Study Protocol: Efficacy and Safety of Radioembolization (REM) as an Early Modality (EM) Therapy for Metastatic Breast Cancer (BR) to the Liver with Y90 (REMEMBR Y90).

PURPOSE: The primary objective of the REMEMBR Y90 study is to evaluate the efficacy of Yttrium-90 (Y90) radioembolization in patients with breast cancer metastases to the liver as a 2nd or 3rd line treatment option with systemic therapy by assessing liver-specific and overall progression-free survival. Secondary objectives include quality of life, overall survival benefit, and toxicity in relation to patients' tumor biology. MATERIALS AND METHODS: This trial is a multi-center, prospective, Phase 2, open-label, IRB-approved, randomized control trial in the final phases of activation. Eligible patients include those over 18 years of age with metastatic breast cancer to the liver with liver-only or liver-dominant disease, and history of tumor progression on 1-2 lines of chemotherapy. 60 patients will be randomized to radioembolization with chemotherapy versus chemotherapy alone. Permissible regimens include capecitabine, eribulin, vinorelbine, and gemcitabine within 2 weeks of enrollment for every patient. Patients receiving radioembolization will receive lobar or segmental treatment within 1-6 weeks of enrollment depending on their lesion. After final radioembolization, patients will receive clinical and imaging follow-up every 12-16 weeks for two years, including contrast-enhanced computed tomography or magnetic resonance imaging of the abdomen and whole-body positron emission tomography/computed tomography. DISCUSSION: This study seeks to elucidate the clinical benefit and toxicity of Y90 in patients with metastatic breast cancer to the liver who are receiving minimal chemotherapy. Given previous data, it is anticipated that the use of Y90 and chemotherapy earlier in the metastatic disease course would improve survival outcomes and reduce toxicity. LEVEL OF EVIDENCE: Level 1b, Randomized Controlled Trial. TRIAL REGISTRATION NUMBER: NCT05315687 on clinicaltrials.gov.

Accuracy of estimated total liver volume formulas before liver resection.

BACKGROUND: Future remnant liver volume is used to predict the risk for liver failure in patients who will undergo major liver resection. Formulas to estimate total liver volume based on biometric data are widely used to calculate future remnant liver volume; however, it remains unclear which formula is most accurate. This study evaluated published estimate total liver volume formulas to determine which formula best predicts the actual future remnant liver volume based on measurements in a large number of patients who underwent associating liver partition and portal vein ligation for staged hepatectomy surgery. METHODS: All patients with complete liver volume data in the associating liver partition and portal vein ligation for staged hepatectomy registry were included in this study. Estimate total liver volume and estimated future remnant liver volume were calculated for 16 published formulas. The median over- or underestimation compared with actual measured volumes were determined for estimate total liver volume and future remnant liver volume. The proportion of patients with an under- or overestimated future remnant liver volume for each formula were compared with each other using a 25% cut-off for each formula. RESULTS: Among 529 studied patients, the formulas ranged from a 19% underestimation to a 63% overestimation of estimate total liver volume. Estimation of future remnant liver volume lead to a 10% underestimation to a 5% overestimation among the formulas. Of all studied formulas, the Vauthey1 formula was the most accurate, generating underestimation of future remnant liver volume in 20% and overestimation of future remnant liver volume in 6% of patients. CONCLUSION: Validation of 16 published total liver volume formulas in a multicenter international cohort of 529 patients that underwent staged hepatectomy revealed that the Vauthey formula (estimate total liver volume = 18.51 × body weight + 191.8) provides the most accurate prediction of the actual future remnant liver volume.

Posterior reversible encephalopathy syndrome (PRES) in mesenteric leiomyosarcoma: A case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a syndrome characterized by headache, confusion, visual loss and seizures. Many factors influence the appearance of this syndrome, predominantly eclampsia, certain medical treatments and malignant hypertension. Diagnosed by typical transient lesions on magnetic resonance imaging. CASE REPORT: We present a case of mesenteric leiomyosarcoma in a 52 year old woman, who had severe headache, abdominal heaviness, and hypertension. Investigations revealed a mesenteric mass and a Posterior Reversible Encephalopathy Syndrome features on brain MRI, suggesting renin secretion by the tumor, causing the patient's symptoms. CONCLUSION: Patient's symptoms disappeared after resection of the tumor, suggesting a renin production cessation.

Data on isolating mesenchymal stromal cells from human adipose tissue using a collagenase-free method.

The present dataset describes a detailed protocol to isolate mesenchymal cells from human fat without the use of collagenase. Human fat specimen, surgically cleaned from non-fat tissues (e.g., blood vessels) and reduced into smaller fat pieces of around 1-3 mm size, is incubated in complete culture media for five to seven days. Then, cells started to spread out from the fat explants and to grow in cultures according to an exponential pattern. Our data showed that primary mesenchymal cells presenting heterogeneous morphology start to acquire more homogenous fibroblastic-like shape when cultured for longer duration or when subcultured into new flasks. Cell isolation efficiency as well as cell doubling time were also calculated throughout the culturing experimentations and illustrated in a separate figure thereafter. This paper contains data previously considered as an alternative protocol to isolate adipose-derived mesenchymal stem cell published in "Proliferation and differentiation of human adipose-derived mesenchymal stem cells (ASCs) into osteoblastic lineage are passage dependent" [1].

Prediction of Mortality After ALPPS Stage-1: An Analysis of 320 Patients From the International ALPPS Registry.

OBJECTIVES: The aim of this study was to identify predictors of 90-day mortality after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), available after stage-1, either to omit or delay stage-2. BACKGROUND DATA: ALPPS is a two-stage hepatectomy for patients with extensive liver tumors with predicted small liver remnants, which has been criticized for its high mortality rate. Risk factors for mortality are unknown. METHODS: Patients in the International Registry undergoing ALPPS from April 2011 to July 2014 were analyzed. Primary outcome was 90-day mortality. Liver function after stage-1 was assessed using the criteria of the International Study Group for Liver Surgery (ISGLS) after stage-1 among others. A multivariable model was used to identify independent predictors of 90-day mortality. RESULTS: Three hundred twenty patients registered by 55 centers worldwide were evaluated. Overall 90-day mortality was 8.8% (28/320). The predominant cause for 90-day mortality was postoperative liver failure in 75% of patients. Fourteen percent of patients developed liver failure according to ISGLS criteria already after stage-1 ALPPS. Those and patients with a model of end-stage liver disease (MELD) score more than 10 before stage-2 were at significantly higher risk for 90-day mortality after stage-2 with an odds ratio (OR) 3.9 [confidence interval (CI) 1.4-10.9, P = 0.01] and OR 4.9 (CI 1.9-12.7, P = 0.006), respectively. Other factors, such as size of future liver remnant (FLR) before stage-2 and time between stages, were not predictive. CONCLUSIONS: This analysis of the largest cohort of ALPPS patients so far identifies those patients in whom stage-2 ALPPS surgery should be delayed or even denied. These findings may help to make ALPPS safer.

Monosegment ALPPS hepatectomy: extending resectability by rapid hypertrophy.

BACKGROUND: Liver remnant function limits major liver resections to generally leave patients with ≥2 Couinaud segments. Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) induces extensive hypertrophy and allows surgeons to perform extreme liver resections. METHODS: The international ALPPS registry (NCT01924741; 2011-2014) was screened for novel resection type with only 1 segment remnant. The anatomy of lesions and indications for ALPPS, operative technique, complications, survival, and recurrence were evaluated. RESULTS: Among 333 patients, 12 underwent monosegment ALPPS hepatectomies in 6 centers, all for extensive bilobar colorectal liver metastases. All patients were considered unresectable by conventional means, and all had a response to or no progression after chemotherapy before surgery. In 2 patients, the liver remnant consisted of segment 2, in 2 of segment 3, in 6 of segment 4, and in 2 of segment 6. Median time to proceed to stage 2 was 13 days and median hypertrophy of the liver remnant was 160%. There was no mortality. Four patients experienced liver failure, but all recovered. Complications higher than Dindo-Clavien IIIa occurred in 4 patients with no long-term sequelae. At a median follow-up of 14 months, 6 patients are tumor free and 6 patients have developed recurrent metastatic disease. CONCLUSION: ALPPS allows systematic liver resections with monosegment remnants, a novelty in liver surgery. Because such resections are difficult to conceive without rapid hypertrophy, we propose to name such resections after the segments constituting the liver remnant rather than the segments removed.

PREDICTORS OF INFLAMMATORY LOCAL RECURRENCE AFTER BREAST-CONSERVING THERAPY FOR BREAST CANCER: MATCHED CASE-CONTROL STUDY.

BACKGROUND: Inflammatory local recurrence (ILR) after breast-conserving surgery for noninflammatory breast cancer (BC) is associated with dismal prognosis. Risk factors for ILR are not well defined. METHODS: Between 2001 and 2010, twelve patients at our hospital developed ILR after breast-conserving surgery, adjuvant chemotherapy, and radiotherapy for BC. We compared their clinico-pathological characteristics to those of 24 patients with noninflammatory local recurrence (non-ILR), 24 patients with distant metastases, and 48 disease-free controls, matched for age and observation period. RESULTS: The median time to ILR was 10 months. In univariate analysis, extent of lymph node involvement (p < 0.05), multifocality (p < 0.05), c-erbB2 overexpression (p < 0.05), and lymphovascular invasion (LVI) (p < 0.001) affected the risk of ILR. Conditional logistic regression analysis showed a significant association between ILR and combined LVI and high histopathological grade. The odds ratio (OR) for ILR versus non-ILR was 6.14 (95% confidence interval [CI] 1.48-25.38) and for ILR versus distant metastases it was 3.05 (95% CI 0.09-97.83) when both LVI and high histopathological grade were present. Patients with family history of BC were more likely to present with ILR than non-ILR (OR 5.47; 95% CI 1.55-19.31) or distant relapse (OR 5.62; 95% CI 0.26-119.95). CONCLUSIONS: Pre- and postmenopausal women with high-grade BC and LVI are at increased risk to develop ILR, especially in the presence of family history of BC. Identification of risk factors for this lethal form of recurrent BC may lead to more effective preventive treatment strategies in properly selected patients.

Residual tumor thickness at the tumor-normal tissue interface predicts the recurrence-free survival in patients with liver metastasis of breast cancer.

Tumor response to neoadjuvant therapy is a significant predictive indicator of recurrence-free survival. We measured tumor response using residual tumor thickness at the tumor-normal tissue interface (TNI) and evaluated its association with outcome in patients with liver metastasis of breast cancer. We included 48 patients who underwent neoadjuvant therapy followed by partial liver resection at MD Anderson Cancer Center between 1997 and 2010. The hematoxylin-eosin-stained tumor sections were evaluated for both pathologic response and the residual tumor thickness at the TNI by 3 pathologists who were blinded to the clinical information, treatment regimen, and patient outcome. The residual tumor thickness at the TNI was correlated with recurrence-free survival using Kaplan-Meier method and log-rank test. Cox proportional hazard model was used to identify predictors of recurrence-free survival. All patients were women with a median age of 43 years. The median duration of follow-up was 52.1 months. Residual tumor thickness less than or equal to 3 mm at the TNI correlated with major pathologic response and was associated with longer recurrence-free survival in both univariate and multivariate analyses. Residual tumor thickness at the TNI predicts recurrence-free survival and provides an objective outcome end point in patients who underwent neoadjuvant therapy and liver resection of metastatic breast cancer. We suggest using both the pathologic response and the residual tumor thickness at the TNI to measure tumor response to therapy to improve accuracy.

Proliferation and differentiation of human adipose-derived mesenchymal stem cells (ASCs) into osteoblastic lineage are passage dependent.

OBJECTIVE: The effect of in vitro expansion of human adipose-derived stem cells (ASCs) on stem cell properties is controversial. We examined serial subcultivation with expansion on the ability of ASCs to grow and differentiate into osteoblastic lineages. DESIGN: Flow cytometric analysis, growth kinetics, cell population doubling time, light microscopy and confocal analysis, and osteogenesis induction were performed to assess growth and osteogenic potential of subcultivated ASCs at passages 2 (P2), P4 and P6. RESULTS: Flow cytometric analysis revealed that ASCs at P2 express classical mesenchymal stem cell markers including CD44, CD73, and CD105, but not CD14, CD19, CD34, CD45, or HLA-DR. Calcium deposition and alkaline phosphatase activity were the highest at P2 but completely abrogated at P4. Increased passage number impaired cell growth; P2 cultures exhibited exponential growth, while cells at P4 and P6 showed near linear growth with cell population doubling times increased from 3.2 at P2 to 4.8 d at P6. Morphologically, cells in various subcultivation stages showed flattened shape at low density but spindle-like structures at confluency as judged by phalloidin staining. CONCLUSIONS: Osteogenic potential of ASCs is impaired by successive passaging and may not serve as a useful clinical source of osteogenic ASCs past P2.

Treatment sequencing strategy for hepatic epithelioid haemangioendothelioma.

BACKGROUND: The biology of hepatic epithelial haemangioendothelioma (HEHE) is variable, lying intermediate to haemangioma and angiosarcoma. Treatments vary owing to the rarity of the disease and frequent misdiagnosis. METHODS: Between 1989 and 2013, patients retrospectively identified with HEHE from a single academic cancer centre were analysed to evaluate clinicopathological factors and initial treatment regimens associated with survival. RESULTS: Fifty patients with confirmed HEHE had a median follow-up of 51 months (range 1-322). There was no difference in 5-year survival between patients presenting with unilateral compared with bilateral hepatic disease (51.4% versus 80.7%, respectively; P = 0.1), localized compared with metastatic disease (69% versus 78.3%, respectively; P = 0.7) or an initial treatment regimen of Surgery, Chemotherapy/Embolization or Observation alone (83.3% versus 71.3% versus 72.4%, respectively; P = 0.9). However, 5-year survival for patients treated with chemotherapy at any point during their disease course was decreased compared with those who did not receive any chemotherapy (43.6% versus 82.9%, respectively; P = 0.02) and was predictive of a decreased overall survival on univariate analysis [HR 3.1 (CI 0.9-10.7), P = 0.02]. CONCLUSIONS: HEHE frequently follows an indolent course, suggesting that immediate treatment may not be the optimal strategy. Initial observation to assess disease behaviour may better stratify treatment options, reserving surgery for those who remain resectable/transplantable. Prospective cooperative trials or registries may confirm this strategy.

Resection of at-risk mesenteric lymph nodes is associated with improved survival in patients with small bowel neuroendocrine tumors.

BACKGROUND: Neuroendocrine tumors of the small intestine commonly metastasize to regional lymph nodes (LNs). Single-institution reports suggest that removal of LNs improves outcome, but comprehensive data are lacking. We hypothesized that the extent of lymphadenectomy reported in a large administrative database would be associated with overall survival for jejunal and ileal neuroendocrine tumors. METHODS: A search of the Surveillance Epidemiology and End Results database was performed for patients with jejunal and ileal neuroendocrine tumors from 1977 to 2004. Descriptive patient characteristics were collected to include age at diagnosis, sex, race, grade, primary tumor size, LN status, number of LNs resected, presence of distant metastasis, and the type of operation. Statistical analyses were limited to patients with only one primary tumor to exclude patients with other malignancies. Univariate and multivariate analyses were performed to analyze the number of LNs resected and the LN ratio (number of positive LNs/total number of LNs removed) to determine the effect on cancer-specific survival. RESULTS: Altogether, 1,364 patients were included in this analysis. Removal of any LNs was associated with improved cancer-specific survival when compared to patients with no LN removal reported (p = 0.0027) on univariate analysis. Among those who had any LNs removed, a median of eight LNs were identified in resection specimens with a median LN ratio of 0.29 (range 0-1). On multivariate analysis (adjusting for age and tumor size), patients with >7 LNs removed experienced better cancer-specific survival than those with ≤ 7 LNs removed (median survival not reached vs. 140 months): hazard ratio and 95 % confidence interval were 0.573 (0.402, 0.817) (p = 0.002). CONCLUSIONS: This review of a large number of surgical patients demonstrates that regional mesenteric lymphadenectomy in conjunction with resection of the primary tumor is associated with improved survival of patients with small bowel neuroendocrine tumors.

Margin status remains an important determinant of survival after surgical resection of colorectal liver metastases in the era of modern chemotherapy.

OBJECTIVE: To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases after modern preoperative chemotherapy. BACKGROUND: In the era of effective chemotherapy for colorectal liver metastases, the association between surgical margin status and survival has become controversial. METHODS: Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy. RESULTS: Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin <1 mm). The 5-year OS rates for patients with R0 resection (margin ≥1 mm) and R1 resection were 55% and 26%, respectively (P = 0.017). Multivariate analysis identified R1 resection (P = 0.03) and a minor pathologic response to chemotherapy (P = 0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs 11%; P = 0.007) than in patients with optimal response (3-year OS rate: 92% vs 88%; P = 0.917) and greater in patients with a minor pathologic response (5-year OS rate: 46% vs 0%; P = 0.002) than in patients with a major response (5-year OS rate: 63% vs 67%; P = 0.587). CONCLUSIONS: In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy.

Locoregional surgical and interventional therapies for advanced colorectal cancer liver metastases: expert consensus statements.

Selection of the optimal surgical and interventional therapies for advanced colorectal cancer liver metastases (CRLM) requires multidisciplinary discussion of treatment strategies early in the trajectory of the individual patient's care. This paper reports on expert consensus on locoregional and interventional therapies for the treatment of advanced CRLM. Resection remains the reference treatment for patients with bilateral CRLM and synchronous presentation of primary and metastatic cancer. Patients with oligonodular bilateral CRLM may be candidates for one-stage multiple segmentectomies; two-stage resection with or without portal vein embolization may allow complete resection in patients with more advanced disease. After downsizing with preoperative systemic and/or regional therapy, curative-intent hepatectomy requires resection of all initial and currently known sites of disease; debulking procedures are not recommended. Many patients with synchronous primary disease and CRLM can safely undergo simultaneous resection of all disease. Staged resections should be considered for patients in whom the volume of the future liver remnant is anticipated to be marginal or inadequate, who have significant medical comorbid condition(s), or in whom extensive resections are required for the primary cancer and/or CRLM. Priority for liver-first or primary-first resection should depend on primary tumour-related symptoms or concern for the progression of marginally resectable CRLM during treatment of the primary disease. Chemotherapy delivered by hepatic arterial infusion represents a valid option in patients with liver-only disease, although it is best delivered in experienced centres. Ablation strategies are not recommended as first-line treatments for resectable CRLM alone or in combination with resection because of high local failure rates and limitations related to tumour size, multiplicity and intrahepatic location.

Morbidity of staged proctectomy after hepatectomy for colorectal cancer: a matched case-control analysis.

BACKGROUND: Proctectomy after hepatectomy, or the reverse approach, is an alternative to traditional sequencing for advanced liver metastases with asymptomatic colorectal primary tumors. We sought to evaluate the surgical morbidity of proctectomy for colorectal cancer after previous liver surgery. METHODS: A single-institution colorectal database was queried for patients treated with proctectomy after previous hepatectomy from 2003 to 2011. Reverse-approach patients (n = 31) were matched 1:2 with a cohort of standard proctectomy patients (n = 62) using operation, age, gender, and surgeon. Perioperative factors were analyzed by univariate/multivariate models for associations with complications graded by Dindo-Clavien criteria. RESULTS: Thirty-one patients with adenocarcinoma ≤ 20 cm from the anal verge underwent proctectomy after hepatectomy. Median time from hepatectomy to proctectomy was 5.1 months. Median tumor distance was 8.5 cm. Before proctectomy, patients underwent 28 (90 %) major hepatectomies and 7 (22 %) portal vein embolizations. There were no perioperative deaths. Reverse-approach patients did not differ from control patients in operation, demographics, body mass index (BMI), comorbidities, tumor distance, operative time, estimated blood loss, length of stay, or complication rates (p > 0.05). Grade 2 or higher complications developed in 42 % of reverse-approach and 27 % of standard proctectomies (p = 0.17). Grade 3 or higher complications developed in 10 % and 8 %, respectively (p = 1.00). Independent predictors of complications of grade 2 or higher were BMI ≥30 kg/m(2) (p = 0.007), operative time ≥300 min (p = 0.012), intraoperative transfusion (p = 0.044), concurrent procedures (p = 0.024), and age ≥50 years (p = 0.030). CONCLUSIONS: Risk factors for morbidity of staged proctectomy are similar to those for standard proctectomy. In selected patients, the reverse-approach proctectomy is safe with acceptable morbidity.

Neither neoadjuvant nor adjuvant therapy increases survival after biliary tract cancer resection with wide negative margins.

BACKGROUND: We investigated the role of neoadjuvant/adjuvant therapies on survival for resectable biliary tract cancer. We hypothesized that neoadjuvant and adjuvant therapy should improve the survival probability in these patients. METHODS: This was a retrospective review of a prospective database of patients resected for gallbladder cancer (GBC) and cholangiocarcinoma (CC). One hundred fifty-seven patients underwent resection for primary GBC (n = 63) and CC (n = 94). Fisher's exact test, Student's t test, the log-rank test, and a Cox proportional hazard model determined significant differences. RESULTS: The 5-year overall survival rate after resection of GBC and CC was 50.6 % and 30.4 %, respectively. Of the patients, 17.8 % received neoadjuvant chemotherapy, 48.7 % received adjuvant chemotherapy, while 15.8 % received adjuvant chemoradiotherapy. Patients with negative margins of at least 1 cm had a 5-year survival rate of 52.4 % (p < 0.01). Adjuvant therapy did not significantly prolong survival. Neoadjuvant therapy delayed surgical resection on average for 6.8 months (p < 0.0001). Immediate resection increased median survival from 42.3 to 53.5 months (p = 0.01). CONCLUSIONS: Early surgical resection of biliary tract malignancies with 1 cm tumor-free margins provides the best probability for long-term survival. Currently available neoadjuvant or adjuvant therapy does not improve survival.

Risk of venous thromboembolism outweighs post-hepatectomy bleeding complications: analysis of 5651 National Surgical Quality Improvement Program patients.

BACKGROUND: Historically, liver surgeons have withheld venous thromboembolism (VTE) chemoprophylaxis due to perceived postoperative bleeding risk and theorized protective anticoagulation effects of a hepatectomy. The relationships between extent of hepatectomy, postoperative VTE and bleeding events were evaluated using the National Surgical Quality Improvement Program (NSQIP) database. METHODS: From 2005 to 2009, all elective open hepatectomies were identified. Factors associated with 30-day rates of VTE, postoperative transfusions and returns to the operating room (ROR), were analysed. RESULTS: The analysis included 5651 hepatectomies with 3376 (59.7%) partial, 585 (10.4%) left, 1134 (20.1%) right, and 556 (9.8%) extended. Complications included deep vein thrombosis (DVT) (1.93%), pulmonary embolism (PE) (1.31%), venous thromboembolism (VTE) (2.88%), postoperative transfusion (0.76%) and ROR with transfusion (0.44%). VTE increased with magnitude of hepatectomy (partial 2.13%, left 2.05%, right 4.15%, extended 5.76%; P < 0.001) and outnumbered bleeding events (P < 0.001). Other factors independently associated with VTE were aspartate aminotransferase (AST) ≥27 (P= 0.022), American Society of Anesthesiologists (ASA) class ≥3 (P < 0.001), operative time >222 min (P= 0.043), organ space infection (P < 0.001) and length of hospital stay ≥7 days (P= 0.004). VTE resulted in 30-day mortality of 7.4% vs. 2.3% with no VTE (P= 0.001). CONCLUSIONS: Contrary to the belief that transient postoperative liver insufficiency is protective, VTE increases with extent of hepatectomy. VTE exceeds major bleeding events and is strongly associated with mortality. These data support routine post-hepatectomy VTE chemoprophylaxis.

Liver resection for liver metastases from nondigestive endocrine cancer: extrahepatic disease burden defines outcome.

BACKGROUND: For patients with hepatic nondigestive endocrine metastases (HNEM), the role of liver resection is not well-defined. METHODS: We reviewed outcomes for patients who underwent liver resection for HNEM at 2 centers to identify predictors of survival. RESULTS: From 1991 to 2010, 51 patients underwent liver resection for HNEM. Primary tumor types were adrenal gland (n = 26), thyroid (n = 11), testicular germ cell (n = 9), and ovarian granulosa cell (n = 5). 28 patients (55%) had synchronous or early (diagnosed within 12 months after primary tumor resection) liver metastases. At liver resection, 26 patients (51%) had extrahepatic metastases, and 7 (14%) had ≥2 sites of extrahepatic metastases. 32 patients (63%) had major liver resection and 19 (37%) had a simultaneous extrahepatic procedure. 90-day postoperative morbidity and mortality rates were 27% and 2%, respectively. After median follow-up of 20 months (range, 1-144), the 5-year overall and recurrence-free survival rates were 58% and 37%, respectively. Survival was not affected by primary tumor type. In multivariate analysis, ≥2 sites of extrahepatic metastases (hazard ratio [HR] = 4.80; 95% confidence interval [CI] = 1.18-19.50; P = .028) and interval of ≤12 months between primary tumor resection and diagnosis of liver metastases (HR = 5.33; 95% CI = 1.11-25.71; P = .037) were associated with worse overall survival after liver resection. CONCLUSION: For selected patients, liver resection for HNEM is associated with long-term survival. The number of extrahepatic sites of metastasis and the timing of appearance of liver metastases should be considered in patient selection.

Resection of liver metastases from breast cancer: estrogen receptor status and response to chemotherapy before metastasectomy define outcome.

BACKGROUND: The oncologic benefit of resecting liver metastases in patients with breast cancer is unclear. This study was performed to identify predictors of survival after hepatectomy. METHODS: Between 1997 and 2010, 86 patients underwent resection of breast cancer liver metastases. Clinicopathologic characteristics of the primary breast neoplasm, timing of metastasis development, and treatment were recorded. Response to prehepatectomy chemotherapy was evaluated according to Response Criteria in Solid Tumors criteria, and the best response to chemotherapy during treatment and the response immediately before hepatectomy were noted. Univariate and multivariate analyses were performed to identify predictors of disease-free survival and overall survival. RESULTS: Fifty-nine patients (69%) had estrogen receptor- or progesterone receptor- positive primary breast neoplasms. Fifty-three patients (62%) had a solitary breast cancer liver metastasis, and 73 (85%) had breast cancer liver metastases ≤5 cm. Sixty-five patients (76%) received prehepatectomy hormonal and/or chemotherapy. Four patients (6%) had progressive disease as the best response, and 19 patients (30%) had progressive disease before hepatectomy (P < .001). Seventy percent of patients who received preoperative chemotherapy or hormonal therapy had either response or stable disease immediately before hepatectomy. No postoperative deaths were observed. At a 62-month median follow-up, the disease-free survival and overall survival were 14 and 57 months, respectively. On univariate analysis, estrogen receptor/progesterone receptor status of the primary breast neoplasm, best radiographic response, and preoperative radiographic response were associated with overall survival. On multivariate analysis, estrogen receptor-negative primary breast disease (P = .009; hazard ratio, 3.3; 95% confidence interval, 1.4-8.2) and preoperative progressive disease (P = .003; hazard ratio, 3.8; 95% confidence interval, 1.6-9.2) were associated with decreased overall survival. CONCLUSION: Resection of breast cancer liver metastases in patients with estrogen receptor-positive disease that is responding to chemotherapy is associated with improved survival. The timing of operative intervention may be critical; resection before progression is associated with a better outcome.

Defined clinical classifications are associated with outcome of patients with anatomically resectable pancreatic adenocarcinoma treated with neoadjuvant therapy.

BACKGROUND: We previously introduced a classification system for patients with localized pancreatic adenocarcinoma that integrates assessments of tumor anatomy, cancer biology, and patient physiology. By means of this system, we sought to analyze outcomes of patients with resectable anatomy but heterogeneous biology and physiology who were treated with neoadjuvant therapy. METHODS: We evaluated consecutive patients (2002-2007) with anatomically potentially resectable cancers treated with chemotherapy or chemoradiation before potential pancreatectomy. We compared clinical factors and outcomes of patients classified as having disease that was clinically resectable (CR; no extrapancreatic disease, preserved performance status); suspicion for extrapancreatic disease (BR-B); or marginal performance status or significant comorbidity (BR-C). Patients with borderline resectable anatomy (BR-A) were excluded. RESULTS: Resection rates for 138 CR, 41 BR-B, and 38 BR-C patients were 75, 46, and 37%, respectively (P < 0.001). Metastases, detected during treatment in 23% of patients, were the most common contraindication to resection among CR (15%) and BR-B (46%) patients. Performance status rarely precluded surgery except among BR-C (32%) patients. Factors associated with selection against surgery were older age, poor performance status, pain, and therapeutic complications (P < 0.05). The median overall survival of all patients was 21 months. Resected and unresected BR-B and BR-C patients had median overall survival durations similar to those of resected and unresected CR patients, respectively (P > 0.22). CONCLUSIONS: This system describes discrete clinical subgroups of patients with pancreatic cancer who have similar, potentially resectable tumor anatomy but heterogeneous physiology and cancer biology. It may be used with neoadjuvant therapy to predict outcomes, individualize treatment algorithms, and optimize survival.