes' stages of the colorectal primaries were: A (10%), B (20%), C (40%), D (28%), and unknown in 2%. Four patients whose liver metastases were discovered at the time of resection of the primary bowel cancer underwent concomitant liver resection, and the remaining patients underwent delayed resections. The hepatic resections performed were right lobectomy (50%), extended right lobectomy (19%), left lobectomy (13%), left lateral segmentectomy (6%), left lobectomy and right wedge (6%), extended left lobectomy (4%), and right lobectomy and left wedge (2%). The overall morbidity rate was 29%. The in-hospital mortality rate was 9%. As of November 1991, 36 patients have recurred. The 5-year actuarial survival was 28%. Flow cytometry could be performed on 37 archival specimens, 15 of which were found to be diploid whereas 22 were aneuploid. All metastases from Dukes A colorectal primaries demonstrated a diploid DNA content. In addition, there was no difference in actuarial survival between diploid and aneuploid tumors. These data suggest that in selected patients, formal hepatic resection of colorectal liver metastases can be performed with an acceptable morbidity rate, mortality rate, and survival, but ploidy of the resected tumor is not of prognostic significance.

Adult↗

PubMed1991

Benign cartilaginous tumors of the upper airway.

Benign cartilaginous neoplasms of the laryngotracheal apparatus are uncommon clinical entities. Two cases of cartilaginous lesions of the upper airway are reported. Resection with maintenance of upper airway structural integrity is the preferred treatment. Temporary tracheostomy is often necessary and can provide access for stenting of the tracheal repair.

Adult↗

PubMed1991

Diagnosis and management of sacrococcygeal chordoma.

Chordoma is a rare, slow-growing but locally aggressive malignant tumor derived from the primitive notochord and located along the axial skeleton. Between 1973 and 1991, of 15 patients with chordomas treated at the Medical College of Virginia, eight originated in the sacrococcygeal area. There was a median one year interval between the onset of symptoms and diagnosis (range of four months to six years) for this latter group. Two patients had undergone coccygectomies and one patient a lumbar discectomy prior to establishing the correct diagnosis of sacral chordoma. Seven patients underwent resection and one refused therapy. The four patients who had an initial wide radical resection had a longer disease-free survival than the three who underwent local excision. Three of four patients had metastatic disease at the time of death. Early diagnosis and aggressive initial surgical resection are necessary for long-term survival.

Adult↗

PubMed1991

Closure of craniofacial defects after cancer resection.

Resection of malignancies of the upper face and skull base may result in complex bone and soft tissue defects. To better define the optimal management of these defects, we conducted a retrospective review of 75 consecutive patients who underwent closure of 76 craniofacial defects after malignant tumor excision from 1966 to 1990. Wound complications requiring further surgery occurred in 30% of the defects (23 of 76). Wound complications at anterior, temporal, or combined sites were correlated with each method of reconstruction (scalp flap or split thickness skin graft, pedicled myocutaneous flap, and free flap). The presence of a large combined defect involving both frontal and temporal areas was the only significant risk factor for development of a wound complication requiring secondary surgery. These data suggest that anterior or temporal craniofacial defects may be closed with either scalp flaps and split thickness skin grafts or pedicled myocutaneous flaps with reasonable wound complication rates of 16% to 22%. Large combined defects have high wound complication rates (90%) when local tissue is used; therefore, other methods of closure such as free tissue transfer should be strongly considered in these patients.

Facial Neoplasms↗

PubMed1989

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↗

PubMed1989

Soft tissue sarcomas.

Soft tissue sarcomas in infants and children differ from those in adults in clinical presentation, histology, and response to therapy. For rhabdomyosarcoma, the most common sarcoma in children, each primary site has special characteristics that affect both treatment programs and survival rates. Some results are so good, from the standpoint of survival data, that studies are now in progress to evaluate means of reducing treatment morbidity. Other ongoing studies focus on improved protocols for metastatic or recurrent rhabdomyosarcoma. Results thus far in the IRS trials have proven the value of cooperative clinical trials in the management of patients with this disease.

Adolescent↗

PubMed1989

Management of biliary obstruction in patients with unresectable carcinoma of the pancreas.

Clinical and pathologic data from 73 patients with unresectable carcinoma of the pancreas treated from 1980 to 1987 were reviewed to evaluate the efficacy of biliary enteric bypass and percutaneous transhepatic biliary drainage (PTBD) in the treatment of malignant biliary obstruction. Fifty-two patients underwent biliary enteric bypass with no operative deaths and with a 15% operative morbidity. These patients had a median postoperative hospitalization of 12 days. Four patients (8%) eventually developed recurrent jaundice, and three of these were successfully treated with PTBD. The median survival for these 52 patients was 7 months. Twenty-one patients underwent PTBD with an 81% technical-success rate. These patients had a 33% early complication rate and a 33% in-hospital mortality. The median hospitalization was 13 days postdrainage. Of the 14 patients surviving the initial hospitalization, 86% developed late complications requiring 16 hospital admissions and ten emergency room visits for a total of 155 days of hospitalization. The median survival for those patients undergoing PTBD was 4 months from the time of diagnosis and 2 months from the time of catheter drainage. Surgical bypass offers excellent palliation for malignant biliary obstruction with extremely low morbidity and mortality in properly selected patients; PTBD is useful in the treatment of those patients with extensive disease, who are poor surgical candidates, or who have failed previous surgical drainage. There is a role for both of these palliative procedures in the management of patients with biliary obstruction from pancreatic cancer.

Adenocarcinoma↗

PubMed1989

Intraoperative ultrasound of the liver affects operative decision making.

The surgeon operating upon patients with primary or metastatic hepatic cancers must determine if resection is feasible and, if it is, the magnitude of required resection. In an attempt to determine which tests best aid the surgeon in these determinations, the authors prospectively compared preoperative computed tomography (CT) of the liver and intraoperative ultrasound (IOU) in 42 patients with liver tumors who underwent 45 exploratory operations. The primary diseases included colorectal cancer metastases in 27 patients, hepatoma in 11 patients, and metastatic cancers of other origins in 4 patients. In the 42 patients there were 89 identified hepatic lesions that were confirmed to be malignant by resection, biopsy, or continued growth on follow-up CT. The sensitivity of either test for detecting these lesions was 69/89 (77%) for CT and 87/89 (98%) for IOU. Resection was not feasible in 13 patients. Five had extrahepatic disease, 4 had more nodules discovered by IOU, 3 were found by IOU to have involvement of all three hepatic veins by tumor and 1 patient had portal-vein invasion. Alternatively, in four patients tumors thought to involve all three hepatic veins by CT were shown to be free of at least one hepatic vein, thereby permitting resection. In one patient who had been previously operated upon, a tumor thought to involve the remaining right hepatic vein was seen to be free of the vein, also permitting resection. Regarding the extent of resection, IOU was also helpful. Lesser procedures than anticipated were proved possible by IOU in seven patients. A more extensive resection was shown to be necessary by IOU in two patients. Thus, IOU affected the operative management in 22 of 45 operative episodes (49%). It was conclude that IOU is superior to both preoperative CT and surgical exploration in assessing both the feasibility and the extent of resection required for primary and secondary hepatic cancers. In the authors' experience, IOU is the most sensitive indicator of number of lesions present in the liver. In addition, the ability of IOU to determine hepatic venous anatomy is a helpful adjunct in determining resectability of liver tumors.

Adult↗

PubMed1989

The potential of hormone receptors in the treatment of various cancers.

Breast cancer, prostate cancer, endometrial cancer, and lymphocytic leukemias may possess steroid hormone receptors that can predict a high probability of response to the appropriate hormone when the receptor is present. The presence or absence of receptor may also be an important prognostic variable and may aid in the selection of patients for appropriate adjuvant therapy. Although putative receptors have been described in many other tumors, their clinical significance is questionable because these tumors generally do not respond to hormonal therapy. In the future, steroid receptors may enable us to target drugs, radioisotopes, or other molecules to tumors by linking these drugs to steroid hormones.

Female↗

PubMed1989

Management of desmoid tumors.

Desmoid tumors are rare, being less than 0.03 per cent of all neoplasms. Because of scarcity of data and relatively small numbers of patients, optimal treatment remains controversial. In this report, our experience with 36 patients evaluated and treated from 1960 to 1987 is analyzed. The most common primary site was the wall of the chest (ten); eight tumors originated in the abdominal wall. Nine patients had a history of previous trauma, and eight of these were women. Thirty-two patients had wide local excision and two had amputations. Clear margins were obtained in only 22 patients despite an attempt at wide resection in all instances. With a mean follow-up period of 41 months and a median of 24 months, only one of 22 patients with negative histologic margins had recurrence of tumor. Among the 11 patients with positive margins, four received postoperative radiation therapy and two remain disease-free; of the seven remaining patients with positive margins, three had recurrences. One patient with unresectable disease was treated with tamoxifen with regression of tumor and remains alive 15 months later. These data suggest that the best treatment of desmoid tumors remains resection with a clear margin of normal tissue surrounding the tumor. Adjuvant radiotherapy did not appear to decrease the rate of local recurrence.

Actuarial Analysis↗

PubMed1988

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↗

PubMed1988

Principles in the management of pediatric intestinal leiomyosarcomas.

Primary intestinal leiomyosarcomas in children are unusual tumors with little known about their natural history. Two patients (aged 9 and 10 years) with leiomyosarcoma of the jejunum treated at our institution are reported and added to the 20 other patients reported in the literature. The first patient had a grade 1 leiomyosarcoma completely resected, received no additional therapy, and remains alive with no evidence of disease 14 years later. The second patient presented with a perforated grade 2 leiomyosarcoma which was incompletely resected; he received combination chemotherapy with an initial good response, but eventually died from sarcomatosis 7 years after initial diagnosis. The 22 cases of pediatric intestinal leiomyosarcoma presented more commonly with obstruction or perforation, were able to be completely resected more often, and appear to have a better prognosis than in adults. Thus, intestinal leiomyosarcomas in children appear to have a natural history different from that of the same tumor arising in adults.

Child↗

PubMed1987

Small bowel metastases from primary carcinoma of the lung.

Although about half of all patients with carcinoma of the lung have metastases at initial presentation, only nine with metastases to the small bowel have been previously reported. This study was performed to determine the incidence of occult and clinically apparent metastases of lung cancer to the small intestine. Small bowel metastases were present in 46 of 431 patients with primary lung cancer who underwent autopsy during an 11-year period. These patients had an average of 4.8 metastatic sites. Small bowel metastases were present in 12 of 31 (39.0%) patients with large cell carcinoma, 13 of 108 (12.3%) with adenocarcinoma, six of 73 (8.0%) with small cell carcinoma, 15 of 199 (7.5%) with squamous cell carcinoma, and none of 20 with undifferentiated carcinoma. During the same interval, six of 78 patients undergoing small bowel resection for metastatic tumor had lung cancer primaries. Among the nine previously reported clinical cases of small bowel metastases and the six in this series, 14 were operated upon for small bowel perforation and one for obstruction. Nine patients died perioperatively, and no patient survived longer than 16 weeks. These data demonstrate that the incidence of lung cancer metastases to the small bowel is higher than is clinically apparent. Lung cancer metastases to the small bowel often present as intestinal perforation and indicate a poor prognosis; surgery is indicated for palliation.

Adenocarcinoma↗

PubMed1987

Gastrointestinal sarcomas. Analysis of prognostic factors.

Clinical and pathologic data from 51 patients with primary sarcomas of the gastrointestinal tract treated from 1951 through 1984 were reviewed to determine clinical presentation, histologic features, treatment, and prognostic factors. The most common signs and symptoms were abdominal pain (62%), gastrointestinal bleeding (40%), and/or abdominal mass (38%). The primary site was stomach in 50%, small bowel in 30%, colorectum in 15%, and esophagus in 5%. Virtually all the sarcomas were leiomyosarcomas. Distribution was uniform among the three histologic grades; although 88% of Grade 1 tumors could be completely excised, only 35% of Grade 3 tumors could be completely resected. The 5-year survival rate was 75% for Grade 1 tumors, 16% for Grade 2 tumors, and 28% for Grade 3 tumors (p = 0.0013, Grade 1 vs. 2 and 3). Thirty of the 51 patients (59%) had curative resection with an operative morbidity rate of 24% and an operative mortality rate of 12%; at 5 years the disease-free survival rate was 58% and the overall survival rate was 63% (48% at 10 years). Eleven patients (42%) had recurrent disease develop at a median interval of 2 years after complete tumor excision. Twenty-one patients (41%) had partial excision or biopsy only of their tumors with an operative morbidity rate of 28%, operative mortality rate of 8%, and median survival of only 9 months. Overall, patients whose tumors were confined to the site of origin had a 58% 5-year survival rate compared with 20% for those whose tumors had invaded adjacent organs (p less than 0.05). If the tumor was less than 10 cm in size, the 5-year survival rate was 78%, significantly better than the 38% for tumors greater than 10 cm (p = 0.03). These data suggest that histologic grade, local invasiveness, size, and extent of resection are the most important prognostic factors for patients with primary gastrointestinal sarcomas. Patients who have resection of all gross tumor, especially if it is well differentiated and localized, have a good prognosis.

Adolescent↗