Limb lengthening in congenital posteromedial bow of the tibia.

Congenital posteromedial bowing of the tibia (PMBT) is a rare condition affecting one lower limb. The bowing of the tibia usually resolves; however, there is associated limb length discrepancy (LLD), which often persists and can cause functional deficits. Advances in limb lengthening techniques allow this issue to be addressed, often with concomitant angular deformity correction. This study examined eleven patients who have had limb lengthening procedures with mean pre-operative LLD of 3.7 cm (range 1.5-5 cm), mean increase in length was 3.9 cm (range 1.5-5.8 cm), and mean LLD at last follow-up was less than 0.6 cm (range 0-2.0 cm). The main complications were minor or moderate grades, such as pin site infection. Greater LLD was found than previously reported, and we believe that the tertiary referrals were those of a severe form of PMBT. The authors conclude that in view of deformity with discrepancy, in select cases, correction and lengthening would be an option rather than only contralateral epiphysiodesis.

Management of lithium in patients with cancer.

This article reviews the management of lithium in patients who require optimum management of cancer and simultaneous prevention of mania or depression in lithium-sensitive affective illness. Two cases are described. Discussion focuses on whether lithium should be continued during chemotherapy and radiation treatment, the complications that would lead to lithium toxicity in an otherwise stable patient, the likely settings for hypothyroidism, and the role of lithium to stabilize steroid-induced affective changes. The authors conclude that lithium may be withheld 1 or 2 days before cytotoxic chemotherapy and restarted when the patient is able to drink. It may be given as usual through routine radiation treatment, but it should be discontinued during cranial radiation. Calcium, renal, cardiac, and thyroid functions should be monitored.

Parathyroid hormone-related peptide mediates hypercalcemia in an islet cell tumor of the pancreas.

Hypercalcemia occurring in a patient with an islet cell carcinoma of the pancreas suggests the diagnosis of Multiple Endocrine Neoplasia Type I and associated hyperparathyroidism. We describe a patient with an islet cell carcinoma and hypercalcemia in whom low concentrations of PTH, the absence of skeletal metastases, hypophosphatemia, and elevated nephrogenous cAMP alternatively suggested the syndrome of humoral hypercalcemia of malignancy. The peptide PTHrP was measured in the patient's serum during the course of therapy by an immunoradiometric assay directed toward the midportion of the molecule. Hypercalcemia was treated with an investigational aminobisphosphonate. The concentration of PTHrP[56-86] increased over time and fell after the patient received chemotherapy directed toward the islet cell tumor.

Invasive bladder carcinoma: preliminary report of selective bladder conservation by transurethral surgery, upfront MCV (methotrexate, cisplatin, and vinblastine) chemotherapy and pelvic irradiation plus cisplatin.

Methotrexate, Cisplatin, and Vinblastine (MCV) was followed by Cisplatin plus radiation therapy in 19 patients with muscle-invading clinical Stage T2-4NXM0 transitional cell carcinoma of the urinary bladder (including cystectomy candidates), to achieve local control and prevent distant metastases. Radical cystectomy was recommended for all patients who failed to reach a complete response (CR = biopsy negative and cytology not positive) following MCV and Cisplatin X 2 plus 4000 cGy. Completely responding patients, and those partially responding patients unsuited for cystectomy, were selected for bladder conservation treated with additional irradiation to the bladder tumor volume (total 6,480 cGy) plus one additional Cisplatin treatment. Dose reductions were required for stomatitis in 26%, mild bone marrow depression in 58%, and renal toxicity in 5% of the patients. During the Cisplatin/4000 cGy, mild dysuria occurred in 68% of patients and 36% had mild bowel hyperactivity. Serious complications have occurred in two patients to date. One patient had recurrent pulmonary emboli, marked reduction in bladder capacity, and diarrhea. A second had bladder perforation during cystoscopic evaluation after MCV and a small bowel obstruction after Cisplatin and 4000 cGy. There was no treatment-related sepsis. Three patients had initial complete transurethral resection of their tumors and therefore 16 patients are evaluable for tumor responsiveness to this protocol. Four patients (25%) were biopsy negative and cytology negative, whereas three additional patients (19%) were biopsy negative but cytology positive following initial MCV. Six patients (38%) were biopsy negative and cytology negative whereas three additional patients (19%) were biopsy negative and cytology positive following MCV and Cisplatin X 2 plus 4000 cGy pelvic radiation. Of the entire group, 9 patients were treated with full-dose radiotherapy. All of these patients are alive without evidence of tumor on rebiopsy of the original tumor site, but one has a persistent positive cytology. Seven patients had a radical cystectomy and 6 are disease free. The treatment of 3 patients deviated from the protocol. Overall, only one patient has developed distant metastases and currently 84% of the patients are disease-free, although follow-up is short. To date, this feasibility study has been clinically practical and well tolerated. The proportion of CR's suggests that this program may prove to be an organ-sparing and curative approach for a significant number of patients, but more experience and follow-up are required.

Intraoperative radiation therapy in patients with bladder cancer. A review of techniques allowing improved tumor doses and providing high cure rates without loss of bladder function.

Conventional external beam irradiation, using modern megavoltage techniques and doses that do not harm bladder function, will permanently eradicate local bladder cancer in 30% to 50% of patients, compared with 70% to 90% with cystectomy. In appropriately chosen patients, open surgery can safely provide excellent exposure for the selective delivery of more radiant energy directly to the tumor and less to the uninvolved portion of the bladder. Intraoperative radiation therapy, by either a removable radium or iridium implant or a large single dose of electrons, has been reported to be safe and can permanently cure the bladder of cancer and also preserve bladder function in more than 75% of patients with solitary tumors that invade into but not beyond the bladder muscle. With the increasing interest in and availability of intraoperative radiation therapy in the US, this curative and bladder-sparing treatment for operable patients with bladder cancer invading the trigone is appropriate for careful clinical trial.

Invasive bladder carcinoma. The importance of initial transurethral surgery and other significant prognostic factors for improved survival with full-dose irradiation.

This review covers recent observations (all retrospective) on useful prognostic indicators in patients treated by radiation for this heterogeneous disease, including presenting clinical characteristics, extent of conservative surgery, radiographic studies, and pathologic subtypes. Although imperfect and incomplete, this review offers some criteria to identify which patients will do well and which quite poorly if treated by bladder-preserving full-dose radiation therapy. Such criteria should help clinicians recommending full-dose radiation therapy, radical cystectomy, or innovative combinations of chemotherapy, radiation, and surgery.

Small cell carcinoma of the lung. A progress report of 15 years' experience.

To assess the results of therapeutic advances in the treatment of small cell carcinoma of the lung (SCCL) achieved during the past 15-year period at a single large institution, 508 patients treated between 1968 and 1982 were divided into two groups: 157 patients (66 in the category of limited-stage disease and 91 in the extensive-stage disease category) treated with low-dose small-volume radiotherapy (RT) (time dose fractionation [TDF] 49-66) and with cyclophosphamide alone or a COPP program during the first period of 7 years (1968-1974); 351 patients (180 in limited and 171 in extensive stage) treated with multidrug chemotherapy (CT) and high-dose large-volume RT (TDF 73-89) during the second period of 8 years (1975-1982). For patients with limited-stage cancer, 5-year actuarial survivals were 3% versus 7% for the periods 1968-1974 versus 1975-1982, respectively, P less than 0.01. For patients with extensive-stage cancer, the median survival time (MST) and 2-year actuarial survivals were 5 months and 2% versus 7 months and 4% for the periods 1968-1974 versus 1975-1982, respectively. To evaluate the outcome of a contemporary approach, i.e., CT alone, with RT reserved for locoregional failure, 180 patients with limited-stage cancer who were treated (1975-1982) were further analyzed for MST, 2- and 5-year actuarial survival figures, and local-tumor control rates according to the therapeutic approaches employed: CT + RT (112); CT alone (36); RT alone (17); and surgery (S) +/- CT +/- RT (15). Although the 36 patients in CT alone seems a small number, 17 of the 36 patients were enrolled in this approach in 1981-1982, reflecting a shift of emphasis from RT to CT. The MST and 2-year actuarial survival figures were 11 months and 0% versus 13 months and 21% for CT alone versus CT + RT respectively, P less than 0.05. CT + RT achieved a 5-year cure rate of 8%. S +/- CT +/- RT or RT alone also achieved 5-year cure rates of 8% and 10.5%, respectively, in selected subsets of patients. Local relapse rates were 80% (29/36) versus 25% (28/112) for CT alone versus CT + RT. These data emphasize the importance of thoracic RT given at the early phase of treatment to improve long-term survival for patients with limited-stage SCCL.

Treatment of colorectal cancer hepatic metastases by hepatic artery chemotherapy.

Our clinical experience with 69 patients with metastatic colorectal cancer to the liver treated with hepatic artery chemotherapy is reviewed. All patients have had a minimum of six months follow-up. The Infusaid implantable drug delivery system was used by direct laparotomy in one third, and via the transaxillary approach in the remaining two thirds. Two thirds of the patients had at least 25 percent of the liver replaced with tumor. Chemotherapeutic agents included FUdR, mitomycin C, and BCNU. The overall response rate was 51 percent and 69 percent for the three-drug combination. Efficacy was not different in patients who had received prior systemic fluorouracil. Median survival from start of hepatic artery chemotherapy was one year.

Intraoperative electron beam irradiation for patients with unresectable pancreatic carcinoma.

Since 1978 we have used electron beam intraoperative radiation therapy (IORT) to deliver higher radiation doses to pancreatic tumors than are possible with external beam techniques while minimizing the dose to the surrounding normal tissues. Twenty-nine patients with localized, unresectable, pancreatic carcinoma were treated by electron beam IORT in combination with conventional external radiation therapy (XRT). The primary tumor was located in the head of the pancreas in 20 patients, in the head and body in six patients, and in the body and tail in three. Adjuvant chemotherapy was given in 23 of the 29 patients. The last 13 patients have received misonidazole (3.5 mg/M2) just prior to IORT (20 Gy). At present 14 patients are alive and 11 are without evidence of disease from 3 to 41 months after IORT. The median survival is 16.5 months. Eight patients have failed locally in the IORT field and two others failed regionally. Twelve patients have developed distant metastases, including five who failed locally or regionally. We have seen no local recurrences in the 12 patients who have been treated with misonidazole and have completed IORT and XRT while 10 of 15 patients treated without misonidazole have recurred locally. Because of the shorter follow-up in the misonidazole group, this apparent improvement is not statistically significant. Fifteen patients (52%) have not had pain following treatment and 22 (76%) have had no upper gastrointestinal or biliary obstruction subsequent to their initial surgical bypasses and radiation treatments. Based on the good palliation generally obtained, the 16.5-month median survival, and the possible added benefit from misonidazole, we are encouraged to continue this approach.

Regional hepatic chemotherapy using an implantable drug infusion pump.

Regional infusion of chemotherapeutic agents in the treatment of liver cancer can greatly increase tumor exposure to certain drugs. Exposure is 100 times greater with floxuridine, 6 times greater with mitomycin C, and 6 times greater with BCNU. The Model 400 Infusaid implantable, refillable drug infusion pump overcomes much of the discomfort and inconvenience associated with previously employed extracorporeal systems. Our experience with our first 50 patients has been presented herein. Forty-one patients had metastatic colorectal cancer, 3 primary cancers, and 6 other metastatic cancers. Eleven pumps and 11 catheters were implanted at laparotomy. Thirty-nine patients had their pumps integrated to angiographically placed catheters. In over 260 patient months there were no pump malfunctions and only one infection. There were no vascular complications in the patients with angiographically placed catheters. Chemotherapeutic programs included floxuridine, floxuridine and radiotherapy, or floxuridine with mitomycin C and BCNU. In 18 patients with evaluable metastatic colorectal cancer who received hepatic arterial combination chemotherapy, there were therapeutic responses in 13 and disease stabilization in 4. The pumps were well tolerated by patients. They offer a reasonable approach to long-term ambulatory regional hepatic chemotherapy.

Evaluation and management of chylous ascites.

Twenty-eight cases of chylous ascites occurring over the past 20 years are analyzed for clinical presentation, cause, yield of diagnostic procedure used, and response to therapy. Malignancies were responsible for 21 of 24 adult cases of chyloperitoneum, with lymphomas predominating (13 cases). The dismal prognosis in adult cases (12 patients died within 3 months) shows the need for appropriate diagnostic assessment including early lymph node biopsy or laparotomy, or both, when indicated. Surgery, chemotherapy, or radiation therapy should be instituted promptly except in cases resulting from surgical trauma to lymphatics, which frequently resolve with conservative management. Three of the four pediatric cases of chylous ascites resulted from congenital lymphatic anomalies; the fourth case resulted from operative trauma. Aggressive diagnostic and therapeutic interventions are not warranted in childhood cases of chylous ascites until conservative management (paracentesis, low-fat diet, medium-chain triglyceride supplementation) has failed; neoplasia is rarely implicated and many cases resolve within a few months.

Vinblastine, infusion, bleomycin, and cis-dichlorodiammine-platinum chemotherapy in metastatic melanoma.

A chemotherapy regimen containing vinblastine-bleomycin-platinum has been studied in 42 patients with advanced malignant melanoma. Forty-seven percent of evaluable and 43% of all patients experienced objective response. Complete responses were seen in visceral sites. Median duration of response has not been reached but will exceed 26 weeks. Toxicity is predominantly marrow suppressive, gastrointestinal, pulmonary, and mucocutaneous. Pulmonary toxicity was never severe when bleomycin dose was limited to less than 300 mg/m2 body surface area. Half of the patients relapsed with CNS metastases as a first presenting sign of recurrence. Because hospitalization is required in this program its dollar cost is high.

Randomized trial of adjuvant therapy for "high risk" primary malignant melanoma.

Retrospective pathological classification of 213 patients with malignant melanoma identified a group at high risk of recurrence (25% developed recurrence in 12 months, 50% by 5 years) after resection for apparent cure. Using these criteria, 70 patients were identified after resection of all apparent disease as being at high risk for recurrent melanoma. They were randomly assigned to one of the three adjuvant treatment arms: chemotherapy with dimethyl triazeno imidazole carboxamide (DTIC), immunotherapy with bacillus Calmette-Guerin (BCG), or combined chemoimmunotherapy. Six of 20 patients receiving DTIC developed recurrence (30%) and four died (20%). Five of 28 patients receiving BCG developed recurrence (18%) and two died (7.5%). There have been no recurrences or deaths in 22 patients receiving combined chemoimmunotherapy. In the prevention of early recurrence, the combined therapy arm was significantly superior to both the immunotherapy arm (p less than 0.05) and the chemotherapy arm (p less than 0.01). In terms of survival, combined therapy also was superior to chemotherapy alone (p less than 0.05).