Adolescence alcohol exposure impairs fear extinction and alters medial prefrontal cortex plasticity.

After experiencing a traumatic event people often turn to alcohol to cope with symptoms. In those with post-traumatic stress disorder (PTSD) and a co-occurring alcohol use disorder (AUD), PTSD symptoms can worsen, suggesting that alcohol changes how traumatic memory is expressed. The objective of this series of experiments is to identify how alcohol drinking (EtOH), following cued fear conditioning and extinction, impacts fear expression in mice. Molecular (activity-regulated cytoskeleton-associated protein, Arc/arg3.1) and structural (dendrite and spine morphometry) markers of neuronal plasticity were measured following remote extinction retrieval. Mouse age (adolescent and adult) and sex were included as interacting variables in a full factorial design. Females drank more EtOH than males and adolescents drank more EtOH than adults. Adolescent females escalated EtOH intake across drinking days. Adolescent drinkers exhibited more conditioned freezing during extinction retrieval, an effect that persisted for at least 20 days. Heightened cued freezing in the adolescent group was associated with greater Arc/arg3.1 expression in layer (L) 2/3 prelimbic (PL) cortex, greater spine density, and reduced basal dendrite complexity. In adults, drinking was associated with reduced L2/3 infralimbic (IL) Arc expression but no behavioral differences. Few sex interactions were uncovered throughout. Overall, these data identify prolonged age-related differences in alcohol-induced fear extinction impairment and medial prefrontal cortex neuroadaptations.

Percutaneous Cholecystostomy for Severe Acute Cholecystitis: A Useful Procedure in High-Risk Patients for Surgery.

BACKGROUND: Acute cholecystitis has the potential to cause sepsis and death, particularly in patients with poor physiological reserve. The gold standard treatment of acute cholecystitis (cholecystectomy) is often not safe in high-risk patients and recourse is made to percutaneous cholecystostomy as either definite treatment or temporizing measure. The aim of this study is to evaluate early and late outcomes following percutaneous cholecystostomy in patients with acute cholecystitis treated at our institution. METHODS: All patients who underwent percutaneous cholecystostomy for acute cholecystitis (excluding patients with malignancy) between January 2005 and September 2014 were included in the study. RESULTS: A total of 53 patients (22 female, median age, 74 years; range, 27-95 years) underwent percutaneous cholecystostomy during the study period. In total, 12 patients (22.6%) had acalculous cholecystitis. The main indications for percutaneous cholecystostomy were significant co-morbidities (n = 28, 52.8%) and patients too unstable for surgery (n = 21, 39.6%). The median time to percutaneous cholecystostomy from diagnosis of acute cholecystitis was 3.6 days (range, 0-45 days). The median length of hospital stay was 27 (range, 4-87) days. The overall 90-day mortality was 9.3% with two further deaths at 12-month follow up. The mortality was significantly higher in patients with American Society of Anesthesiology grade 4-5 (18% vs 0% in American Society of Anesthesiology grade 2-3, p = 0.026) and in patients with acalculous cholecystitis (25% vs 4.5%, p = 0.035). The overall readmission rate was 18%. A total of 24 (45.2%) patients had surgery: laparoscopic cholecystectomy, n = 11; laparoscopic converted to open, n = 5; open total cholecystectomy, n = 5; open cholecystectomy, n = 1; laparotomy and washout, n = 1; laparotomy partial cholecystectomy and closure of perforated small intestine and gastrostomy, n = 1. CONCLUSION: Percutaneous cholecystostomy is a useful temporary or permanent procedure in patients with acute cholecystitis of both calculous and acalculous origin, who are unfit for surgery.

Intralymphatic injection of BCG into rhesus monkeys.

Since the route of administration of BCG may have an important function in immunotherapy, we investigated intralymphatic administration to direct BCG to the lymph nodes. Multiple injections of high doses of BCG were administered to 6 rhesus monkeys via the dorsal lymphatics of the lower limb. A suppurative lymphadenitis was observed along the lower limb and in the inguinal area in 5 of the 6 monkeys. However, many of the complications reported with other routes of administration were not observed. Granulomatous reactions and histiocytic responses developed in lymph nodes on the injected sides of the pelvis and distant nodes as well as in the liver. The intralymphatic route is the method by which high doses of nonspecific immunostimulants were delivered to regional lymph nodes. The efficacy of this approach remains to be established in tumor-bearing animals and humans.

Ammonia recovery from anaerobically digested cattle manure by steam stripping.

Ammonia recovery from anaerobically digested cattle manure effluents through steam stripping was studied at a stripping tower temperature of 98-99 degrees C and a steam-water ratio approximately 56-72 g/L. The digested manure effluents were first treated by microfiltration and then the permeate was used as feed in steam stripping. The stripping performance was evaluated under different feed pH values, ammonia concentrations and temperatures. The increase of the initial feed pH does not significantly improve ammonia stripping efficiency due to the fact that the stripped effluent pH is increased during steam stripping. This suggests that steam stripping of anaerobically digested manure effluents for ammonia recovery may not need pre-raised pH. In contrast, the pH value of the synthetic ammonia wastewater containing NH4Cl dramatically decreases after steam stripping. Increasing the feed temperature slightly improves ammonia stripping efficiency, but reduces the concentration of the recovered ammonia in the condensate due to an increased condensate volume at a higher feed temperature. Therefore, the feed temperature should be controlled at an optimum point that can compromise the condensate ammonia concentration and the ammonia stripping efficiency. Experimental results indicate that recovery of ammonia from anaerobically digested cattle manure effluents as NH4OH is technically feasible.

A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study.

After hysterectomy, 156 evaluable patients with stage I (limited to the corpus) or stage II (limited to the corpus and cervix) uterine sarcomas were randomly assigned to adjuvant chemotherapy with Adriamycin (Adria Laboratories, Columbus, Ohio) for six months or to no further treatment. Pelvic irradiation (external or intracavitary) was optional before randomization. Of 75 patients receiving Adriamycin, 31 have suffered recurrences compared with 43 of 81 receiving no adjuvant chemotherapy. This difference is not statistically significant. Moreover, there is no difference in progression-free interval or survival. The optional radiotherapy did not influence the outcome although there was a suggestion that vaginal recurrence was decreased by pelvic radiotherapy. The recurrence rates in specific cell types (leiomyosarcoma, homologous mixed mesodermal sarcoma, or heterologous mixed mesodermal sarcoma) were not significantly different although the pattern of recurrence differed, with pulmonary metastases being more common in leiomyosarcoma and extrapulmonary recurrence being more common in mixed mesodermal sarcoma. The outcome with respect to chemotherapy was not altered even after adjusting for maldistribution of cases. Thus, we could not show a benefit for this dose schedule of Adriamycin as adjuvant treatment for uterine sarcomas.

Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.

PURPOSE: To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs). MATERIALS AND METHODS: Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest. RESULTS: The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001). CONCLUSION: Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.

Sequential changes in serum iron and ferritin in patients undergoing high-dose chemotherapy and radiation with autologous bone marrow transplantation: possible implications for treatment related toxicity.

In an effort to define the pattern of iron flux during high-dose chemotherapy or chemo/radiotherapy, we prospectively measured serum iron, iron binding capacity, and ferritin in patients undergoing autologous bone marrow transplantation for various malignancies. Sequential measurement of serum iron from days -7 to +12 was carried out in 88 evaluable patients, and simultaneous measurement of iron, ferritin, and total iron binding capacity was carried out in 32 patients. We found that there was a predictable rise in serum iron on day -2 or -3, and that this was accompanied by an increase in the saturation of transferrin. In addition, there was a similar increase in serum ferritin levels, which peaked by day +2. We suggest that the timing of this change in serum iron and saturation of transferrin may be important in mediating endothelial cell damage and, hence, organ toxicity in the setting of AuBMT. Based on these findings, we suggest that large clinical studies could be a source of patient samples to measure surrogate endpoints such as lipid peroxidation products (malondialdehyde or isoprostanes), or protein oxidation products following high-dose chemo/radiotherapy to determine the role of iron in cellular injury. It is possible that pharmacological manipulations to reduce free radical production or to chelate iron during the days prior to bone marrow reinfusion might help to reduce tissue injury in the setting of bone marrow transplantation.

Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: a gynecologic oncology group study.

PURPOSE: To determine if patients with carcinoma of the vulva, with N2/N3 lymph nodes, could undergo resection of the lymph nodes and primary tumor following preoperative chemo-radiation. METHODS AND MATERILAS: Fifty-two patients were entered in the study, but six patients did not meet the criteria of the protocol and were excluded. The remaining 46 patients are the subject of this report. Patients underwent a split course of radiation, 4760 cGy to the primary and lymph nodes, with concurrent chemotherapy, cisplatin/5-FU, followed by surgery. RESULTS: Four patients did not complete the chemo-radiation, because three expired and one refused to complete the treatment. Four patients who completed chemo-radiation did not undergo surgery, because two of them died of non-cancer-related causes, and in the other two patients, the nodes remained unresectable. Following chemo-radiation, the disease in the lymph nodes became resectable in 38/40 patients. Two patients who completed the course of chemo-radiation did not undergo surgery as per protocol because of pulmonary metastasis. One underwent radical vulvectomy and unilateral node dissection and the other radical vulvectomy only. The specimen of the lymph nodes was histologically negative in 15/37 patients. Nineteen patients developed recurrent and/or metastatic disease. The sites of failure were as follows: primary area only, 9; lymph node area only, 1; primary area and distant metastasis, 1; distant metastasis only, 8. Local control of the disease in the lymph nodes was achieved in 36/37 and in the primary area in 29/38 of the patients. Twenty patients are alive and disease-free, and five have expired without evidence of recurrence or metastasis. Two patients died of treatment-related complications. CONCLUSION: High resectability and local control rates of the lymph nodes were obtained in patients with carcinoma of the vulva with N2/N3 nodes treated preoperatively with chemo-radiation.

High-dose chemotherapy, autologous bone marrow or stem cell transplantation and post-transplant consolidation chemotherapy in patients with advanced breast cancer.

This study was designed to determine the complete response (CR) rate, event-free survival (EFS) and overall survival (OS) in patients with metastatic breast cancer treated with an adriamycin-based induction regimen, high-dose chemotherapy consisting of cyclophosphamide and thiotepa with autologous bone marrow or stem cell reinfusion, followed by post-transplant 5-fluorouracil and cisplatin. Forty-eight consecutive patients were enrolled and 35 received two to four cycles of a cytoreductive chemotherapy regimen followed by high-dose chemotherapy which included cyclophosphamide and thiotepa. Thirty-three patients with non-progressive disease received at least one cycle of post-transplant 5-fluorouracil and cisplatin. Fifty percent of patients with evaluable disease responded to induction chemotherapy. Three of the 34 patients (9%) evaluable for response to high-dose chemotherapy achieved CR, eight (24%) achieved partial response (PR), 12 (35%) had stable disease (SD) and 11 (32%) had progressive disease (PD). The median time to neutrophil recovery was 11.5 days (range, 8 to 40 days) post- reinfusion. The median time to platelet independence was 14.5 days (range, 8 to 44 days). The median follow-up is 24.5 months (range, 1 to 96 months). The actuarial probability of EFS for all patients is 17% at 4 years. The EFS for patients receiving all four cycles of post-transplant chemotherapy is 27% at 4 years, compared to 36% at 1 year for patients not receiving any post-transplant chemotherapy. Ten of the 48 patients (21%) are alive, and seven of these (15%) have no evidence of disease. High-dose chemotherapy with autologous bone marrow or peripheral blood-derived stem cell transplantation followed by post-transplant consolidation chemotherapy in patients with metastatic breast cancer results in a proportion of patients without evidence of disease at 4 years.

Plasma hormones in DES-exposed females.

Random blood samples were obtained from 114 women with history of diethylstilbestrol (DES) exposure in utero and were analyzed for follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone (E1), estradiol (E2), androstenedione (A), testosterone (T), and progesterone (P) by respective radioimmunoassays. Colposcopic examinations of the lower genital tract and biopsies of suspicious areas of vaginal mucosa were performed in every patient. The mean age of these patients was 21.6 +/- 0.3 years (mean +/- SE) and mean age of menarche was 12.6 +/- 1.0 years. The incidence of irregular menses was 16.7%. A positive colposcopic finding was observed in 73.7% of all patients, 69.5% of patients with regular menses, and 94.7% of patients with irregular menses. Histologically confirmed vaginal adenosis was found in 43% of all patients, 46.3% of patients with regular menses, and 42.1% of patients with irregular menses. No significant differences were observed between DES-exposed versus unexposed females with regular menses in all hormones except testosterone. An elevated testosterone level was noted in postovulatory and perimenstrual phases of DES-exposed females. Elevated testosterone was also observed in DES-exposed females with irregular menses. Cross-analysis of hormone levels among the patients with lower genital tract pathology failed to show any statistical differences.

Extended carbon dioxide laser vaporization in the treatment of subclinical papillomavirus infection of the lower genital tract.

This study examined the use of extended carbon dioxide laser vaporization in 25 women with histologically confirmed, multicentric subclinical papillomavirus infection of the lower genital tract to determine whether carbon dioxide laser can eradicate subclinical papillomavirus infection. An extended carbon dioxide laser procedure involved vaporization of the epithelium of the entire lower genital tract. We performed the procedure under colposcopic guidance. Vaporization was carried out in continuity, to an appropriate tissue depth, while using recommended power densities for the respective target tissue. For sexually active study patients, male consorts were evaluated and treated concurrently to reduce the risk of recurrent infection. Postoperative morbidity was considerable, with moderate to severe vulvar pain and febrile reactions occurring in 100 and 76% of patients, respectively. Histologic persistence of subclinical papillomavirus infection was documented in 88% of study patients at follow-up examination. Neither treatment of the male consort nor sexual abstinence significantly improved treatment outcome. These data suggest that extended carbon dioxide laser procedures cause significant short-term morbidity without effectively eradicating subclinical papillomavirus infection of the female lower genital tract.

Elevated serum cathepsin B1 and vaginal pathology after prenatal DES exposure.

Activities of the lysosomal enzymes, cathepsin B1 (CBI), beta-glucuronidase, and beta-N-acetyl-D-glucosaminidase, as well as sialyl transferase, alkaline phosphatase, and placenta-like alkaline phosphatase, were determined on blind-coded serums from 99 women exposed to diethylstilbestrol (DES) in utero and 40 unexposed subjects of comparable age range. Cathepsin B1 averaged 100%, 1040% (P less than 0.001), 2720 % (P less than 0.001), and 4760% (P less than 0.001) of controls in DES-exposed women with no genital tract abnormalities (N = 11), adenosis (N = 68), adenosis with concomitant dysplasia (N = 15), and clear-cell adenocarcinoma (N = 5), respectively. The later two groups also exhibited 0.01). Activities of the other four enzymes in serums of DES-exposed women were unchanged from those controls, suggesting that alterations in CBI were not due to generalized increases in lysosomal membrane instability or other gross cellular damage. In 2 DES-exposed women with clear-cell adenocardinoma, from whom serial samples were available, preoperative levels of serum CBl fell from a mean of 4280% to values indistinguishable from controls by 7--12 days after tumor excision, concurrently with objective signs of remission. Recrudescence of serum CBI levels preceded by at least 3 months clinical evidence of persistent adenosis accompanied by vaginal dysplasia. Although the nature of the increments in CBI-like activity in the majority of subjects with DES-related pathology remains to be determined, the findings may complement present methods of physical diagnosis and prognosis.

Pregnancy outcome in 98 women exposed to diethylstilbestrol in utero, their mothers, and unexposed siblings.

The reproductive capability and labor complications of 98 women exposed to diethylstilbestrol (DES) in utero were compared with those of 3 separate control groups. The controls consisted of 167 age-matched, normal women, 20 siblings not exposed to DES who had achieved pregnancy, and their mothers. Spontaneous abortion, ectopic pregnancy, incompetent cervix, and premature labor occurred significantly more often in the DES-exposed population than in the normal controls. The controls also achieved a higher percentage of desired pregnancies overall; this was statistically significant (89.6 versus 75.0%, P less than .001). When compared with their mothers, however, the DES-exposed population achieved a greater percentage of desired, viable pregnancies (75.6 versus 67.0%, P less than .001). The unexposed siblings of the DES women achieved a higher percentage of desired, viable pregnancies than did their exposed sisters (86.9 versus 73.6%, P = .274), but less than the normal population (86.9 versus 89.6%).

Applications of the monitoring process model to coping with severe long-term medical threats.

Guided by the monitoring process model (MPM), the authors explored the illness responses of 2 samples: high monitors (who are cognitively vigilant to and amplify threat-related cues) and low monitors (who avoid them and blunt their impact). Both samples-101 women with human papillomavirus-related precancerous cervical dysplasia and 75 HIV-infected gay men-were undergoing long-term medical follow-up and management. Structural equation analysis showed an adequate fit of the MPM to the data within each sample, supporting the model's heuristic value: High monitors experienced greater disease-related intrusive ideation, which triggered greater avoidant ideation to forestall panic, particularly in the more threatened HIV-positive sample. However, efforts to avoid disturbing intrusive thoughts were ineffective, requiring increasingly extreme defensive strategies (i.e., denial and mental and behavioral disengagement).

Monitoring styles in women at risk for cervical cancer: implications for the framing of health-relevant messages.

We explored the interaction effects of individual attentional style (high versus low monitoring) and the framing of informational messages on the responses of women undergoing diagnostic follow-up (colposcopy) for precancerous cervical lesions. Prior to the colposcopic procedure, patients (N=76) were randomly assigned to one of three preparatory conditions: (a) Loss-framed message, which emphasized the cost of nonadherence to screening recommendations; (b) Gain-framed message, which emphasized the benefit of adherence; and (c) Neutrally-framed message. It was hypothesized that low monitors (who are more positively biased about their health) would show a more adaptive pattern of response to loss-framed information than high monitors (who are more negatively biased about their health). The results of a series of hierarchical multiple regression analyses were consistent with this prediction. Low monitoring was associated with greater knowledge retention (beta=.61, p<.05) and less canceling/rescheduling of follow-up appointments in the loss condition than in the neutral condition (beta=.82, p<.002). High monitoring, however, was associated with greater intrusive ideation when information was presented in the loss-oriented frame as compared to the neutral frame (beta=.99, p<.01). Knowledge retention and screening adherence were not affected by the framing manipulation. The differences between high versus low monitors as a function of loss or neutral frame suggest an interaction effect, wherein both the type of framing message and the individual's attentional style lead to distinctive cognitive-affective and behavioral patterns. The findings may have clinical implications for the tailoring of health messages to the individual's signature style.

Interacting effects of information and coping style in adapting to gynecologic stress: should the doctor tell all?

This study explored the interacting effects of personal dispositions and situational conditions on the stress response. Forty gynecologic patients about to undergo a diagnostic procedure (colposcopy) were divided into information seekers (monitors) and information avoiders (blunters). Half in each group were exposed to voluminous preparatory information, and half to the usual low level of information. Subjective, physiological, and behavioral measures of arousal and discomfort were obtained before, during, and after the procedure. Overall, low-information patients expressed less subjective arousal than high-information patients, and blunters showed less subjective and behavioral arousal than monitors. In addition, patients' level of psychophysiological arousal was lower when the level of preparatory information was consistent with their coping style; that is, blunters were less aroused with low information and monitors were less aroused with high information. Further evidence was gained for the utility and validity of a new scale for identifying monitors and blunters.

ICRF-159 (razoxane) in patients with advanced squamous cell carcinoma of the uterine cervix. For the Gynecologic Oncology Group.

Thirty-one patients with advanced squamous cell carcinoma of the cervix were entered onto this phase II study evaluating the efficacy of ICRF-159 (razoxane). Three of these patients were excluded; one had no tumor, one had a second primary, and one received no therapy. ICRF-159 was administered orally at a dose of 2.5 g/m2 weekly until progression, unacceptable toxicity, or death. Adverse effects were primarily hematologic in nature. Twenty-three of the 28 patients exhibited leukopenia which in ten instances was severe (below 2000/mm3). Seven cases had thrombocytopenia (one case below 50,000/mm3). Other toxicity, including fever and anorexia, was mild to moderate. There was tumor response in five (18%) patients (one CR, four PRs) ranging from 1 to 5 months. Fifteen patients with stable disease and eight with progressive disease had a median survival duration of 3.8+ and 3.5+ months, respectively. ICRF-159 showed limited activity in this patient population. However, it might be considered for combination with other low myelosuppressive agents.

Levels of urinary cathepsin B-like substance in patients with gynecologic malignancy.

Because certain proteolytic enzymes are thought to be released by malignant cells, we have measured the activity of cathepsin B in the urine samples of 57 patients with gynecologic malignancies and 60 disease-free controls. A unit (U) of enzyme activity is the release of one n-mol of 7-amino-4-fluoromethylcoumarin (AFC) from BZ-val-lys-lys-arg-MNA min-1 ml-1. Units of activity in the malignant group (10.6 +/- 9.8) differed significantly (p less than 0.0001) from controls (2.8 +/- 3.3). Although enzyme activity in both groups correlated with increasing age, the difference between those subjects with malignancies and those with none remained significant (p = 0.049) by analysis of covariance after adjusting for age. There was no correlation between titers and the race or weight of the subjects in either group. Enzyme activity of subjects with malignant disease correlated (p = 0.003) with the clinical stage of disease. Optimum sensitivity and specificity as determined by Receiver Operator Characteristic Analysis with an upper normal level of 5 U were 84.2% and 86.7%, respectively. Our findings suggest that measurement of urinary cathepsin B might be useful in detecting and managing patients with gynecologic tumors.

Malignant pericardial effusions: pathophysiology and clinical correlates.

Cardiac tamponade resulting from malignant pericardial effusions is a life-threatening oncologic emergency. As many as 21% of all patients with cancer may be at risk for this complication. A malignant effusion often signifies progressing disease, creating stress and anxiety for patients and their families. By understanding the pathophysiology and pertinent risk factors, the nurse may identify an effusion before it progresses to cardiac tamponade. The goal of management is removal of fluid, restoration of hemodynamic functioning, and prevention of fluid reaccumulation. Emotional support and reassurance, as well as accurate information regarding the disease and treatment, also are critical in assisting patients to adapt to these changes in disease status.

Mild cervical dysplasia. Experience in a family planning clinic.

To evaluate mild cervical dysplasia, the results of Papanicolaou smears were reviewed for a six-month period in an inner-city family planning program. Papanicolaou smear evidence of mild dysplasia was consistent with the biopsy diagnosis in most cases. A single Papanicolaou smear is not a reliable indication of condylomata, nor is a single normal Papanicolaou smear in this setting completely reassuring. Persistent mild dysplasia is an indicator of high risk for cervical dysplasia and cervical infection. Aggressive initial cervical surgery is not indicated, but close follow-up is required.