Robotic versus laparoscopic gastrectomy for adenocarcinoma in the US: a propensity score-matching analysis of 11,173 patients on oncological adequacy.

INTRODUCTION: Surgery remains the cornerstone treatment for gastric cancer. Previous studies have reported better lymphadenectomy with minimally invasive approaches. There is a paucity of data comparing robotic and laparoscopic gastrectomy in the US. Herein, we examined whether oncological adequacy differs between laparoscopic and robotic approaches. METHODS: The National Cancer Database was utilized to identify patients who underwent gastrectomy for adenocarcinoma between 2010 and 2019. A propensity score-matching analysis between robotic gastrectomy (RG) versus laparoscopic gastrectomy (LG) was performed. The primary outcomes were lymphadenectomy ≥ 16 nodes and surgical margins. RESULTS: A total of 11,173 patients underwent minimally invasive surgery for gastric adenocarcinoma between 2010 and 2019. Of those 8320 underwent LG and 2853 RG. Comparing the unmatched cohorts, RG was associated with a higher rate of adequate lymphadenectomy (63.5% vs 57.1%, p < .0.0001), higher rate of negative margins (93.8% vs 91.9%, p < 0.001), lower rate of prolonged length of stay (26.0% vs 29.6%, p < .0.001), lower 90-day mortality (3.7% vs 5.0%, p < 0.0001), and a better 5-year overall survival (OS) (56% vs 54%, p = 0.03). A propensity score-matching cohort with a 1:1 ratio was created utilizing the variables associated with lymphadenectomy ≥ 16 nodes. The matched analysis revealed that the rate of adequate lymphadenectomy was significantly higher for RG compared to LG, 63.5% vs 60.4% (p = 0.01), respectively. There was no longer a significant difference between RG and LG regarding the rate of negative margins, prolonged length of stay, 90-day mortality, rate of receipt of postoperative chemotherapy, and OS. CONCLUSIONS: This propensity score-matching analysis with a large US cohort shows that RG was associated with a higher rate of adequate lymphadenectomy compared to LR. RG and LG had a similar rate of negative margins, prolonged length of stay, receipt of postoperative chemotherapy, 90-day mortality, and OS, suggesting that RG is a comparable surgical approach, if not superior to LG.

Trends and outcomes of minimally invasive surgery for gastrointestinal stromal tumors (GIST).

OBJECTIVE: Minimally invasive surgery (MIS) is increasingly being utilized for the resection of gastrointestinal cancers. National trends for perioperative and oncologic outcomes of MIS for gastrointestinal stromal tumors (GIST) are unknown. We hypothesized that with increased use of MIS, the perioperative outcomes and survival for GIST are preserved. METHODS: The National Cancer Database (2010-2016) was utilized to assess perioperative and oncologic outcomes for GIST of the stomach and small bowel. Kaplan-Meier method and log rank test were used to compare survival outcomes. RESULTS: Data from 8923 gastric and 3683 small bowel resections were analyzed. Over the study period, MIS became the prevalent modality for gastrectomies (2010: robotic: 2.4%, laparoscopic: 26.1%, open: 71.5% vs. 2016: robotic: 9.6%, laparoscopic: 48.8%, open: 41.6%; p < 0.001), with a smaller increase in enterectomies (2010: robotic: 1%, laparoscopic: 17.3%, open: 81.6% vs. 2016: robotic: 3.9%, laparoscopic: 27.2%, open: 68.9%; p < 0.001). Age and Charlson comorbidity index were similar among groups. MIS approaches were associated with fewer readmissions and lower 90 day mortality for gastrectomies and similar rates for enterectomies. MIS did not compromise patient survival even in patients who underwent neoadjuvant treatment or harbored tumors ≥ 10 cm. CONCLUSION: Minimally invasive surgery is increasingly being utilized for resection of gastric and small bowel GIST, with improved postoperative outcomes. In this retrospective review, overall survival after minimally invasive or open surgery was comparable, even in challenging scenarios of neoadjuvant treatment or large tumors (≥ 10 cm).

Aspartate Aminotransferase-to-Platelet Ratio Index Predicts Liver Failure After Resection of Colorectal Liver Metastases.

BACKGROUND: Chemotherapy agents for metastatic colorectal cancer can cause liver injury, increasing the risk of post-hepatectomy liver failure after hepatectomy for metastases. The role of noninvasive fibrosis markers in this setting is not well established. AIMS: To evaluate the aspartate aminotransferase-to-platelet ratio index (APRI) as a predictor of postoperative liver failure. METHODS: The National Surgical Quality Improvement Program database was utilized to identify patients who received preoperative chemotherapy and underwent hepatectomy for colorectal metastases between 2015 and 2017. Concordance index analysis was conducted to determine APRI's contribution to the prediction of liver failure. The optimal cutoff value was defined and its ability to predict post-hepatectomy liver failure and perioperative bleeding were examined. RESULTS: A total of 2374 patients were identified and included in the analysis. APRI demonstrated to be a better predictor of postoperative liver failure than MELD score, with a statistically significant larger area under the curve. The optimal APRI cutoff value to predict liver failure was 0.365. The multivariable logistic regression showed that APRI ≥ 0.365 was independently associated with PHLF, odds ratio (OR) 2.51, 95% confidence interval (CI) 1.67-3.77, P < .0001. Likewise, APRI ≥ 0.365 was independently associated with perioperative bleeding complications requiring transfusions, OR 1.41, 95% CI 1.13-1.77, P = 0.002. MELD score was not statistically associated with PHLF or bleeding complications. CONCLUSIONS: APRI was independently associated with post-hepatectomy liver failure and perioperative bleeding requiring transfusions after resection of colorectal metastases in patients who received preoperative chemotherapy. Concordance index showed APRI to add significant contribution as a predictor of postoperative liver failure.

Minimally invasive vs open pancreatoduodenectomy on oncological adequacy: a propensity score-matched analysis.

BACKGROUND: The adoption of minimally invasive pancreatoduodenectomy (MIPD) has increased over the last decade. Most of the data on perioperative and oncological outcomes derives from single-center high-volume hospitals. The impact of MIPD on oncological outcomes in a multicenter setting is poorly understood. METHODS: The National Cancer Database was utilized to perform a propensity score matching analysis between MIPD vs open pancreatoduodenectomy (OPD). The primary outcomes were lymphadenectomy ≥ 15 nodes and surgical margins. Secondary outcomes were 90-day mortality, length of stay, and overall survival. RESULTS: A total of 10,246 patients underwent pancreatoduodenectomy for ductal adenocarcinoma between 2010 and 2016. Among these patients, 1739 underwent MIPD. A propensity score matching analysis with a 1:2 ratio showed that the rate of lymphadenectomy ≥ 15 nodes was significantly higher for MIPD compared to OPD, 68.4% vs 62.5% (P < .0001), respectively. There was no statistically significant difference in the rate of positive margins, 90-day mortality, and overall survival. OPD was associated with an increased rate of length of stay > 10 days, 36.6% vs 33% for MIPD (P < .01). Trend analysis for the patients who underwent MIPD revealed that the rate of adequate lymphadenectomy increased during the study period, 73.1% between 2015 and 2016 vs 63.2% between 2010 and 2012 (P < .001). In addition, the rate of conversion to OPD decreased over time, 29.3% between 2010 and 2012 vs 20.2% between 2015 and 2016 (P < .001). CONCLUSION: In this propensity score matching analysis, the MIPD approach was associated with a higher rate of adequate lymphadenectomy and a shorter length of stay compared to OPD. The surgical margins status, 90-day mortality, and overall survival were similar between the groups.

The impact of minimally invasive surgery and frailty on post-hepatectomy outcomes.

BACKGROUND: The impact of patient frailty on post-hepatectomy outcomes is not well studied. We hypothesized that patient frailty is a strong predictor of 30-day post-hepatectomy complications. METHODS: The liver-targeted National Surgical Quality Improvement Program (NSQIP) database for 2014-2019 was reviewed. A validated modified frailty index (mFI) was used. RESULTS: A total of 24,150 hepatectomies were reviewed. Worsening frailty was associated with increased incidence of Clavien-Dindo grade IV complications (mFI 0, 1, 2, 3, 4 was 3.9%, 6.3%, 10%, 8.1%, 50% respectively; p < 0.001). Minimally invasive hepatectomies had a lower rate of Clavien-Dindo grade IV complications for non-frail (Laparoscopic: 1%, Robotic: 2.6%, Open: 4.6%; p < 0.001) and frail patients (Laparoscopic: 3%, Robotic: 2.3%, Open: 7.7%; p < 0.001). Frail patients experienced higher incidence of post-hepatectomy liver failure (5.4% vs 4.1% for non-frail; p < 0.001) and grade C liver failure (28% vs 21.1% for non-frail; p = 0.03). Incorporating mFI to Albumin-Bilirubin score (ALBI) improved its ability to predict Clavien-Dindo grade IV complications (AUC improved from 0.609 to 0.647; p < 0.001) and 30-day mortality (AUC improved from 0.663 to 0.72; p < 0.001). CONCLUSION: Worsening frailty correlates with increased incidence of Clavien-Dindo grade IV complications post-hepatectomy, whereas minimally invasive approaches decrease this risk. Incorporating frailty assessment to ALBI improves its ability to predict major postoperative complications and 30-day mortality.

National postoperative and oncologic outcomes after pelvic exenteration for T4b rectal cancer.

BACKGROUND AND OBJECTIVES: Studies reporting outcomes after pelvic exenteration for rectal cancer are limited. The objective of this study was to evaluate early postoperative and oncologic outcomes in a national multi-institutional cohort. METHODS: Using the National Cancer Database (NCDB), which collects data from over 1500 commission on cancer (CoC)-accredited hospitals, we analyzed patients undergoing pelvic exenteration for T4b rectal adenocarcinoma. RESULTS: There were 1367 pelvic exenterations performed in 552 hospitals. Median age was 60 years, the majority of patients (n = 831; 60.8%) were female. Neoadjuvant radiation was used only in 57%; 24.3% of resections had positive margins. Following exenteration, 30-day mortality rate, 90-day mortality rate, and readmission rates were: 1.8%, 4.4%, and 7.4%. Age ≥ 60 years and higher Charlson-Deyo comorbidity index were independently associated with increased 90-day mortality (P < .001). Overall survival (OS) was 50 months. After adjustment of significant covariates, negative margin status (adjusted HR, 0.6, 95% CI, 0.5-0.8; P < .001) and receipt of perioperative radiation or chemoradiation (adjusted HR, 0.5; 95% CI, 0.4-0.6; P < .001) were significantly associated with decreased risk of death. Only 71% of the patients received perioperative radiation. CONCLUSIONS: Pelvic exenterations are being performed safely in Coc-accredited hospitals. However, up to one fourth of patients undergo resections with positive margins or are subject to underutilization of perioperative radiation therapy. Increased use of radiation may increase negative margin resections and improve patient outcomes.

Trends and outcomes of robotic surgery for gastrointestinal (GI) cancers in the USA: maintaining perioperative and oncologic safety.

OBJECTIVE: Minimally invasive surgery (MIS) continues to gain traction as a feasible approach for the operative management of gastrointestinal (GI) malignancies. The aim of this study is to quantify national trends, perioperative and oncologic outcomes of MIS for the most common GI malignancies including the esophagus, stomach, pancreas, colon, and rectum. We hypothesize that with more widespread use of MIS techniques, perioperative outcomes and oncologic resection quality will remain preserved. METHODS: The National Cancer Database (2010-2014) was utilized to assess perioperative outcomes and pathologic quality of MIS (robotic and laparoscopic) compared to open, in patients who underwent resection for cancers of the esophagus, stomach, pancreas, colon, and rectum. Multilevel logistic regression models were constructed to identify independent factors associated with postoperative and long-term outcomes. RESULTS: Data from 11,023 esophageal, 30,664 gastric, 30,689 pancreas, 260,669 colon, and 52,239 rectal resections were analyzed. Although laparoscopy is the most prevalent MIS approach, the number of robotic resections increased nearly fourfold from 2010 to 2014 in all organ sites (increase by factor: esophagus: 3.8, stomach: 4.4, pancreas: 4.4, colon: 3.8 and rectum: 4). The number of laparoscopic resections increased at a slower rate (factor: 1.3-1.9), whereas the number of open resections decreased (factor: 0.67-0.77). Patients who underwent robotic-assisted resections were younger for stomach and colorectal resections and with lower Charlson Comorbidity Index across all sites. Patients who underwent robotic or laparoscopic resections had shorter hospitalizations, fewer readmissions (with the exception of rectal resections) and lower postoperative mortality at 90 days. Robotic-assisted resections had comparable negative margin resections and number of lymph nodes to laparoscopic and open resections across all sites. CONCLUSION: The utilization of robotic-assisted resections of GI cancers is rapidly increasing with more frequent use in younger and healthier patients. This study demonstrates that with the rising utilization of robotic-assisted resections, perioperative outcomes and oncologic safety have not been compromised.

Primary liver sarcomas in the modern era: Resection or transplantation?

BACKGROUND AND OBJECTIVES: Primary liver sarcomas (PLS) are rare. Published series are limited by small numbers of patients. METHODS: We reviewed the National Cancer Database (2004-2014) for patients who underwent surgical resection of PLS. RESULTS: Of 237 patients identified, the majority were female (60.8%), with median age of 52 years. Histologies were: epithelioid hemangioendothelioma (n = 67), angiosarcoma (n = 64), leiomyosarcoma (n = 33), embryonal rhabdomyosarcoma (n = 31), carcinosarcoma (n = 16), giant cell sarcoma (n = 14), spindle cell sarcoma (n = 12). Ninety-seven (40.9%) patients underwent lobectomies or extended lobectomies, 41 patients (17.3%) underwent transplantation. Surgical margins were negative in 82.9%. Tumors were well differentiated in 11.3%. Histology type correlated with outcome with the best prognosis for epithelioid hemangioendothelioma (OS: not reached, similar for resection and transplantation) and the worst for angiosarcoma (OS:16.6 mo with resection; 6 mo with transplantation; P = 0.04). Resections with microscopically negative margins were associated with improved survival (58.7 vs 11.3 mo for positive margins; P < 0.001). Chemotherapy and radiation therapy were used in a minority of patients (32.9% and 4.3% respectively) with no improvement in outcomes. CONCLUSIONS: Both hepatic resection and liver transplantation can be associated with long term survival for selected primary liver sarcomas such as epitheliod hemangioendotheliomas. Histology type and the ability to resect the tumor with negative margins correlate with outcomes and the decision to operate should be carefully weighed for subtypes with particularly dismal prognosis such as angiosarcomas.

Robotic total pancreatectomy with splenectomy: technique and outcomes.

BACKGROUND: Robotic total pancreatectomy (TP) represents a minimally invasive approach to a major intra-abdominal operation. Its utility, technique, and outcomes are evolving. METHODS: In this video, we describe a systematic approach to a robotic total pancreatectomy performed for multifocal intraductal papillary mucinous neoplasm (IPMN). Additionally, we reviewed the National Cancer Database (NCDB) to examine the outcomes of robotic TP compared to laparoscopic and open TP between 2010 and 2014. RESULTS: The patient is a 61-year-old female who was diagnosed with multifocal IPMN. A total of 6 robotic ports were placed and the da Vinci Xi robotic system was used with the patient supine. The approach entailed as follows: (1) Diagnostic laparoscopy; (2) Entry into the lesser sac; (3) Division of the short gastric vessels; (4) Exposure and dissection of the inferior pancreas border; (5) Dissection and transection of the splenic artery; (6) Mobilization of the pancreas tail/spleen; (7) Exposure of the splenic vein-superior mesenteric vein confluence; (8) Kocher maneuver; (9) Release of the ligament of Treitz and transection of the proximal jejunum; (10) Transection of the distal stomach; (11) Portal lymphadenectomy; (12) Dissection and transection of the gastroduodenal artery; (13) Superior mesenteric vein exposure/dissection of the uncinate process; (14) Hepaticojejunostomy; (15) Cholecystectomy; and (16) Gastrojejunostomy. NCDB database review of 73 patients who underwent robotic TP revealed similar rates of margin negative resections and retrieved lymph nodes between robotic, laparoscopic, and open TP, whereas robotic and laparoscopic TP were associated with shorter in-hospital stay and reduced mortality at 30 and 90 days compared to open TP. Overall median survival of pancreatic adenocarcinoma patients who underwent TP was similar between robotic, laparoscopic, and open approaches. CONCLUSION: Robotic total pancreatectomy with splenectomy offers a minimally invasive approach to a major abdominal operation and is feasible in a stepwise, reproducible technique. It is associated with improved postoperative outcomes and equivalent oncologic outcomes compared to open TP.

Frailty Correlates with Postoperative Mortality and Major Morbidity After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Frailty is increasingly being recognized as a powerful predictor of postoperative outcomes for cancer patients. This study examined the role of the modified frailty index (MFI) in predicting outcomes for patients undergoing cytoreduction (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Data from National Surgical Quality Improvement Program (NSQIP) patients who underwent CRS/HIPEC between 2005 and 2014 were reviewed. The MFI, validated for use in NSQIP, was used to determine correlation between frailty and postoperative outcomes. RESULTS: The analysis included 1171 patients. The patients were divided into three groups: non-frail (MFI 0), mildly frail (MFI 1 or 2), or severely frail (MFI ≥ 3). More than 90% of patients had an MFI of 0 or 1. The MFI was 0 for 716 patients (61.1%), 1 for 373 patients (31.9%), 2 for 76 patients (6.5%), 3 for 5 patients (0.4%), and 4 for 1 patient (0.1%). Overall, grade 4 Clavien morbidity was observed in 99 patients (8.5%) and mortality in 26 patients (2.2%). For non-frail, mildly frail, and severely frail patients, worsening frailty correlated respectively with increases in grade 4 Clavien morbidity (6.7% vs. 10.9% vs. 33.3%; p = 0.004) and mortality (1.3% vs. 3.3% vs. 33.3%; p < 0.001). In the multivariate analysis, which included age of 70 years or older and albumin level of 3 or lower, frailty was the only factor that correlated with postoperative mortality: non-frail:reference, mildly frail [odds ratio (OR) 2.76, 95% confidence interval (CI) 1.14-6.73; p = 0.025], severely frail (OR 29.1, 95% CI 4-210.87; p = 0.01), age of 70 years or older (OR 1.16, 95% CI 0.34-3.93; p = 0.81), and albumin level of 3 or lower (OR 2.42, 95% CI 0.84-6.98; p = 0.1). CONCLUSIONS: Frailty is a strong predictor of major grade 4 morbidity and mortality after CRS/HIPEC. Severe frailty should be a relative contraindication to CRS/HIPEC. Frailty correlates should be a selection factor in the evaluation of all candidates for CRS/HIPEC.

Robotic Total Pelvic Exenteration: Video-Illustrated Technique.

BACKGROUND: Robotic-assisted total pelvic exenteration (TPE) can offer a minimally invasive approach to a major multi-organ operation. METHODS: In this video, we summarize a stepwise approach to robotic TPE in a 70 year-old female Jehovah's witness with a history of cervical cancer post-chemoradiation and radical hysterectomy who experienced local recurrence at the vaginal cuff involving the rectum and bladder. RESULTS: The patient was placed in the lithotomy position. A total of six robotic ports were used and the da Vinci Si robotic system was docked between the legs. We proceeded as follows: (1) the abdomen and pelvis were thoroughly explored for evidence of metastatic disease; (2) the pelvic sidewalls were mobilized and bilateral ureters identified; (3) the mesorectal plane was dissected to the level of the levators; (4) the lateral and anterior pelvic structures were completely mobilized, and parametrial tissues were mobilized to the pelvic wall; (5) the bladder was separated from the pubis symphysis, the space of Retzius entered, and the bladder and proximal urethra freed; (6) a perineal incision was made around the vagina, perineal body, and anus, which were excised; (7) an Alloderm mesh secured the pelvic floor, and an omental J flap was mobilized; and (8) a 6 cm incision was utilized for creation of an ileal conduit and a permanent-end colostomy. Final pathology was consistent with recurrent cervical squamous cell carcinoma invading into the vaginal, bladder, and rectal walls. Surgical margins and seven lymph nodes were negative for carcinoma. CONCLUSION: Robotic-assisted TPE is technically feasible in a Jehovah's witness under a multidisciplinary surgical team, even in the setting of prior radical hysterectomy and irradiated tissue.

Interval between cytoreductions as a marker of tumor biology in selecting patients for repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: Repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for recurrence of peritoneal surface malignancies is safe and effective. Patient selection and factors associated with a favorable outcome are still evolving. METHODS: A prospectively maintained institutional database consisting of 1314 CRS/HIPEC procedures performed between February 1993 and December 2015 was reviewed. Clinicopathologic data from 103 patients and 112 (8.5%) repeat CRS/HIPEC procedures were retrospectively analyzed. RESULTS: Primary tumors were appendiceal for 60 patients (58.3%), mesothelioma for 14 (13.6%), colorectal for 9 (8.7%), ovarian for 8 (7.8%). R0/R1 resection was achieved in 46 (46.5%) patients. The time interval between the initial and the repeat CRS/HIPEC was <1 year for 21 (20.4%), 1-2 years for 40 (38.8%), and >2 years for 42 patients (40.8%). Overall median survival was 4.3 years and correlated with the time interval (1.3 years for <1 years, 3.7 years for 1-2 years, and 7 years for >2 years; P < 0.001). In multivariate analysis, the R status (P = 0.005) and a time interval of more than 2 years (P = 0.0002) were strongly associated with survival with each additional month between the surgeries conferring a 2.6% reduction in the risk of death. CONCLUSIONS: The current series validates time interval between cytoreductions as a major surrogate of tumor biology in selection of patients with recurrent peritoneal surface malignancies for repeat CRS/HIPEC. Complete repeat cytoreduction more than 2 years from the initial surgery is associated with a favorable outcome.

Minimally invasive distal pancreatectomy: greatest benefit for the frail.

OBJECTIVE: The benefits of minimally invasive distal pancreatectomy (MIDP) over open surgery continue to be investigated. Frailty is a known predictor of postoperative outcome. We hypothesized that the benefit of minimally invasive distal pancreatectomy is the greatest for the frailest of patients. METHODS: Data from the pancreas-targeted National Surgical Quality Improvement Program (NSQIP) database for 2014 were reviewed. A modified frailty index (mFI) with 11 preoperative variables previously validated for use in NSQIP was used to determine the correlation between frailty and postoperative outcomes, including Clavien grade IV complications. Patients were classified into non-frail (mFI = 0) or frail (mIF > 0), in which they were subclassified into mildly frail (mFI 1 or 2) or severely frail (mFI = 3). RESULTS: A total of 1,038 distal pancreatectomies (DP) were included in the analysis, of which 387 were minimally invasive (MIDP: laparoscopic: 285, robotic: 102), 558 open DP (ODP), and 93 MIDP converted to open (MIDPcODP: laparoscopic: 80, robotic: 13). More than 90% of patients had an mFI of 0 or 1 (mFI 0 = 473 (45.6%), 1 = 466 (44.9%), 2 = 94 (9.1%), and 3 = 5 (0.5%), respectively). Overall, 4.6% of patients experienced Clavien grade IV complications and 1.1% a mortality. Non-frail patients experienced a similar rate of grade IV Clavien complications with MIDP vs. ODP vs. MIDPcOP (2.3 vs. 2.3 vs. 4.9%; p = 0.6), whereas frail patients (mFI > 0) had a lower rate of complications with MIDP (2.4 vs. 8.3 vs. 11.5; p = 0.007). Worsening frailty correlated with an increase in complications (non-frail: 2.5%; mildly frail: 6.3%; severely frail: 20%; p = 0.005). CONCLUSION: MIDP is associated with a lower risk of Clavien grade IV complications compared to ODP for frail patients, especially for benign disease. Thus, minimally invasive approach may mitigate risk in frail patients.

Unresectable intrahepatic cholangiocarcinoma: Systemic plus hepatic arterial infusion chemotherapy is associated with longer survival in comparison with systemic chemotherapy alone.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is associated with poor survival. This study compared the outcomes of patients with unresectable ICC treated with hepatic arterial infusion (HAI) plus systemic chemotherapy (SYS) with the outcomes of patients treated with SYS alone. METHODS: Consecutive patients with ICC were retrospectively reviewed. Clinicopathologic data were reviewed. Survival rates were compared by Kaplan-Meier analysis and log-rank testing. RESULTS: Between January 2000 and August 2012, 525 patients with ICC were evaluated at Memorial Sloan Kettering Cancer Center, and 236 patients with unresectable tumors (locally advanced or metastatic) were analyzed. Disease was confined to the liver in 104 patients, who underwent treatment with combined HAI and SYS (n = 78 or 75%) or SYS alone (n = 26 or 25%). The response rate in the combined group was better than the rate in the group receiving SYS alone, although this did not reach statistical significance (59% vs 39%, P = .11). Overall survival for the combined group was longer than overall survival for the patients who received SYS alone (30.8 vs 18.4 months, P < .001), and this difference was maintained when patients with portal lymph node disease were included in the survival analysis (29.6 months with HAI and SYS [n = 93] vs 15.9 months with SYS [n = 74], P < .001). Eight patients who initially presented with unresectable tumors responded enough to undergo complete resection and had a median overall survival of 37 months (range, 10.4-92.3 months). CONCLUSIONS: In patients with unresectable ICC confined to the liver or with limited regional nodal disease, a combination of SYS and HAI chemotherapy is associated with greater survival than SYS alone. Cancer 2016;122:758-765. © 2015 American Cancer Society.

The Ability to Diagnose Intrahepatic Cholangiocarcinoma Definitively Using Novel Branched DNA-Enhanced Albumin RNA In Situ Hybridization Technology.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) often is a diagnosis determined by exclusion. Distinguishing ICC from other metastatic adenocarcinomas based on histopathologic or immunohistochemical analysis often is difficult and requires an extensive workup. This study aimed to determine whether albumin, whose expression is restricted to the liver, has potential as a biomarker for ICC using a novel and highly sensitive RNA in situ hybridization (ISH) platform. METHODS: Modified branched DNA probes were developed for albumin RNA ISH. The study evaluated 467 patient samples of primary and metastatic lesions. RESULTS: Of the 467 samples evaluated, 83 were ICCs, 42 were hepatocellular carcinomas (HCCs), and 332 were nonhepatic carcinomas including tumors arising from the perihilar region and bile duct, pancreas, stomach, esophagus, colon, breast, ovary, endometrium, kidney, and urinary bladder. Albumin RNA ISH was highly sensitive for cancers of liver origin, staining positive in 82 (99 %) of 83 ICCs and in 42 HCCs (100 %). Perihilar and distal bile duct carcinomas as well as carcinomas arising at other sites tested negative for albumin. Notably, 6 (22 %) of 27 intrahepatic tumors previously diagnosed as carcinomas of undetermined origin tested positive for albumin. CONCLUSIONS: Albumin RNA ISH is a sensitive and highly specific diagnostic tool for distinguishing ICC from metastatic adenocarcinoma to the liver or carcinoma of unknown origin. Albumin RNA ISH could replace the extensive diagnostic workup, leading to timely confirmation of the ICC diagnosis. Additionally, the assay could serve as a guide to distinguish ICC from perihilar adenocarcinoma.

Observation after a positive sentinel lymph node biopsy in patients with melanoma.

BACKGROUND: The benefit of completion lymph node dissection (CLND) in melanoma patients with a positive sentinel lymph node (SLN) remains unknown. METHODS: We identified patients with a positive SLN from 1994 to 2012. Patient and tumor characteristics, reasons for not undergoing CLND, patterns of recurrence, and melanoma-specific survival data were analyzed. RESULTS: Of 4,310 patients undergoing SLN biopsy (SLNB), 495 (11 %) had a positive SLN-167 (34 %) patients underwent nodal observation and 328 (66 %) had immediate CLND. Patients in the no-CLND group were older (66 vs. 56 years; p < 0.001) and more likely to have lower extremity lesions (57 vs. 42 %; p = 0.006). There were no differences in tumor thickness, Clark level of invasion, ulceration, or SLN tumor burden. Median follow-up was 23 and 80 months for the no-CLND and CLND groups, respectively, and median time to recurrence was similar at 9 and 12 months, respectively (p = 0.48). There was no difference in local and in transit recurrence rates between groups (16 %, no CLND, and 18 %, CLND; p = 0.48). Nodal disease as a site of first recurrence occurred in 15 % of patients in the no-CLND group and 6 % of CLND patients (p = 0.002). In contrast, systemic recurrences occurred in 8 % of no-CLND patients compared with 27 % of CLND patients (p < 0.001). While median recurrence-free survival was higher after CLND (34.5 vs. 20.9 months; p = 0.02), melanoma-specific survival was similar (not reached, no CLND vs. 110 months, CLND; p = 0.09). CONCLUSIONS: Immediate CLND after a positive SLNB is associated with fewer initial nodal basin recurrences but similar melanoma-specific survival. These results support ongoing equipoise in the Multicenter Selective Lymphadenectomy Trial II (MSLT-II).

Regional chemotherapy for unresectable intrahepatic cholangiocarcinoma: a potential role for dynamic magnetic resonance imaging as an imaging biomarker and a survival update from two prospective clinical trials.

BACKGROUND: For patients with unresectable intrahepatic cholangiocarcinoma (ICC), treatment options are limited and survival is poor. This study summarizes the long-term outcome of two previously reported clinical trials using hepatic arterial infusion (HAI) with floxuridine and dexamethasone (with or without bevacizumab) in advanced ICC. METHODS: Prospectively collected clinicopathologic and survival data were retrospectively reviewed. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST). Pre-HAI dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images were reviewed, and tumor perfusion data correlated with outcome. RESULTS: Forty-four patients were analyzed (floxuridine, 26; floxuridine/bevacizumab, 18). At a median follow-up of 29.3 months, 41 patients had died of disease. Partial response by RECIST was observed in 48 %, and 50 % had stable disease. Three patients underwent resection after response, and 82 % received additional HAI after removal from the trials. Median survival was similar in both trials (floxuridine 29.3 months vs. floxuridine/bevacizumab 28.5 months; p = 0.96). Ten (23 %) patients survived ≥3 years, including 5 (11 %) who survived ≥5 years. Tumor perfusion measured on pre-treatment DCE-MRI [area under the gadolinium concentration curve at 90 and 180 s (AUC90 and AUC180, respectively)] was significantly higher in ≥3-year survivors and was the only factor that distinguished this group from <3-year survivors (mean AUC90 22.6 vs. 15.9 mM s, p = 0.025, and mean AUC180 48.9 vs. 32.3 mM s, p = 0.003, respectively). Median hepatic progression-free survival was longer in ≥3-year survivors (12.9 vs. 9.3 months, respectively; p = 0.008). CONCLUSIONS: HAI chemotherapy can result in prolonged survival in unresectable ICC. Pre-HAI DCE-MRI may predict treatment outcome.

Predicting recurrence patterns after resection of hepatocellular cancer.

BACKGROUND: The reliable prediction of hepatocellular carcinoma (HCC) recurrence patterns potentially allows for the prioritization of patients for liver resection (LR) or transplantation. OBJECTIVES: The aim of this study was to analyse clinicopathological factors and preoperative Milan criteria (MC) status in predicting patterns of HCC recurrence. METHODS: During 1992-2012, 320 patients undergoing LR for HCC were categorized preoperatively as being within or beyond the MC, as were recurrences. RESULTS: After a median follow-up of 47 months, 183 patients developed recurrence, giving a 5-year cumulative incidence of recurrence of 62.5%. Patients with preoperative disease within the MC had better survival outcomes than those with preoperative disease beyond the MC (median survival: 102 months versus 45 months; P < 0.001). Overall, 31% of patients had preoperative disease within the MC and 69% had preoperative disease beyond the MC. Estimated rates of recurrence-free survival at 5 years were 61.8% for all patients and 53.8% for patients with initial beyond-MC status. Independent factors for recurrence beyond-MC status included preoperative disease beyond the MC, the presence of microsatellite or multiple tumours and lymphovascular invasion (all: P < 0.001). A clinical risk score was used to predict survival and the likelihood of recurrence beyond the MC; patients with scores of 0, 1, 2 and 3 had 5- year incidence of recurring beyond-MC of 9.0%, 29.5%, 48.8% and 75.4%, respectively (P < 0.0001). CONCLUSIONS: Regardless of initial MC status, at 5 years the majority of patients remained disease-free or experienced recurrence within the MC after LR, and thus were potentially eligible for salvage transplantation (ST). Incorporating clinicopathological parameters into the MC allows for better risk stratification, which improves the selection of patients for ST and identifies patients in need of closer surveillance.

Pancreatic ductal adenocarcinoma: is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a "true" R0 resection?

OBJECTIVE: Patients who undergo an R0 resection of their pancreatic ductal adenocarcinoma (PDAC) have an improved survival compared with patients who undergo an R1 resection. It is unclear whether an R1 resection confers a survival benefit over locally advanced (LA) unresectable tumors. Our aim was to compare the survival of patients undergoing an R1 resection with those having LA tumors and to explore the prognostic significance of a 1-mm surgical margin. METHODS: Clinicopathologic data from a pancreatic cancer database between January 1993 and July 2008 were reviewed. Locally advanced tumors had no evidence of metastatic disease at exploration. RESULTS: A total of 1705 patients were evaluated for PDAC in the Department of Surgery. Of the 1084 (64%) patients who were surgically explored, 530 (49%) were considered unresectable (286 locally unresectable, 244 with distant metastasis). One hundred fifty-seven (28%) of the resected PDACs had an R1 resection. Patients undergoing an R1 resection had a slightly longer survival compared with those who had locally advanced unresectable cancers (14 vs 11 months; P < 0.001). Patients with R0 resections had a favorable survival compared with those with R1 resections (23 vs 14 months; P < 0.001), but survival after resections with 1-mm margin or less (R0-close) were similar to R1 resections: both groups had a significantly shorter median survival than patients with a margin of greater than 1 mm (R0-wide) (16 vs 14 vs 35 months, respectively; P < 0.001). CONCLUSIONS: Patients undergoing an R1 resection still have an improved survival compared with patients with locally advanced unresectable pancreatic adenocarcinoma. R0 resections have an improved survival compared with R1 resections, but this survival benefit is lost when the tumor is within 1 mm of the resection margin.

Incidentally discovered pancreatic intraepithelial neoplasia: what is its clinical significance?

PURPOSE: Pancreatic intraepithelial neoplasia (PanIN) is a presumed precursor of pancreatic ductal adenocarcinoma (PDAC). We assessed the relationship between incidental PanIN after resection of non-adenocarcinoma lesions and the development of metachronous PDAC in the remnant. METHODS: We retrospectively reviewed the clinicopathologic data of patients who underwent pancreatectomy for non-PDAC from January 2000 to January 2010. Intraductal papillary mucinous lesions were excluded. All available postoperative imaging and clinical follow-up data were reviewed; the risk of developing PDAC was assessed in patients with a minimum follow-up time of 6 months and with imaging studies available for review. RESULTS: A total of 584 patients were analyzed. Median age was 59 years (range 10-85 years), and 338 (58 %) were female. The most common lesions for which resection was performed were serous cystic neoplasms (17 %), pancreatic neuroendocrine tumors (38 %), metastatic tumors (9 %), and mucinous cystic neoplasms (7 %). PanIN was identified in 153 (26 %) patients. The majority of these patients had PanIN-1 or -2 (50 and 41 %, respectively), whereas 13 (8 %) had PanIN-3. Of the 506 (87 %) patients with adequate follow-up (median 3.7 years, range 0.5-12.6 years), 1 patient (0.2 %) with PanIN identified at the time of initial resection developed cancer in the remnant. This occurred 4.4 years after a distal pancreatectomy in the setting of PanIN-1B. No patient with PanIN-3 developed cancer during follow-up. CONCLUSIONS: PanIN was identified in 26 % of patients who underwent resection for histopathology other than PDAC. The presence of PanIN of any grade did not result in an appreciable cancer risk in the pancreatic remnant after short-term follow-up.