Biomedical subjects
Frederic E Eckhauser
Publications and source records attributed to Frederic E Eckhauser.
Adjuvant therapy in pancreatic cancer: Phase I trial of radiation dose escalation with concurrent full-dose gemcitabine.
PURPOSE: To determine the maximal tolerated dose of radiation delivered to the primary tumor bed, in combination with full-dose gemcitabine (1000 mg/m(2) weekly x 3), after resection of pancreatic cancer. METHODS AND MATERIALS: Patients with resected pancreatic carcinoma and poor prognostic features, a positive resection margin, or involved lymph nodes were eligible. Radiotherapy (RT) was directed at the preoperative tumor volume with a conformal technique. Regional lymph node basins were not included. The initial starting radiation dose was 24 Gy in 1.6-Gy fractions. Escalation was achieved by increasing the fraction size in 0.2-Gy increments, keeping the duration of RT to 3 weeks. Gemcitabine was given i.v. for 30-40 min at a dose of 1000 mg/m(2) before RT on Days 1, 8, and 15 of a 28-day cycle. After completion of RT and chemotherapy, an additional cycle of gemcitabine was delivered. RESULTS: Between November 1997 and October 2001, 32 patients were entered: 30 after Whipple resection (positive margins in 2, positive nodes in 22, and both in 6), 1 after distal pancreatectomy, and 1 after incomplete resection of a tumor involving the body (both patients with positive margins and nodes). Treatment was well tolerated. Of the 32 patients, 27 completed all protocol therapy and 29 maintained their pretreatment weight within 5%. Five patients experienced dose-limiting toxicity, four with Grade 3 vomiting requiring hospitalization and one fatal toxicity secondary to pneumonia/sepsis. At the final radiation dose level (42 Gy), 2 patients experienced GI dose-limiting toxicity. At the 39-Gy-dose level, 5 of 6 patients were without dose-limiting toxicity. Isolated local or regional progression was documented in 1 patient. Distant progression was documented in 26 of 32 patients (6 with concurrent local or regional progression). The median survival was 16.5 months (95% confidence interval 12.3-19.9) CONCLUSION: The results of our study indicate that the maximal tolerated radiation dose, administered using conformal techniques targeted to the tumor bed, is 39 Gy. In this high-risk population, data on locoregional control suggest that the reduction in radiation dose and field size minimizes toxicity and does not result in excess failures at these sites.
Carcinoid tumor of the biliary tract: treating a rare cause of bile duct obstruction.
Biliary carcinoids are rare with fewer than 30 cases reported in the English literature. The objective of this report is to describe an additional patient found to have a biliary carcinoid and to define the presentation, diagnosis, and management of patients with this rare biliary tumor. In our case the patient initially presented with clinical jaundice and elevated transaminases. Endoscopic retrograde cholangiogram established a mass suspicious for cholangiocarcinoma (Klatskin tumor). The patient was initially managed with an endostent, which was later removed in favor of a percutaneous transhepatic cholangiogram tube. At the time of surgery successful removal of a firm nodular mass at the area of the ductal bifurcation was achieved and biliary continuity re-established with a Roux-en-Y hepaticojejunostomy. Pathology revealed carcinoid tumor of the bile duct with one lymph node positive for tumor. The patient did not receive any adjuvant radiation or chemotherapy. This case serves to highlight that extrahepatic biliary carcinoids constitute a rare but identifiable subset of bile duct tumors. Diagnostic workup should include US, CT, and cholangiography. Surgical exploration is universally indicated in physiologically fit patients with operative management to include resection and re-establishment of biliary continuity. Data on adjuvant therapy remain investigational; however, available information suggests that patients with biliary carcinoid have an overall favorable prognosis after aggressive surgical management.
Resectional therapy for cystic neoplasms of the pancreas.
Currently there is uncertainty in diagnosis between the serous (benign) and mucinous (premalignant) forms of cystic neoplasms of the pancreas without operation. Our objective is to evaluate resectional therapy as a treatment for these lesions. A retrospective review of cases from 1985 to 1999 were performed. There were 14 cases of serous cystadenoma (SCA), 11 cases of mucinous cystadenoma (MCA), and five cases of mucinous cystadenocarcinoma (MCAC). A female predominance was seen in all lesions (100% in SCA, 64% in MCA, and 80% in MCAC) with a mean age at presentation of 59 years. Most patients presented with pain (SCA = 64%, MCA = 55%, and MCAC = 80%). Weight loss was seen in 35 per cent of all patients and was present in all cases of MCAC. Importantly 36 per cent of MCA patients were asymptomatic. Lesions were identified as multicystic on CT reports of 62 per cent of SCA patients, 50 per cent of MCA patients and 75 per cent of MCAC patients. Size was similar between groups. All patients were treated with surgical resection; operative morbidity was 27 per cent and mortality was zero. Actuarial 5-year survival for SCA, MCA, and MCAC was 100, 100, and 33 per cent, respectively. Differentiating serous from mucinous is not possible based on presenting symptoms and radiologic findings. Surgical resection is justified on the basis of low morbidity and negligible mortality rates.
Influence of functional bowel disease on outcome of surgical antireflux procedures.
Patients with gastroesophageal reflux disease (GERD) have a coexisting diagnosis of functional bowel disease (FBD) in approximately 30% of cases. Symptom improvement after surgical therapy for GERD may be less in patients with FBD when compared to patients without this coexisting problem. A retrospective review of patients undergoing Nissen fundoplication between 1996 and 2000 evaluated patients with documented FBD or FBD symptoms to determine operative outcome. Poor postoperative outcome included recurrent heartburn, gas bloat syndrome, dysphagia requiring reoperation or dilation, or delay in resumption of normal diet. Bivariate comparison and multivariate logistic regression evaluated the independent impact of a documented diagnosis of FBD or preoperative symptoms of FBD on outcome. This study examined 155 patients: 32% reported having symptoms of FBD and 10% had a confirmed diagnosis of FBD. Poor postoperative outcomes occurred in 27%. Patients with a documented diagnosis of FBD were significantly more likely to have a poor outcome when compared to patients without symptoms of FBD (53% vs. 23%, P = 0.01). Patients with preoperative symptoms of FBD (but without a documented diagnosis of FBD) also had a higher incidence of poor outcome (5% vs. 23%, P = 0.09). Patients with FBD are at increased risk of poor results after antireflux surgery. Patients with these conditions should be counseled preoperatively regarding the potential for recurrent postoperative symptoms.
Surgical resection following radiation therapy with concurrent gemcitabine in patients with previously unresectable adenocarcinoma of the pancreas.
The combination of gemcitabine with concurrent radiation therapy (Gem/RT) is a promising new approach that is being investigated in patients with unresectable pancreatic cancer. However, substantial toxicity with this combination has also been observed. This review was conducted to determine whether Gem/RT could be safely delivered in the neoadjuvant setting, based on our experience with this combined therapy in a cohort of patients with previously unresectable pancreatic cancer, who subsequently underwent surgical resection. Between July 1996 and June 2001, a total of 67 patients with locally unresectable pancreatic cancer, without distant metastatic disease, received Gem/RT at our institution. Seventeen patients (25%) underwent exploratory surgery following Gem/RT, and nine underwent standard Whipple resection. Thus 9 (52%) of 17 patients who had exploratory operations or 9 (13%) of 67 patients, underwent surgical resection. Thirty-day mortality after resection was 0%, and there were no major surgical complications. Median length of hospital stay was 14 days (range 11 to 19 days). With a median follow-up of 32 months, median survival for the resected patients was 17.6 months (95% confidence interval 12.6 to 37.3 months). Median survival for the remaining 58 patients was 11.9 months (95% confidence interval 9.6 to 14.7 months, P=0.013). We conclude that surgical resection may be safely performed after Gem/RT in a select group of patients initially considered to have unresectable pancreatic cancer. The use of Gem/RT in a neoadjuvant setting is currently being investigated in a multi-institutional phase II trial.