13523 Background: Advances in systemic therapy for metastatic colon cancer may render patients (pts) candidates for hepatic metastasectomy (HM) with curative intent. We retrospectively reviewed our experience with HM following oxaliplatin chemotherapy. Methods: Pts were identified from the records of 5 surgeons who performed HM at two institutions. Pts were included if FOLFOX (bolus 5-FU/leucovorin d1 or d 1 + 2, followed by 46 hour 5-FU infusion; oxaliplatin 85–130mg/m2 d 1 q 14 d) chemotherapy had been given for > 1 cycle prior to HM and complete resection of hepatic metastases was achieved. Data on radiographic (RECIST) and pathologic response and outcome were collected. Pathologic complete response (pCR) was defined as no residual cancer. Near pCR was defined as residual mucin in the liver, without residual cancer cells, or necrosis with atypical glands. Results: Thirty-six pts were identified. Males 21/36, median age 55 (range 37–77), rectum/rectosigmoid primary 5 (13.9%), adenocarcinoma 100%, synchronous metastases or metastases within 6 months (m) of primary diagnosis 24/32 (75%), median cycles of FOLFOX = 7 (range 2 to >30), bevacizumab (B) 9 (25%). Mean number of hepatic lesions pre-chemotherapy 1.9 (range 1–7), tumor size 1 to >10cm. Radiographic responses to pre-operative FOLFOX included partial response (PR) 9/30 (30%), CR 2/30 (6.7%), progressive disease 3/30 (10%), stable disease 16/30 (53.5%). Operations included right (R) hepatectomy 12, extended (ext) R hepatectomy 3, partial R hepatectomy 2, left (L) hepatectomy 3, partial L hepatectomy 1, ext L hepatectomy 1, trisegmentectomy 2, caudate lobectomy 1, multiple wedge resections ± radiofrequency ablation 7. pCR 2 (5.6%); near pCR 3 (8.3%). At a median follow up of 12.9 m from HM, 9/36 (25%) recurred; liver only (3), portal lymph nodes (1), other extrahepatic sites (5). One pt died at 18.3 m. Conclusions: HM after FOLFOX chemotherapy, with or without B, results in a high progression-free and overall survival at 12.9 m. This retrospectively identified population included pts with conventionally adverse prognostic features including rectal cancers, synchronous metastases, large lesions and/or high lesion number. Prospective studies of the utility of pre-HM chemotherapy are warranted. [Table: see text]

PURPOSE:A Patterns of Care Study examined the records of patients with esophageal cancer (EC) treated with radiation in 1992 through 1994 to determine the national practice processes of care and outcomes and to compare the results with those of clinical trials.PATIENTS AND METHODS:A national survey of 63 institutions was conducted using two-stage cluster sampling, and specific information was collected on 400 patients with squamous cell (62%) or adenocarcinoma (37%) of the thoracic esophagus who received radiation therapy (RT) as part of primary or adjuvant treatment. Patients were staged according to a modified 1983 American Joint Committee on Cancer staging system. Fifteen percent of patients had clinical stage (CS) I disease, 40% had CS II disease, and 30% had CS III disease. Twenty-six percent of patients underwent esophagectomy. Seventy-five percent of patients received chemotherapy; 84% of these received concurrent chemotherapy and radiation (CRT).RESULTS:Significant variables for overall survival in multivariate analysis include the use of esophagectomy (risk ratio [RR] = 0.62), the use of chemotherapy (RR = 0.63), Karnofsky performance status (KPS) greater than 80 (RR = 0.61), CS I or II disease (RR = 0.66), and facility type (RR = 0.72). Age, sex, and histology were not significant. Preoperative CRT resulted in a nonsignificantly higher 2-year survival rate compared with definitive CRT alone (63% v 39%; P =.11), whereas 2-year survival by planned treatment rather than treatment given was 47.7% for preoperative CRT and 35.4% for definitive CRT (P =.23). Definitive CRT compared with definitive RT alone resulted in significantly higher 2-year survival (39% v 20.6%; P =.027) and lower 2-year local regional failure (30% v 57.9%; P =. 0031).CONCLUSION:This study confirms the value of CRT in EC treatment. It indicates that the results obtained in practice settings nationwide are similar to those obtained in clinical trials and that KPS and the 1983 clinical staging system are useful prognostic indicators. The suggested value of esophagectomy and superiority of preoperative CRT over CRT alone in this study should be tested in a randomized trial.

BACKGROUND. For the first time, a Patterns of Care Study (PCS) was conducted in 1992-1994 to determine the national practice standards in evaluating and treating patients with esophageal carcinoma and to determine the degree to which clinical trials have been incorporated into national practice.METHODS. A national survey of 61 institutions using 2-stage cluster sampling was conducted, and specific information was collected on 400 patients with squamous cell carcinoma or adenocarcinoma of the thoracic esophagus who received radiation therapy (RT) as part of definitive or adjuvant management of their disease. Patients were staged according to a modified 1983 American joint Committee on Cancer staging system. Chi-square tests for significant differences between academic and nonacademic institutions for a particular variable were performed.RESULTS. The median age of patients was 66.7 years (range, 26-89 years); 76.5% were male and 23.5% were female. Karnofsky performance status was greater than or equal to 80 for 88.3% of patients. Squamous cell carcinoma was diagnosed in 61.5% and adenocarcinoma in 36.8%. Fifteen percent were Clinical Stage (CS) I, 39.5% CS II, and 29.5% CS III. Evaluative procedures included endoscopy (>93%), computed tomography (CT) of the chest (86%), CT of the abdomen (75%), esophagography (68.5%), and endoscopic ultrasound (3.5%). Endoscopic ultrasound and CT of the chest were performed significantly more frequently at academic than nonacademic facilities (6.1% vs. 1.0% and 91.9% vs. 81.3%, respectively). Three-quarters of all patients received chemotherapy and RT and 62.5% received concurrent chemotherapy and RT as part of their treatment. Treatments included chemotherapy plus RT (54.0%), RT alone (20.3%), preoperative chemotherapy + RT (13.3%), postoperative chemotherapy + RT (7.7%), postoperative RT (3.5%), and preoperative RT (1.2%). The chemotherapeutic agents most frequently used were 5-fluorouracil (84%), cisplatin (64%), and mitomycin (9%); academic institutions used cisplatin significantly more often and mitomycin significantly less often than nonacademic institutions. Brachytherapy was used in 8.5% of cases. The median total dose of external beam radiation was 50.4 gray and the median dose per fraction was 1.8 gray.CONCLUSIONS. This study establishes the national benchmarks for the evaluation and treatment of patients with esophageal carcinoma at radiation facilities in the U.S. It also indicates that the majority of patients given RT as a component of treatment for esophageal carcinoma receive chemoradiation rather than RT alone, as supported by clinical trials. Although some differences in the evaluation of esophageal carcinoma were noted between academic and nonacademic facilities, there was no difference in the frequency of use of chemoradiation versus RT by facility type. Cancer 1999;85:2499-505. (C) 1999 American Cancer Society.

Two groups of patients with adenocarcinoma of the pancreas treated with either preoperative chemoradiation (preop CTRT) or postoperative chemoradiation (postop CTRT) were retrospectively analyzed for various treatment-related parameters. Between November 1986 and October 1996, a total of 70 patients with pancreatic adenocarcinoma were enrolled into preop CTRT protocols at our institution. Twenty-five patients with adenocarcinoma of the head of the pancreas underwent pancreaticoduodenectomy with curative intent. After the closure of the preop CTRT protocols, we had the opportunity to perform 23 pancreatic resections without preop CTRT. After surgery, these patients were advised to undergo CTRT. These two groups of patients were therefore selected consecutively, dependent only on the time of referral and no other bias. These two cohorts of patients are compared for various intraoperative parameters, length of hospital stay, pathologic findings, time to recurrence, and survival. Mean age was 65 and 66 years in the preop and postop CTRT groups, respectively. Sex distribution was almost equal. Treatment breaks resulting in greater than 1 week delay in the radiotherapy occurred in 2 (8%) of 25 patients in the preop CTRT group (myelotoxicity in 1 case and biliary sepsis in 1 case), whereas no treatment breaks >1 week occurred in those receiving postop CTRT. Eleven patients in preop CTRT had grade 3 or 4 toxicity, whereas none was noted in those with postop CTRT. There was one postoperative death in the preop CTRT group and none in the postop CTRT group. Mean time to the start of CTRT was 45 days (range, 20-66 days) after pancreaticoduodenectomy. Delay of >60 days to the onset of CTRT occurred in 2 (22%) patients and was attributable to patient delays in time to recover from surgery or patient noncompliance. Furthermore, 5 of 23 patients (22%) in the postop CTRT group did not receive treatment for various reasons. Average estimated operative blood loss was 1933 mL (median 1550) and 1060 mL (median 1000) for preop and postop CTRT groups, respectively. Mean length of operation was 488 minutes (median 480) and 486 minutes (median 480). Median length of postoperative stay was 22 and 20 days (ranges, 9-144 and 10-38). Pathological findings in the resected specimens showed significantly fewer involved nodes in the preop CTRT group (28 vs 87%; P = 0.0006), whereas similar numbers of nodes/patient were counted in each group (14 vs 22, P = 0.11). More negative resection margins were observed in the preop CTRT group (28 vs 56%; P = not significant). A significantly greater amount of fibrosis replacing the tumor was observed in the preop CTRT group (70 vs 40%; P = 0.0001). There were no significant survival differences observed (median 20 months vs 25 months; P = 0.48), in follow-up that ranged from 4 to 76 months (median 44 months for surviving patients) for the preop group and 4 to 40 months (median 16 months for surviving patients) for those with postop CTRT. Local failure either alone or as a component of distant failure occurred in 16 per cent (4 of 25 patients) with preop CTRT and 16.6 per cent (3 of 18) with postop CTRT. Analysis of differences between those treated with preoperative and postoperative CTRT demonstrates similarity in toxicity and effects. However, 22 per cent of patients intended for postoperative therapy did not receive treatment.

A 9-year experience with fine-needle aspiration (FNA) in patients with resectable pancreatic adenocarcinoma was reviewed to determine whether this procedure is associated with positive peritoneal cytology, peritoneal recurrences, or decreased survival in patients who had pancreatic resection with curative intent. Forty-one patients underwent pancreatic resection for primary pancreatic adenocarcinoma from July 1987 to February 1996. Nine patients had open biopsies prior to definitive resection and were excluded from this study. Of the remaining 32 patients, 21 (66%) had preoperative computed tomography-guided or fluoroscopically guided FNA biopsy of the pancreas for diagnosis. FNA confirmed the diagnosis of adenocarcinoma in 17 of 21 patients (80%). Fifteen of 21 FNA biopsies were performed in patients who went on to receive neoadjuvant chemoradiation. Twenty-eight of 32 patients (87%) had peritoneal washings at the time of laparotomy. Five patients had suspicious or positive washings (18%), and 23 patients had negative washings (82%). Three of 18 patients (16.7%) who had both FNA and peritoneal washings and 2 of 10 patients (20%) who had no FNA but had peritoneal washings had positive or suspicious peritoneal cytology. Eight of 32 patients ultimately failed in the peritoneum. Six of 21 patients (28%) who had prior FNA and 2 of 11 (18%) who had no prior FNA failed in the peritoneum. Although the number of patients is small, none of these differences proved to be statistically significant. No difference in median survival was observed between the FNA and no FNA groups. We conclude that FNA is a safe and useful tool to confirm the diagnosis of pancreatic cancer when patients are to be treated with neoadjuvant chemoradiation.

Surgical resection remains the only curative therapy for hepatic metastases from colon and rectal carcinoma. Many patients will be unresectable or have close microscopic margins. Cryoablation may improve local control and survival in those cases. From February 1992 to May 1995, patients with metastatic colon and rectal carcinoma who underwent cryoablation of surgical margins following hepatic resection or cryoablation of hepatic metastases were reviewed with attention to patient and tumor characteristics, clinical course, local control, and survival. Twenty-four patients (10 female, 14 male) with a mean age of 63 years (range, 34-84 years) underwent cryosurgical ablation for hepatic metastases. Twelve were for central lesions and 12 for gross or microscopically positive resection margins. Surgery was performed with curative intent for 21 and for palliation in 3 patients. The mean hospital stay was 8.4 days (range, 5-15 days). Complications included three cases of parenchymal cracking and a single bile leak. Two of 14 patients who developed pleural effusions required treatment. Perioperative mortality was 8.3 per cent (2 of 24): one myocardial infarction and one cerebrovascular accident. Four of 21 treated for cure had hepatic recurrence, and six had only extrahepatic recurrence. Median time to recurrence was 9.5 months. With median follow-up of 19 months, mean actuarial disease-free (DFS) and overall survival (OS) rates are as follows. Those with central lesions (n = 12) had a mean OS rate of 31 months and a mean DFS rate of 23 months. Those with close resection margins (n = 12) had a mean OS rate of 31 months and a median DFS rate of 19.5 months. Total patients (n = 24) had a mean OS rate of 32.7 months and a mean DFS rate of 23.5 months. We conclude that cryoablation of unresectable hepatic metastases or close resection margins is safe and may allow for improved survival in selected patients with metastatic colon and rectal carcinoma.

The treatment of patients with pancreatic cancer requires the expertise of medical oncologists, radiation oncologists, radiologists, and surgical oncologists. The surgeon's role in the management of patients with pancreatic cancer extends beyond the performance of surgical resection and bypass procedures to include diagnosis, staging (including determination of resectability), and therapy (both curative and palliative). If a lesion is deemed resectable, the surgeon's goal is to achieve clear pathologic margins in order to optimize the patient's chances for cure. The surgeon also plays a key role in the palliation of disease in patients with unresectable lesions. Biliary and duodenal bypass, endoscopic stenting, laparoscopy, and celiac ganglion injection may be needed to maximize a patient's remaining quality of life. In addition, the surgical oncologist should be involved in clinical trials testing neoadjuvant or adjuvant chemoradiotherapies that may lead to the development of more effective therapies for pancreatic cancer.

Local or regional recurrence is frequent in patients treated for rectal cancer. Many will die with regional disease in the absence of distant metastases. To achieve cure or palliation, radical surgery resulting in large pelvic defects may be warranted. Myocutaneous flap reconstruction may be used to achieve satisfactory closure. From 1988 to 1993, nine patients (5 female, 4 male) underwent 10 myocutaneous flap reconstructions for large perineal or pelvic defects following surgical extirpation of recurrent rectal cancer at Fox Chase Cancer Center. All nine patients had been previously treated with radiation therapy. Their clinical course was reviewed and quality of life assessed. The mean age at diagnosis of recurrence was 56 years. In six, this was a first, and in three patients a second recurrence. Clinical presentation was most often bleeding, abscess, or perineal pain. Resection was determined by extent of recurrence and included perineal resection, pelvic exenteration, cystectomy, sacrectomy, or coccygectomy. Extent of disease necessitated intraoperative radiation therapy in one case and placement of brachytherapy catheters in four. Bilateral gracilis flaps were used in four, unilateral in three, gluteus maximus in two, and combined gluteal and gracilis flaps in one patient. Six perineal and four combined perineal and vaginal defects were reconstructed. The mean length of surgery was 9.1 hours, and the length of hospitalization averaged 17.5 days. In nine of 10 cases, patients had prehospital level of function at discharge. Acute surgical flap-related complications included three cases of minor wound infection or separation, two of minimal but persistent drainage, and one of vaginal colonization.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND:The authors performed reexcision lumpectomy on patients with breast cancer with tumor at or close to the resection margin or if the margin status was unknown. Frozen section analysis (FSA) of reexcision lumpectomy margins was performed to allow additional excision of margins or mastectomy, saving the patient another operation or an additional radiation boost.METHODS:The authors reviewed the accuracy of FSA of margins in 107 patients undergoing reexcision lumpectomy between 1987 and 1992. There were 359 frozen sections performed on 156 specimens. Sensitivity and specificity of FSA for each frozen section margin, specimen, and patient were evaluated, as was gross inspection of tumor involvement at the resection margins. The accuracy of each pathologist's use of FSA also was evaluated.RESULTS:FSA sensitivity per frozen section margin, specimen, and patient was 0.90, 0.89, and 0.85, respectively. The specificity of gross inspection was 0.97, 0.96, and 0.96 (sensitivity, 0.44), which was significantly less accurate than that of FSA (P = 0.0015) or permanent section (P = 0.019). There was no significant discordance between FSA and permanent section. Of 19 pathologists doing FSA, 6 evaluated 10 or more specimens. The error rate ranged from 4% to 10% among pathologists with 10 or more readings, whereas 12 of 13 pathologists with fewer readings had no errors. The final pathologist had a 100% error rate, significantly worse (range, P = 0.0085-0.02) than any experienced pathologist. Thirty-four (32%) patients underwent additional excision (24 patients) or mastectomy (10 patients) based on the results of FSA, which saved the patients from undergoing another operation. No one required an additional operation or a mastectomy because of a false FSA result.CONCLUSION:FSA is safe and accurate in evaluating reexcision lumpectomy margins. Gross inspection is not reliable in margin evaluation. FSA saved an additional operation 32% of the time. Obtaining clear margins during one procedure eliminates the necessity of an additional radiation boost and probably will improve cosmesis.

BACKGROUND:Low resectability rate and high locoregional recurrence are major factors contributing to the failure of surgical treatment for localized pancreatic adenocarcinoma. A Phase II study involving preoperative 5-fluorouracil (5-FU) and mitomycin C and radiation therapy was evaluated.METHODS:Thirty-one patients with biopsy-proven carcinoma (24, head of pancreas; 2, body; 5 duodenum) were treated with preoperative radiation therapy, 5040 cGy (180 cGy/fraction, 5 days/week), concurrent with 5-FU, 1000 mg/m2/day continuous infusion (days 2-5, 28-32) and mitomycin C 10 mg/m2 bolus (day 2). Ten patients had previous laparotomy or bypass surgery and were deemed unresectable; 21 had percutaneous, endoscopic retrograde choleangiopancreatic, or transhepatic stent biopsies.RESULTS:Toxicity included neutropenic fever (2 patients), biliary sepsis (2 patients), and nausea and vomiting requiring total parenteral nutrition. One patient died of biliary sepsis before completion of chemoradiation and 11 patients showed evidence of metastatic disease (clinical or occult). Resectability rate was 38% (10/26) for pancreatic carcinoma and 80% (4/5) for duodenal carcinoma. Pathology of the resected specimens revealed extensive necrosis and hyalinization with clear margins in all cases. Lymph node metastases were found in one case of pancreatic carcinoma. The four resected duodenal carcinomas contained no residual tumor in the specimens. At a median follow-up of 29 months, the median survival time for those with pancreatic carcinoma was not yet reached in the resection group and was 8 months in the nonresection group. The corresponding actuarial 5-year survival rates were 58% and 0%, respectively.CONCLUSIONS:Neoadjuvant chemoradiation therapy was given safely to patients with pancreatic and duodenal carcinoma. It facilitated complete resection in 38% of patients with pancreatic carcinoma and 80% of those with duodenal carcinoma. A significant downstaging of positive margins and regional lymph nodes occurs as a result of preoperative chemoradiation.

Between 1986 and 1990, 16 patients were enrolled in a prospective Phase I/II study of transanal local excision and combined preoperative and postoperative radiation therapy (RT). All patients had biopsy-proven adenocarcinoma extending to within 6 cm of the anal verge and involvement of at least one third of the rectal circumference with tumor. Five of 16 patients (32%) had T3 tumors, and only two patients had T1 tumors. Patients received a single 500 cGy fraction of RT to the pelvis within 24 hours before surgery and underwent transanal excision followed by postoperative RT (median dose, 5040 cGy). With a median follow-up of 33 months, overall 3-year actuarial survival was 94%. Two patients had isolated local recurrences (both successfully salvaged), and four had distant metastases but maintained local control. The 3-year actuarial rates of continuous freedom from any relapse, continuous local control, and no evidence of disease at last follow-up were 53%, 80%, and 71%, respectively. Only three of 16 patients required colostomy, resulting in a 3-year actuarial colostomy-free rate of 77%. There was a trend toward a higher rate of relapse (P = 0.066) in patients with T3 tumors than those with T1 and T2 tumors. Sphincter-preserving therapy for low-lying rectal carcinomas using local excision and combined preoperative and postoperative RT is feasible, although improved local and adjuvant therapy is needed for patients with T3 lesions.

Long-term therapy of oncology patients has been facilitated by permanent indwelling central venous catheters, but catheter-related infections remain a serious complication of their use. Using a retrospective matched cohort design, we compared the risk of catheter-related infection in 47 adult solid tumor patients with right atrial Hickman catheters and 94 patients with totally implanted port catheters. Patients were matched for primary solid tumor, presence of metastases, age, gender, and date of catheter insertion. Seven of 47 patients with Hickman catheters developed catheter-related infection (1.8 infections/1,000 catheter days at risk) compared with 10 of 94 patients with implanted port catheters (0.4/1000 catheter days, P < 0.0002). Hickman catheters were used more often for terminally ill patients than were port catheters which was a potential source of bias, but results were unchanged after stratifying patients on lifespan. Our study suggests that there are fewer infections in port than in Hickman catheters in adult patients with solid tumors, but prospective randomized studies are needed.