Alan D. Turnbull

Liver resection for colorectal metastases.

PURPOSE More than 50,000 patients in the United States will present each year with liver metastases from colorectal cancers. The current study was performed to determine if liver resection for colorectal metastases is safe and effective and to evaluate predictors of outcome. MATERIALS AND METHODS Data for 456 consecutive resections performed between July 1985 and December 1991 in a tertiary referral center were analyzed. RESULTS The perioperative mortality rate was 2.8%, with a mortality rate of 4.6% for resections that involved a lobectomy or more. The median hospital stay was 12 days and only 9% of patients were admitted to the intensive care unit. The 5-year survival rate is 38%, with a median survival duration of 46 months. By univariate analysis, nodal status of the primary lesion, short disease-free interval before detection of liver metastases, carcinoembryonic antigen (CEA) level greater than 200 ng/mL, multiple liver tumors, extrahepatic disease, large tumors, or positive resection margin was predictive of poorer outcome. Sex, age greater than 70 years, site of primary tumor, or perioperative transfusion was not predictive of outcome. By multivariate analysis, positive margin, size greater than 10 cm, disease-free interval less than 12 months, multiple tumors, and extrahepatic disease were independent predictors of poorer outcome. Short disease-free interval or multiple tumors were nevertheless associated with a 5-year survival rate greater than 24%. CONCLUSION Liver resection for colorectal metastases is safe and effective therapy and currently represents the only potentially curative therapy for metastatic colorectal cancer. The only absolute contraindication to resection is extrahepatic disease. A randomized trial to examine efficacy of surgical resection cannot ethically be performed. Liver resection should be considered standard therapy for all fit patients with colorectal metastases isolated to the liver.

Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer.

BACKGROUND Two years after undergoing resection of liver metastases from colorectal cancer, about 65 percent of patients are alive and 25 percent are free of detectable disease. We tried to improve these outcomes by treating patients with hepatic arterial infusion of floxuridine plus systemic fluorouracil after liver resection. METHODS We randomly assigned 156 patients at the time of resection of hepatic metastases from colorectal cancer to receive six cycles of hepatic arterial infusion with floxuridine and dexamethasone plus intravenous fluorouracil, with or without leucovorin, or six weeks of similar systemic therapy alone. Patients were stratified according to previous treatment and the number of liver metastases identified at operation. The study end points were overall survival, survival without recurrence of hepatic metastases, and survival without any metastases at two years. RESULTS The actuarial rate of overall survival at two years was 86 percent in the group treated with local plus systemic chemotherapy and 72 percent in the group given systemic therapy alone (P=0.03). The median survival was 72.2 months in the combined-therapy group and 59.3 months in the monotherapy group, with a median follow-up of 62.7 months. After two years, the rates of survival free of hepatic recurrence were 90 percent in the monotherapy group and 60 percent in the monotherapy group (P<0.001), and the respective rates of progression-free survival were 57 percent and 42 percent (P=0.07). At two years, the risk ratio for death was 2.34 among patients treated with systemic therapy alone, as compared with patients who received combined therapy (95 percent confidence interval, 1.10 to 4.98; P=0.027), after adjustment for important variables. The rates of adverse effects of at least moderate severity were similar in the two groups, except for a higher frequency of diarrhea and hepatic effects in the combined-therapy group. CONCLUSIONS For patients who undergo resection of liver metastases from colorectal cancer, postoperative treatment with a combination of hepatic arterial infusion of floxuridine and intravenous fluorouracil improves the outcome at two years.

Patterns of Initial Recurrence in Completely Resected Gastric Adenocarcinoma

Objective:To review recurrence patterns in completely resected gastric adenocarcinoma. Summary Background Data:Despite improvements in the surgical treatment of gastric adenocarcinoma, recurrence rates remain high in patients with advanced stage disease. Understanding the timing and patterns of recurrence is essential to develop effective adjuvant treatment strategies. Methods:A retrospective review of a prospectively maintained gastric cancer database was carried out. The timing and pattern of recurrence were reviewed. Univariate and multivariate analyses were performed to identify factors predictive of recurrence patterns. Results:From July 1985 through June 2000, 1172 patients underwent an R0 resection. Of these, 496 (42%) had recurrence and complete data on recurrence could be obtained in 367 patients (74%). Among the documented recurrences, 79% were detected within 2 years of operation. Locoregional sites were involved as any part of the recurrence pattern in 199 patients (54%). Distant sites were involved as any part of the recurrence in 188 patients (51%) and peritoneal recurrence was detected as any part of the recurrence in 108 patients (29%). On multivariate analysis, peritoneal recurrence was associated with female gender, advanced T-stage, and distal and diffuse type tumors; locoregional recurrence was associated with male gender and proximal location; distant recurrence was associated with proximal location, early T stage, and intestinal type tumors. The median time to death from the time of recurrence was 6 months. Conclusions:Recurrence after complete resection of gastric adenocarcinoma usually occurs within 2 years and is rapidly fatal. Patterns of recurrence are variable and may be associated with specific clinicopathologic factors.

Whole Body 18FDG-PET and the Response of Esophageal Cancer to Induction Therapy: Results of a Prospective Trial

PURPOSE Whole-body 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) imaging before and after induction therapy was prospectively evaluated in patients with esophageal cancer to determine whether changes in PET images could measure response to therapy. PATIENTS AND METHODS Between April 1997 and April 1999, 39 patients (34 men and five women; median age, 59 years; range, 36 to 76 years) with esophageal cancer were prospectively enrolled in a single-institution clinical trial of staging, including PET, induction therapy, restaging including PET, and esophagectomy. All patients undergoing esophagectomy after induction therapy (n = 17) were followed either to recurrence, to death, or through a disease-free interval of at least 24 months. RESULTS PET after standard staging studies and before therapy imaged undetected sites of metastatic disease in six patients (15%). Restaging (including PET) after induction therapy did not identify any patients with disease progression or any patients with loco-regionally unresectable disease at exploration. The median decrease in the standardized uptake value (SUV) during induction therapy was 59%. After R0 esophagectomy, the 2-year disease-free and overall survival was 38% and 63%, respectively, among patients who had a less than 60% decrease in SUV, and 67% and 89%, respectively, among patients who had a greater than 60% decrease in SUV (P =.055 and P =.088, respectively). CONCLUSION Compared with conventional imaging, PET detects additional sites of metastatic disease at initial evaluation. After induction therapy, PET did not add to the estimation of loco-regional resectability and did not detect new distant metastases. However, changes in [18F]FDG PET may predict disease-free and overall survival after induction therapy and resection in patients with esophageal cancer. Further evaluation in larger trials is warranted.

Regional pancreatectomy: en bloc pancreatic, portal vein and lymph node resection.

Eighteen patients are reported who have had a regional pancreatectomy. The pancreatic segment of portal vein was excised with en bloc total pancreatectomy and regional lymph node dissection in all 18. Venous repair was by end-to-end anastomosis without a graft. Five of the 18 also had various arterial resections and reconstructions. Sixteen of the 18 had been explored and deemed nonresectable elsewhere. This operation has doubled the resectability rate in this institution. The 30-day operative mortality rate was 16.6%. Acurarial survival is 62% at one year compared with 36% one year survival rate for patients undergoing pancreaticoduodenectomy for less advanced cancer in previous years. A more valid comparison would be between those who had a palliative procedure since most patients in the present series were initially considered unresectable. One year survival for these patients was 22%. The quality of life was good for most patients.

The continuing challenge of retroperitoneal sarcomas

Treatment of 158 patients with retroperitoneal sarcomas (1951–1977) resulted in a mean five‐year survival of 40% (range 37–45%) after complete excision. Only 22% (range 19–25%) of the patients were free of disease. Survival for five years after incomplete excision was 3%. Operative mortality after complete excision declined from 21 to 2% during this period. Anatomical barriers to wide resection, high‐grade histology, and local recurrence were the most important factors determining survival. The need for adjuvant therapy is emphasized by a 77% recurrence rate among patients with apparent complete excision. Brachytherapy (125Iodine, 192Iridium) afterloading techniques and supplemental external radiation are recommended to improve local control and chemotherapy is indicated to diminish the potential for metastatic spread. The contribution of adjuvant therapy after complete excision in this series was difficult to assess because of the number of uncontrolled variables, different histologic types, and limited number of patients treated by multimodality therapy. Although radiation and chemotherapy may be beneficial after incomplete resection, prolonged survival was only seen in patients with liposarcoma and low‐grade fibrosarcoma.

Prospective study of infections in indwelling central venous catheters using quantitative blood cultures

PURPOSE Surgically implanted central venous catheters are widely used in cancer patients in whom there is a need for prolonged venous access for chemotherapy, parenteral nutrition, antibiotics, and blood sampling. This study evaluated catheter infectious complications, including catheter-related sepsis, exit site infection, and tunnel infection. Specifically, an evaluation of the incidence, type, and response to treatment of indwelling catheter infections was performed, and conditions under which the catheter should be removed were delineated. PATIENTS AND METHODS During the year of this study, 488 central venous catheters were implanted. Records were maintained on demographic variables, date of catheter implantation, surgeon, white blood cell count, absolute neutrophil count, and underlying diagnosis. Blood for both aerobic and anaerobic culture was collected from each patient. For patients in whom infection developed, clinical features, white blood cell count, absolute neutrophil count, and microbiologic data were noted, as were the clinical course and response to treatment. RESULTS A total of 142 episodes of infectious complications were documented. There were 88 episodes of catheter-related sepsis, and 33 of 54 evaluable episodes (61 percent) were successfully treated with antibiotics. There were 34 episodes of exit site infection, and 20 of the 29 evaluable episodes (69 percent) were successfully treated with antibiotics and local care. Of the 20 tunnel infections, only five (25 percent) were successfully treated with antibiotics, and the other 15 required catheter removal for cure. Twelve of the 15 cases requiring catheter removal were caused by Pseudomonas species. CONCLUSION On the basis of these results, compulsory removal of the catheter is not required in cases of catheter-related sepsis. Similarly, exit site infections can often be cured by means of antibiotics and local care. However, catheter removal is required to achieve cure in most tunnel infections, particularly if Pseudomonas species are cultured from the exit sites of patients with tunnel infection.

Major hepatic resection for neoplasia: personal experience in 108 patients.

One hundred eight patients have undergone major hepatic resection by the senior author during the eight year period April 1970 to April 1978. Primary liver cancer was present in 36; metastatic colorectal cancer in 25, miscellaneous metastatic cancers in 15, hepatoblastoma in 5, gallbladder cancer in 4, and bile duct cancer in 3. Benign tumors, principally giant hemangioma, were resected in 20 additional patients. The 30 day operative mortality rate was 9% overall. Prior to 1975, 41 of the resections were done using the vascular isolation perfusion technique. The operative mortality rate of 17% for this technique is a reflection of early experience and the advanced stage of disease of many patients. The operative mortality for the standard resection has been only 4%. Subphrenic abscess has developed in only 13% of patients during the past three years. Postoperative hospitalization has been shortened, being a median of 13 days. The resectability rate for malignant disease was 33%. Forty-six per cent of the resections were performed with curative intent. Fifty-four per cent were palliative, performed in individuals with regional spread or distant metastasis. After curative surgery, three year survival was 88% for individuals with primary liver cancer and 72% with metastatic colorectal cancer. After palliative resection, the rates were 31 and 0%, respectively. The three year survival rate is 46% overall, being 81% for the curative resection group and 18% for the palliative group. Tumor markers proved useful in monitoring patients after hepatic resection.

Metastatic breast cancer masquerading as gastrointestinal primary

Seven patients with metastatic breast cancer presenting as gastrointestinal primary are described. These included six gastric and one colonic lesions. None of the patients had known systemic metastases at the time of diagnosis. The mean age at presentation was 66.7 yr (range 55–78). Median interval between breast cancer and gastrointestinal metastasis diagnosis was 6 yr (range 0.25–12.5). Original breast cancer histology included infiltrating lobular cancer (n = 4), infiltrating ductal cancer (n = 1), and a mixed type (n = 2). All patients with gastric involvement presented with epigastric pain and early satiety; the patient with colonic involvement had heme-positive stool. In three cases of gastric tumor and the one case of colonic tumor presentation, a definitive diagnosis of metastatic breast cancer was only confirmed after surgical resection of a presumed primary gastric or colonic malignancy. In the other three cases, pathological diagnostic confirmation was obtained through endoscopic biopsies and comparison to breast biopsy material, and operative treatment was avoided in favor of systemic cytotoxic therapy. The diagnosis was confirmed through similarities between mammary and gastric histopathology with regard to growth pattern, hormone receptor status, or gross cystic disease fluid protein. A high level of suspicion for metastatic breast cancer and a detailed pathological analysis will help avoid unnecessary surgical treatment in patients with a history of mammary carcinoma presenting with a newly diagnosed gastrointestinal neoplasm.

Clinical experience with high frequency jet ventilation.

: High frequency jet ventilation (HFJV) has been used in recent years in some forms of respiratory failure, where the presence of barotrauma limited the application of high peak inspiratory pressure. In the present report, the authors describe the clinical experience with 17 patients, who could not be supported with conventional mechanical support and were placed on HFJV. Rates of 100 breath/min, inspiratory/expiratory ratio of 1:2 and cannula size of 1.06--1.62 mm (18--14) gauge were used. Driving pressure required to maintain a PaCO2 of 40--45 torr was 14--45 psig; however, except in 2 patients who developed hemorrhagic tracheitis with subtotal obstruction of both mainstem bronchi, a driving pressure higher than 27 psig was never required, even when PEEP up to 32 cm H2O was used. Of 17 patients treated, 8 survived. In all cases, alveolar ventilation could be maintained within the desired range with high frequency ventilation, even in those patients who eventually died; mechanical support never provided better oxygenation or alveolar ventilation than high frequency ventilation. Hemodynamic function was essentially unchanged with high frequency ventilation; indeed, in three cases, inotropic support with dopamine could be discontinued after initiation of high frequency ventilation.