A comparison of weekly versus 3-weekly cisplatin during adjuvant radiotherapy for high-risk head and neck cancer.

OBJECTIVES: To compare cumulative cisplatin dose and toxicity between patients who received 3-weekly versus weekly cisplatin during adjuvant radiotherapy for high-risk head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Consecutive HNSCC patients with involved resection margins and/or extra-capsular extension in two tertiary cancer centers with different institutional practices were identified. Cumulative cisplatin dose was calculated and information on toxicity reviewed and compared between patients who received 3-weekly versus weekly cisplatin. RESULTS: Of 270 high risk patients, 60 received 3-weekly 100mg/m(2) and 48 received weekly 50mg/m(2) cisplatin during adjuvant radiotherapy (60-66Gy in 30-33 fractions). Fourteen patients received other chemotherapy schedules and 148 received no chemotherapy. Mean cumulative cisplatin dose was 199.4mg/m(2) (standard error (SE) 5.4) in 3-weekly versus 239.8mg/m(2) (SE 11.0, P=0.001) in weekly treated patients. Cumulative cisplatin ⩾200mg/m(2) was given to 67.7% of patients in the 3-weekly cohort and 85.2% (P=0.039) in the weekly cohort. The rate of feeding tube dependency 6months after treatment, osteoradionecrosis, neutropenic fever, and persistent renal function decline were not statistically different. CONCLUSIONS: About one half of high-risk HNSCC patients are not eligible for cisplatin during postoperative radiotherapy. Patients treated with weekly 50mg/m(2) cisplatin received a higher cumulative dose with comparable toxicity as patients who received 3-weekly 100mg/m(2) cisplatin. Efficacy and applicability to the frequently used weekly 40mg/m(2) schedule remains to be evaluated.

Autodigestion of the glans penis and urethra by activated transplant pancreatic exocrine enzymes.

A case of synchronous kidney and pancreas transplantation in which a whole pancreas graft had been drained to the urinary bladder is discussed. On the 137th postoperative day, the patient presented with symptomatic balanitis and urethritis. Documented enzymatic activation of the trypsinogen/chymotrypsinogen, which is not present in symptom-free control patients, was thus thought to be responsible for these symptoms. Conversion to enteric drainage by means of a Roux-en-Y loop resulted in resolution of both symptoms and urinary enzymatic activation. Recurrent urinary tract infections were thought to be the most likely mechanism responsible for these findings.

Pancreatic allograft exocrine urinary tract diversion. Pathophysiology.

Exocrine secretions of 16 of 22 pancreas allografts were drained into the urinary tract. Seven of these 16 patients have functioning allografts, six with pancreaticocystostomies and one with duct-to-ureter anastomosis. A notable problem has been a chronic metabolic acidosis, along with weight loss and hypotension, secondary to chronic bicarbonate loss and volume depletion through the urinary pancreatic fistula. This occurred as early as one week posttransplant, and intermittently thereafter up to four years. The syndrome was aggravated by episodes of renal dysfunction (acute tubular necrosis or rejection), and febrile syndromes. An inverse relationship between serum and urine bicarbonate concentrations existed, with a correlation coefficient, r = -0.746, (P less than 0.05). A negative correlation was also noted between serum bicarbonate and serum creatinine, r = 0.726, (P less than 0.05). Hyperchloremic metabolic acidosis with normal anion gap occurred despite periods of marginal pancreas allograft function resulting from ongoing rejection. Treatment consisted of intravenous and/or oral bicarbonate supplementation, and bicarbonate dialysis for uremic patients. In addition, one patient was first seen with severe balanitis and urethritis due to documented activation of trypsinogen and chymotrypsinogen, presumably caused by recurrent episodes of urinary tract infection. Urinary assay revealed a 10(2-3) increase in activated trypsin and chymotrypsin in comparison with other asymptomatic allograft recipients. Conversion to ductal enteric drainage led to resolution of both the balanitis and bicarbonate wasting. Measurement of urinary amylase levels were gross indicators of graft viability since no correlation could be found between these levels, onset of hyperglycemia, and eventual graft rejection confirmed by pathological examination.

The efficacy of direct, 24-hour culture, and mitotic synchronization methods for cytogenetic analysis of bone marrow in neoplastic hematologic disorders.

Bone marrow aspirates from 90 patients suspected of having a hematologic disorder were processed by using different cytogenetic methods to determine if any procedure was more likely to reveal a chromosomally abnormal clone or produce better-quality metaphases. All specimens were processed by a direct technique and 24-hr culture without mitogens; 50 specimens were also processed by an amethopterin mitotic synchronization method. In each case, the microscope slides were coded by the processing technologist and analyzed by two other experienced cytogenetic technologists. The results were not known to any of the investigators until all 90 specimens were analyzed. With the exception of one specimen, in which a chromosomally abnormal clone was identified only in the direct preparation, no apparent differences were found in the karyotypes among the three methods. Also, the differences in the quality or number of metaphases found among the three methods were not statistically significant; however, 24-hr unstimulated cultures produced more metaphases than the mitotic synchronization procedure. The greatest source of discordance was caused by one test yielding either no metaphases or an uncertain result when the other tests produced a successful study. We suggest that in routine practice at least two different methods should be used, and it may be best if at least one of these methods is a direct technique.

Safer intraoperative carotid arteriography.

A new technique of intraoperative carotid arteriography after endarterectomy is described. Placement under direct vision of a plastic angiocatheter through the superior thyroid artery into the lumen of the common carotid artery facilitates arteriography without the potential complications of puncture of the common carotid artery wall.

A nonoperative approach to the adult ruptured spleen sustained from blunt trauma.

From 1978 to 1983, 53 consecutive adult patients with ruptured spleens documented by radionuclide studies, computerized axial tomography, or surgery, were evaluated at William Beaumont Hospital. Thirty-four patients (64%) underwent an exploratory laparotomy; 33 resulted in a splenectomy and one patient had an attempted splenorraphy which failed. Nineteen patients (36%) were hemodynamically stable on admission, or had transient episodes of hypotension readily reversed by intravenous fluids. They were placed at strict bedrest under intensive monitoring. Two patients deteriorated clinically and were taken to surgery, resulting in a splenectomy on the fourth and sixth hospital day, respectively. Seventeen patients (32%) were successfully treated nonoperatively, representing an 89 per cent success rate. The average admitting hemoglobin in the nonoperative group was 13.2 gm/dl, with an average drop of 1.6 gm/dl, and an average total blood transfusion of 1.2 units. These patients were followed for an average of 19.2 months, with no sequelae from their splenic injury. In a hemodynamically stable adult patient with a splenic injury sustained from blunt trauma, a nonoperative approach is a viable alternative when close intensive monitoring is available.

Steroid effect on capillary permeability in gram-negative septic shock. Evaluation by vitreous fluorophotometry.

The purpose of this study was to use vitreous fluorophotometry to evaluate the effects of glucocorticoids on capillary permeability during gram-negative septic shock. Twelve preconditioned mongrel dogs were cannulated with arterial lines and Swan-Ganz catheters for complete hemodynamic monitoring. All 12 dogs were injected with fluorescein and live Escherichia coli intravenously. Six of the 12 dogs were administered methylprednisolone at set intervals after the initiation of the E coli infusion. Vitreous fluorophotometric recordings were taken hourly. Leakage of fluorescein into the extravascular space occurred in both groups, up to several hours after E coli infusion. However, in the steroid group, the capillary permeability decreased and stabilized following the initial increase in permeability. We conclude that steroids, when administered during the development of gram-negative septic shock, may modify capillary permeability changes.

Fluorophotometric evaluation of capillary permeability in gram-negative shock.

We developed a new method by which capillary permeability changes secondary to gram-negative sepsis can be easily monitored. In a preliminary trial, ten dogs were injected intravenously with live Escherichia coli. Progressive extravasation of fluorescein from the retinal capillary bed was demonstrated by retinal angiography, thus indicating "capillary leak." In a subsequent trial, fluorophotometry facilitated direct quantitation of this leak. Three control and three septic dogs underwent continuous hemodynamic and physiologic monitoring. Hourly retinal fluorophotometric measurements were recorded. The control group demonstrated no capillary leak nor any change in hemodynamic and physiologic status. In the septic group, there was a dramatic increase in extravascular fluorescein concentration two to four hours after E coli infusion, correlating well with hemodynamic and physiologic parameters typical of gram-negative shock.