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Echinomycin is a novel bifunctional intercalating agent derived from Streptomyces echinatus. A phase II clinical trial of echinomycin in patients with advanced, measurable colorectal cancer was initiated to determine the efficacy and toxicities of this agent. Echinomycin, 1.5 mg/m2, was given initially as a 30- to 60-min infusion every 4 weeks. After 4 episodes of anaphylaxis had occurred among the first 14 patients, the schedule was changed to a 24-h infusion, and an additional 16 patients were treated on this schedule. Treatment was given every 3 weeks. A total of 30 patients were eligible and evaluable; there were 3 (10%; 90% confidence interval, 3%-23%) clinical responses lasting 3, 3+, and 12 months, respectively. The most serious toxicity encountered was anaphylaxis, which occurred in 5 patients, although with no serious sequelae. A premedication regimen with dexamethasone, diphenhydramine, and cimetidine and a change of the duration of the infusion to 24 h reduced the incidence of this complication. Grade 2-3 vomiting occurred among earlier patients treated; however, with the 24-h schedule this toxicity was substantially reduced. The sole important case of hematologic toxicity was a single patient with grade 3 thrombocytopenia. Echinomycin employed in this dose and schedule had modest activity against colorectal cancer, comparable with that observed with 5-fluorouracil. Further studies in patients with gastrointestinal malignancies using a 24-h infusion with a dexamethasone premedication regimen similar to that employed prior to administration of taxol may be warranted. [ABSTRACT FROM AUTHOR]

BACKGROUNDAppropriate staging and follow-up evaluation of patients with liver metastases from colorectal cancer undergoing regional ablative treatment often require multiple imaging techniques and blood tests. We investigated the role of positron emission tomography (PET) in accurate staging and in monitoring the response to radiofrequency interstitial tissue ablation (RITA) of liver metastases from colorectal cancer.METHODSPatients with unresectable metastases from colorectal cancer confined to the liver and evaluated for the RITA procedure plus postablation chemotherapy were prospectively evaluated by the use of standard cross-sectional imaging (computed tomography/ magnetic resonance imaging), estimation of carcinoembryonic antigen levels, and PET. The patients were followed up after surgery for 6 months by standard criteria of physical evaluation, laboratory tests, and imaging studies, including PET.RESULTSOur colorectal liver metastases PET database accrued 26 patients during the period of December 1998 to August 2000. In this group, a cohort of 18 patients evaluated for the clinical trial of RITA plus chemotherapy was analyzed for elucidation of the benefit of PET in accurate staging before treatment and in response estimation 6 months following the RITA procedure. In 16.7% of patients (three of 18), PET demonstrated extrahepatic disease that had not been demonstrable by crosssectional anatomic imaging studies. Of the 15 patients undergoing RITA plus chemotherapy, 11 are evaluable after 6 months' follow-up. Correlation between computed tomography and PET demonstrated that in 55% of patients (six of 11), PET is of discriminant value in distinguishing the inactive, treated lesions from recurrent disease, whereas computed tomography is unable to do so. In the remaining 45% of patients, there was concordance between PET and computed tomography in estimating progressive disease. We propose a system of four groups (groups I to IV) based on PET's prognostic value.CONCLUSIONSPET enhances the staging accuracy in patients with unresectable colorectal metastases limited to the liver in whom regional ablative therapy is a consideration. PET is of value in the assessment of tumor response to radiofrequency ablative therapy in most patients. [ABSTRACT FROM AUTHOR]

The left ventricular assist device (LVAD) is an implanted mechanical pump that supports circulatory function for patients with advanced heart failure. LVAD survival has continuously improved over the last decade with an increasing number of patients requiring non-cardiac surgeries. We discuss a 77-year-old, LVAD-dependent male with an enlarging, indurated right testicular mass. Radical inguinal orchiectomy confirmed pure seminoma. The case highlights perioperative considerations in this unique cohort of patients., (© 2021 Published by Elsevier Inc.)

HeartMate II left ventricular assist device (LVAD) assists heart failure patients by generating continuous flow via axial flow pump placed in the left ventricle. Little is known of the effect of continuous flow on intestinal anastomoses. This is the first case visually documenting altered perfusion patterns in patients with LVADs using indocyanine green (ICG). A 72-year-old male required a colon resection, for adenocarcinoma, following implantation of an LVAD. Perfusion of the anastomosis was evaluated using indocyanine. During the assessment, an unusual perfusion pattern was noticed. Normally, flow as measured by SPY is seen as an initial blush of contrast followed by a gradual, pulsatile increase in the progression of the indocyanine through the tissues. In this patient, instead of the usual initial blush, a continuous beam of ICG was seen to flow though the blood vessels. This novel perfusion pattern is consistent with flow generated from LVAD., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2020.)

Background: The surgical management of patients with morbid obesity (body mass index ≥ 40) is notable for a relatively high risk of complications. To address this problem, a perioperative care map was developed using precautions and best practices commonly employed in bariatric surgery. It requires additional medical assessments, sleep apnea surveillance, more stringent guidelines for anesthetic management, and readily available bariatric operating room equipment, among other items. This care map was implemented in 2013 at 4 major urban teaching hospitals for use in patients undergoing all types of nonambulatory surgery with a body mass index greater than 40 kg/m 2 . The impact on patient outcomes was evaluated., Methods: The American College of Surgeons National Surgical Quality Improvement Program database was used to compare 30-day outcomes of morbidly obese patients before the year 2013 and after the years 2015 care-map implementation. In addition, trends in 30-day outcomes for morbidly obese patients were compared with those for non-obese patients., Results: Morbidly obese patients, between 2013 and 2015, saw an adjusted decrease in the rate of unplanned return to the operating room (OR = 0.49; P = .039), unplanned readmission (OR = 0.57; P = .006), total duration of stay (-0.87 days; P = .009), and postoperative duration of stay (-0.69 days; P = .007). Of these, total duration of stay (-0.86 days; P = .015), and postoperative duration of stay (-0.69 days; P = .012) improved significantly more for morbidly obese patients than for nonmorbidly obese patients., Conclusion: Outcomes in morbidly obese patients improved from 2013 to 2015. Implementation of a perioperative care map may have contributed to these improvements. The care map should be further investigated and considered for more widespread use., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Morbid obesity can complicate perioperative management. Best practice guidelines have been published but are typically followed only in bariatric patients. Little is known regarding physician awareness of and compliance with these clinical recommendations for nonbariatric operations. Our study evaluated if an educational intervention could improve physician recognition of and compliance with established best practices for all morbidly obese operatively treated patients., Methods: A care map outlining best practices for morbidly obese patients was distributed to all surgeons and anesthesiologists at 4 teaching hospitals in 2013. Pre- and postintervention surveys were sent to participants in 2012 and in 2015 to evaluate changes in clinical practice. A chart audit performed postintervention determined physician compliance with distributed guidelines., Results: In the study, 567 physicians completed the survey in 2012 and 375 physicians completed the survey in 2015. Postintervention, statistically significant improvements were seen in the percentage of surgeons and anesthesiologists combined who reported changing their management of morbidly obese, operatively treated patients to comply with best practices preoperatively (89% vs 59%), intraoperatively (71% vs 54%), postoperatively (80% vs 57%), and overall (88% vs 72%). Results were similar when surgeons and anesthesiologists were analyzed separately. A chart audit of 170 cases from the 4 hospitals found that 167 (98%) cases were compliant with best practices., Conclusion: After care map distribution, the percentage of physicians who reported changing their management to match best practices significantly improved. These findings highlight the beneficial impact this educational intervention can have on physician behavior. Continued investigation is needed to evaluate the influence of this intervention on clinical outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Resected carcinoma patients were immunized 3-5 times with ovine submaxillary gland mucin (OSM) containing predominantly sialylated Tn (sTn), completely desialylated ovine submaxillary gland mucin (dOSM) containing predominantly Tn, or 50% desialylated OSM containing Tn and sTn plus bacillus Calmette-Guerin (BCG) as an immunologic adjuvant. Pre- and postimmunization sera were quantified by ELISA, whole-cell ELISA, and immune stain dot blots. Fifteen of 17 patients produced IgG antibody titers from 40 to 5120 times more reactive with OSM and dOSM postimmunization. More importantly, these IgG antibodies reacted with LS-174T, a human colon carcinoma cell line. Significant DTH-like responses (1-17 cm) were observed in 15 of 17 patients; the strength of these responses was dependent on the presence or absence of sialic acid. Biopsies of these DTH-like reactions revealed infiltration with some CD8+ lymphocytes and mast cells. These results suggest that a single 9-carbon sugar can affect cellular immune responses to mucin antigens. It is thought that these large erythematous, nonindurated cellular reactions are antibody-mediated Arthus-like reactions. OSM, and especially dOSM, were also found to inhibit lymphocyte proliferation.

Objectives: Laparoscopic management of adrenal masses has been well described. Immunologically compromised patients can obtain significant benefit from these minimally invasive procedures. We describe a case of an enlarging smooth muscle tumor of the adrenal gland in an acquired immunodeficiency syndrome (AIDS) patient and review the sparse literature available on this subject., Case Report: A 49-year-old female with AIDS complaining of vague abdominal discomfort was found to have a left adrenal mass. Significant enlargement of the mass was noted during routine follow-up. The patient underwent an elective laparoscopic left adrenalectomy without complications. Pathological review found the mass to be a rare adrenal leiomyoma., Discussion: Benign, smooth muscle tumors arising from the adrenal glands are rare. A review of the literature does reveal a propensity for these tumors to occur in the immunocompromised population., Conclusion: The ability to manage these tumors laparoscopically is of significant benefit to patients.

Purpose: Combined inhibition of ribonucleotide reductase (RR) and thymidylate synthase (TS), the enzymes responsible for a balanced supply of nucleotides for DNA synthesis, has been shown to induce synergistic antiproliferative effects in vitro. In the clinic, prolonged infusion of the RR inhibitor, hydroxyurea (HU), may be more effective than bolus or oral administration of drug. The purpose of the current study was to determine whether dose intensification of parenteral hydroxyurea in combination with fluorouracil could enhance the response rates of the combination against refractory upper gastrointestinal malignancies., Methods: A clinical trial of parenteral, weekly, high-dose HU in combination with weekly, high-dose infusional fluorouracil (5FU) was initiated in patients with advanced pancreatic and gastric cancer. Patients received 5FU 1.3 g/m(2) by continuous intravenous infusion (CIVI) daily over 48 h weekly in combination with HU 4.3 g/m(2) CIVI per day over 48 h weekly. Patients also received the biologic agent interferon alfa-2a 9 MU subcutaneously (s.c.) three times per week and filgrastim 480 microg s.c. on days 3 (starting after midday), 4, 5, and 6 each week. Each cycle required treatment on days 1 and 8 every 22 days., Results: Enrolled in the study were 32 patients, of whom 30 were evaluable. The median age was 56 years. Primary sites included pancreas (18), gastric (13) and islet cell (1). Despite filgrastim, the major toxicities were hematologic with 15 of 30 patients developing grade 3/4 granulocytopenia. Of the 30 patients, 4 developed grade 3/4 diarrhea. Interferon-mediated fatigue was mild. Of 12 evaluable patients with gastric cancer, 1 had a partial response, and there were no responders among patients with pancreatic cancer., Conclusions: Combined inhibition of RR and TS using this high-dose, weekly, 48-h infusional regimen is not an improvement over single-agent therapy in these tumor types.

Purpose: ONYX-015 is a chimeric, E1B-deleted adenovirus designed to replicate preferentially in p53-deficient tumor cells; however, little is understood about its actual replication potential in human tumors. We hypothesized that replication of a late viral gene, hexon, would demonstrate replication of virus in human tissues., Experimental Design: In the course of a clinical trial, a patient with paired abdominal wall implants from a primary gall bladder carcinoma was injected with ONYX-015, 1 x 10(10) viral particles/lesion, followed by sequential excision of the lesions at 37 h and 7 days. Tissue sections were analyzed for evidence of viral replication., Results: In situ Reverse transcription-PCR was used to measure expression of hexon. Strong signals were obtained in gland-forming tumor cells both at 37 h and at 7 days. Signal was predominantly observed in the cytoplasm. The signal was also observed in adjacent normal stromal cells. Analysis of p53 status of the tumor by immunohistochemistry and Affymetrix Genechip demonstrated an inactivating mutation in p53. Routine H&E staining of the tumor sections revealed no evidence of necrosis at 37 h or 7 days after injection of virus. Presence of viral protein at both 37 h and 7 days was confirmed by immunohistochemistry using antibodies directed against hexon, penton, and fiber proteins., Conclusions: Evidence for replication of hexon confirms that ONYX-015 is not only present but capable of replicating in tumor cells up to 1 week after intralesional injection and that replication is not confined to p53-mutated tumor cells.

Locoregional therapies are useful in treating patients with colorectal cancer metastatic to the liver. A prospective randomized phase II trial of hepatic artery embolization versus hepatic artery chemoembolization was conducted to evaluate the response rates and toxicities of these therapies in the second-line setting. Patients were required to have biopsy-proven adenocarcinoma of the colon or rectum metastatic to the liver, with the liver as the sole or predominant site of metastatic disease. All patients had measurable disease and had failed at least one prior systemic chemotherapy treatment for metastatic disease. Patients were randomized to receive either embolization therapy with polyvinyl alcohol foam (Ivalon) administered as a single agent or chemoembolization using polyvinyl alcohol foam mixed with 750 mg/m2 of 5-fluorouracil and 9 million units of interferon. Drugs and embolic material were administered via the hepatic artery as a slurry with polyvinyl alcohol foam. Fifty eligible patients were enrolled. There were 24 patients in the chemoembolization arm and 26 in the embolization arm. Sixty-four percent of patients in both treatment arms had the liver as the sole metastatic site. The most common National Cancer Institute common toxicity criteria grade 3/4 toxicities were diarrhea (17%) and hepatic toxicity (8%). There was 1 (4%) treatment-related mortality due to a hepatic abscess. Four patients (15.4%) treated with embolization had a partial response (PR), and 5 patients (20.8%) treated with chemoembolization had a PR. The median survival for all patients was 11 months (95% confidence interval [CI], 8-15 months). Survival in patients with extrahepatic disease was 8 months (95% CI, 6-10 months). Survival in patients with liver-only metastases was 15 months (95% CI, 10-17 months). Embolization of the liver as second-line therapy in patients with liver-predominant metastases is safe and effective. Median survivals are comparable to other second-line therapies

Purpose: Combined depletion of pyrimidine and purine DNA precursors has resulted in therapeutic synergism in vitro. The aims of the current study were to test this strategy in patients with refractory tumors and to assess its effects on selected nucleotide pools., Patients and Methods: A single-institution phase II trial was initiated in patients with advanced carcinomas of the stomach and pancreas. Patients had measurable disease and had no prior chemotherapy except adjuvant fluorouracil (5FU) or gemcitabine. 5FU was administered by CADD + pump at 2.6 g/m(2) intravenously by 24-hour infusion on days 1, 8, 15, 22, 29, and 36. Parenteral hydroxyurea (HU) was administered at 4.3 g/m(2) as a 24-hour infusion concurrently with 5FU. Interferon alfa-2a (IFN-alpha2a) was administered at 9 million units subcutaneously on days 1, 3, and 5 each week. No drug was administered in weeks 7 and 8. Pharmacodynamic studies were performed to assess drug effects on levels of deoxyuridine triphosphate (dUTP) and thymidine triphosphate (TTP) pools in peripheral-blood mononuclear cells (PBMCs) before and 6 hours after treatment using a highly sensitive DNA polymerase assay., Results: There were 53 patients enrolled onto the study (gastric carcinoma, 31; pancreatic carcinoma, 22). The median age was 61 years, with 22% of patients > or = 70 years old. The predominant grade 3 to 4 toxicities were leukopenia (49%), granulocytopenia (55%), and thrombocytopenia (22%). Severe diarrhea occurred in 12%, mucositis in 0%, and vomiting in 10% of patients. Patients > or = 70 years had no greater incidence of toxicities. Among the 30 assessable patients with gastric carcinoma, there were two (7%) complete responders and 11 (37%) partial responders (median duration, 7 months). Among the 21 assessable patients with pancreatic carcinoma, there was one responder. Median survival among all patients with gastric carcinoma was 10 months and 13 months for patients with pancreatic carcinoma. Twenty-three patients had samples studied for levels of dUTP and TTP. There was no change in the levels of TTP before and after treatment. Furthermore, dUTP was detected in only five of 28 samples after treatment with no increase in the dUTP/TTP ratio., Conclusion: Combination therapy with high-dose, weekly infusional HU and 5FU with IFN-alpha2a modulation was well-tolerated with activity in gastric cancer. Patients > or = 70 years tolerated therapy as well as younger patients. This was the first study to correlate levels of TTP and dUTP after treatment with clinical outcome. In PBMCs used as a surrogate tissue, HU abrogated the 5FU-induced increase in dUTP levels without reversing the overall efficacy of the regimen.

Background: Preclinical and early clinical trials suggested that the biologic agent interferon beta ser (IFN beta ser) may augment the anticancer activity of 5-fluorouracil (5-FU). The current studies were undertaken to explore the optimal schedule of IFN beta ser and to determine whether the hematopoietic growth factor sargramostim (granulocyte-macrophage colony-stimulating factor) could reduce the hematologic and gastrointestinal toxicities of the chemotherapy., Methods: Three sequential, single-institution phase II trials using different regimens were initiated. Patients were required to have advanced, histologically documented colorectal carcinoma with no prior chemotherapy; to have adequate bone marrow, renal, and hepatic function; to be fully ambulatory; and to give informed consent. All patients received 5-FU, 750 mg/m2 intravenously as an infusion daily for 5 days, followed by 5-FU, 750 mg/m2, as an intravenous bolus every week beginning day 15. Patients in arm A received IFN beta ser, 9 MU subcutaneously, three times a week. Patients in arm B received IFN beta ser, 9 MU subcutaneously every day. Patients in arm C were treated exactly as in arm B but also received sargramostim, 250 micrograms subcutaneously on days they did not receive 5-FU. Beginning day 15, all patients received IFN beta ser exactly 10 minutes before receiving the 5-FU bolus., Results: There were 81 patients enrolled: 19 in arm A; 40 in arm B; and 22 in arm C. Myelosuppression and diarrhea were the most common toxicities. Increasing the frequency of IFN beta ser administration in arm B resulted in a doubling of the rate of diarrhea from 11% to 22%, and the addition of sargramostim in arm C failed to reduce this. Sargramostim did reduce the incidence of grade 3 to 4 leukopenia, but this did not allow intensification of dosing or result in improved response or survival among patients in arm C. IFN-mediated fatigue was also common, occurring in 37% to 43% of patients. Patients receiving IFN beta ser on the intermittent schedule tolerated full-dose therapy longer than those on the daily schedule (10 weeks versus 5 weeks, P < 0.01). The response rates in the three arms were 21%, 35%, and 27%; there was no difference in median survival (15 months for all three arms)., Conclusions: The combination of 5-FU and IFN beta ser was active in patients with advanced colorectal carcinoma, and survival with this regimen was comparable to or better than that with other modulating regimens. The intermittent schedule of IFN beta ser was better tolerated than than the daily schedule.

The term acute mesenteric ischemia (AMI) is applied to a wide spectrum of bowel injury within the distribution of the superior mesenteric vessels, ranging from reversible alterations in bowel function to transmural necrosis of the bowel wall. Intensivists not only are called upon to manage this catastrophic disease but also may be faced with AMI as a consequence of other illnesses that they treat.

The treatment of symptomatic congenital hepatic cysts is surgical. Aspiration does not provide definitive therapy and carries a high recurrence rate. Surgical exploration and drainage intraperitoneally, externally, and internally to a segment of bowel have been described. With the recent explosion in the applications of laparoscopic guided surgery, we report a simple method for the excision of congenital solid hepatic cyst with subsequent intraperitoneal drainage and follow-up.

Objectives: Intramuscular injection is a commonly used route of parenteral drug administration. We studied the fat vs muscle location, the depth of calcified buttock granulomas, and the thickness of subcutaneous fat. Data were assessed with respect to the length of a needle commonly used in intramuscular buttock injections., Design: Three hundred thirty-eight sequential pelvic computed tomographic scans were studied. Subcutaneous fat thickness was measured for each patient at the upper outer quadrant of the buttock. The location and depth of each calcified granuloma were also recorded., Setting: Tertiary care academic teaching hospital., Results: One hundred sixty-four calcified granulomas were found in 67 patients. One hundred fifty-two of these granulomas were in fat and 12 were in muscle; this was statistically significant using a single-sample binomial distribution (P < .001;95% confidence interval, 0.04 to 0.13). The mean (+/- SD) subcutaneous fat thickness at the upper outer quadrant of the buttock was 5.0 +/- 1.9 cm, with female patients having a mean subcutaneous fat thickness of 5.7 +/- 1.8 cm vs 4.4 +/- 1.7 cm for male patients., Conclusions: The finding that buttock subcutaneous fat thickness exceeds the length of the most commonly used needle for intramuscular buttock injection (3.8 cm), together with the preponderance of calcified granulomas found in the fat of female patients, suggests that the currently used injection technique may not be therapeutically optimal. We suggest that longer needles be used for intramuscular buttock injections in adults.

The incidence of acute mesenteric ischemia (AMI) has increased substantially over the last few decades. Death rates of 70% to 90% have been reported for traditional methods of diagnosis and therapy. Use of an aggressive radiologic, pharmacologic and surgical approach has decreased the mortality and morbidity associated with AMI. The cornerstones of management are prompt diagnosis by the earlier and more liberal use of angiography and the incorporation of intra-arterial papaverine in the treatment of both occlusive and nonocclusive AMI. Widespread adoption of this protocol in patients at risk might improve the overall results of treatment of AMI.

An aggressive diagnostic and therapeutic approach to acute mesenteric ischemia can dramatically lower the mortality of this lethal disease. The cornerstones of this approach are the earlier and more liberal use of angiography and the use of intra-arterial infusions of vasodilators in the treatment of both nonocclusive and occlusive mesenteric ischemia.

Intestinal ischemia can result from a host of pathophysiologic disturbances and, in turn, may produce a variety of adverse local and systemic consequences. Mechanisms of ischemic injury and the central role of vasoconstriction are discussed.

Mesenteric venous occlusion produces a spectrum of clinical presentations, the most common of which is the acute onset of abdominal pain with progressive signs and symptoms of bowel infarction. This acute form of mesenteric venous thrombosis, compared with other forms of acute mesenteric infarction, occurs in younger patients, typically has a more indolent and nonspecific course, involves shorter segments of bowel, and has a lower mortality rate. In contradistinction to our recommended therapy in other forms of acute mesenteric infarction, immediate anticoagulation is indicated for mesenteric venous thrombosis. Second-look operations are used, as in other forms of acute mesenteric infarction, whenever portions of bowel of questionable viability are not resected at the primary operation. Chronic mesenteric venous thrombosis may produce no symptoms or may cause gastrointestinal bleeding from portal hypertension. Newer imaging techniques have increased the ability to diagnose and define the extent of all forms of mesenteric venous thrombosis and have added to the therapeutic options available to manage them.

Cyclosporin, a potent new immunosuppressive agent, was used (alone or in combination with other drugs) in 28 canine single lung allograft recipients. Mean recipient survival with good allograft function was 155 days with cyclosporin and far exceeded that obtained in previous single lung allograft recipients treated with standard immunosuppression (15 to 22 days). The results of these experiments were as follows: (1) 20% of the recipient animals exhibited no evidence of rejection whatsoever; (2) four of 28 animals survived more than 350 days with good allograft function; (3) 79% of the animals exhibited some evidence of rejection that was easily reversed in 74% of instances with corticosteroids; (4) 10 of 28 animals exhibited good lung allograft function 5 months or more after operation; (5) in cyclosporin-treated lung allograft recipients, rejection was diagnosed by the presence of infiltrate on chest roentgenogram, analysis of the cellular content of bronchoalveolar lavage samples, and decreased perfusion on 99mtechnetium lung scan; (6) complete healing without stenosis of the bronchial anastomosis occurred in 82% of the animals studied. One of two patients treated with cyclosporin after undergoing single lung allografting survived 7 weeks after transplantation and 4 weeks after contralateral pneumonectomy. Episodes of rejection were reversible, and the bronchial anastomosis healed normally. This overall experience indicates that cyclosporin, although not a perfect immunosuppressive agent, increases the likelihood of success with therapeutic single lung transplantation.

The urinary excretion of leucine aminopeptidase (LAP), N-acetyl-beta-glucosaminidase (NAG), and beta 2-microglobulin was measured in 12 cancer patients receiving cis-platinum to evaluate the sensitivity of these indices for renal tubular damage. NAG and LAP excretion rose markedly in all patients, and beta 2-microglobulin rose in 11. Seven of the 9 patients who had received cis-platinum 6 wk before the study had prestudy dose elevations of one or more of these indices. We conclude that these urinary proteins are sensitive indicators of proximal renal tubular injury and may provide greater sensitivity for comparison of the nephrotoxic potential of future platinum analogs or for assessing the efficacy of regimens designed to protect the kidney from platinum nephrotoxicity than other measurements. The persistence of high excretion vales for these indices 6 wk after a dose demonstrates the persistent renal injury by cis-platinum.