Splenectomy for massive splenomegaly: long-term results and risks for mortality.

OBJECTIVE: To evaluate long-term outcomes after splenectomy for massive splenomegaly in a series of 222 consecutive patients. BACKGROUND: Splenectomy for massive splenomegaly (>1500 g) provides palliation but is associated with a high rate of perioperative complications in a population of patients with advanced hematological malignancies. Predictive factors for survival and whether the palliative goals are achieved in the long-term are not well defined. METHODS: Patients with various hematological disorders who underwent splenectomy between 1998 and 2009 were followed until death or for at least 2 years. Linear and logistic regression analyses were used to ascertain the impact of demographical factors, diagnoses, and preoperative transfusion parameters on the postoperative survival. RESULTS: Splenectomy for massive splenomegaly was performed most commonly for non-Hodgkin lymphoma (48%) and myeloid metaplasia (31%). Mean ± standard deviation splenic weight was 2731 ± 1393 g (range, 1500-13,085 g). Average operating time was 115 minutes, with a range from 46 to 346 minutes. Thirty-day mortality was 1.8%, and the complication rate was 20%. The most common complications were hemorrhage (9%) and portal venous thrombosis (9.9%). Relief from pressure-related symptoms was achieved in 98.5%, and durable remission of anemia and thrombocytopenia persisted in half of the patients at 2 years. Sex, age, and intraoperative blood loss were not significantly associated with survival. Preoperative need for red blood cell and platelet transfusions were the most significant risk factors associated with decreased survival. CONCLUSIONS: Splenectomy for massive splenomegaly can be performed safely and offers durable palliation. Preoperative transfusion requirement is an indicator of hematological disease severity and predictor of decreased survival.

Distance bias and surgical outcomes.

BACKGROUND: A body of research has found that patients who travel a significant distance to obtain medical treatment experience better outcomes, a phenomenon termed "distance bias." This study uses risk-adjusted surgical outcomes data to analyze distance bias in a population of patients treated surgically at a tertiary care institution. METHODS: We used risk-adjusted surgical outcomes data from the National Surgical Quality Improvement Project at the Mayo Clinic to calculate observed and expected risk of a severe complication. Operations were stratified into quintiles based on the distance traveled by the patient. RESULTS: The average age of patients in our cohort was 56.7 years, and 59.2% were female; patients traveled an average of 226 miles for treatment. Patients living closest to the Mayo Clinic (quintile 1) had lower observed and expected risks of a severe complication relative to patients in quintiles 2-5. Patients from quintile 1 had outcomes which were better than predicted [observed:expected risk ratio of 0.82 (range, 0.63-0.99)]. Patients traveling intermediate distances (quintile 2) had outcomes which were worse than predicted [observed:expected risk ratio of 1.18 (range, 1.00-1.42)]. Operations performed on patients from greater distances (quintiles 3-5) had an observed risk of severe complications which was similar to expected. DISCUSSION: The phenomenon of distance bias which has previously been documented in medical and oncologic treatment is not demonstrated in this study. An opposite phenomenon may be more pertinent, where patients who are treated locally are less likely to have a severe complication and have outcomes which are better than predicted.

Immediate post-resection diabetes mellitus after pancreaticoduodenectomy: incidence and risk factors.

BACKGROUND: New-onset diabetes mellitus after a pancreaticoduodenectomy (PD) remains poorly defined. The aim of this study was to define the incidence and predictive factors of immediate post-resection diabetes mellitus (iPRDM). METHODS: Retrospective review of patients undergoing PD from January 2004 through to July 2010. Immediate post-resection diabetes mellitus was defined as diabetes requiring pharmacological treatment within 30 days post-operatively. Logistic regression was conducted to identify factors predictive of iPRDM. RESULTS: Of 778 patients undergoing PD, 214 were excluded owing to pre-operative diabetes (n= 192), declined research authorization (n= 14) or death prior to hospital discharge (n= 8); the remaining 564 patients comprised the study population. iPRDM occurred in 22 patients (4%) who were more likely to be male, have pre-operative glucose intolerance, or an increased creatinine, body mass index (BMI), pre-operative glucose, operative time, tumour size or specimen length compared with patients without iPRDM (P < 0.05). On multivariate analysis, pre-operative impaired glucose intolerance (P < 0.001), pre-operative glucose ≥ 126 (P < 0.001) and specimen length (P= 0.002) were independent predictors of iPRDM. A predictive model using these three factors demonstrated a c-index of 0.842. DISCUSSION: New-onset, post-resection diabetes occurs in 4% of patients undergoing PD. Factors predictive of iPRDM include pre-operative glucose intolerance, elevated pre-operative glucose and increased specimen length. These data are important for patient education and predicting outcomes after PD.

Role of operative therapy in treatment of metastatic gastrointestinal stromal tumors.

BACKGROUND: Operative resection of metastatic gastrointestinal stromal tumors (GIST) is controversial. Current treatment strategies rely on the response to tyrosine kinase inhibitors (TKIs), with resultant individualization of operative intervention. We investigated the role of operative therapy in patients with metastatic GIST. METHODS: This retrospective cohort study included all consecutive patients treated for metastatic and/or recurrent GIST from January 2002 to June 2011. The patients were stratified by the use of operative therapy and disease response to TKI therapy. Kaplan-Meier survival analyses with log-rank comparisons tested the effects of operative therapy and the response to TKIs on survival. RESULTS: Of the 438 patients treated for GIST during the study period, 87 (median age 61 y, interquartile range 50-71; 55% male) had metastatic GIST (84% metastatic, 3% recurrent, and 13% metastatic and recurrent). Of these patients, 54 (62%) underwent operative exploration. Subtotal resection for palliative debulking (R2 resection) were performed in 19 patients; 32 patients underwent R0 resection. Operative intervention was associated with improved overall survival (OS) compared with systemic therapy alone (1 y OS, 98% versus 80% and 5-y OS, 65% versus 11%, respectively; P < 0.001). A TKI was used before resection in 32 patients. The disease response was partial in 13 patients, stable in 10, and progressive in 9. The 1- and 5-y OS and progression-free survival were strongly associated with the preoperative response to TKI and an R0 resection (all P ≤ 0.002). CONCLUSIONS: Among patients with metastatic GIST, preoperative response to TKI therapy and margin-negative resection were strongly associated with improved progression-free and OS.

Gastrointestinal stromal tumour of the duodenum: single institution experience.

BACKGROUND: Primary gastrointestinal stromal tumours (GISTs) of the duodenum are rare. The aim of this study was to review the surgical management of GISTs in this anatomically complex region. METHODS: Retrospective review from January 1999 to August 2011 of patients with primary GISTs of the duodenum. RESULTS: Forty-one patients underwent resection of duodenal GISTs. All operations were performed with intent to cure with negative margins of resection. The most common location of origin was the second portion of the duodenum. Local excision (n= 19), segmental resection with primary anastomosis (n= 11) and a pancreatoduodenectomy (n= 11) were performed. Two patients underwent an ampullectomy with local excision. Peri-operative mortality and overall morbidity were 0 and 12, respectively. Patients with high-risk GISTs (P= 0.008) and those who underwent a pancreatoduodenectomy (P= 0.021) were at a greater risk for morbidity. The median follow-up was 18 months. Eight patients developed recurrence. High-risk GISTs and neoplasms with ulceration had the greatest risk for recurrence (P= 0.017, P= 0.029 respectively). The actuarial 3- and 5-year survivals were 85% and 74%, respectively. CONCLUSION: The choice and type of resection depends on the proximity to the ampulla of Vater, involvement of adjacent organs and the ability to obtain negative margins. The morbidity depends on the type of procedure for GIST.

Surveillance strategies for gastrointestinal stromal tumors.

Although only 10-30% of gastrointestinal stromal tumors (GISTs) are clinically malignant, all have some degree of malignant potential. The management of high risk patients should be evidence based. However, prospective data and a consensus for guidelines concerning the screening of asymptomatic high risk patients and surveillance following multidisciplinary treatment do not exist. This review provides an overview of GIST, with an emphasis on the available data regarding screening and surveillance of certain populations with GISTs.

Axillary recurrence in breast cancer patients with isolated tumor cells in the sentinel lymph node [AJCC N0(i+)].

BACKGROUND: Completion axillary lymph node dissection (CALND) is controversial in patients with sentinel lymph node (SLN) metastases ≤ 0.2 mm [N0(i+)]. Our goal was to characterize patients with SLN isolated tumor cells regarding surgical management and axillary recurrence. MATERIALS AND METHODS: An Institutional Review Board (IRB)-approved retrospective chart review identified 677 consecutive patients with positive SLN biopsy for breast cancer between October 1997 and June 2004, and N0(i+) patients were identified. Clinicopathologic characteristics, predicted probability of nonsentinel node disease, axillary surgery, and recurrences were recorded. RESULTS: Of 81 patients with SLN N0(i+) metastasis, 31 underwent CALND and 50 did not. The two groups of patients showed no statistical differences in tumor size, stage, grade, number of SLNs removed, and number of positive SLNs. Predicted probability of additional axillary metastasis was somewhat higher among those who underwent CALND compared with those who did not. Patients undergoing CALND were significantly younger than those who did not (mean age 50 vs. 57, P = 0.01). Of the 31 patients with CALND, 4 (12.9%) had additional nodal metastases. Radiation to nodal fields was administered to 8 patients in the CALND group (25.8%) and to 7 in the group without axillary dissection (14.0%, P = 0.44). No axillary recurrences were noted at a median follow-up of 38 months. CONCLUSION: Among breast cancer patients with SLN isolated tumor cells, a small percentage have additional metastasis in other axillary nodes. However, the risk of axillary recurrence appears low in those who do not undergo CALND.

Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis.

BACKGROUND: Adjuvant imatinib mesylate prolongs recurrence-free survival (RFS) after resection of localised primary gastrointestinal stromal tumours (GIST). We aimed to develop a nomogram to predict RFS after surgery in the absence of adjuvant therapy to help guide patient selection for adjuvant imatinib therapy. METHODS: A nomogram to predict RFS based on tumour size (cm), location (stomach, small intestine, colon/rectum, or other), and mitotic index (<5 or > or =5 mitoses per 50 high-power fields) was developed from 127 patients treated at Memorial Sloan-Kettering Cancer Center (MSKCC), New York, NY, USA. The nomogram was tested in patients from the Spanish Group for Research on Sarcomas (GEIS; n=212) and the Mayo Clinic, Rochester, MN, USA (Mayo; n=148). The nomogram was assessed by calculating concordance probabilities and testing calibration of predicted RFS with observed RFS. Concordance probabilities were also compared with those of three commonly used staging systems. FINDINGS: The nomogram had a concordance probability of 0.78 (SE 0.02) in the MSKCC dataset, and 0.76 (0.03) and 0.80 (0.02) in the validation cohorts. Nomogram predictions were well calibrated. Inclusion of tyrosine kinase mutation status in the nomogram did not improve its discriminatory ability. Concordance probabilities of the nomogram were better than those of the two NIH staging systems (0.76 [0.03] vs 0.70 [0.04, p=0.04] and 0.66 [0.04, p=0.01] in the GEIS validation cohort; 0.80 [0.02] vs 0.74 [0.02, p=0.04] and 0.78 [0.02, p=0.05] in the Mayo cohort) and similar to those of the AFIP-Miettinen staging system (0.76 [0.03] vs 0.73 [0.004, p=0.28] in the GEIS cohort; 0.80 [0.02] vs 0.76 [0.003, p=0.09] in the Mayo cohort). Nomogram predictions of RFS seemed better calibrated than predictions made with the AFIP-Miettinen system. INTERPRETATION: The nomogram accurately predicts RFS after resection of localised primary GIST and could be used to select patients for adjuvant imatinib therapy.

Intraperitoneal treatment for peritoneal mucinous carcinomatosis of appendiceal origin after operative management: long-term follow-up of the Mayo Clinic experience.

OBJECTIVE: To determine prognostic factors and the impact of intraperitoneal (IP) treatment after surgical resection of peritoneal mucinous carcinomatosis (PMC) of appendiceal origin. SUMMARY OF BACKGROUND DATA: PMC is a rare, malignant, intra-abdominal neoplasm that produces large amounts of mucin. Patients typically present with diffuse peritoneal disease. After surgical treatment, multiple locoregional recurrences are common; recurrences outside the abdomen are infrequent. Treatment regimens include debulking, radiotherapy with IP radioisotopes, and chemotherapies (IP, systemic, or both). Because reported data are variable and heterogeneous, treatment evaluations are challenging. METHODS: We retrospectively reviewed 115 consecutive patients with PMC who underwent maximal surgical resection with or without postoperative therapy between 1985 and 2000 at Mayo Clinic Rochester. After maximal resection, 37 patients received IP 5-fluorouracil, 35 of whom also received IP chromic phosphate P 32. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival. RESULTS: All gross disease was removed in 61% of patients. With a median follow-up of 6.1 years, the median OS was 8.1 years. Median OS for patients receiving versus not receiving IP therapy was 23.5 years versus 7.5 years, respectively. The 5-, 10-, and 15-year OS for those receiving and not receiving IP therapy was 82%, 65%, and 52% versus 60%, 27%, and 15%, respectively. Adverse prognostic factors for OS identified by univariate analysis included partial mucin debulking, adenocarcinoma histology, systemic chemotherapy, diffuse IP disease at presentation, and no IP therapy. On multivariate analysis, diffuse IP disease at presentation and no IP therapy remained significant. A separate analysis was performed for the 70 patients who underwent gross total resection, 51% of whom received IP therapy. Adverse prognostic factors for OS included adenocarcinoma histology, systemic chemotherapy, and no IP therapy. CONCLUSIONS: This large, single-institution, retrospective series with long-term follow-up suggests that IP chromic phosphate P 32 and 5-fluorouracil after maximal surgical resection of PMC of appendiceal origin is associated with improved OS and disease-free survival.

Intraductal papillary mucinous neoplasm of the biliary tract: a real disease?

BACKGROUND: Despite increasing numbers of reports, biliary tract intraductal papillary mucinous neoplasm (BT-IPMN) is not yet recognized as a unique neoplasm. The aim of the present study was to define the presence of BT-IPMN in a large series of resected biliary neoplasms. METHODS: From May 1994 to December 2006, BT-IPMN cases were identified by reviewing pathology specimens of all resected cholangiocarcinomas and other biliary neoplasms when cystic, papillary or mucinous features were cited in pathology reports. RESULTS: BT-IPMN was identified in 23 out of 253 (9%) specimens using the strict histopathological criteria of IPMN. The most common presenting symptom was abdominal discomfort which was present in 15 patients (65%). Only one of the original operative pathology reports used the term IPMN; 16 (70%) used the terms cystic, mucinous and/or papillary. BT-IPMN was isolated to non-hilar extra-hepatic ducts in 12 (52%), intra-hepatic ducts in 6 (26%) and hilar extra-hepatic ducts in 5 patients (22%). Carcinoma was found in association with BT-IPMN in 19 patients (83%); 5-year survival was 38% after resection. CONCLUSION: BT-IPMN occurs throughout the intra- and extra-hepatic biliary system and can be identified readily as a unique neoplasm. Broader acceptance of BT-IPMN as a unique neoplasm may lead to a better understanding of the pathogenesis of biliary malignancies.

Surgically managed gastrointestinal stromal tumors: a comparative and prognostic analysis.

BACKGROUND: Tyrosine kinase inhibitors have been shown to have marked clinical efficacy in patients with unresectable or metastatic gastrointestinal stromal tumors (GIST). We performed a comparative and prognostic analysis of our experience with surgically managed GIST to determine factors associated with adverse oncologic outcomes. METHODS: Oncologic outcomes of 191 patients with primary GIST surgically managed between 1978 and 2004 at a single institution were reviewed. Prognostic factors were analyzed by Cox analysis (hazard ratio [HR] and 95% confidence interval [95% CI]) and included age, sex, disease presentation (asymptomatic vs. symptomatic), tumor site (stomach, small bowel, colorectal), disease extent (localized vs. metastatic) and risk levels (high, intermediate, low, very-low) assigned on the basis of size and number of mitoses according to current National Institutes of Health recommendations. Primary end points were disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: A total of 186 patients (97%) had c-kit-positive GIST. There were 54% high, 22% intermediate, 18% low, and 8% very low risk GIST originating from the stomach (54%), small bowel (36%), and colon and rectum (10%). Median patient age was 65 (range, 13-91) years, and 108 subjects (57%) were male. Seventy-two percent of patients had symptomatic local disease, and 21% patients had synchronous metastases. Most (95%) underwent R0 resections of their primary tumor. Among 146 patients (76%) with localized disease at presentation undergoing R0 resection, the 5-year DFS was 65%. High-risk GIST (HR 12, 95% CI, 5-32, P < .0001), symptomatic presentation (HR 2.5, 95% CI, 1.1-6, P = .04), and GIST in the small bowel (HR 2.8, 95% CI, 1-5, P = .003) were independently associated with decreased DFS. After a median follow-up of 63 months among survivors, the 5-year DSS was 68%. High-risk disease (HR 14.3, 95% CI, 5-41, P < .0001), symptomatic presentation (HR 3.1, 95% CI, 1.2-7.9, P = .02), and GIST in the small bowel (2.6,3 95% CI, 1-5, P = .006) were independently associated with decreased DSS. CONCLUSIONS: High-risk GIST are associated with increased disease recurrence and decreased survival despite complete surgical resection. These patients should receive adjuvant therapy in the form of tyrosine kinase inhibitors.

Diagnosis and surgical management of gallbladder cancer: a review.

Gallbladder cancer is one of the most lethal carcinomas and continues to pose many challenges for surgeons. Identifiable risk factors for carcinoma of the gallbladder include cholelithiasis, an anomalous pancreaticobiliary junction, and focal mucosal microcalcifications. Adenocarcinoma is the primary histologic type in most patients and the tumor is frequently associated with Kras and p53 mutations. Radiologic and endoscopic advances in endoscopic ultrasonography and magnetic resonance cholangiopancreatogram, plus helical computed tomography, have enhanced preoperative staging. Surgical options include cholecystectomy for disease limited to the mucosa (Tis/T1) or a radical cholecystectomy (subsegmental resection of segments IVB and V plus a hepatoduodenal ligament lymphadenectomy) for advanced disease without signs of distant metastasis (T2-4/N0-N2). Some surgeons have advocated more radical hepatic resection including extended right hepatectomy or central bisegmentectomy plus caudate lobectomy. Japanese surgeons have reported studies that included patients having a pancreaticoduodenectomy to improve distal ductal margins and lymphadenectomy for T3 and T4 cancers. These patients have a lower rate of local recurrence but no survival advantage. Options for adjuvant therapy remain limited. Radiation therapy with fluorouracil radiosensitization is the most commonly used postoperative treatments. Current trials are investigating the role of capecitabine, oxaliplatin, and bevacizumab in the management of gallbladder carcinoma.

Treatment of gastric adenocarcinoma may differ among hospital types in the United States, a report from theNational Cancer Data Base.

The concept that complex surgical procedures should be performed at high-volume centers to improve surgical morbidity and mortality is becoming widely accepted. We wanted to determine if there were differences in the treatment of patients with gastric cancer between community cancer centers and teaching hospitals in the United States. Data from the 2001 Gastric Cancer Patient Care Evaluation Study of the National Cancer Data Base comprising 6,047 patients with gastric adenocarcinoma treated at 691 hospitals were assessed. The mean number of patients treated was larger at teaching hospitals (14/year) when compared to community centers (5-9/year) (p<0.05). The utilization of laparoscopy and endoscopic ultrasonography were significantly more common at teaching centers (p<0.01). Pathologic assessment of greater than 15 nodes was documented in 31% of specimen at community hospitals and 38% at teaching hospitals (p<0.01). Adjusted for cancer stage, chemotherapy and radiation therapy were utilized with equal frequency at all types of treatment centers. The 30-day postoperative mortality was lowest at teaching hospitals (5.5%) and highest at community hospitals (9.9%) (p<0.01). These data support previous publications demonstrating that patients with diseases requiring specialized treatment have lower operative mortality when treated at high-volume centers.

Satisfaction after contralateral prophylactic mastectomy: the significance of mastectomy type, reconstructive complications, and body appearance.

PURPOSE: Contralateral prophylactic mastectomy (CPM) is one option for reducing the risk of a second breast cancer in women with a personal and family history of breast cancer. Few data are available regarding satisfaction, psychological, and social function after CPM. The purpose of this research is to evaluate women's long-term satisfaction with CPM, factors influencing satisfaction, and psychological and social function after CPM. PATIENTS AND METHODS: This was a descriptive study of all women with a family history of breast cancer, known to be alive, who elected CPM at Mayo Clinic (Rochester, MN) between 1960 and 1993 (n = 621). Ninety-four percent of the women (n = 583) completed a study-specific questionnaire. RESULTS: A mean of 10.3 years after the procedure, the majority of women (83%) were satisfied with their CPM. A smaller number were neutral (8%) or dissatisfied (9%). Women who had a subcutaneous mastectomy had more problems with reconstruction, and fewer of these women were satisfied than women with simple mastectomy. Decreased satisfaction with CPM was associated with decreased satisfaction with appearance, complications with reconstruction, reconstruction after CPM, and increased level of stress in life. The majority of women experienced no change or favorable effects in self-esteem (83%), level of stress in life (83%), and emotional stability (88%). Satisfaction with body appearance, feelings of femininity, and sexual relationships were the most adversely affected with 33%, 26%, and 23% of the women responding negatively. CONCLUSION: Although most women are satisfied with CPM, each woman should weigh the benefits alongside the potential adverse effects.

Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study.

PURPOSE: Surgical resection of liver-only metastases from colorectal cancer has undergone extensive evaluation and review. The use of neoadjuvant chemotherapy to improve the likelihood of resection in disease that is not optimally resectable has not been as well studied. PATIENTS AND METHODS: Patients with liver-only metastases from colorectal cancer deemed not optimally resectable by a surgeon with expertise in liver surgery received fluorouracil, leucovorin, and oxaliplatin (FOLFOX4). Patients were periodically reassessed for resectability. Surgical response was classified as completely resectable (S-CR), partially resectable (S-PR), or unresectable (S-UR). Study design specified the accrual of 39 patients, with two or more S-CRs considered evidence of promising activity with respect to increasing the S-CR rate. RESULTS: Forty-two of 44 patients were assessable for this analysis. Twenty-five patients (60%) had tumor reduction by serial imaging. Seventeen patients (40%) underwent surgery (S-CR, n = 14; S-PR, n = 1; and S-UR, n = 2) after a median of 6 months of chemotherapy. With a median postsurgical follow-up of 22 months (range, 13 to 32 months), 11 recurrences have occurred in the 15 S-CR and S-PR patients. Median survival time was 26 months. CONCLUSION: Our data suggest that FOLFOX4 has a high response rate (complete response, partial response, or reduction) in patients with liver-only metastases from colorectal cancer, allowing for successful resection of disease in a portion of patients initially not judged to be optimally resectable. However, a high recurrence rate after surgery was observed, which, in 73% of patients, involved the liver. Further trials are indicated based on the promising results observed in this trial.

Adjuvant therapy for ampullary carcinomas: the Mayo Clinic experience.

PURPOSE: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. METHODS AND MATERIALS: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. RESULTS: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p=0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p=0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. CONCLUSIONS: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed.

A single-center experience with inflammatory breast cancer, 1985-2003.

HYPOTHESIS: "Up-front" surgery improves survival in inflammatory breast cancer (IBC). DESIGN: Retrospective cohort, 1985-2003. SETTING: Tertiary referral center. PATIENTS: Consecutive patients with a primary occurrence of IBC. MAIN OUTCOME MEASURES: All-cause and disease-free survival. RESULTS: One-hundred fifty-six patients were identified with IBC; 28 patients with metastatic disease were excluded from further analysis. The mean age of the remaining 128 patients was 53 years; 57% of women were postmenopausal. One hundred twenty-two patients had clinically apparent IBC. Tumors were palpable in 83 patients (mean diameter, 9.1 cm). Neoadjuvant chemotherapy was the initial therapy in 106 patients, while surgery was the initial therapy in 22 patients. The overall median survival was 37 months, with a median disease-free interval of 23 months. The 5-year survival was 42%, with a disease-free survival of 21%. Univariate analysis of recurrence identified previous hormone therapy (relative risk [RR], 0.50; P = .03), menopause (RR, 0.55; P = .01), and palpable adenopathy (RR, 1.57; P = .04) as significant factors. Univariate survival analysis highlighted previous hormone therapy (RR, 0.48; P = .04), radiotherapy (RR, 0.39; P = .02), sequence of therapy (P = .001), family history (RR, 0.47; P = .01), and palpable adenopathy (RR, 2.22; P<.001) as being important. Multivariate analysis of recurrence identified menopausal status as the key factor. Adenopathy at the initial examination was associated with decreased length of survival, while radiotherapy was associated with better survival. CONCLUSIONS: Survival from IBC remains poor. Although adenopathy and radiotherapy affected survival by multivariate analysis, the sequence of therapy was not associated with improved outcome.

The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease.

Celiac disease is associated with an increased risk of small bowel adenocarcinoma. The aims of this study were to investigate the molecular basis, assess outcomes, and identify clinicopathologic characteristics of small bowel adenocarcinoma in celiac disease. Retrospective case control cohort study of all celiac disease patients treated at our institution for small bowel adenocarcinoma and matched control patients with sporadic small bowel adenocarcinoma from July 1960 to November 2002. Mismatch repair (MMR) status was accessed by testing tissue for microsatellite instability (MSI) and for hMLH1 and hMSH2 protein expression. Over a 40-year time period, 18 patients with small bowel adenocarcinoma and celiac disease were treated at the Mayo Clinic. One celiac disease patient was excluded. High-frequency MSI (MSI-H) was identified in 8 of 11 (73%) and 2 of 22 (9%) available small bowel adenocarcinoma specimens in the celiac disease and control groups, respectively. In the celiac disease group, MSI-H was associated with loss of hMLH1 and hMSH2 in 6 and 1 specimens, respectively. Loss of hMLH1 occurred in both control tumors. Stage was associated with celiac disease status (P = 0.018), and 78% of controls were stage III or IV compared with 47% of celiac disease patients. Overall, survival was better (P = 0.025) in the celiac disease group compared with stage-matched controls. Celiac disease patients with small bowel adenocarcinoma had a high incidence defective MMR (73%) compared with controls and had better survival compared with stage-matched controls. In addition, celiac disease patients presented more frequently with early-stage small bowel adenocarcinoma. The better survival and earlier presentation of small bowel adenocarcinoma in celiac disease appears to be biologically associated with defective MMR.

Phase III study of adjuvant chemotherapy and radiation therapy compared with chemotherapy alone in the surgical adjuvant treatment of colon cancer: results of intergroup protocol 0130.

PURPOSE: Some patients with colon cancer have a high risk of local recurrence postoperatively. This trial was undertaken to determine whether radiation therapy added to an adjuvant chemotherapy regimen improves outcome in high-risk patients. PATIENTS AND METHODS: Patients with resected colon cancer with tumor adherence or invasion of surrounding structures, or with T3N1 or T3N2 tumors of the ascending or descending colon were randomly assigned to receive fluorouracil and levamisole therapy with or without radiation therapy. Patients who received chemotherapy and radiation therapy (chemoRT) received 45 to 50.4 Gy in 25 to 28 fractions beginning 28 days after starting chemotherapy. Patient enrollment was terminated because of slow accrual after 222 patients enrolled (original goal was 700 patients); 187 patients were assessable. RESULTS: Overall 5-year survival was 62% for chemotherapy patients and 58% for chemoRT patients (P >.50); 5-year disease-free survival was 51% for both groups (P >.50). Toxicity (>/= grade 3) occurred in 42% of chemotherapy patients and 54% of chemoRT patients (P =.04). Leukopenia (>/= grade 3) occurred in 10% of chemotherapy patients and 22% of chemoRT patients (P =.02). No significant difference in nonhematologic toxicity (>/= grade 3) was observed between chemoRT and chemotherapy patients (35% v 44%; P =.26). CONCLUSION: Patients who received chemotherapy or chemoRT had similar overall survival and disease-free survival. Toxicity was higher among chemoRT patients. These results must be interpreted with caution because of the high number of ineligible patients and the limited power of the study to detect potentially meaningful differences.

Laparoscopy for the definitive diagnosis of intra-abdominal lymphoma.

OBJECTIVE: To assess the efficacy of laparoscopy in the diagnosis of intra-abdominal lymphoma. PATIENTS AND METHODS: The medical records of patients with suspected primary or recurrent lymphoma who underwent laparoscopy between March 1991 and March 2003 were reviewed. Demographic, clinical, operative, and pathologic data were collected. The feasibility, safety, and effectiveness of the laparoscopic procedure were assessed. RESULTS: Laparoscopic biopsy was attempted in 94 patients. In 78 patients (83%), the procedure was completed laparoscopically. Conversion to laparotomy was undertaken in 16 patients (17%), most commonly because of inadequate exposure, insufficient tissue, or postoperative adhesions. Among the 69 cases of lymphoma, 55 (80%) were diagnosed via laparoscopy only, 9 (13%) via laparotomy, and 5 (7%) with later procedures. Of the remaining 25 patients, 7 had nonlymphoma disease (4 occult carcinomas, 1 multiple myeloma, 1 epithelioid leiomyosarcoma, and 1 neuroblastoma), and 18 had benign lymphadenopathy (no evidence of lymphoma with a mean follow-up of 53 months). The laparoscopic procedure resulted in false-negative results in 6 patients (6%). The mean hospital stay for patients having a laparotomy was 6 days (range, 3-10 days); the remaining patients were all outpatients. The only Intraoperative laparoscopic complication was hemorrhage that required laparotomy. This event occurred in a patient with a previously undiagnosed neuroblastoma. CONCLUSION: Laparoscopic lymph node biopsy safely provides adequate tissue for full histological evaluation on an outpatient basis in most patients with intra-abdominal lymphoma.