James P. Neifeld

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.

Pancreatic and periampullary carcinoma: Experience with 200 patients over a 12 year period

The operative management of 200 patients with pancreatic and periampullary cancer was reviewed. Patients with metastatic disease and biliary obstruction are best treated by the nonoperative techniques of biopsy and internal biliary drainage if technically feasible. For patients who undergo exploration and are found to be candidates for a bypass procedure, both biliary and gastroduodenal bypass should be performed. Lymph node involvement and age of the patient were found to be significant variables in determining the candidates suitable for curative resection. A definite incidence of multicentricity was found in patients undergoing total pancreatectomy for ductal carcinoma of the pancreas; however, significant problems with diabetic management arose from this procedure. The primary site of the lesion as well as the intelligence and socioeconomic background of the patient should dictate the type of resection employed. Pancreatoduodenectomy (Whipple procedure) is recommended for periampullary cancers other than pancreatic carcinoma, while total pancreatectomy may be appropriate in selected patients. However, there has been no evidence thus far in this early trial with total pancreatectomy that more complete resection of the pancreas leads to longer survival.

The pectoralis major myocutaneous flap in head and neck reconstruction: Analysis of complications☆

Sixty-seven patients underwent 73 pectoralis major myocutaneous flap procedures for the immediate reconstruction of defects after resection of head and neck cancers. Thirty-six patients experienced a total of 50 complications for an overall complication rate of 54 percent. There were 3 instances of total flap necrosis, 9 of partial flap necrosis, 12 orocutaneous fistulas, 9 suture line separations, 8 neck wound complications, 1 donor site complication, and 8 mandibular replacement complications. Most complications were minor and did not require a second procedure for correction; however, 36 percent did require a second operation. Eight of 10 patients in whom a metal appliance was placed to restore mandibular continuity required the removal of that appliance due to either flap necrosis, fistula formation, or exposure. Based on our experience, we conclude that attention to flap design, operative technique, and post-operative management were useful in reducing the incidence of complications. We also conclude that a metal appliance was an unsatisfactory means of restoring mandibular continuity when utilized beneath a pectoralis major myocutaneous flap. Although the overall incidence of complications was high, the actual incidence of flaps failing to accomplish their intended purpose and requiring secondary repair was acceptable. The pectoralis major myocutaneous flap was reliable in the reconstruction of defects in the head and neck region.

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.

Risk of subsequent contralateral breast carcinoma in a population of patients with in-situ breast carcinoma

One hundred ninety‐one cases of unilateral noninvasive breast carcinoma were studied with regard to the development of subsequent cancers in the contralateral breast. The majority of patients were treated by mastectomy and have been followed for an average of nine years. Their overall survival did not differ significantly from that of age‐specific population survival figures for U. S. women. Among all cases, 13 or 6.8% subsequently developed contralateral carcinoma; 3.1% of these contralateral tumors were invasive. The authors found only one histological type, namely lobular carcinoma in‐situ for which the development of subsequent contralateral carcinomas was statistically significant. Seven of the 68 women with this type developed second breast cancers (10.3%; 4.4% of these were invasive). These data suggest that the occurrence of clinically apparent subsequent cancers developing in the opposite breast following the diagnosis of in‐situ carcinoma is relatively small.

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.

Biochemical, hematologic, and immunologic alterations following hepatic cryotherapy

Hepatic cryosurgery causes hepatocellular damage primarily by inducing the formation of ice crystals. Cell necrosis is enhanced using two or more freeze-thaw cycles. The resultant damage to hepatocytes induces alterations in a number of biochemical and hematologic parameters, including hepatic function tests, serum bilirubin, serum and urine myoglobin, platelet count, and coagulation measures. Further, in experimental models, cryogenic surgery appears to stimulate the immune system of the host leading to an anti-tumor immune response. These perturbations in biochemical and hematologic parameters are usually transient, and long-term adverse sequelae are uncommon and preventable.

Effects of steroid hormones on phytohemagglutinin-stimulated human peripheral blood lymphocytes.

The interactions of steroid hormones and human peripheral blood lymphocytes (PBLs) have been investigated following glass-wool column separation of PBLs and incubation in a serum-free medium in the presence of phytohemagglutinin (PHA). Addition of hydrocortisone or progesterone above physiological concentrations resulted in inhibition of [14C]2-TdR incorporation. 17beta-Estradiol and 5alpha-dihydrotestosterone inhibited [14C]2-TdR incorporation only at steroid concentrations thousands of times higher than the physiological concentrations. The kinetics of hydrocortisone and progesterone inhibition appeared to be similar and suggested that events occurring early after PHA addition were most sensitive to steroid inhibition and that addition of steroid at 28 hr, at the end of the early prereplicative phase of the cell cycle, inhibited DNA synthesis only at very high concentrations. The PHA-induced increase in RNA synthesis could be prevented by hydrocortisone addition even if delayed for up to 4 hr; morphological transformation was similarly affected. These data, and other investigations showing that progesterone binds to a specific glucocorticoid receptor in PBLs suggest that the progesterone inhibition of macromolecular synthesis in human PBLs is exerted via a glucocorticoid-like mechanism, and that glucocorticoid sensitivity is greatest during the early phases of lymphocyte activation. These results also provide a rationale for the apparent in vivo immunosuppressive capability of progesterone.

The role of orchiectomy in the management of advanced male breast cancer

Nine men with advanced carcinoma of the breast were evaluated after orchiectomy at the National Institutes of Health over 19 years. Of patients followed for greater than one year, five had complete remissions, one had a partial remission, and two patients did not respond to orchiectomy. The average disease‐free interval was 20 months; the average survival from the time of orchiectomy in those who responded was 55.8 months and in non‐responders was 26.7 months. Orchiectomy appears to be a safe and effective way to produce an objective response and prolong survival in over 50 percent of men with advanced breast cancer.

Gemcitabine following radiotherapy with concurrent 5-fluorouracil for nonmetastatic adenocarcinoma of the pancreas

Gemcitabine has been shown to be an active agent in the treatment of pancreatic cancer. This study was conducted to prospectively examine the tolerance and early efficacy of adjuvant gemcitabine following radiotherapy with concurrent 5‐fluorouracil (5‐FU) for nonmetastatic pancreatic adenocarcinoma. Twenty‐three patients, median age 64 years, were treated with combined modality therapy. Nine patients underwent tumor resection before chemoradiation; 14 patients with locally unresectable tumors received definitive chemoradiation. Radiotherapy utilized four fields to the tumor and lymphatics to 45 Gy, plus a lateral boost to 50.4 Gy. Concurrent 5‐FU 500 mg/m2/day was administered on days 1–3 and 29–31, followed by 4 months of gemcitabine 1,000 mg/m2/week for 3 weeks (fourth week break). Adjuvant gemcitabine was well tolerated. Eighty‐three percent of the patients completed three to four cycles. The primary dose‐limiting toxicity was leukopenia, which was observed in 10 patients (43%). Nonhematologic toxicities were reported in five patients (22%). There were no cases of gemcitabine‐induced radiation recall and there have been no deaths attributed to treatment toxicity. Median follow‐up for the 23 patients was 12 months (range, 5–50); the actuarial median survival was 13 months. This report confirms that adjuvant gemcitabine following radiotherapy with concurrent 5‐FU for nonmetastatic pancreatic adenocarcinoma can be safely administered.