The use of a biodegradable mesh to prevent radiation-associated small-bowel injury.

Radiation-associated small bowel injury occurs in up to 50% of patients receiving postoperative radiotherapy following pelvic cancer surgery. We describe our experience using a biodegradable mesh that allows the small bowel to be supported above the pelvic inlet and is totally absorbed following radiation therapy. Between 1985 and 1989, 45 procedures were performed in patients with carcinoma of the rectum (anterior resection in 15 patients, abdominoperineal resection in 23 patients, pelvic exenteration in six patients, and proctocolectomy in one patient). In 30 patients a polyglycolic acid (Dexon) mesh was used, and in 15 patients a polyglactin 910 (Vicryl) mesh was used. Forty-four patients received postoperative radiotherapy. The mean (+/- SEM) dose was 56.8 +/- 18.4 Gy. There were no immediate complications related to the mesh. Follow-up ranged from 12 to 53 months (median follow-up, 34 months). With the exception of two patients who had a polyglactin 910 mesh and who developed bowel obstruction due to adhesions under the anterior abdominal wall, there has been no documented incidence of clinical radiation-associated small bowel injury. The use of the absorbable mesh may permit us to use higher doses of postoperative radiotherapy without the associated hazard of radiation-associated small bowel injury.

alpha-Difluoromethylornithine inhibits liver metastasis produced by intrasplenic injection of human tumor cells into nude mice.

The purpose of these studies was to examine metastatic potentials of a human colon tumor xenograft (T6) and three different human tumor cell lines (LS174T, HT29 and A549) using the intrasplenic-nude mouse model system (ISMS model system). A further objective was to study the activity of alpha-difluoromethyl-ornithine (DFMO) against primary and metastatic growth of the xenograft and the three cell lines. DFMO is an irreversible inhibitor of ornithine decarboxylase, a rate-limiting step in polyamine biosynthesis. Tumor burdens in the liver of nude mice were observed 6 weeks after the intrasplenic injection with LS174T and 12-14 weeks after intrasplenic injections with T6, HT29 and A549. Most of the mice developed primary tumor growth in the spleens. DFMO showed significant activity against liver metastases but had little or no activity against primary tumor growth in the spleens of the ISMS model and against s.c. growth of the xenograft. The studies demonstrated that the ISMS model system is an excellent system for studying metastatic behavior of human tumors and for studying the antimetastatic activity of experimental drugs.

Inflammatory pseudotumor of the liver.

Inflammatory pseudotumors (plasma cell granulomas) are localized lesions consisting of a fibrous stroma, chronic inflammatory infiltrate with a predominance of plasma cells, and an absence of anaplasia, which can mimic malignant disease by their gross appearance. Reported in many sites, they are most frequently described in the lung. Twelve cases involving the liver and biliary tract have previously been reported. Here, a 77-year-old man who presented with fever and malaise was found to have a lesion in the left lobe of the liver, which, on exploration, was found to be an inflammatory pseudotumor. This patient, and each of those previously reported, has recovered uneventfully. Because of the benign course of this lesion, hepatectomy should be considered only in those instances in which the mass effect of the lesion is producing symptoms or in those cases in which a firm histologic diagnosis cannot be made preoperatively or by frozen section intraoperatively.

Rationale for aggressive colonoscopy in patients with colorectal neoplasia.

The role of colonoscopy in patients with colorectal neoplasia is not well established. The results of colonoscopy, from 1982 through 1987, in 42 patients with cancers who underwent preoperative colonoscopy (group 1), 64 patients with benign polyps (group 2), and 51 patients who were examined only postoperatively (group 3) were reviewed. These results indicated that (1) approximately one third of all findings would have been missed if endoscopy had been performed to only 60 cm; (2) there was a high incidence of synchronous lesions (33.3%) in group 1 and 34.4% in group 2); (3) 57% of patients with synchronous cancer and 63.6% of patients with synchronous polyps developed metachronous lesions, compared with 10.7% and 11.9% of patients with a single lesion; (4) there was a higher incidence of metachronous lesions seen in group 3, compared with group 1; and (5) the median interval for noting metachronous lesions in patients who underwent colonoscopy preoperatively was approximately 18 months. These findings endorsed preoperative colonoscopy and aggressive follow-up in patients with colorectal tumors.

Interposition spiral saphenous vein graft bypass in bilateral simultaneous radical neck dissection.

We advocate the use of the spiral saphenous vein bypass of the IJV when bilateral radical neck dissections are performed with the sacrifice of both IJV. The technique we have described herein is uniformly successful in this setting and associated with only 30 minutes to one hour of increased operative time. This bypass will decrease the postoperative facial edema and associated complications and allow the patient to go on to radiation and chemotherapy in an expeditious and safe manner.

Red blood cell deformability in human and experimental sepsis.

Red blood cell (RBC) "deformability" is necessary for maintenance of normal microcirculation. To determine whether RBC deformability was affected in human or murine sepsis, a deformability index was determined in a human study and a murine model. Deformability was decreased postoperatively in patients with sepsis (0.49 +/- 0.12) compared with patients without sepsis (1.62 +/- 0.13) and normal control volunteers (1.51 +/- 0.17). Deformability was decreased in rats that had undergone cecal ligation and puncture (0.37 +/- 0.06) compared with that of sham-operated rats (0.76 +/- 0.12), as well as in endotoxemic rats (0.38 +/- 0.4) compared with control rats (0.82 +/- 0.11). These data suggest that RBC deformability decreases in both human and murine sepsis. This effect could be an important factor in the disordered oxygen utilization noted in human sepsis, and its correction could lead to better tissue oxygenation and preserved organ function.

Unsuspected perforation in bleeding duodenal ulcers.

A combination of bleeding and perforation rarely occurs simultaneously in peptic ulcer disease. The charts of 127 patients undergoing surgery for either complication were reviewed (bleeding, 91; perforation, 36). Nine of 91 (9.9%) patients in the bleeding group were found at operation to have a unsuspected perforated duodenal ulcer. The operative mortality in the patients with the combined complications (44%, 4/9) was significantly higher than that in patients with bleeding alone (8/82, 9.8, P less than 0.001) or those with perforation alone (4/36, 11.00, P less than 0.025). The mean age of nonsurvivors was significantly higher than that of the survivors (74 +/- 8.01 vs 50.4 +/- 5.65 years, P less than 0.005). The duration of symptoms until operation was longer in patients who died (63 +/- 12.7 hours) than in survivors (40.2 +/- 6.02 hours, P = NS). All patients who died, and three of five survivors, had preoperative fever (greater than 99.0 F), leukocytosis (greater than 12,000/mm3), and persistent tachycardia despite adequate hydration and blood replacement. Perforation in bleeding peptic ulcers is not an uncommon finding, and was present in 9.9 per cent of patients. The presenting symptom of bleeding may obscure signs of perforation, delay surgery, and contribute to the higher mortality rate. The presence of fever, leukocytosis, and tachycardia despite adequate fluid and blood replacement warrants a suspicion of perforation in patients with bleeding peptic ulcer.

Lung cancer in patients with head and neck cancer. Incidence and long-term survival.

Of the 3,907 cases of primary head and neck or lung cancer diagnosed between 1961 and 1984, 94 patients were identified with a history of cancer at both sites. The total incidence of lung cancer in our head and neck cancer patients was 5.4 percent. Of the 94 patients, 73 had both cancers diagnosed at our institution. These 73 patients were further analyzed. Squamous cell carcinoma accounted for 63 percent of the lung cancers. Twenty of the lung cancers were synchronous and 47 were metachronous after head and neck cancer. Of the synchronous lung cancers, 50 percent were postoperative stage I, whereas only 11 percent of the metachronous cancers were postoperative stage I. The lung cancer survival rate was significantly better for the synchronous cancer group at 5 years (34 percent) than for the metachronous cancer group (5 percent). The better survival rate was evidently due to the greater proportion of early-stage lung lesions. The relatively large number of advanced-stage lung lesions in the metachronous cancer group suggests that aggressive screening of head and neck cancer patients for lung cancer may detect more metachronous lung cancers at an earlier stage and thus improve the survival rate of these patients.

An assessment of monocyte procoagulant activity in patients with solid tumors.

Generation of thromboplastin by monocytes has been shown to play a vital role in hypercoagulable states seen in malignancy. The purpose of this study was to compare the procoagulant activity in cancer patients and controls. Recalcification times (RT) of whole blood from 19 normal volunteers, 8 patients with benign polyps, 12 patients previously treated by surgery for head and neck (H&N) or colon cancer, and 13 untreated patients with various stages of H&N or colon cancer were determined. Tests were performed with and without stimulation with Escherichia coli endotoxin. The mean RT in saline (RTS) of untreated patients with early cancer (4.58 +/- 0.83 min) and that of patients with advanced cancer (5.23 +/- 1.16 min) were lower than that of controls (6.55 +/- 0.82 min), P less than 0.01 and P less than 0.05, respectively. The RTS of patients previously treated and of those with benign polyps were no different from those of controls. Activation with endotoxin significantly lowered the recalcification times (RTE) in the early (3.90 +/- 0.58 min) and advanced cancer patients (4.23 +/- 0.66 min) compared to the RTE of controls (5.69 +/- 0.75 min, P less than 0.01 for both groups) as well as compared to those with benign tumors, P less than 0.05. The mean RTE of previously treated patients (4.72 +/- 0.58 min) was also lower than that of controls, P less than 0.05. Our results suggest that RT is significantly reduced in cancer patients compared to that of controls. Furthermore, monocyte activation with endotoxin may enable us to distinguish cancer patients from controls as well as from those with benign tumors.

Surgical endoscopy training in a university program.

Recent directives from the American Board of Surgery requires that applicants become familiar with a variety of endoscopic procedures. The purpose of this report is to review the VA Medical Center's two and a half year experience following the establishment of a surgical endoscopy unit. During the first year, July 1982-June 1983, 212 procedures were performed. These included 64 Colonoscopies (C), 98 Gastroscopies (G), 42 Flexible Sigmoidoscopies (S) and 8 Choledochoscopies (CD). The following year 564 procedures were performed (C-201, G-269, S-86, CD-8). Over the last 6 months 210 procedures were performed (C-98, G-86, S-22, CD-4). Senior surgical residents in their fourth or fifth year of training spent 4 months in the endoscopy service as part of their surgical oncology rotation. Technical and diagnostic competency was achieved in 2 to 4 months. This review indicates that the volume of cases, currently averaging 45 per month, is adequate to train surgical residents and support an independent endoscopy service. The establishment of the unit has also been associated with the development of screening programs for colon and esophageal cancers as well as broader applications of some of the newer indications of fiberoptic endoscopy. Future plans include introduction of variceal sclerotherapy and ERCP.

Evaluation of adenosine deaminase activity in patients with head and neck cancer.

ADA is a key enzyme in the mammalian purine salvage pathway. The lack of ADA activity has been linked to a lack of cellular immunity in various immune and myeloproliferative disorders. Data on its role in patients with solid tumors are scant and inconclusive. In this report, we have evaluated the activity of this enzyme in the peripheral lymphocytes of patients with head and neck squamous cell cancer (HNC). The mean ADA activity in Stage IV patients (0.57 +/- 0.08 SEM, n = 12) was significantly lower than that of controls (1.55 +/- 0.25 SEM, P less than 0.05, n = 14) and also significantly lower that the mean ADA activity in patients with Stages I, II, and III (1.14 +/- 0.10 SEM, P less than 0.05, n = 17). Fourteen out of 19 controls, Stage I, II, and III patients had positive skin tests compared to 7 out of 10 Stage IV patients. These differences were not statistically significant. There was also no correlation between ADA activity and the absolute lymphocyte counts. Our results indicate that ADA activity in lymphocytes of patients with advanced HNC is lower than that of controls or patients with earlier stages of the disease. ADA may be a more sensitive indicator of suppressed cellular immunity than delayed cutaneous hypersensitivity reactions, or monitoring absolute lymphocyte counts.

Management of squamous cell carcinoma of unknown origin in cervical lymph nodes.

Forty-three patients with the diagnosis of metastatic squamous cell carcinoma from unknown primary to the cervical lymph nodes were treated in EOVAMC between 1962-1982. Six of these patients were N1, 19 N2, and 18 N3. Five-year survival was 41 per cent for N1, 15 per cent for N2, and 6 per cent for N3 nodes. There was no significant difference in the treatment failure of those patients treated with unimodality versus multimodality. A subsequent primary was detected in the head and neck in 23 per cent of these patients (10/43), and eight of these patients had received previous radiotherapy. The most common site for these subsequent primaries was hypopharynx. Nine of the 43 patients developed distant metastasis with no correlation to stage of disease or treatment modality. These data show that the survival of these patients correlates with the stage of nodal disease, and that radiotherapy did not decrease the subsequent appearance of the primary lesions.

Cancer of the tonsil. Improved survival with combination therapy.

One hundred seventy-four cases of squamous cell cancer of the tonsil (SCCT) were reviewed. Radiation therapy (RT) alone was used in 81 patients, surgery alone (S) in 19 patients, preoperative RT + S in 49 patients, and chemotherapy [( C] methotrexate plus bleomycin plus cisplatin) in 25 patients. The 5-year survival was 83% in Stage I (n = 21), 72% in Stage II (n = 19), 23% in Stage III (n = 34), and 15% in Stage IV (n = 100). RT and S were equally effective in Stages I and II. In Stage III, the 5-year survival for RT + S was 31% versus 11% for RT alone; and in Stage IV, the respective 3- and 5-year survivals for RT + S were 24% and 15% versus 6% and 0%, respectively, for RT alone. There was an 84% response rate to C, and the patients who completed C + RT + S had 3- and 5-year survival rates of 41.7% and 32%, respectively. Our results indicate that RT + S appears to offer better survival in Stage III and IV SCCT. The high response rate in early survival data seen with C + RT + S suggests a promising role for this approach.

A prospective evaluation of 5-fluorouracil plus cisplatin in advanced squamous-cell cancer of the head and neck.

Recent studies have shown improved efficacy of chemotherapy in patients with advanced squamous-cell cancer of the head and neck. Our purpose was to evaluate prospectively the activity of cisplatin plus 5-fluorouracil (5FU) in 37 patients with advanced stage IV squamous-cell cancer of the head and neck. There were two groups. Group 1 consisted of 19 previously untreated patients with either T4 or N3 disease. They received 100 mg/m2 cisplatin (days 1 and 28) and 120-hour infusion of 1,000 mg/m2/24 hours 5FU (days 1 to 5 and 28 to 32). They subsequently were offered preoperative radiotherapy (RT) and surgery. Group 2 consisted of 18 previously treated patients. They received 5FU and cisplatin in the same dosage every 28 days for either recurrent or metastatic disease. It was found that in group 1 there was an 84% response rate (five complete responses (CR) and 11 partial responses (PR) ). Three of those with PR achieved a CR after RT. Seven patients have had RT plus surgery and are disease free at 8 to 27 month follow-up. Six patients (one CR, five PR) refused surgery and progressed within 4 months. In group 2 there was an 11% response rate after two cycles (two PR), three patients had a minimal response (MR, less than 50% response) and received a mean of four cycles of treatment. Three patients with stable disease received a mean of four cycles of chemotherapy until progression. Two of 11 patients who had received previous chemotherapy plus RT showed an MR; nine of these patients had shown a response to their previous chemotherapy. Only one of 14 patients who had RT plus chemotherapy had a PR, and three had MR. Of five patients who had previous surgery, only one had a PR. All five had received chemotherapy as well. It was concluded that 5FU plus cisplatin is an effective combination in previously untreated patients. In previously treated patients with recurrent disease, there is a substantially lower response rate.

Multimodality preoperative treatment for advanced cancer of the head and neck.

Neoadjuvant induction chemotherapy with cisplatin, methotrexate, and bleomycin appears to improve the results of treatment of advanced stage IV head and neck cancer, compared with results in historical control subjects. Patients treated with induction chemotherapy and radiation therapy had a 29 percent overall survival rate at 3 years, which represents approximately a twofold improvement in the survival rate. Patients who were treated with chemotherapy and radiation therapy followed by surgery had more than a threefold increase in the survival rate (49 percent at 3 years), compared with historical data from our institution and elsewhere for such patients [9-11]. Distant metastases developed in 25 percent of the patients, and it thus appears that long-term, effective consolidation and maintenance chemotherapy [12,13] need to be developed for patients who receive combination therapy before surgery for head and neck cancer.

Prevention of adriamycin (ADR)-induced cardiotoxicity in rats using methylprednisolone (MP).

Adriamycin (ADR) is a useful antitumor agent but causes severe cardiotoxicity requiring dose limitation. Methylprednisolone (MP) has been shown to stabilize cell membranes and, in ischemic heart models, to protect mitochondria lysosomes and sarcolemma. The purpose of this study was to determine if MP could prevent ADR-induced cardiotoxicity in rats. Twenty-eight normal, male, Wistar rats were placed in two groups of 14 each. One group received ADR 2 mg/kg iv weekly for 3 weeks, followed by 2 mg/kg subcutaneously weekly. The other group received the same dosage of ADR but also MP 20 mg/kg subcutaneously 3 hr before, with ADR and 3 hr after ADR. Seven rats in each group were sacrificed after the 10th week of treatment. At autopsy 7/7 (100%) of the rats in the ADR groups had obvious ascites and pleural effusion whereas 0/7 in the ADR + MP group developed this complication (P less than 0.01). Microscopic examination of the hearts revealed vacuole formation, loss of muscle mass, tapering off of myocardial cells, or inflammatory changes in 7/7 (100%) of the rats in the ADR group and in 2/7 (28%) of the ADR and MP group (P less than 0.05). Among the rats left to monitor survival, at 11 weeks from the initiation of treatment, 4/7 (57%) in the ADR group and 7/7 (100%) in the ADR + MP group were alive. These data indicate that MP provides some protection from Adriamycin-induced cardiotoxicity in rats.

Therapeutic groin dissection in malignant melanoma.

In a retrospective review of therapeutic dissections of the groin, 22 patients underwent radical groin dissection and seven were alive at five years, whereas 26 patients underwent a superficial groin dissection and two were alive at five years, p less than 0.05. Involvement of the deep nodes is not always equivalent with systemic disease. A radical groin dissection should be used to eradicate the disease locally. The survival rate for the patients following groin dissection correlated significantly with the disease-free interval prior to occurrence of inguinal lymphadenopathy.

Extensive resections of isolated metastasis from carcinoma of the colon and rectum.

The results of this study show that hepatic resection for metastatic carcinoma of the colon and rectum is an effective treatment modality. The duration and quality of survival are better than those achieved by an other treatment modalities. The results of this study also show that hepatic resection is a safe procedure; however, a 50 per cent, two of four, mortality rate in patients undergoing a trisegmentectomy for metastatic disease points toward a need for better selection of patients. Adjuvant chemotherapy following hepatic resection has not been shown to be of any benefit in this series.