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.

A comparison of survival at different degrees of hemorrhagic shock in germ-free and germ-bearing rats.

We have previously reported superior survival after one level of hemorrhagic shock in germ-free (GF) rats compared with germ-bearing (GB) rats. The objective of this study was to determine the effect of the GF state on survival at different degrees of hemorrhagic shock. GF and GB rats were bled to a mean arterial blood pressure of 30 mmHg. Shock was terminated after 10, 20, 40, or 80% of the maximum shed blood volume was reabsorbed spontaneously. Both shock time and time to decompensation were significantly longer in GF rats (p < .05). Comparative survival was greater for GF rats at most levels of shock (p < .01). This superiority in survival was greatest at moderate shock levels and decreased at severe shock levels. There may be several reasons for the increased tolerance of GF animals to hemorrhagic shock such as metabolic or immunologic variations. It is hard to avoid the fact, however, that the most notable difference between the GF and GB rat is the presence or absence of bacteria.

The use of teaching examinations in surgical instruction.

A mode of teaching is described which introduces a new concept to clinical instruction in addition to the seminars, lectures, conferences, and audiovisual tools ordinarily used. It has the following advantages: (1) It allows the student to evaluate himself. (2) It allows him to detect and repair defects in his knowledge without damage to his class standing or to his ego. (3) It evaluates the areas of strength and weakness in the teaching programs. (4) It is a dynamic teaching process in which the student participates and which appears to stimulate a greater interest in and a greater retention of the material administered.

Changing attitudes in the management of cancer of the breast.

Opportunity to assess changes in the management of cancer of the breast over the past 7 years was afforded by analysis of responses to questionnaires that were part of an annual questionnaire course. Comparison of responses to questionnaires conducted in 1971 and 1977 identified important features of approaches to this disease and indicated the way in which changes have occurred. Diagnostic needle aspiration increased from 24% (1971) to 54% (1977). In both surveys surgeons reported employing mammography infrequently. Use of modified radical mastectomy increased from 15% (1971) to 60% (1977). Employment of classical radical mastectomy decreased from 83% (1971) to 37% (1977). Surgeons considering biopsy of the contralateral breast to be unnecessary decreased from 47% (1971) to 14% (1977). Skin grafting, after a mastectomy, decreased from 40% (1971) to 24% (1977). Though oophorectomy is still the preferred initial treatment for premenopausal patients with advanced disease, preference for chemotherapy in postmenopausal patients increased from 5% (1971) to 23% (1977). Surgeons approving of reconstruction with implants after mastectomy for carcinoma increased from 30% (1971) to 49% (1977). Following mastectomy in patients with positive axillary nodes, 58% of our respondents employ chemotherapy with several drugs and 34% prefer irradiation.

Interval breast cancer: a more aggressive subset of breast neoplasias.

It has been suggested that interval breast cancer (breast cancer found within 12 months of a negative screening examination) exhibits a more virulent behavior than those found by the screening clinic. To test this hypothesis, 120 new cases of breast cancer were retrospectively reviewed from our Breast Screening Center. These patients were divided into three groups--interval cancer cases, lesions found at initial screening, and lesions found at subsequent screening. Statistically significant differences seen in our interval cancer cases included a higher percentage of positive axillary nodes, higher overall mortality rate, and lower 6-year survival rate as calculated by left table analysis. The remaining data, although not statistically significant, demonstrate a parallel trend toward a more malignant behavior. It is concluded that interval breast cancers are more aggressive forms of breast neoplasias.

Hemorrhagic shock inhibits lipopolysaccharide-induced myelopoiesis in both germ-free and conventional rats.

BACKGROUND: Bacterial translocation has been implicated in the alteration of the immune response after shock and trauma. This study examined the effect of bacterial translocation on myelopoiesis after hemorrhagic shock in germ-free and conventional rats. METHODS: Awake, unrestrained germ-free and conventional rats were bled to a mean arterial pressure of 30 mm Hg until the animal required infusion of 10% of the shed blood. Rats were resuscitated with shed blood and crystalloid. Sham rats were catheterized but not bled. Twenty-four hours after shock or sham, rats were administered lipopolysaccharide 100 micrograms or saline intraperitoneally. Twenty-four hours later, bone marrow cells were cultured for growth of granulocyte-macrophage colony-stimulating factor (CFU-GM). RESULTS: Lipopolysaccharide increased the number of CFU-GM/femur in sham germ-free rats (801 +/- 129 versus 455 +/- 110; p less than 0.05) and conventional rats (1458 +/- 200 versus 492 +/- 59; p less than 0.05) compared with saline-treated rats. In contrast, hemorrhagic shock inhibited lipopolysaccharide-induced CFU-GM growth in both germ-free and conventional rats. Shock, itself, was a stimulus for CFU-GM growth in germ-free but not conventional rats. Bone marrow white blood cell counts were unaffected by shock, lipopolysaccharide administration, or the germ-free state. CONCLUSIONS: Hemorrhagic shock inhibited lipopolysaccharide-induced CFU-GM proliferation independent of the germ-bearing status of the rat, and bacterial translocation exerted no influence on myelopoietic dysfunction after hemorrhagic shock.

Survival distribution in breast cancer.

It has been stated that breast cancer survival rates follow an exponential distribution. This would mean that the mortality rate is constant. Survival distribution was analyzed by the clinical life table method in one series of 10,752 patients and in another of 656 patients followed up to 8 and 18 years, respectively. Part of the larger series' table is (table: see text). Necessarily, clinical survival data are censored progressively. These kinds of data are analyzed best by examining the hazard function, which is the instantaneous death rate, or force of mortality. If an exponential distribution described survival in breast cancer correctly, the hazard function would be constant. These data clearly are not consistent with an exponential distribution, as the hazard function decreases. The survival distribution calculated from these data shows that the chance of dying of cancer decreases the longer a patient survives. This is more optimistic and consistent with clinical experience than is the exponential distribution.

The effect of ATP-MgCl2 infusion on hepatic cell permeability and metabolism after hemorrhagic shock.

The ability of exogenous ATP-MgCl2 to reverse the inhibition of ATP-dependent intracellular reactions by hemorrhagic shock was studied. Levels of ornithine in the postperfusion fluid were lower in animals receiving ATP-MgCl2 than in placebo-treated control animals (338.6 +/- 167.0 versus 692.1 +/- 67.2 mumol). Arginine levels were higher (399.1 +/- 130.1 versus 34.3 +/- 59.1 mumol) in ATP-MgCl2-treated animals. Ability of in vitro ATP to enter the cell and inhibit lactate formation (Crabtree effect) was significantly less in those animals receiving in vivo ATP-MgCl2 (81.4 +/- 11.1% versus 57.7 +/- 10.1%). Glutamate levels were not decreased by shock but were significantly increased by treatment with ATP-MgCl2 compared to placebo (190.5 +/- 48.8 versus 122.6 +/- 36.3 mumol). These data indicate that exogenously administered ATP-MgCl2 can reverse the inhibition of ornithine metabolism and the changes in lactate inhibition seen in hemorrhagic shock. These are both intracellular ATP-dependent reactions.

Correlation between red blood cell deformability and changes in hemodynamic function.

BACKGROUND: In sepsis red blood cells (RBCs) have been shown to be less deformable (i.e., more rigid) and have been implicated in decreasing nutrient blood supply and possibly leading to organ dysfunction. However, no studies have demonstrated an association between organ dysfunction and rigid RBCs. This study examined cardiovascular physiologic and histologic changes in two different models to determine whether a relationship may exist between RBC deformability and organ function. METHODS: In the following two experiments, cardiac index (CI) was continuously measured, whereas both deformability index and histology were examined at the end of the experimental periods. The first experiment studied nonanesthetized, hydrated rats after a cecal ligation and puncture (CLP), a slow-developing means of inducing RBC rigidity. In a second experiment animals were anesthetized and received a 20% total blood volume transfusion of either diamide-treated (rigid) RBCs or normal RBCs. RESULTS: CLP-treated animals' CI gradually decreased during 18 hours (232 +/- 60 ml/min/kg to 123 +/- 90 ml/min/kg; p = 0.05), with an increase in systemic vascular resistance (1459 +/- 517 dyne.sec/cm5.m2 to 2337 +/- 1213 dyne.sec/cm5.m2; p = 0.02). Diamide-treated animals had a rapid decrease in CI (86 +/- 7.0 ml/min/kg to 58 +/- 13 ml/min/kg; p = 0.05) and increase in SVR (2269 +/- 373 dyne.sec/cm5.m2 to 3897 +/- 988 dyne.sec/cm5.m2; p = 0.05) from baseline to 120 minutes after treatment respectively. The DI was significantly lower in both CLP and diamide groups (p < 0.03) when compared with control animals. Histologic evidence of subendocardial necrosis was shown in both the CLP- and Diamide-treated animals. CONCLUSIONS: These data suggest an association with RBC deformability and organ function in both septic and nonseptic animal models.

The incidence of decreased red blood cell deformability in sepsis and the association with oxygen free radical damage and multiple-system organ failure.

We studied the incidence of decreased red blood cell deformability (RBCD) in sepsis and the association between decreased RBCD and oxygen free radical generation (as measured by malonyldialdehyde) and the occurrence of multiple-system organ failure (MSOF). Patients were divided into three groups: septic (n = 28), nonseptic (n = 15), and control (n = 5). Serial measurements of deformability index, malonyldialdehyde, and MSOF were made. The deformability index for the septic group (0.23 +/- 0.17) was significantly less than that for the nonseptic (1.12 +/- 0.48) and control (1.11 +/- 0.25) groups. The malonyldialdehyde levels for the septic group (4.5 +/- 1.0 nmol/mL) were significantly greater than those for the nonseptic (2.7 +/- 0.9 nmol/mL) and control (2.6 +/- 0.8 nmol/mL) groups. The MSOF index for the septic group (10.1 +/- 2.5) was significantly greater than that for the nonseptic (7.6 +/- 1.7) and control (6.0 +/- 0.0) groups. An inverse correlation existed between malonyldialdehyde and deformability index ( = .501, less than .001, n = 40) and between deformability index and MSOF index (= .350, less than .05, n = 61). We conclude that RBCD is decreased during human sepsis; free radicals generated during sepsis may play a role in the decrease in RBCD. Decreased RBCD may contribute to the MSOF that occurs during sepsis.

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.

Temporal relationship of hepatocellular dysfunction and ischemia in sepsis.

To determine whether hepatic dysfunction in sepsis results from hypoperfusion or direct cellular injury, Sprague-Dawley rats underwent either cecal ligation and puncture or sham operation. After either two or six hours, effective hepatic blood flow was measured using the galactose clearance method. Hepatocytes were isolated and intracellular sodium and potassium and glucose production were measured. Hepatic blood flow in septic rats decreased as early as two hours after sepsis when compared with sham-operated rats (3.8 +/- 1.4 vs 8.7 +/- 3.1 mL/min/100 g body weight). Intracellular sodium and potassium levels and glucose production in septic rats were not significantly different when compared with controls at two hours. After six hours, hepatic blood flow remained depressed and intracellular sodium level was increased compared with sham-operated rats (41.7 +/- 10.4 vs 31.4 +/- 5.9 mmol/L [41.7 +/- 10.4 vs 31.4 +/- 5.9 mEq/L]) and potassium decreased compared with controls (90.7 +/- 7.9 vs 111.5 +/- 6.7 mmol/L [90.7 +/- 7.9 vs 111.5 +/- 6.7 mEq/L]). Glucose production was decreased in septic rats after six hours when compared with controls (4.7 +/- 1.5 vs 15.4 +/- 6.4 mumol/g hepatocytes). These data suggest that hepatic blood flow is decreased before alterations in intracellular sodium and potassium as well as glucose production.

Head and neck cancer in a young age group: high incidence in black patients.

From the Tumor Registries of the East Orange, New Jersey, Veterans Administration Medical Center, and the College of Medicine and Dentistry of New Jersey/New Jersey Medical School, 1,066 cases of head and neck cancer were reviewed. Blacks comprised 32% of the population reviewed. Charts of 70 patients, 45 years old or younger, were examined. Seventy percent of this group was black. At diagnosis, the proportion of patients 45 years old or younger was 14% for blacks and 2.9% for whites, a significant difference (P less than 0.001). Seventy-six percent of lesions in black patients and 86% in white patients were situated above the hypopharynx. Sixty-one percent of all patients 45 years old or younger had Stage III or IV lesions when first diagnosed, regardless of race. Black-to-white survival rates were 23 to 40% after 2 years, and 5 to 13% for those at risk after 5 years. Prognosis is poor for younger patients, in general, and worse for young black patients than for whites.

Emergency subclavian vein catheterization and intravenous hyperalimentation.

One hundred consecutive subclavian catheter insertions were performed by the surgical house staff of Martland Hospital, Newark, New Jersey, over a ten month period. The only complications were three punctures of the subclavian artery and one systemic infection. The following conclusions were drawn from these data. Maintaining a closed intravenous system with minimal manipulation of the catheter is the most important factor in avoiding infectious complication. Neither the routine use of irrigation of the catheter with amphotericin B nor insertion of the catheter under strict aseptic conditions is necessary to minimize infectious complications. The morbidity related to insertion of the catheter can be kept to a minimum if the catheters are inserted by experienced personnel.

A medial approach to thyroidectomy.

Thyroidectomy initiated by transecting the isthmus and peeling the lobes laterally away from the midline exposes the three vital elements of thyroid anatomy, namely the vessels, the recurrent laryngeal nerves and the parathyroid glands, by an almost bloodless dissection conducted at a distance from these vital structures. Part or all of the lobe or lobes can be removed while the parathyroid glands and recurrent laryngeal nerves remain clearly under view at all times.

Construction of a neolarynx after radiation and laryngectomy.

We have developed a technique for forming a new larynx from a cervical "bucket handle" flap to replace the larynx after laryngectomy in patients who have had radiation of the neck. Experience with the technique in six patients suggests that it is more successful than previous procedures used in such patients and may offer some advantages as a general technique of laryngeal construction. The procedure is designed to preserve speech and swallowing without aspiration, but translaryngeal breathing is sacrificed and respiration requires a permanent tracheostomy tube.

Construction of a pseudolarynx after laryngectomy and radical neck dissection. A preliminary report.

Voice rehabilitation is a major problem after laryngectomy. A new method to construct a pseudolarynx after total laryngectomy by suturing the trachea to the hyoid bone is described. The surgical technic is relatively simple. Patients are able to speak in the immediate postoperative period without intensive therapy. The quality of speech is good. Aspiration of liquids is a common problem, but in time patients learn to swallow with minimal or no aspiration. This procedure could be utilized in selected cases for good voice rehabilitation after total laryngectomy.

Evaluation of polylactic acid-carbon mesh for repair of ventral herniorrhaphy.

Large ventral hernias are a difficult surgical problem. Previous attempts to repair large defects in the abdominal wall with prostheses have been associated with recurrences and infection. A filamentous polylactic acid-carbon tissue mesh is a possible alternative prosthesis. We evaluated and compared polylactic acid-carbon mesh and Marlex mesh in repairing a large defect of the abdominal wall in a rat model. The polylactic acid-carbon mesh led to as strong a repair as Marlex mesh for the same time periods postoperatively; furthermore, no infection was noted with the former, whereas a 5.3 percent incidence of infection was noted with Marlex mesh. One mesh disruption was also noted with Marlex mesh. Polylactic acid-carbon mesh was found to have a more marked fibrotic response and a lesser inflammatory response. Polylactic acid-carbon mesh, therefore, appears to be more biocompatible, with more fibrosis, less inflammatory reaction, and equal strength to Marlex mesh. It is therefore a more appropriate synthetic material for a large ventral herniorrhaphy.

The use of cervical flaps from irradiated necks in immediate reconstruction.

The use of cervical flaps for immediate reconstruction after operation in twenty-one patients in whom the neck received 4,000 to 6,000 r six weeks prior to operation is reported. Successful repair was achieved in a majority of these patients. We conclude that such flaps can be safely used imost instances, assuming they are designed to achieve maximum blood supply or are in an area that received minimal radiation exposure. We recommend this approach only when the radiation given is part of a course of previously planned, integrated therapy combining radiation and operation and when the major portion of the flap has not been exposed to more than 4,000 r.

The gut as source of sepsis after hemorrhagic shock.

In a model of severe hemorrhagic shock in rats, blood culture findings became positive within 2 to 4 hours of shock. The organisms cultured were primarily gram-negative. To test the hypothesis that the gut was the source of the bacteria, E. coli labeled with carbon-14 oleic acid were fed to rats undergoing hemorrhagic shock. Their plasma was then assayed for carbon-14 activity. Seven of the 14 shocked animals demonstrated increased plasma carbon-14 activity during or after shock. The mortality rate was 100 percent 80 hours postshock, and all animals had E. coli on subsequent blood culture. The seven rats without increased plasma carbon-14 activity had a survival rate of 83 percent postshock. Sham-shocked animals did not exhibit plasma carbon-14 levels greater than the background levels. These data suggest that bacterial translocation occurs during hemorrhagic shock and that the gut is the source of the bacteremia seen during hemorrhagic shock.