Hector R. Nava

Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial

BACKGROUND Photodynamic therapy (PDT) is a different type of laser treatment from Nd:YAG thermal ablation for palliation of dysphagia from esophageal cancer. METHODS In this prospective, multicenter study, patients with advanced esophageal cancer were randomized to receive PDT with porfimer sodium and argon-pumped dye laser or Nd:YAG laser therapy. RESULTS Two hundred thirty-six patients were randomized and 218 treated (PDT 110, Nd:YAG 108) at 24 centers. Improvement in dysphagia was equivalent between the two treatment groups. Objective tumor response was also equivalent at week 1, but at month 1 was 32% after PDT and 20% after Nd:YAG (p < 0.05). Nine complete tumor responses occurred after PDT and two after Nd:YAG. Trends for improved responses for PDT were seen in tumors located in the upper and lower third of the esophagus, in long tumors, and in patients who had prior therapy. More mild to moderate complications followed PDT, including sunburn in 19% of patients. Perforations from laser treatments or associated dilations occurred after PDT in 1%, Nd:YAG 7% (p < 0.05). Termination of laser sessions due to adverse events occurred in 3% with PDT and in 19% with Nd:YAG (p < 0.05). CONCLUSIONS Photodynamic therapy with porfimer sodium has overall equal efficacy to Nd:YAG laser thermal ablation for palliation of dysphagia in esophageal cancer, and equal or better objective tumor response rate. Temporary photosensitivity is a limitation, but PDT is carried out with greater ease and is associated with fewer acute perforations than Nd:YAG laser therapy.

Neutropenic enterocolitis. Clinical diagnosis and treatment.

Review of the consultation records of the Gastrointestinal Surgical Oncology service at Roswell Park Memorial Institute from 1982 to 1987 revealed 22 patients with a finical diagnosis of neutropenic enterocolitis. Ninety one percent of the patients had hematologic malignancies and 95% were receiving cytotoxic chemotherapy, Sixteen patients were treated nonsurgically; 11 died. Of those 11 cases, autopsies were performed in 9. At autopsy, the clinical diagnosis was confirmed in four cases; four cases were found to have normal intestinal tracts, and one case had a small bowel volvulus. In none of the four cases for which autopsy proved neutropenic enterocolitis was transmural bowel necrosis or perforation found. Laparotomy was performed in six patients; three survived. The clinical diagnosis was verified in four of the six patients. Neutropenic enterocolitis must be considered a diagnosis of exclusion. Care of these patients should be individualized. Nonoperative management with bowel rest, decompression, nutritional support, and broad spectrum antibiotics is recommended initially. Operative intervention is recommended for those with perforation or those whose condition deteriorates clinically during close, frequent observation.

Predictive factors associated with long-term survival in patients with neuroendocrine tumors of the pancreas

BackgroundNeuroendocrine tumors of the pancreas are rare tumors. We identified predictive factors that are associated with long-term survival (≥5 years).MethodsFifty patients with a diagnosis of neuroendocrine tumors of the pancreas were retrospectively evaluated. The following factors were evaluated for disease-specific mortality: age, sex, primary tumor location, functional status, type of primary tumor treatment, presence or absence of liver metastases, timing of liver metastases occurrence, and type of liver metastases treatment. Aggressive treatment of the liver metastases included surgery, chemoembolization, or intrahepatic arterial infusion chemotherapy.ResultsTwenty-three patients (47%) had tumor located in the head of the pancreas, and 29 patients (58%) had nonfunctioning tumor. Thirty-nine patients (78%) had liver metastases. The median follow-up for the entire group was 35 months (range, 76–206 months). The median survival for the entire group was 40 months, and the overall 1-, 2-, and 5-year survival rates were 84%, 69%, and 36%, respectively. Factors that had a significant favorable effect on survival included curative resection of the primary tumor, metachronous liver metastases, absence of liver metastases, and aggressive treatment of the liver metastases.ConclusionsDefinitive surgical resection of the primary tumor, absence of liver metastases, metachronous liver metastases, and aggressive treatment of the liver metastases were predictors of long-term survival in patients with neuroendocrine tumors of the pancreas.

Oxaliplatin in Combination With Protracted-Infusion Fluorouracil and Radiation: Report of a Clinical Trial for Patients With Esophageal Cancer

PURPOSE To identify a dose and schedule of oxaliplatin (OXP) to be safely administered in combination with protracted-infusion (PI) fluorouracil (5-FU) and external-beam radiation therapy (XRT) for patients with primary esophageal carcinoma (EC). PATIENTS AND METHODS Eligibility included therapeutically naïve EC patients with clinical disease stages II, III, or IV. Initial doses and schedules for cycle 1 consisted of OXP 85 mg/m(2) on days 1, 15, and 29; PI 5-FU 180 mg/m(2) for 24 hours for 35 days; and XRT 1.8 Gy in 28 fractions starting on day 8. At completion of cycle 1, eligible patients could undergo an operation or begin cycle 2 without XRT. Postoperative patients were eligible for cycle 2. Stage IV patients were allowed three cycles in the absence of disease progression. OXP and 5-FU increases were based on dose-limiting toxicity (DLT) encountered in cohorts of three consecutive patients. RESULTS Thirty-eight eligible patients received therapy: 22 noninvasively staged as IV and 16 noninvasively staged as II and III. Thirty-six patients completed cycle 1, 29 patients started cycle 2, and 24 patients completed cycle 2. The combined-modality therapy was well tolerated, but DLT prevented OXP and 5-FU escalation. No grade 4 hematologic toxicity was noted. Eleven grade 3 and two grade 4 clinical toxicities were noted in eight patients. After cycle 1, 29 patients (81%) had no cancer in the esophageal mucosa. Thirteen patients underwent an operation with intent to resect the esophagus; five patients (38%) exhibited pathologic complete responses. CONCLUSION OXP 85 mg/m(2) on days 1, 15, and 29 administered with PI 5-FU and XRT is safe, tolerable, and seems effective against primary EC. The role of OXP in multimodality regimens against EC deserves further evaluation.

Esophageal resection for carcinoma in patients older than 70 years.

BackgroundA larger number of older patients are presenting as candidates for esophageal resection. An aggressive surgical approach in this population is controversial.MethodsFour hundred thirteen patients with esophageal cancer who presented to Roswell Park Cancer Institute from 1991 to 1998 were retrospectively reviewed. Clinical data, perioperative details, and postoperative courses were compared for patients older and younger than 70 years.ResultsOne hundred forty-seven patients (36%) were older than 70 years. Risk factors, clinical symptoms, histology, and stage at presentation were equivalent for both age groups. A higher percentage of patients <70 years were candidates for curative resection. There were no significant differences between groups for estimated blood loss, intraoperative transfusions, length of stay, overall morbidity, or mortality. Only postoperative myocardial infarction and atrial fibrillation were increased in the older group. Excluding stage IV disease, there was a significant and similar improvement in median survival after resection for patients both <70 years and >70 years.ConclusionsIn conclusion, esophageal cancer in older patients warrants surgical resection because the benefit to the patient is the same as it is for younger patients, without a significant increase in operative morbidity or mortality.

Squamous Overgrowth Is Not a Safety Concern for Photodynamic Therapy for Barrett's Esophagus With High-Grade Dysplasia

BACKGROUND & AIMS Photodynamic therapy with porfimer sodium combined with acid suppression (PHOPDT) is used to treat patients with Barretts esophagus (BE) with high-grade dysplasia (HGD). A 5-year phase 3 trial was conducted to determine the extent of squamous overgrowth of BE with HGD after PHOPDT. METHODS Squamous overgrowth was compared in patients with BE with HGD randomly assigned (2:1) to receive PHOPDT (n=138) or 20 mg omeprazole twice daily (n=70). Patients underwent 4-quadrant jumbo esophageal biopsies every 2 cm throughout the pretreatment length of BE until 4 consecutive quarterly follow-up results were negative for HGD and then biannually up to 5 years or treatment failure. Endoscopies were reviewed by blinded gastroenterology pathologists. RESULTS Histologic assessment of 33,658 biopsies showed no significant difference (P> .05) in squamous overgrowth between groups when compared per patient (30% vs 33%) or per biopsy (0.5% vs 1.3%), or when the average number of biopsies with squamous overgrowth were compared per patient (0.48 vs 0.66). The highest grade of neoplasia per endoscopy was not found exclusively beneath squamous mucosa in any patient. CONCLUSIONS No difference was observed in squamous overgrowth between patients given PHOPDT plus omeprazole compared with only omeprazole. Squamous overgrowth did not obscure the most advanced neoplasia in any patient. Treatment of HGD with PHOPDT in patients with BE does not present a long-term risk of failure to detect subsquamous dysplasia or carcinoma.

Carcinoma of the gallbladder. The Roswell Park experience.

The median survival, from diagnosis, of patients with cancer of the gallbladder is 6 months. Our purpose in reviewing our experience was to identify factors, either in patient characteristics or treatment, that influence this statistic. In 22 years 71 cases of gallbladder carcinoma were referred to Roswell Park Memorial Institute in Buffalo, New York. Most had a cholecystectomy that revealed an unsuspected neoplasm, before referral. Mean age was 62 years and 75% were female. Symptoms, signs, and laboratory and imaging studies were uniformly unhelpful in determining the diagnosis. Early diagnosis at a stage amenable to surgical excision remains the sole salvation. Patients who receive chemotherapy did better than those who did not, but this is probably a reflection of patient selection. Newer treatment modalities are urgently needed.

A phase II trial of 5-fluorouracil and high-dose intravenous leucovorin in gastric carcinoma.

Twenty-eight patients with advanced measurable gastric carcinoma were treated with leucovorin (dl-CF; folinic acid; dl-5-formyltetrahydrofolic acid) 500 mg/m2 administered as a two-hour infusion and 5-fluorouracil (5-FU) 600 mg/m2 intravenous (IV) push midinfusion. Treatment was administered weekly for 6 weeks followed by a 2-week rest. Twenty-five patients were evaluable for response. Twelve of them had received previous combination chemotherapy that included 5-FU. Median age was 59 years, and median Eastern Cooperative Oncology Group (ECOG) performance status was 2. Three patients had partial responses and two of them had been treated previously with 5-FU. Twelve patients had stable disease. Five of these patients had subjective improvement with improved performance status and/or decreased dysphagia. The 95% confidence interval for response is 3% to 32%. Median survival time for all 28 patients enrolled in the study was 22 weeks. Toxicity was moderate and consisted primarily of diarrhea. Myelosuppression, skin rash, and increased lacrimation also occurred. Plasma concentrations of the active reduced folates, I-CF and 5-methyltetrahydrofolic acid (5-CH3FH4), were greater than the 10 mumol/L levels that potentiate 5-FU activity in in vitro models, for more than four hours in all five patients in whom pharmacokinetics were studied. 5-FU and high-dose dl-CF has activity in patients with gastric carcinoma including patients who had previously progressed on 5-FU-containing combinations. Further study in a larger patient population is necessary to determine the usefulness of this regimen in gastric carcinoma.

Adenocarcinoma of the small intestine: 21-Year review of diagnosis, treatment, and prognosis

AbstractBackground: The purpose of this study was to evaluate the tumor characteristics and treatment associated with an improved overall survival in patients with adenocarcinoma of the small intestine. Methods: The records of all patients with primary adenocarcinoma of the small bowel seen between January 1971 and December 1991 were reviewed retrospectively. The study comprised 38 patients, 22 (58%) with duodenal tumors, 11 (29%) with jejunal tumors, and five (13%) with ileal tumors. Results: Although not statistically significant, the patients with duodenal adenocarcinoma lived longer than the patients with jejunal or ileal lesions (p=0.77). The overall survival was 23% and seemed to correlate best with absence of lymph node metastases (p=0.04) and pancreaticoduodenectomy for localized duodenal tumors (p=0.04). The patients age, duration of symptoms, disease-free interval, tumor location, type of recurrence, and histologic grade did not significantly influence survival. Conclusions: The lethality of small-intestinal adenocarcinoma appears to be related to a delay in diagnosis and treatment. When a definitive surgical procedure is performed before lymph node metastases appear, the patients chance for long-term survival is greatly improved.

Small cell carcinoma of the gallbladder

Small cell carcinoma of the gallbladder is rare with only 36 cases reported in the literature. Early reports demonstrated an extremely poor prognosis for this histologic type. Five new cases are reported and the previous experience in the literature is reviewed to further clarify the clinical behavior of this malignancy.