Impact of multimodal therapy in locally recurrent rectal cancer.

BACKGROUND: The practice of salvaging recurrent rectal cancer has evolved. The aim of this study was to define the evolving salvage potential over time among patients with locally recurrent disease, and to identify durable determinants of long-term success. METHODS: The study included consecutive patients with recurrent rectal cancer undergoing multimodal salvage with curative intent between 1988 and 2012. Predictors of long-term survival were defined by Cox regression analysis and compared over time. Re-recurrence and subsequent treatments were evaluated. RESULTS: After multidisciplinary evaluation of 229 patients, salvage therapy with curative intent included preoperative chemotherapy and/or radiotherapy (73·4 per cent; with 41·3 per cent undergoing repeat pelvic irradiation), surgical salvage resection with or without intraoperative irradiation (36·2 per cent), followed by postoperative adjuvant chemotherapy (38·0 per cent). Multivisceral resection was undertaken in 47·2 per cent and bone resection in 29·7 per cent. The R0 resection rate was 80·3 per cent. After a median follow-up of 56·5 months, the 5-year overall survival rate was 50 per cent in 2005-2012, markedly increased from 32 per cent in 1988-1996 (P = 0·044). Long-term success was associated with R0 resection (P = 0·017) and lack of secondary failure (P = 0·003). Some 125 patients (54·6 per cent) developed further recurrence at a median of 19·4 months after salvage surgery. Repeat operative rescue was feasible in 21 of 48 patients with local re-recurrence alone and in 17 of 77 with distant re-recurrence, with a median survival of 19·8 months after further recurrence. CONCLUSION: The long-term salvage potential for recurrent rectal cancer improved significantly over time, with the introduction of an individualized treatment algorithm of multimodal treatments and surgical salvage. Durable predictors of long-term success were R0 resection at salvage operation, avoidance of secondary failure, and feasibility of repeat rescue after re-recurrence.

Meeting the 12 lymph node (LN) benchmark in colon cancer.

BACKGROUND: Examining >or=12 LN in colon cancer has been suggested as a quality metric. The purpose of this study was to determine whether the 12 LN benchmark is achieved at NCCN centers compared to a US population-based sample. METHODS: Patients with stage I-III disease resected at NCCN centers were identified from a prospective database (n = 718) and were compared to 12,845 stage I-III patients diagnosed in a SEER region. Age, gender, location, stage, number of positive nodes were compared for NCCN and SEER data in regards to number of nodes evaluated. Multivariate logistic regression models were developed to identify factors associated with evaluating 12 LNs. RESULTS: 92% of NCCN and 58% of SEER patients had >or=12 LN evaluated. For patients treated at NCCN centers, factors associated with not meeting the 12 LN target were left-sided tumors, stage I disease and BMI >30. CONCLUSIONS: >or=12 LN are almost always evaluated in NCCN patients. In contrast, this target is achieved in 58% of SEER patients. With longer follow-up of the NCCN cohort we will be able to link this quality metric to patterns of recurrence and survival and thereby better understand whether increasing the number of nodes evaluated is a priority for cancer control.

Effect of lymph node retrieval rates on the utilization of adjuvant chemotherapy in stage II colon cancer.

BACKGROUND: Failing to meet the benchmark of 12 lymph nodes in resection specimens is an indication for adjuvant chemotherapy in stage II colon cancer. METHODS: Among consecutive eligible patients with pathologic stage II colon cancer treated at eight NCI-designated comprehensive cancer centers between September 1, 2005 and February 19, 2008, we analyzed receipt of adjuvant chemotherapy, with less than 12 versus 12+ lymph nodes removed and examined the primary explanatory variable of interest. RESULTS: Among 258 patients, 46% received adjuvant chemotherapy. An oxaliplatin-containing regimen was used 67% of the time. Younger age (<50 years, P < 0.001), presence of lymphovascular invasion (P = 0.007), and higher T stage (P = 0.007) were independently associated with adjuvant chemotherapy use. There was significant inter-institutional variability in practice with the proportion receiving treatment ranging from 17% to 64% (P < 0.05). Notably, presence of less than 12 lymph nodes in the surgical specimen was a strong predictor of treatment (P = 0.008). CONCLUSIONS: Adjuvant chemotherapy use after resection of stage II colon cancer is common, but by no means standard practice at National Comprehensive Cancer Network (NCCN) institutions. More attention to achieving the recommended benchmark for lymph node dissection has the potential to decrease exposure to the toxicity of adjuvant treatment.

Cardiorespiratory effects of immunotherapy with interleukin-2.

The administration of interleukin 2 (IL-2) and lymphokine-activated killer (LAK) cells can mediate the regression of cancer. Treatment with IL-2 is associated with significant cardiorespiratory effects, as well as a leaky capillary syndrome requiring careful fluid management. A mild reversible depression of cardiac function is also associated with IL-2 treatment. All patients treated with recombinant IL-2 alone, with transfer of LAK cells, or with cyclophosphamide between December 1984 and September 1987 (total of 423 treatment courses in 317 total patients) were evaluated as to the development of significant cardiorespiratory toxicity. Of the 423 treatment courses, only 1.8% were associated with severe peripheral edema and only 2.8% and 3.1% respectively, were associated with significant ascites or pleural effusions. Thirty-nine of 423 patients (9.2%) had severe respiratory distress and 27 patients required intubation (6.4%). Cardiovascular effects included tachycardia and hypotension requiring vasopressor administration in 65% and intravenous (IV) fluid administration. Weight gain greater than or equal to 10% of body weight was noted in 32% of the 423 patients. Arrhythmias were primarily supraventricular (9.7%) and responded well to conventional medical treatments. Angina or ischemic changes were noted in 2.6% of patients and myocardial infarction in 1.2%. IL-2 caused peripheral vasodilation, with a significant decrease in peripheral vascular resistance (2,254 +/- 398 v 1,303 +/- 351 dyne.s.cm-5, P less than .0001), and an increase in heart rate (66.2 +/- 10 v 104.3 +/- 9.6 beats/min, P less than .0001). There was also evidence of mild cardiac dysfunction, with a significant decrease in the left ventricular stroke work (LVSW) index (P less than .0001) and ejection fraction (LVEF) (from 58% +/- 10% to 52% +/- 9%, P less than .03). A repeat LVEF performed after 1 to 3 months, had returned to baseline values (60% +/- 10%). A mean 64% increase in the rate of disappearance of radioactive iodine (125I) albumin (P less than .05) consistent with the development of a leaky capillary syndrome was noted. Patients with underlying cardiorespiratory diseases may be at greater risk during IL-2 administration and should not be selected to undergo this treatment.

Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation.

Wild-type p53 gene transfer into the SW620 colorectal carcinoma cell line was performed using the replication-defective adenovirus Ad5/CMV/p53 to evaluate the effect of wild-type p53 expression on radiation sensitivity. The results indicated that infection with Ad5/CMV/p53 sensitized the cells. The survival at 2 Gy was reduced from 55 to 23%. Flow cytometric analysis of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-labeled cells and in situ TUNEL staining of xenograft tumors demonstrated an increase in labeled cells with combination treatment, indicating increased apoptosis in cells treated with Ad5/CMV/p53 before irradiation. A significant enhancement of tumor growth suppression by this combination strategy was observed in a s. c. tumor animal model compared to p53 gene therapy alone. The delay in regrowth to control tumor size of 1000 mm3 was 2 days for 5 Gy, 15 days for Ad5/CMV/p53, and 37 days for Ad5/CMV/p53 + 5 Gy, indicating synergistic interactions. These data indicate that the delivery of wild-type p53 to cells with p53 mutations increases their radiation sensitivity, and this may be accomplished by adenoviral-mediated gene therapy.

p53 immunohistochemical staining predicts residual disease after chemoradiation in patients with high-risk rectal cancer.

This study was conducted to investigate the value of p53 immunohistochemical staining of pretreatment biopsy specimens in predicting the response of rectal cancer to chemoradiation. The study group comprised 42 patients with high-risk rectal cancer treated between July 1990 and July 1995 with a preoperative chemoradiation regimen of 45 Gy of external-beam irradiation and continuous-infusion 5-fluorouracil followed by surgical resection. p53 immunohistochemical staining was performed on pretreatment biopsy specimens. p53 immunohistochemical staining pattern and standard clinical and pathological parameters were correlated with extent of residual cancer in the surgical specimen. Twenty tumors were positive for p53 on immunohistochemical staining, 19 were negative, and 3 were focally positive. Thirteen patients experienced a complete response to chemoradiation. Aberrant p53 protein accumulation, as measured by immunohistochemical staining, correlated inversely with a complete pathological response to chemoradiation (P = 0.005; correlation coefficient = -0.43) and directly with an increased likelihood of residual cancer in the lymph nodes of surgical specimens (P = 0.02; correlation coefficient = 0.39). p53 immunohistochemical staining of pretreatment biopsy specimens correlates with the extent of residual disease after chemoradiation in patients with high-risk rectal cancer.

Preoperative infusional chemoradiation and surgery with or without an electron beam intraoperative boost for advanced primary rectal cancer.

PURPOSE: To compare the multimodality treatment results of surgical resection plus preoperative radiotherapy with concomitant protracted infusion chemotherapy (preop-chemoXRT), with or without an electron beam intraoperative radiotherapy (EB-IORT) boost, in 37 patients having advanced primary rectal cancer, with the results of a protocol using only preoperative radiotherapy (preop-XRT) plus surgical resection in a historic control group of 36 patients. METHODS AND MATERIALS: Thirty-eight patients with tethered T3 or T4 primary rectal cancer were treated with 45 Gy delivered in 25 fractions over 5 weeks plus infusional chemotherapy. Thirty-seven patients underwent surgical resection: 13 (35%) had restorative operations, and the remainder had either abdomino-perineal resection (APR) or pelvic exenteration (PE). Electron beam intraoperative radiotherapy (EB-IORT) was used in doses of 10-20 Gy for 11 patients with adherent pelvic tumor. In the 36 historic control patients, the preop-XRT dose was 45 Gy, and 93% of them had APR or PE. RESULTS: The local recurrence rate was 3% for the preop-chemoXRT group and 33% for the historic control group. The 3-year survival rate for patients treated with preop-chemoXRT plus resection was 82% compared with 62% for the historic control group. Distant metastases occurred more frequently in patients treated with an EB-IORT boost than in patients who were not (64% vs. 19%, p < 0.05), and the overall 3-year survival rate was lower for the former (67% vs. 96%, p < 0.05). Acute and late toxicities were acceptable. CONCLUSIONS: Preop-chemoXRT for advanced primary rectal cancer results in better control of pelvic disease and better overall survival rates than does preop-XRT alone. With preop-chemoXRT, acute chemoradiation toxicity is increased whereas late morbidity is unchanged compared with preop-XRT alone. Local control in patients with areas of residual or clinically adherent disease is improved by the use of EB-IORT; however, patients treated with EB-IORT had poorer survival rates than those treated without EB-IORT.

Preoperative infusional chemoradiation therapy for stage T3 rectal cancer.

PURPOSE: To evaluate preoperative infusional chemoradiation for patients with operable rectal cancer. METHODS AND MATERIALS: Preoperative chemoradiation therapy using infusional 5-fluorouracil (5-FU), (300 mg/m2/day) together with daily irradiation (45 Gy/25 fractions/5 weeks) was administered to 77 patients with clinically Stage T3 rectal cancer. Endoscopic ultrasound confirmed the digital rectal exam in 63 patients. Surgery was performed approximately 6 weeks after the completion of chemoradiation therapy and included 25 abdominoperineal resections and 52 anal-sphincter-preserving procedures. RESULTS: Posttreatment tumor stages were T1-2, N0 in 35%, T3 N0 in 25%, and T1-3, N1 in 11%; 29% had no evidence of tumor. Local tumor control after chemoradiation was seen in 96% (74 out of 77); 2 patients had recurrent disease at the anastomosis site and were treated successfully with abdominoperineal resection. Overall, pelvic control was obtained in 99% (76 out of 77). The survival after chemoradiation was higher in patients without node involvement than in those having node involvement (p = n.s.). More patients with pathologic complete responses or only microscopic foci survived than did patients who had gross residual tumor (p = 0.07). The actuarial survival rate was 83% at 3 years; the median follow-up was 27 months, with a range of 3 to 68 months. Acute, perioperative, and late complications were not more numerous or more severe with chemoradiation therapy than with traditional radiation therapy (XRT) alone. CONCLUSIONS: Excellent treatment response allowed two-thirds of the patients to have an anal-sphincter-sparing procedure. Gross residual disease in the resected specimen indicates a poor prognosis, and therapies specifically targeting these patients may improve survival further.

Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer.

BACKGROUND AND PURPOSE: To evaluate the influence of response to preoperative infusional chemoradiation on outcome parameters among patients with locally advanced rectal cancer. MATERIALS AND METHODS: Preoperative chemoradiotherapy, 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2 per day), was given to 117 patients. As determined by pretreatment endorectal ultrasound (EUS), 96% of cases were Stage T3, and 51% had EUS evidence of perirectal adenopathy. Surgery was performed approximately 6 weeks after chemoradiation therapy. Postoperatively adjuvant systemic therapy, consisting of 400-425 mg/m2 of 5-fluorouracil plus 20 mg/m2 leucovorin for 5 days, was administered every 28 days for six cycles. Outcome parameters of local control (LC), freedom from distant metastases (DMC), disease-free survival (DFS) and cancer specific survival (CSS) were evaluated relative to primary tumor characteristics. RESULTS: The final post-treatment pathological tumor stages were complete response in 27%, Tis-2 N0 in 26%, T2 N1 in 5%, T3 N0 in 21%, T3 N1 in 15%, T4 N0 in 5% and T4 N1 in 1%. Down-staging occurred in 61% of cases. The pretreatment primary tumor size only influenced rates of local control (P < 0.03) and had no other influence on outcome parameters. Pretreatment evidence of perirectal lymph node involvement had no impact on outcome parameters. Pathologic evidence of nodal involvement did affect DMC (P < 0.002) and DFS (P < 0.003). Pathologic evidence of response did influence freedom from the development of distant metastases (P < 0.004). On pairwise analysis this relationship held only when responders were compared to non-responders. No difference was observed based on the level of downstaging at the primary tumor. Correspondingly, DFS was improved when non-responders were compared to downstaged patients (P < 0.01). Response to preoperative chemoradiation failed to affect rates of LC or CSS. For the group as a whole, adjuvant chemotherapy improved only CSS (P < 0.03). Adjuvant chemotherapy was given to 74 patients, 36 of whom had responded to preoperative chemoradiation. Improvements were only seen in DFS (P < 0.03) when down-staged patients were compared to the non-responders who received adjuvant chemotherapy. In addition, the DFS rates were lower in the non-responder group who received adjuvant chemotherapy even when they were compared to down-staged patients who did not receive adjuvant chemotherapy (P < 0.04). CONCLUSION: Consistent with other reports, disease free survival and subsequent development of distant metastases is reduced in the more than 60% of patients who respond to preoperative infusional chemoradiation. Evidence of response appears more significant than the degree of response. At present, no impact is seen on cancer specific survival rates. Consideration should be given for strategies that base selection of subsequent adjuvant chemotherapy on response to preoperative chemoradiation.

Development of mucinous adenocarcinoma in chronic Crohn's disease fistulae without luminal involvement.

SUMMARY: A patient with Crohn's disease who developed mucinous adenocarcinoma in chronic fistulae is reported. Malignancy may complicate chronic nonhealing Crohn's sinus tracts and fistulae, even with no mucosal involvement by carcinoma. Persistent non-remitting perianal induration and pain should alert the physician to the possibility of underlying malignancy. Prompt examination under anesthesia and biopsy or fine-needle aspiration may facilitate diagnosis and therapy of the carcinoma at an early stage.

Evidence that protein kinase C-alpha activation is a critical event in phorbol ester-induced multiple drug resistance in human colon cancer cells.

We previously designed and characterized an in vitro model of the intrinsic drug resistance of human colon cancer. The human colonic epithelium is chronically exposed to endogenous protein kinase C (PKC) stimulatory factors, and our model demonstrated that activation of PKC induces resistance to multiple anticancer drugs in the metastatic human colon cancer cell line KM12L4a. PKC is an isozyme family with ten members, eight of which are phorbol ester-responsive. In this report, we show that thymeleatoxin (Tx), a daphnane tumor promoter that selectively activates the phorbol ester-responsive isozymes cPKC-alpha, -beta 1, -beta 2, and -gamma, was just as effective in inducing drug resistance in KM12L4a cells as phorbol dibutyrate, a potent activator of all phorbol ester-responsive PKC isozymes. The induction of resistance by Tx was associated with a reduction in cytotoxic drug accumulation in KM12L4a cells. We demonstrated by immunoblot analysis and hydroxylapatite chromatography that KM12L4a cells express active cPKC-alpha but not cPKC-beta 1, -beta 2, or gamma. Our results provide strong evidence that phorbol-ester activation of cPKC-alpha is sufficient for the induction of resistance observed in KM12L4a cells. The possibility that endogenous PKC activators may induce intrinsic drug resistance in clinical colon cancer by an analogous mechanism is strongly suggested by our detection of active cPKC-alpha in surgical specimens of human colon carcinomas.

Successful management of hepatic abscesses by percutaneous catheter drainage in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a disorder of polymorphonuclear leukocytes that can cause multiple recurrent hepatic abscesses in 40% of those patients with the disorder. The mortality rate from this complication of CGD is estimated at 27%. Treatment has consisted of extensive surgical debridement and drainage and prolonged antibiotic therapy; however, this approach is accompanied by high morbidity and the frequent need for reoperation. Successful percutaneous drainage of multiple hepatic abscesses in a patient who had previously undergone 10 operative procedures to manage hepatic abscesses is reported. With the development of imaging and percutaneous drainage techniques, as well as the recurrent nature of this problem, percutaneous management should be given consideration in appropriate patients with CGD with hepatic abscesses.

Limb-sparing surgery for soft tissue sarcomas: wound related morbidity in patients undergoing wide local excision.

When feasible, limb-sparing surgery has become an accepted form of treatment for sarcoma of the extremities. In a review of 100 consecutive cases of local excisions in patients with soft tissue sarcomas, which were performed at the National Cancer Institute, we identified factors associated with the development of wound-related morbidity. The incidence of these wound complications, which include infection, seromas, and skin loss, was 34.4%. Serious complications that necessitated rehospitalization or reoperation occurred in fewer than 10% of the patients. Preoperative factors associated with wound morbidity were patient age greater than 40 years (P2 less than 0.029) and tumor in the lower extremity (P2 less than 0.014). Treatment-related factors associated with morbidity were increased blood loss (p less than 0.01) and an increased volume (p less than 0.006) and duration (p less than 0.002) of wound drainage. The complications significantly delayed the start of adjuvant radiation therapy and lengthened the hospital stay. Measures to prevent these complications are discussed.

Computerized technetium/thallium scans and parathyroid reoperation.

Twenty-three consecutive patients who underwent reoperation for persistent primary hyperparathyroidism were studied with computerized technetium/thallium scans to evaluate it as a localization test. Prospective and blinded retrospective readings of the scans were correlated with findings at surgery. Computerized technetium/thallium scanning detected 52% of the parathyroid adenomas found at surgery. Forty-two percent of adenomas were localized exactly. There were no false positive scans. No normal parathyroid glands were imaged. No mediastinal glands were imaged. The study was not observer dependent. We conclude that computerized technetium/thallium scanning is helpful in patients undergoing parathyroid reoperation. If positive, it can accurately localize adenomas. If negative, we recommend more invasive studies.

Indications for immediate tissue transfer for soft tissue reconstruction in visceral pelvic surgery.

BACKGROUND: Perineal wound complications may occur after visceral pelvic surgery. We reviewed our experience to determine indications for immediate tissue transfer (TT) to prevent complications. METHODS: Hospital records and computerized data were reviewed on 175 perineal repairs in 156 patients treated at The University of Texas M.D. Anderson Cancer Center for tumors involving the alimentary tract (135 of 175), genitourinary tract (15 of 175), perineum (19 of 175), or sacrum (6 of 175). Patients had either resection of only the colorectum and anus (APR) (46 of 175) or multivisceral resection (MVR) (129 of 175), and the perineal wound was closed by using TT (108 of 175) or primary closure (PC) (67 of 175) on the basis of the surgeon's judgment. Complications were compared between PC and TT groups. RESULTS: Complications occurred in 57% (100 of 175). There was no significant difference overall in PC and TT procedures or in the APR subgroup. There were significantly fewer complications for TT patients in the MVR subgroup (P =.0001). There were significantly fewer complications for TT patients with prior irradiation in both APR (P =.01) and MVR (P =.007) subgroups. CONCLUSIONS: Immediate TT for perineal wound closure is associated with fewer healing complications than PC in a subset of patients with multivisceral resection or prior radiotherapy. Surgical planning in these cases should consider immediate soft tissue reconstruction.

Pelvic exenteration for locally advanced rectal carcinoma: factors predicting improved survival.

BACKGROUND: The purpose of this retrospective review was to determine whether a number of clinicopathologic factors (age, gender, type of exenteration, tumor extent, adjuvant therapy, tumor DNA ploidy, and S-phase fraction) that could be determined before operation were useful in predicting survival in patients undergoing pelvic exenteration for rectal cancer. METHODS: Between 1983 and 1992, 40 patients (15 male and 25 female) at our institution underwent pelvic exenteration for rectal adenocarcinoma in which tumor-free pathologic margins were obtained. Twenty-nine patients presented with primary tumors; 11 had recurrent disease. A total exenteration was performed in 20 patients, posterior exenteration in 18 patients, and an anterior exenteration in 2 patients. RESULTS: By multivariate (Cox proportional hazards regression) analysis, age, preoperative chemoradiation therapy, and an S phase of 10% or greater were found to be significant predictors of survival. Age older than 55 years was associated with a relative risk for cancer-related death (RR) of 0.13 (p = 0.02), and chemoradiation had an RR of 0.05 (p = 0.01), indicating their beneficial effect. An S-phase fraction of 10% or greater had an RR of 16.97 (p = 0.03), indicating a poor survival. The clinicopathologic factors listed above were used to derive a prognostic index (PI). A PI of less than 1.37 was associated with a 5-year survival rate of 65% (low risk), whereas patients with a PI of 1.37 or greater had a 5-year survival rate of 20% (high risk) (p = 0.005). CONCLUSIONS: These results indicate that adjuvant chemoradiation may significantly improve survival in patients who require pelvic exenteration for resection of locally advanced rectal carcinoma. An S-phase fraction of 10% or greater is also predictive of a poor outcome. Use of these factors allowed the generation of a PI that identifies high- and low-risk patients. Consideration of the ability to deliver chemoradiation and the determinates of the tumor S-phase fraction in patients requiring pelvic exenteration for rectal cancer may be helpful in predicting outcome and planning therapy.

Nonfunctioning islet cell carcinoma of the pancreas.

BACKGROUND: Nonfunctioning islet cell carcinoma of the pancreas has a variable and often indolent natural history, which has resulted in a wide range of treatment recommendations. To more clearly define the natural history and appropriate treatment of this disease, we reviewed our institutional experience over the last 39 years. METHODS: The records of all patients confirmed to have a nonfunctioning islet cell carcinoma of the pancreas were retrospectively reviewed. Kaplan-Meier life tables were constructed and log-rank comparisons were performed. RESULTS: The 73 patients studied had an overall 5-year actuarial survival rate of 50%. Patients with localized disease at presentation (n = 39) had a significantly higher survival rate (p = 0.03) compared with patients with metastatic disease (n = 34). The 19 patients who underwent a potentially curative resection of the primary tumor had a significantly higher survival rate (p = 0.03) compared with the 20 patients with locally advanced, unresectable, nonmetastatic disease. Nine of these 20 patients died of complications of the primary tumor. In contrast, only 2 of 22 cancer-related deaths in the 34 patients with metastatic disease at diagnosis were due to the primary tumor. CONCLUSIONS: (1) Surgical resection should be performed in patients with resectable nonmetastatic disease. (2) Resection of the primary tumor in the presence of metastatic disease is rarely indicated. (3) Innovative treatment strategies are needed for patients with locally advanced, unresectable, nonmetastatic tumors of the pancreatic head.

Evaluation and surgical resection of adrenal masses in patients with a history of extra-adrenal malignancy.

BACKGROUND: Adrenal abnormalities are often identified on imaging studies performed during the staging of patients presenting with a new malignancy or restaging of patients with a history of a malignancy. METHODS: We reviewed the records of patients who underwent surgical resection of an adrenal mass identified in the setting of previously or newly diagnosed extra-adrenal malignancy. RESULTS: Eighty-one patients with an adrenal mass and recently diagnosed malignancy (n = 24) or history of a malignancy (n = 57) underwent adrenalectomy. In 42 patients (52%) the adrenal mass was a metastasis. In 39 patients (48%) the adrenal mass was an additional primary adrenal tumor process: 19 pheochromocytomas, (14 syndrome-associated, 5 sporadic), 13 cortical adenomas, 3 adrenocortical carcinomas, 2 ganglioneuromas, and 2 cases of nodular hyperplasia. CONCLUSIONS: In this series nearly half of the patients with cancer and an adrenal mass had adrenal pathologic condition independent of their primary malignancy. Despite the presence of a newly diagnosed malignancy or history of malignancy, all patients with an adrenal mass should undergo a standard hormone evaluation to confirm that the mass is not a functional neoplasm. An assumption that the adrenal mass is metastatic disease will be wrong in up to 50% of such patients.

Rapid intra-abdominal spread of pancreatic cancer. Influence of multiple operative biopsy procedures.

Intra-abdominal spread of tumor is a common cause of treatment failure in patients with pancreatic cancer. We have reviewed 62 patients with pancreatic cancer undergoing repeat laparotomy in order to learn what factors are associated with the high risk of intra-abdominal metastases. Patients who underwent two or more operative biopsy procedures were at a markedly increased risk of developing intra-abdominal tumor seeding. These metastases were not detectable by preoperative computed tomography scan or ultrasound. This information affirms that multiple biopsies of pancreatic tumors increase the risk of local disease failure, and regimens based on nonoperative staging are likely to incorrectly minimize the extent of tumor involvement.

Sacral chordoma: 40-year experience at a major cancer center.

OBJECTIVE: Sacral chordomas are relatively rare, locally invasive, malignant neoplasms. Despite surgical resection, adjuvant radiation therapy, and chemotherapy, recurrence is common. This study reviews our experience during the last 40 years at The University of Texas M.D. Anderson Cancer Center, to determine the effects of various treatment methods on the overall course of this disease process. METHODS: A retrospective study was performed. From 1954 to 1994, 27 patients with sacral chordomas were evaluated at our institution. RESULTS: There were 19 male and 8 female patients, with a mean age of 56 years (range, 27-80 yr). All except one of the patients presented with pain, and 17 of 27 showed evidence of autonomic dysfunction at initial presentation. Based on microscopic examination of surgical specimen margins, surgical procedures were categorized as either radical resection or subtotal excision. All patients underwent at least one surgical procedure, for a total of 67 procedures (28 radical resections and 39 subtotal excisions). Twelve patients underwent one operation, whereas nine underwent two procedures and six underwent more than two operations (range, 3-16 operations). Radiation therapy was used in conjunction with 13 of the 67 surgical procedures. The median Kaplan-Meier estimate of the overall survival time for the entire group was 7.38 years (range, 4 mo to 34 yr). Tumors recurred after 47 of the 67 procedures. The overall disease-free interval for patients undergoing radical resection was 2.27 years for each procedure, compared with 8 months for each procedure for patients treated with subtotal excision (log-rank test for the inequality between the two curves, 19.58; P<0.0001). The addition of radiation therapy prolonged the disease-free interval for patients undergoing subtotal resection (2.12 yr versus 8 mo; log-rank test for the inequality between the two curves, 5.82; P<0.02). CONCLUSION: Our results suggest frequent recurrences in the majority of patients with chordomas. Radical resection is associated with a significantly longer disease-free interval, compared with subtotal removal of the tumor. Addition of radiation after subtotal resection improves the disease-free interval, although radiation therapy can generally be used only once. Based on these findings, we think that, whenever possible, radical resection should be the treatment of choice for sacral chordomas.