Evaluation of the effectiveness of postoperative radiation therapy for the control of local disease

Although we agree that postoperative irradiation does improve the local and regional control, our findings indicate that the rate of control, especially local control, is somewhat less than 90 percent. Our data reveal a recurrence rate of 32.7 percent in advanced, stage III and IV, squamous cell carcinomas in the head and neck treated by surgery and post-operative irradiation; this rate may be even greater with longer follow-up. We recommend that surgeons avoid “close” surgical margins (less than 5 mm) when resecting primary cancers and not rely too heavily on radiation therapy to control residual subclinical disease. It appears that continued study is needed to establish the true efficacy of irradiation in the control of subclinical disease, and that local recurrence must be differentiated from regional recurrence when reporting these results.     

Resectional management of thyroid carcinoma invading the airway.

Fifty-two patients had thyroid carcinoma invading the airway. Thirty-four underwent resection; 18 were male and 16 female. Age ranged from 17 to 79 years. Twenty-seven had resection with airway reconstruction (1 wedge excision, 10 sleeve tracheal resections, 6 tracheal resections with a portion of the cricoid cartilage, and 10 complex laryngotracheoplastic resections). Seven required cervicomediastinal exenteration with mediastinal tracheostomy; 3 of these had esophagectomy with colon interposition. Nineteen tumors were papillary, 6 follicular, 4 mixed papillary and follicular, 1 squamous, 2 undifferentiated giant cell, 1 anaplastic spindle cell carcinoma, and 1 carcinosarcoma. Three postoperative deaths occurred. Thirteen of the 31 survivors died of cancer from 1/4 to 10 1/4 years postoperatively (average, 4.4 years). Four died of other diseases. Fourteen are alive from 1/12 to 14 1/3 years postoperatively (average, 5.3 years). Only 2 patients had airway recurrence. Resection of the airway invaded by thyroid malignancy in the absence of extensive metastases offers prolonged palliation, avoids suffocation due to bleeding or obstruction, and may produce cure. Airway reconstruction should be performed whenever technically feasible.     

Pneumomediastinum and retropneumoperitoneum: An unusual complication of syrup-of-ipecac-induced emesis

A young woman returned to the emergency department two hours after discharge because of persistent vomiting and chest pain. Six hours earlier she had received syrup of ipecac to induce emesis following a drug overdose. Radiologic examination in the emergency department revealed pneumomediastinum and retropneumoperitoneum. A nasogastric tube was inserted in the emergency department. The patient was admitted to the ICU and placed on prophylactic antibiotics. Barium and gastrograffin esophagrams revealed no evidence of extravasation. Gastrointestinal endoscopy showed distal esophagitis. Gastroscopy and duodenoscopy were unremarkable. The patient did well following discharge.     

The clinical significance of routine histopathologic study of the resected appendix and safety of appendiceal inversion

A prospective study was done on 1,699 patients operated upon for appendicitis to correlate the operative diagnosis of the surgeon and the histopathologic diagnosis of the pathologist. There are surgeons who only send the appendices for histopathologic study when the operative findings are inconclusive and surgeons who invert rather than resect the appendices on finding a grossly normal appendix at operation. This study was done to find out whether or not these practices of leaving some of the appendix unexamined histopathologically are clinically safe. In this study, surgeons missed abnormal pathologic findings in the appendix in ten of 13 patients and this is irrespective of whether the appendix was normal, acutely inflamed, gangrenous or perforated. The majority of these lesions either require further investigation, treatment or they affected the prognosis of the patient. Nineteen per cent of the patients diagnosed as having normal appendices grossly were found to have acute appendicitis and 7.7 per cent diagnosed as acute appendicitis were normal. Based upon these data, we conclude that the operative diagnosis of the surgeon cannot be relied on to detect abnormal pathologic findings in the appendix. Additional important clinical information can be gained by routine histopathologic study of the resected specimens, and inversion of the appendix is clinically not safe.     

Cisplatin potentiation of radiotherapy. Long-term follow-up

Thirty-three patients with inoperable squamous cell carcinoma of the head and neck were treated with cisplatin, 15 mg/sq m, administered synchronously with high-dose radiation therapy. Twenty-nine patients (88%) responded to the regimen; of these, 20 had complete regression of all disease. Eight of the 20 had a relapse in less than one year of their treatment. Among those patients who did not have a relapse, the follow-up period was short. It is concluded that a clinical regression response is more likely with this treatment regimen than with radiation therapy alone, and that that response may be a better palliation. Further study of this combination of treatment modalities is warranted.     

CpG oligodeoxynucleotides and interleukin-12 improve the efficacy of Mycobacterium bovis BCG vaccination in mice challenged with M. tuberculosis

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine approved for prevention of tuberculosis. It has been postulated that serial passage of BCG over the years may have resulted in attenuation of its effectiveness. Because interleukin-12 (IL-12) and oligodeoxynucleotides (ODN) containing cytidine phosphate guanosine (CpG) motifs have been shown to enhance Th1 responses in vivo, they were chosen as adjuvants to increase the effectiveness of BCG vaccination. In this report, mice were vaccinated with BCG with or without IL-12 or CpG ODN and then challenged 6 weeks later via the aerosol route with the Erdman strain of M. tuberculosis. Mice vaccinated with BCG alone showed a 1- to 2-log reduction in bacterial load compared with control mice that did not receive any vaccination prior to M. tuberculosis challenge. Moreover, the bacterial loads of mice vaccinated with BCG plus IL-12 or CpG ODN were a further two- to fivefold lower than those of mice vaccinated with BCG alone. As an immune correlate, the antigen-specific production IFN-gamma and mRNA expression in spleen cells prior to challenge were evaluated. Mice vaccinated with BCG plus IL-12 or CpG ODN showed enhanced production of IFN-gamma compared with mice vaccinated with BCG alone. Finally, granulomas in BCG-vaccinated mice were smaller and more lymphocyte rich than those in unvaccinated mice; however, the addition of IL-12 or CpG ODN to BCG vaccination did not alter granuloma formation or result in added pulmonary damage. These observations support a role for immune adjuvants given with BCG vaccination to enhance its biologic efficacy.     

Role of the IGF system in trophoblast invasion and pre-eclampsia

Insulin-like growth factor-II (IGF-II) and IGF binding protein-1 (IGFBP-1) appear to play an important role in paracrine interactions at the maternal-fetal interface in human pregnancy. Patterns of expression of IGF-II and IGFBP-1 at the decidual-trophoblast interface suggest paracrine interactions occur between the IGF-II-expressing invading cytotrophoblast and maternal decidua-derived IGFBP-1. Autocrine/paracrine actions of trophoblast-derived IGF-II may be important in invasion, and for both trophoblast and decidual function. The actions of IGFBP-1 in binding IGF, and as an integrin ligand, suggest it may have multiple roles in the interactions between the invading trophoblast and the maternal decidua. Abundant decidual IGFBP-1 may interact with the IGF-II-expressing, protease-secreting trophoblast to modulate invasion. In-vitro studies of trophoblast-decidual cell interactions in invasion, and clinical observations in a gestational disorder with shallow placental invasion such as pre-eclampsia, have provided new insights into the possible role(s) of IGFBP-1 in trophoblast invasion. The precise mechanisms underlying IGF and IGFBP-1 action at the decidual-trophoblast interface remain to be elucidated. The potential predictive value of serum IGFBP-1 concentrations in pre-eclampsia also remains to be established.