Albert Bothe

Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome.

OBJECTIVE To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure. SUMMARY BACKGROUND DATA Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy. METHODS Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss. RESULTS Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined. CONCLUSIONS Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.

Phase I study of protracted venous infusion of 5-fluorouracil

A Phase I study of protracted continuous infusion 5‐fluorouracil was undertaken at a starting dose of 200 mg/m2/day. The drug was delivered via a tunneled subclavian venous access site by a portable infusion pump (Cor‐Med) permitting ambulatory monitoring. Seventeen patients were administered 19 courses at incremental dose rates from 200 mg/m2/day to 600 mg/m2/day; treatment was terminated at the onset of stomatitis. At dose rates of 300 mg/m2/day or less, the treatment did not require interruption for up to 60 days or up to 36 g cumulative dose. For dose rates of 350 to 600 mg/m2/day, the treatment always required interruption: mean duration 20 day for 350 mg/m2/day; 9 day for 400 mg/m2/day; and 14 day for 600 mg/m2/day. Mean cumulative dose at the higher dose rates was 10.9 g (350 mg/m2/day); 7.9 g (400 mg/m2/day); and 15.3 g (600 mg/m2/day). Mean cumulative dose at 200 mg/m2/day was 11.5 g and at 300 mg/m2/day, was 22.6 g. Protracted venous infusion allows for a substantial cumulative dose of 5‐FU and at dose rate delivery of 300 mg/m2day may be administered for up to 60 days without adverse effects due to the drug or to the presence of an indwelling venous access line.

Nutritional assessment and patient outcome during oncological therapy

Protein‐calorie malnutrition is the single most common secondary diagnosis in patients with cancer, and is a direct consequence of the anorexia of malignancy and altered host metabolism induced by tumor. One hundred and sixty‐one cancer patients were nutritionally assessed prior to receiving oncological therapy (surgery, chemotherapy, and/or radiation therapy). Eighty‐four percent (27/32) of the patients who were initially anergic became immunocompetent with nutritional therapy and had a mortality rate of 11% as compared to 100% mortality in the 5 patients who remained anergic throughout their hospital stay. Thirty‐nine percent (14/36) of the patients initially immune competent became anergic and had a concomitant mortality rate of 50% vs. a mortality rate of only 14% in the 22 patients whose immune function was preserved (p < 0.05). Those patients who were discharged at the completion of their therapy also exhibited a higher initial serum albumin (3.5 ± 0.1 vs. 3.1 ± 0.1 g/dl, p < 0.001) and serum transferrin (149 ± 7 vs. 125 ± 7 mg/dl, p < 0.05). A significant increase (p < 0.025) occurred in serum transferrin (Δ23 ± 9 mg/dl) after 3 or more weeks of nutritional support. The detection and treatment of protein‐calorie malnutrition prior to or in conjunction with oncological therapy has been associated with a decrease in mortality rate.

ProvenCareSM: a provider-driven pay-for-performance program for acute episodic cardiac surgical care.

Objective:To test whether an integrated delivery system could successfully implement an evidence-based pay-for-performance program for coronary artery bypass graft (CABG) surgery. Methods:The program consisted of 3 components: (1) establishing implementable best practices; (2) developing risk-based pricing; (3) establishing a mechanism for patient engagement. Surgeons reviewed all class I and IIa “2004 American Heart Association/American College of Cardiology Guidelines for CABG Surgery” and translated them into 40 verifiable behaviors. These were imbedded within a new ProvenCareSM program and “hardwired” within the electronic health record system, including order sets, templates, and “time outs”. Concurrently preoperative, inpatient, and postoperative care within 90 days was packaged into a fixed price. A Patient Compact was developed to highlight the importance of patient activation. All elective CABG patients treated between February 2, 2006 and February 2, 2007 were included (ProvenCareSM Group) and compared with 137 patients treated in 2005 (Conventional Care Group). Results:Initially, only 59% of patients received all 40 best practice components. At 3 months, program compliance reached 100%, but fell transiently to 86% over the next 3 months. Reliability subsequently increased to 100% and was sustained for the remainder of the study period. The overall trend in reliability was significant at P = 0.001. Thirty-day clinical outcomes showed improved trends (Table 1) but only the likelihood of discharge to home reached statistical significance. Length of stay decreased by 16% and mean hospital charges fell 5.2%. TABLE 1. Thirty-day Clinical Outcomes Conclusion:A provider-driven pay-for-performance process for CABG, enabled by an electronic health record system, can reliably deliver evidence-based care, fundamentally alter reimbursement incentives, and may ultimately improve outcomes and reduce resource use.

Implantable central venous access system

Prolonged central venous access for outpatient chemotherapy was achieved in 74 patients utilizing a totally implantable access disc system. The system consists of a stainless steel drug reservoir implanted in the subcutaneous tissue of the anterior chest wall. The reservoir is attached to a Silastic catheter which is then tunneled to a central vein and positioned in the superior vena cava. In 6,762 patient days of observation, there was a high degree of patient acceptance and a low incidence of complications. There were four instances of thrombosis and two of catheter-related sepsis among 17 complications. Seven access discs required removal. The implantable nature of this system offers an attractive alternative to other available methods of prolonged central venous access.

Locally advanced rectal carcinoma: pelvic control and morbidity following preoperative radiation therapy, resection and intraoperative radiation therapy

PURPOSE To determine the impact of intraoperative radiation therapy (IORT) combined with preoperative external beam irradiation and surgical resection in patients with locally advanced, unresectable rectal carcinoma. METHODS AND MATERIALS Between 1982 and 1993, 40 patients with locally advanced colorectal cancer unresectable at initial presentation were treated with preoperative external beam radiation therapy (median dose 50.4 Gy). Thirty patients received concurrent 5-fluorouracil. Twenty-seven patients had primary tumors and 13 had recurrent disease; 1 patient had a solitary hepatic metastasis at the time of surgery. Four to 6 weeks after radiation, surgical resection was undertaken, and if microscopic or gross residual disease was encountered, IORT was delivered to the tumor bed. Patients with an unevaluable or high-risk margin were also considered for IORT. IORT was delivered through a dedicated 300-kVp orthovoltage unit. The median dose of IORT was 12.5 Gy (range 8-20). The dose was typically prescribed to a depth of 1-2 cm. The median follow-up was 33 months (range 5-100). RESULTS Thirty-three patients were able to undergo a curative resection (83%). Five patients had gross residual disease despite aggressive surgery. Seven patients did not receive IORT: six because of clear margins, and one with gross disease that could not be treated for technical reasons. The remainder of the patients (26) received IORT to the site of pelvic adherence. The crude local control rates for patients following complete resection with negative margins were 92% for patients treated with IORT and 33% for patients without IORT. IORT was ineffective for gross residual disease. Pelvic control was none of four in this setting. The crude local control rate of patients with primary cancer was 73% (16 of 22), as opposed to 27% (3 of 11) for these with recurrent cancer. The 5-year actuarial overall survival and local control rates for patients undergoing gross complete resection and IORT were 64% and 75%, respectively. Seventeen of the 26 patients (65%) who received IORT experienced pelvic complications, as opposed to two patients (28%) who did not receive IORT. The incidence of complications was similar in the patients with primary versus recurrent disease. All cases were successfully treated with the placement of a posterior thigh myocutaneous flap. Of note, no pelvic osteoradionecrosis was seen in this series. CONCLUSION Patients with locally advanced carcinoma of the rectum were aggressively treated with combined modality therapy consisting of preoperative external beam radiotherapy, surgery, and IORT. The pelvic control rate was 82% for patients with minimal residual disease. IORT failed to control gross residual disease. The incidence of pelvic wound healing problems was 65% in this series; however, a reconstructive procedure which replaced irradiated tissue with a vascularized myocutaneous flap was successful in treating this complication. We believe that IORT has therapeutic merit in the treatment of locally advanced rectal cancer, particularly in the setting of minimal residual disease.

In vivo demonstration of nitrogen-sparing mechanisms for glucose and amino acids in the injured rat.

Changes in protein metabolism 8 hr after anesthesia and femur fracture were studied in healthy rats fasted or receiving either intravenous glucose or crystalline amino acids. Whole body rates of amino acid turnover (flux) and release from protein (breakdown) as well as fractional synthetic rates of mixed muscle, liver, and plasma protein were measured using the constant infusion of L-(I-14C)-leucine. Injury resulted in a 24% increase in the synthesis of liver (p less than 0.05) and plasma proteins (p less than 0.01), respectively. Amino acid infusions in the injured animals further increased the synthesis of liver protein (from 36.6% to 44.3%/day, p less than 0.05) and increased muscle protein synthesis (from 7.0% to 9.3%/day, p less than 0.05) without altering rates of protein breakdown. Glucose infusions, in contrast, reduced whole body protein breakdown 36% (p less than 0.05) when compared to fasting, and depleted the plasma essential amino acid pool (p less than 0.05). The usual increases in liver protein synthesis observed in fasted rats following injury were not seen when the animals were receiving intravenous glucose. The nitrogen-sparing mechanism of these two infusions are different. Protein-free glucose infusions impair the normal response to injury aimed at increasing visceral protein synthesis and maintaining plasma essential amino acid concentrations.

Gastric restrictive operations for morbid obesity

Gastric restrictive surgery has evolved over the past decade as the treatment of choice for morbid obesity. We reviewed our experience with 289 patients who underwent gastric surgery for morbid obesity. Comorbid diseases included respiratory insufficiency in 19 percent of the patients, hypertension in 36 percent, diabetes in 15 percent, arthritis in 30 percent, and heart disease in 6 percent. Operative mortality was 0. The follow-up rate was 93 percent. Overall mortality was 1 percent, with no death directly attributed to the operative procedure. Weight loss was studied over the 6-year study period. Four to 6 years postoperatively, overall weight loss was 50 to 64 percent of excess weight. The treatment failure rate 12 to 18 months postoperatively was 5 percent. The experience with gastric restrictive surgery in 12 centers involving 5,178 patients was reviewed and compared with our results. Overall operative and late mortality rates were quite similar to observed death rates for nonobese men and women between 25 and 64 years of age. These data suggest that gastric surgery for morbid obesity results in a significant reduction in health risk.

Budd-Chiari syndrome: Historical and clinical review with an analysis of surgical corrective procedures☆

Seventeen patients who fulfilled the criteria for the Budd-Chiari syndrome (centrilobular congestion and necrosis, a defined postsinusoidal block, and rapid onset of ascites) have been analyzed in terms of cause, prognosis, and treatment. Causal factors included caval web or tumor, hepatic tumor, a hypocoagulable state, myeloproliferative disease, and veno-occlusive disease. Location of the outflow block was suprahepatic (vena cava or major hepatic veins) in 13 patients and intrahepatic in 4. In five patients, a side-to-side portacaval shunt was effective in dissipating ascites with restoration to a normal lifestyle, as were transatrial fracture of a caval web (one patient) and resection of a huge cystadenoma of the liver (one patient). A peritoneal shunt provided effective palliation in three patients.

Pulmonary complications of orthotopic liver transplantation.

Pulmonary complications following orthotopic liver transplantation (OLT) were prospectively evaluated in 18 individuals transplanted at the New England Deaconess Hospital. Of sixteen patients who survived the immediate postoperative period, 12 (75%) sustained a pulmonary complication. Of these complications, 64% were noninfectious--whereas 22% were infectious, and 14% probably infectious. Six of eight documented infections were caused by viruses of the herpes group. In four cases of viral pneumonitis other pulmonary pathogens were isolated (fungi-3, protozoan-1, bacteria-1). Unlike noninfectious complications, pulmonary infections were associated with a fatal outcome in five of six patients who died after OLT. Pulmonary complications are frequent and serious occurrences after OLT, and contribute to both the morbidity and mortality of this procedure. Compared with pulmonary complications seen after transplantation of other organs, OLT was associated with a higher proportion of noninfectious complications but a similar spectrum of pulmonary infections.