Carcinoma of the anus treated with primary radiation therapy and chemotherapy.

Between 1983 to 1989, 24 patients with previously untreated carcinoma of the anal canal (less than 3 centimeters in five patients and more than 3 centimeters in 19 patients) were entered in a prospective nonrandomized protocol of primary radiotherapy (4,050-4,500 cGy days one to 28) and chemotherapy (10 milligrams per meter squared of mitomycin C, on day two and 1,000 milligrams of 5-fluorouracil per molar squared for days two to five and 28 to 32). Therapy was discontinued for two patients because of severe (grade 4) skin reactions. The remaining patients tolerated the regimen well, with the exception of two patients who had grade 3 hematologic toxicity and three patients with grade 3 to 4 complications of the gastrointestinal tract. All of the patients who completed the regimen had a complete clinical and pathologic response when restaged six weeks after completion of therapy. All patients with lesions of less than 3 centimeters and 13 of 19 patients with lesions greater than 3 centimeters have remained free of disease (median follow-up period of 41 months; median survival rate of 36 months). Before 1983, 19 patients underwent abdominal perineal resection as primary treatment for carcinoma of the anus. Only six of seven patients with lesions less than 3 centimeters and zero of the 12 patients with lesions equal or greater than 3 centimeters have remained alive and free of disease. Eighteen of 24 patients treated with chemotherapy and radiotherapy only have remained free of disease and have preserved anal function. These results are superior to those reported with primary surgical treatment and primary radiotherapy only.

Preoperative chemotherapy and radiotherapy for cancer of the esophagus.

BACKGROUND: We wished to determine the role and significance of preoperative chemotherapy and radiotherapy in management of operable cancer of the esophagus. METHODS: Twenty-two patients with clinical stage I-II cancer of the esophagus were entered in a prospective study of preoperative chemotherapy (5-fluorouracil/cisplatin) and radiotherapy (3405 cGy) administered concomitantly during 21 days followed by restaging and total esophagectomy. RESULTS: Five patients did not complete the protocol (three had toxicity, one refused surgery, and one had interim distant metastasis). Seventeen patients underwent total esophagectomy with cervical anastomosis. Two postoperative deaths resulted from sepsis. Thirteen (76%) of 17 patients were considered to have complete clinical response (esophagoscopy and computed axial tomographic scanning) before surgery, but only 5 (29%) of 17 were free of cancer. The median survival was 18 months (median follow-up 57 months). No difference in survival was seen between complete and partial pathologic response. CONCLUSIONS: (1) Preoperative chemotherapy and radiotherapy did not result in increased survival compared with historic controls (surgery alone). (2) Preoperative chemotherapy and radiotherapy clinical staging overestimates the incidence of complete tumor response. (3) Combination chemotherapy is well tolerated, but until newly developed drugs show their efficacy for treatment, surgery should continue to be the major modality for local control and an integral part of clinical investigational trials.

Acalculous cholecystitis in bone marrow transplant patients.

BACKGROUND: Acalculous cholecystitis (ACC) is an uncommon disorder of the biliary tract, accounting for approximately 6% of acute cholecystitis cases. In this study, cholecystitis was seen in 8 of 770 bone marrow transplant recipients, with ACC occurring in five (63%). METHODS: Records of 592 allogenic and 150 autologous BMT patients were reviewed for risk factors associated with ACC. RESULTS: Only the number of blood transfusions administered and the use of total parenteral nutrition were associated with ACC development. ACC occurred in 4 of 42 (9%) allogeneic recipients who required exchange transfusion for ABO incompatibility. ACC developed in one autogolous recipient alongside venoocclusive disease of the liver. There was no association between ACC development and preparative regimen, cyclosporine usage, graft versus host disease, or cytomegalovirus infection. CONCLUSIONS: ACC occurs more frequently in patients after ABO incompatible BMT requiring exchange transfusion than in other transplant recipients.

Extended indications for functional limb-sparing surgery in extremity sarcoma using complex reconstruction.

From 1980 to 1991, 29 patients underwent complex reconstruction following extremity sarcoma resection. Soft tissue was the site of origin in 15 patients (52%) and bone was the site of origin in 14 patients (48%), with 20 sarcomas (69%) in the lower extremity. Resection consisted of the following procedures: extended anatomical soft-tissue resections (21 patients [72%]), bone resections (18 patients [62%]), and joint resections (14 patients [48%]). Reconstruction involved the following: myocutaneous flaps (20 patients [69%]), joint prosthesis (eight patients [28%]), and bone reconstruction (15 patients [52%]). There was no surgical mortality; one patient required an amputation owing to surgical complications. The site of the first failure was local (four [31%] of 13 patients), lung (five patients [38%]), others (four patients [31%]). At a median follow-up of 23 months, 18 patients (62%) had no evidence of disease, 27 (93%) had no local disease, 21 (72%) had good extremity function, three (10%) had major disabilities, and five (17%) underwent amputations. Local control improved when the margin of resection was larger than 10 mm. Disease-free survival was 67% at 3 years. Overall survival was 51% at 5 years. Tumor size was an independent predictor of overall survival. Local recurrence did not affect overall survival.

Survival of patients with metastatic breast cancer diagnosed between 1955 and 1980.

In order to determine whether current programs for the management of metastatic breast cancer have led to improved patient survival, we determined the median survival times for five-year intervals of 849 patients admitted to the City of Hope National Medical Center with metastatic breast cancer from 1955 to 1980. Survival curves were constructed from the dates of first diagnosis of breast cancer and to the first metastasis for all population subsets and clinical subsets: menopausal status, presence or absence of visceral metastases, length of disease-free interval, and pattern of palliative therapy. In this analysis, the median survival in each successive interval of five years from diagnosis of the primary tumor was 52.1, 45.0, 49.9, 41.1, and 36.0 months, and the survival times from the first metastasis were 31.9, 23.0, 24.2, 23.9, and 18.7 months. Survival times in each of the clinical subsets remained unchanged during the period of observation, regardless of the therapeutic modalities included in the treatment regimens. This study indicates that changes in palliative therapy for metastatic breast cancer during the 25 years of observation have not influenced overall survival. Therefore, it seems appropriate that the therapeutic risk/benefit ratio and impact on quality of life should be reassessed when asymptomatic patients are treated, or when aggressive palliative therapy is used outside a clinical research setting.

The value of symptom directed evaluation in the surveillance for recurrence of carcinoma of the breast.

Specific postoperative tests used to diagnose recurrent carcinoma of the breast were evaluated for their ability to have an impact on the over-all course of the disease. Sixty-four patients with recurrent or new contralateral primary disease were divided into two groups based on the method of diagnosis. Those patients with a new complaint at an interval between scheduled follow-up visits and who went on to have tests to document a recurrence were categorized as interval follow-up. Those who were seen at a prearranged regular follow-up period and received tests as recommended by the attending physician or surgeon and had a documented recurrence were classified as routine follow-up. Thirteen patients presented with new contralateral primary disease and 51 with metastatic disease (16, bone; 13, lung; 11, local; three, liver, and eight, multiple). The median time to discovery of recurrence from the primary treatment was 29 and 28 months for the interval and routine groups, respectively. Ninety per cent of the failures occurred by 53 months. The survival time after recurrence was significantly greater in those patients diagnosed routinely (p = 0.003). However, the over-all survival time (from primary therapy to death) was only significantly improved for the routine group when the contralateral new primary diseases were included (p = 0.009). The method of diagnosis of a contralateral primary carcinoma was physical examination and mammogram. Strong recommendations for follow-up testing can be limited to mammogram and physical examination.

A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver.

Over a 4-year period (1982 to 1986), 91 patients with solitary or multiple metastases from colorectal cancer were stratified, based on findings at laparotomy, to one of three groups and then prospectively randomized to one of two treatment arms within each group. Group A patients had solitary resectable metastases, group B patients had multiple, resectable metastases, and group C patients had multiple, unresectable metastases. Patients were randomized to one of two treatment arms within a group: group A-arm A1: resection only, arm A2: resection and continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUdR); group B-arm B1: resection and CHAI, arm B2: CHAI only; group C-arm C1: CHAI, arm C2: systemic fluorouracil followed by CHAI. Median time to failure (TTF) was 31.8, 11.1, and 8.8 months for groups A, B, and C, respectively. Arm A2 had an improved TTF when compared with arm A1 (P = .03). Median survival correlated with extent of disease and was 37.3, 22.4, and 13.8 months for groups A, B, and C, respectively. Survival was not changed by treatment variation (arms) within each group. Two- and 5-year cumulative survivals for groups A, B, and C were 72.7% and 45.4%; 45.8% and 16.7%; and 31.7% and 3.2%, respectively. In patients with multiple metastases (groups B and C), those patients whose original tumor was a Dukes' B had a significantly improved TTF and survival over those patients whose tumor was a Dukes' C (P less than or equal to .02).

Parascapular free flaps for head and neck reconstruction.

We report our experience with single-stage, primary reconstruction of the head and neck in 29 consecutive patients using parascapular free flaps. The commonest indications were for craniofacial defects (9), oropharyngeal soft tissue defects (10), and combined mandibular and soft tissue losses (4). Ablative surgery was performed for squamous carcinoma (22), melanoma (2), and malignant fibrous histiocytoma (2). Seven patients died of recurrent disease during a 3 1/2 year follow-up. Seven patients are alive with recurrence. Flap complications included total loss (2) due to unsalvageable microvascular thrombosis, wound breakdown with oropharyngeal fistula (2), mandibular osteomyelitis (1), trismus (2), neck contracture (1), and donor site wound dehiscence (1). The overall success of this reconstruction was 93%. Primary wound healing was the general rule with lower morbidity than with other reconstructive techniques. The flap is thin, pliable, and conforms well to three-dimensional defects. The lateral border of the scapula can be incorporated on the same vascular pedicle for single-stage mandibular reconstruction. No muscle is sacrificed, and the posterior donor defect is an added advantage. The parascapular flap is our first choice for reconstruction of major defects in the head and neck.

Translumbar amputation.

Six patients underwent translumbar amputation (TLA), a life-saving procedure, after standard modalities of therapy failed to control the progression of the disease. The primary diagnoses were as follows: pelvic arterial-venous (A-V) malformation, 1; sacral chordoma, 3; giant cell tumor of the sacrum, 1; and paraplegia with squamous cell cancer arising in intractable decubitus, 1. There were no operative deaths. The following postoperative complications developed in five patients: urinary fistulae, 2; small bowel obstruction, 1; intraabdominal bleeding, 1; hypertension, 2; small bowel fistula, 1; and dehiscence of skin closure, 1. Two patients died with distant metastases (24 months) and distant metastases with local recurrence (6 months). The remaining four patients were alive and well 72, 56, 48, and 18 months after the surgical procedure. All of these patients have reached the rehabilitation goals.

A prospective, randomized double-blind study of the use of antibiotics at the time of mastectomy.

The ability of perioperative cefazolin to reduce the incidence of postoperative wound infection in patients undergoing ablative surgical treatment for carcinoma of the breast was tested in this prospective, randomized, double-blinded study. From May 1983 until December 1985, 118 women were divided into two groups at random. Group 1 consisted of 59 patients and received cefazolin and group 2 was made up of 59 patients who received a placebo. The groups were similar with respect to age, operative procedure, operative time and time to discharge after operation. Three infections occurred among those in group 1 and five among those in group 2 (p = 0.72). The time to onset of infection was delayed in the patients in group 1 versus those in group 2 (17.7 days versus 9.6 days, p = 0.04). Six of eight infections occurred in patients in whom an interval between biopsy and definitive surgical treatment was present. Prophylactic antibiotics in mammary operations did not reduce postoperative wound infections in this study.

Central venous thrombosis related to the silastic Hickman-Broviac catheter in an oncologic population.

The use of subcutaneously implanted, Dacron cuffed, central venous silastic catheters (Hickman/Broviac catheter [HC/BC]) has not eliminated catheter related-central venous thrombosis (CR-CVT). HC/BC related CR-CVT was identified and followed in 15 oncology patients. Median time period to CR-CVT was 155 days (range 15-638). No correlation was established to patient age, sex, diagnosis, coagulation status, use, longevity, technique, or site of placement. Fourteen patients were treated with anticoagulation and/or thrombolytic therapy. Of seven patients treated with HC/BC in situ, one required HC/BC removal to achieve CR-CVT resolution. Median follow-up post-CR-CVT was 362 days (range 34-1622). No patient suffered untoward long-term sequelae. Nine patients had 11 catheters placed following resolution of CR-CVT. None had repeat thrombosis. CR-CVT incidence in a single 12-month period was 3.7% (7/190). The placement of HC/BC in an oncology population is an acceptably safe method for long-term venous access.

Evaluation of a short-stay program for patients undergoing mastectomy.

Two hundred twenty-eight patients were included in a retrospective study to evaluate the morbidity and feasibility of early discharge after mastectomy. Group I (early discharge, n = 75) patients were given pre- and postoperative instruction related to wound and drain care. Group II (concurrent control, n = 44) was given similar postoperative instruction, but received no preoperative teaching. Group III (historical controls, n = 109) underwent surgery during a period of more liberal hospitalization and discharge policies. The groups were similar in age, cultural background, operations performed, and pathologic diagnosis. Length of stay for groups I, II, and III was 5.5 +/- 0.4, 3.5 +/- 0.2, and 8.6 +/- 0.3 days, respectively. Groups I and II had a significantly shorter stay than group III. There was no difference among the groups for the presence of wound erythema, rate of primary healing, seroma formation, or wound infection. The practice of same-day admission and early discharge to limit length of stay for patients undergoing mastectomy is safe and effective.

Tumor DNA content in resectable, primary colorectal carcinoma.

Tumor DNA content was measured in patients with colorectal carcinoma in order to determine whether tumor ploidy was a prognostic indicator independent of standard clinical and pathologic characteristics. One hundred forty-seven patients were analyzed who had their primary resectable colorectal carcinomas resected with curative intent from 1974 to 1981. Aneuploid colorectal cancers (i.e., tumors with abnormal DNA content) tended to be less well-differentiated, to invade the serosa or extend beyond, and to have lymph node metastases rather than diploid tumors (i.e., tumors with normal DNA content). A significantly increased rate of recurrent disease was demonstrated in patients with aneuploid tumors as opposed to those with diploid tumors (46.7% vs. 4.8%, respectively [p less than 0.001]). In addition, patients with aneuploid tumors exhibited a significantly decreased disease-free and overall survival in comparison with patients with diploid colorectal carcinomas. A Cox regression analysis demonstrated that tumor DNA content was the single most important factor in predicting recurrence or death from colorectal carcinoma.

Complications of abdominal operations for malignant disease.

The incidence of morbidity and mortality in 365 consecutive patients with a mean age of 60 years who underwent intraabdominal operation for a variety of cancers involving different organ systems over a recent 2-year period was analyzed. The primary tumor sites were the esophagus (21 patients), gastroduodenum (33 patients), liver and gallbladder (6 patients), pancreas (15 patients), colorectum (101 patients), lymphoproliferative disorders (35 patients), abdominal carcinomatosis (45 patients), genitourinary and gynecologic systems (94 patients), and other sites (15 patients). One hundred eighty-two patients (49 percent) had 1 or more complications (grouped as gastrointestinal, septic, cardiopulmonary, and nonseptic) and 47 patients died (12.9 percent). The 145 patients who underwent a palliative procedure had the highest morbidity and mortality rates (41 percent and 21 percent, respectively). In the 168 patients who had curative resection, the morbidity and mortality rates were 39 percent and 9 percent, respectively, and in 51 patients with a diagnostic laparotomy, 20 percent and 4 percent, respectively. Age was not a contributory factor. The 177 malnourished patients had a significantly higher incidence of complications (72 percent) and postoperative death (23 percent) than the well-nourished patients (29 percent and 4 percent, respectively; p less than 0.001). These differences also existed with each form of complication. Of those patients without complications, the majority resumed consuming 60 percent of their caloric requirements by postoperative day 9. In the majority of patients with complications, resumption of adequate oral intake occurred by postoperative day 20.

Tumor DNA content as a prognostic indicator in squamous cell carcinoma of the head and neck region.

Our purpose in this study was to determine whether tumor DNA content is a prognostic factor independent of other standard clinical and histologic parameters in squamous cell carcinoma (SCC) of the head and neck region. Tumor DNA content was determined in 76 patients with primary resectable SCC of the oral cavity, larynx, or pharynx who were treated from 1978 to 1984 at the City of Hope. In addition, we measured various clinical and pathologic parameters in all patients. In comparison to patients with diploid SCC, those with aneuploid SCC had significantly decreased relapse-free and overall survival rates (p less than 0.001 for both). A Cox regression analysis demonstrated that tumor DNA content was a prognostic factor independent of all clinicopathologic features examined. By regression analysis, it was the single most important prognostic factor in determining relapse and death from SCC (p less than 0.001 for both).

The inferior trapezius musculocutaneous flap in head and neck reconstruction.

The trapezius musculocutaneous flap based on the descending branch of the transverse cervical vessels has been used to reconstruct a variety of large and complex defects in the head and neck region. Forty-three flaps were performed in 41 patients over a period of 26 months. Excellent reconstruction was achieved in 37 patients. Six total and nine partial flap failures were noted. There were 8 deaths during this time, 2 attributable directly to flap failure. Patient positioning during surgery and the tedious dissection are disadvantageous. The advantages of this flap are its thinness, long reach, and a posterior donor defect. These attributes are ideally suited for certain complex reconstructive endeavors in the head and neck.

Radiographic evaluation for pulmonary metastases in sarcoma patients.

The records of 130 patients with soft tissue and bone sarcomas were retrospectively analyzed to identify the subgroups of patients that would benefit from tomographic studies for pulmonary metastasis. Sixty-six of 96 patients with a normal conventional chest roentgenogram (CXR) had tomography to diagnose pulmonary metastasis. Of the 53 patients who had primary disease and a normal CXR followed by tomography, only 1 (1.9%) had metastases identified on tomograms. Of the 13 patients who had locally recurrent sarcoma and a CXR plus tomographic studies, 2 (15%) had metastases detected on tomogram only. Tomographic studies detected significantly more sarcoma patients with pulmonary metastasis in the group with locally recurrent disease than in the group with primary disease (P less than 0.05).

Predicting the need for prolonged enteral supplementation in the patient with head and neck cancer.

Nutritional support is an important consideration in the management of the head and neck cancer patient. In our series, characteristics significantly associated with the need for long-term postoperative nutritional support included stage IV cancers, primary pharyngeal tumors, combined treatment utilizing surgery and radiotherapy, and preoperative weight loss of more than 10 pounds. In planning nutritional support, nasogastric tube feeding is appropriate for short-term use. In contrast, gastrostomy tube feeding is preferable for those head and neck cancer patients with a high probability of requiring long-term nutritional support postoperatively.

Postoperative radiation as adjuvant treatment for carcinoma of the oral cavity, larynx, and pharynx: preliminary report of a prospective randomized trial.

A prospective randomized trial was performed in patients with advanced squamous cell carcinomas (SCC) of the oral cavity, larynx, and pharynx to examine the effect of adjuvant postoperative radiation therapy on locoregional recurrence and survival following "curative" resection. Fifty-one patients with stage III or IV SCC treated from 1981 through 1984 were randomized to receive either surgery alone (n = 27) or surgery with postoperative radiation (n = 24). Five patients were excluded from the study after randomization because of ineligibility or protocol violations. Overall recurrence rates of 55.6% and 36.8% were noted in the surgery and surgery with adjuvant radiotherapy arms, respectively (p = NS). This trend towards a higher recurrence rate in the surgery only arm was in part due to the development of lymph node metastases in the contralateral, nonoperated neck. Thus far, no significant differences in either locoregional or overall survival have been noted between the two treatment arms. In this preliminary analysis, adjuvant postoperative radiotherapy does not appear to improve disease-free or overall survival.