Long-term overall survival in patients undergoing liver resection for metastatic anal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: There is limited research on management of metastatic anal canal squamous cell carcinoma (SCC) to the liver. This study aimed to describe outcomes for patients undergoing liver resection of anal SCC metastases. METHODS: A multicenter, retrospective cohort study was conducted by three tertiary-referral centers. Patients undergoing liver surgery between 2008 and 2022 were included. Cox regression analysis was performed to evaluate predictors of recurrence and survival and Kaplan-Meier analysis was performed for 1-, 3-, and 5-year survival. RESULTS: Twenty-one patients underwent liver resection and/or ablation. None were HIV positive and 24% had known HPV infection. 20/21(95%) patients had undergone Nigro protocol for management of the primary tumor with 12/21 (57%) patients experiencing complete response. 4/21 (19%) patients had synchronous liver metastases at time of diagnosis. Median tumor size was 5.0 cm and median tumor number was one. At analysis, 52% remained alive. Median overall survival was 32.2 months. 5-year overall survival was 50%. Median recurrence-free survival was 7.7 months and 5-year recurrence-free survival was 30%. Need for salvage abdominoperineal resection was negatively associated with recurrence-free survival. The most common site of recurrence was the liver. CONCLUSIONS: Liver resection for metastatic anal SCC can be beneficial for appropriately selected patients.

Model to predict major complications following liver resection for HCC in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. AIMS: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. MATERIALS AND METHODS: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. RESULTS: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). CONCLUSIONS: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Long-term oncological outcomes for HALS/Hybrid vs pure laparoscopic approach in colorectal liver metastases: a propensity score matched analysis.

BACKGROUND: Studies comparing hand-assisted laparoscopic (HALS)/Hybrid and pure laparoscopic (PLS) resection for colorectal cancer liver metastasis have focused on short-term results, while long-term oncological outcomes remain understudied. METHODS: We established a multi-institutional retrospective cohort study from four centers with experience in minimally invasive surgery between 2004 and 2020. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Other endpoints analyzed were intraoperative and postoperative outcomes. Propensity score matching (PSM) was used to minimize baseline differences. RESULTS: A total of 219 HALS/Hybrid (57.8%) and 160 PLS (42.2%) patients were included. After PSM, 155 patients remained in each group. Operative time (182 vs. 248 min, p = 0.012), use of intraoperative ablation (12.3 vs. 4.5%, p = 0.024), positive resection margin (4.5 vs 13.2%, p = 0.012), and pringle time (21 vs. 37 min, p = 0.001) were higher in PLS group. DFS at 1, 3, 5, and 7 years in HALS/Hybrid and PLS groups were 65.4%, 39.3%, 37.5%, and 36.3% vs. 64.9%, 38.0%, 33.1%, and 33.1%, respectively (p = 0.84). OS at 1, 3, 5, and 7 years in HALS/Hybrid and PLS groups were 94.5%, 71.4%, 54.3%, and 46.0% vs. 96.0%, 68.5%, 51.2%, and 41.2%, respectively (p = 0.73). CONCLUSION: Our study suggests no differences in long-term oncologic outcomes between the two techniques. We discovered that longer total operative, pringle time, higher rates of intraoperative ablation, and positive resection margins were associated with PLS. These differences in favor of HALS/Hybrid could be due to a shorter learning curve and a greater ability to control hemorrhage.

Textbook Outcomes After Open Live Donor Right Hepatectomy and Open Right Hepatic Lobectomy for Cancer in 686 patients: Redefining the Benchmark.

OBJECTIVE: To compare textbook outcomes (TO) of open live donor right hepatectomy (RH) versus open right hepatic lobectomy for cancer in a single Western center and to identify clinical factors associated with failure to achieve a TO. BACKGROUND: TO, a composite quality measure that captures multiple aspects of perioperative care, has not been thoroughly studied in open RH. We hypothesized that TO rates after RH for live donor transplant could represent the "best-achievable" results of this operation and could serve as the benchmark for RH performed for an oncologic indication. METHODS: A prospective database was reviewed to compare TO rates after RH for live donor purposes versus RH for cancer at a single center from 2010 to 2020. A TO was defined as achieving 7 metrics: no perioperative transfusion, no major postoperative complications, no significant bile leak, no unplanned transfer to the ICU, no 30-day mortality, no 30-day readmission, and no R1 margins for cancer cases. RESULTS: Among 686 RH patients (371 live donor and 315 cancer cases), a TO was achieved in 92.2% of RH donors and 53.7% of RH cancer cases. Live donor patients tended to be younger, healthier, and thinner. Among donors, increased intraoperative blood loss, and in cancer cases, male sex, tumor size, and increased intraoperative blood loss were associated with TO failure. CONCLUSIONS: A TO can be achieved in over 90% of patients undergoing living donor RH and in approximately half of RH cancer cases. These metrics represent a new benchmark for "real-world" TO after open RH.

Pancreaticoduodenectomy for benign and premalignant pancreatic and ampullary disease: is robotic surgery the better approach?

BACKGROUND: The robotic platform is increasingly being utilized in pancreatic surgery, yet its overall merits and putative advantages remain to be adjudicated. We hypothesize that the benefits of minimally invasive pancreatic surgery are maximized in pancreatic benign and premalignant disease, in the setting of friable pancreatic tissue and small pancreatic duct. METHODS: Retrospective analysis of our prospectively maintained pancreatic database of all consecutive patients who underwent pancreaticoduodenectomy (PD) for benign or premalignant conditions between 2010 and 2020. Peri-operative outcomes and long-term complications were compared between robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD). RESULTS: One hundred and eighty eight (n = 188) patients met our inclusion criteria, of which 68 were OPD and 120 RPD. Malignant histologies were excluded. There were only minor differences in baseline characteristics between the two groups. Post-operative merits of the RPD included lower clinically relevant post-operative pancreatic fistula 10 (8.3%) vs 24 (35.3%), p < 0.001, fewer surgical site infections; 9 (7.5%) vs 11 (16.2%), p = 0.024, shorter operative time, greater lymph node yield; 29 (IQR 21, 38) vs 21 (IQR 13, 34), p = 0.001, and lower 90 days mortality; 1 (0.8%) vs 4 (5.9%), p = 0.039. Rates of long-term complications were similar, exception made for a higher occurrence of small bowel obstruction (SBO) 2 (1.7%) vs 4 (5.9%), p = 0.031 and need for surgical intervention for SBO 0 (0.0%) vs 2 (2.9%), p = 0.019 in the OPD group. CONCLUSION: Our study suggests that RPD benefits include lower 90-day mortality, shorter LOS, and lower rates of selected complications compared to open pancreaticoduodenectomy.

Tumor Biology Impacts Survival in Surgically Managed Primary Hepatic Vascular Malignancies.

BACKGROUND: Hepatic angiosarcoma (AS) and hepatic epithelioid hemangioendothelioma (HEHE) are rare primary hepatic vascular malignancies (PHVM) that remain poorly understood. To guide management, we sought to identify factors and trends predicting survival after surgical intervention using a national database. MATERIALS AND METHODS: In a retrospective analysis of the National Cancer Database patients with a diagnosis of PHVM were identified. Clinicopathologic factors were extracted and compared. Overall survival (OS) was estimated and predictors of survival were identified. RESULTS: Three hundred ninty patients with AS and 216 with HEHE were identified. Only 16% of AS and 36% of HEHE patients underwent surgery. The median OS for patients who underwent surgical intervention was 97 months, with 5-year OS of 30% for AS versus 69% for HEHE patients (P< 0.001). Tumor biology strongly impacted OS, with AS histology (Hazard Ratio [HR] of 3.61 [1.55-8.42]), moderate/poor tumor differentiation (HR = 3.86 [1.03-14.46]) and tumor size (HR = 1.01 [1.00-1.01]) conferring worse prognosis. The presence of metastatic disease in the surgically managed cohort (HR = 5.22 [2.01-13.57]) and involved surgical margins (HR = 3.87 [1.59-9.42]), were independently associated with worse survival. CONCLUSIONS: In this national cohort of PHVM, tumor biology, in the form of angiosarcoma histology, tumor differentiation and tumor size, was strongly associated with worse survival after surgery. Additionally, residual tumor burden after resection, in the form of positive surgical margins or the presence of metastasis, was also negatively associated with survival. Long-term clinical outcomes remain poor for patients with the above high-risk features, emphasizing the need to develop effective forms of adjuvant systemic therapies for this group of malignancies.

Peritonitis from perforated sigmoid mass as the first manifestation of metastatic squamous cell lung cancer: a case report and review of literature.

Lung cancer (LC) is an aggressive malignancy with early metastatic spread and poor prognosis. Gastrointestinal metastases from primary LC are extremely rare with highly variable presentations. In this report, we review the case of a patient who presented with peritonitis secondary to perforated sigmoid mass as the first manifestation of metastatic squamous cell LC.

Neuroendocrine Tumors in Meckel's Diverticulum: Recommendation for Lymphadenectomy Regardless of Tumor Size Based on the NCDB Experience.

BACKGROUND: Meckel's diverticulum (MD) is an anomaly of the small intestine from which malignancy may arise. Among MD neoplasms, neuroendocrine tumors (NETs) are considered the most common. However, their metastatic potential and optimal surgical therapy remain ill-defined. METHODS: In a retrospective analysis of the National Cancer Database (2004-2015), patients with a diagnosis of MD malignancy were identified. Clinicopathologic factors were extracted and tumors arising in MD were compared. In the subgroup of patients with NET, the association between tumor factors and node involvement was investigated. RESULTS: Three hundred twenty primary MD malignancies were captured in the National Cancer Database, consisting of 280 (87.5%) NET. The median age at diagnosis was 64 years. Patients were predominantly male (207, 73.9%) and white (269, 96.1%). Most tumors were well-differentiated (118, 42.1%) and sub-centimeter (median size, 0.7 cm). Distant metastasis was present in a minority (16, 5.7%), and the median overall survival was 114 months in the entire cohort. The regional lymph node status was known in 87 NET patients, out of which 39 (44.8%) harbored node metastasis. Although the risk of node involvement increased with larger tumor size, it remained significant even among sub-centimeter (9 out of 34, 26.5%) and well-differentiated (18 out of 44, 41%) tumors. Regional node involvement was associated with the presence of distant metastasis (p < 0.001). CONCLUSION: Lymph node involvement was common irrespective of the size and grade of NET arising from Meckel's diverticulum. Therefore, regional lymphadenectomy should be considered in the curative-intent surgical management of these neoplasms regardless of tumor size and grade.

Incidence and comparative outcomes of periampullary cancer: A population-based analysis demonstrating improved outcomes and increased use of adjuvant therapy from 2004 to 2012.

BACKGROUND AND OBJECTIVES: Periampullary adenocarcinoma (PAC) is stratified anatomically: ampullary adenocarcinoma (AA), distal cholangiocarcinoma (DCC), duodenal adenocarcinoma (DA), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine differences in incidence, prognosis, and treatment in stage-matched PAC patients in a longitudinal study. METHODS: PAC patients were identified in The National Cancer Database from 2004 to 2012. Clinicopathological variables were compared between subtypes. Covariate-adjusted treatment use and OS were compared. RESULTS: The 116 705 patients with PAC were identified: 1320 (9%) AA, 3732 (3%) DCC, 7142 (6%) DA, and 95 511 (82%) PDAC. DA, DCC, and PDAC were associated with worse survival compared with AA (hazard ratio [HR], 1.10; 95% CI, 1.1-1.1; HR, 1.50; 95% CI, 1.4-1.6, and HR, 1.90; 95% CI, 1.8-1.9). Among resected patients, DA was associated with improved survival compared with AA (HR, 0.70; 95% CI, 0.67-0.75); DCC and PDAC were associated with worse survival (HR, 1.41; 95% CI, 1.31-1.53 and HR, 2.041; 95% CI, 1.07-2.12). Resected AA, PDAC, and DA, but not DCC, demonstrated significantly improved survival over the studied period. While all patients had increased adjuvant therapy (AT) receipt over time (P < 0.001), only patients with PDAC had increased neoadjuvant therapy (NAT) receipt ( P < 0.001). CONCLUSION: Resected PDAC, AA, and DA were associated with clinically significant improved survival over time, mirroring a concurrent associated increased receipt of AT.

Can echogenic appearance of neuroendocrine liver metastases on intraoperative ultrasonography predict tumor biology and prognosis?

BACKGROUND: Determining the biologic behavior of neuroendocrine liver metastases (NELM) is important when managing patients with this disease. We sought to define the intraoperative ultrasound (IOUS) characteristics of NELM and correlate with tumor biology and prognosis. METHODS: Prospective data on patients who underwent IOUS and surgical intervention for NELM were collected, with images digitally recorded, blindly reviewed, and scored for echogenicity. Association between sonographic appearance, clinicopathologic factors and long-term outcomes was analyzed. RESULTS: A total of 216 lesions from 65 patients were analyzed, with IOUS identifying at least one additional metastasis than preoperative imaging in 41 patients (63.1%) with subsequent change of surgical strategy in 14 patients (21.5%). Most NELM appeared hypoechoic (49.1%) on IOUS, while 38.9% demonstrated hyperechogenicity and 12% isoechogenicity. Hypoechoic lesions were associated with poorly-differentiated tumor (p = 0.005) and smaller tumor size (p = 0.004). Patients with hypoechoic metastases demonstrated significantly shorter median disease-free survival compared with isoechoic or hyperechoic lesions (9 vs 20 vs 18 months, p = 0.049). DISCUSSION: In addition to improved tumor detection of NELM, IOUS was found to be associated with features of tumor biology, specifically tumor grade and risk-of-recurrence. Echogenicity should be considered a potential prognostic factor in the management of patients with neuroendocrine tumors.

Hepatoid Adenocarcinoma of Unknown Primary Masquerading as a Pancreatic Tumor.

Hepatoid adenocarcinoma is a rare type of extrahepatic cancer characterized by hepatocellular carcinoma-like histology. We present a case of a large solitary mass in the peripancreatic region found to be an isolated lymph node metastasis from an unknown primary hepatoid adenocarcinoma masquerading as an acinar carcinoma of the pancreas.

Duodenal and Ampullary Carcinoid Tumors: Size Predicts Necessity for Lymphadenectomy.

BACKGROUND: Unlike other neuroendocrine tumors of the gastrointestinal tract, management of duodenal and periampullary carcinoids remains controversial. We aimed to determine the metastatic potential and optimal choice of therapy for these neoplasms. METHODS: A retrospective review of all patients treated at the Johns Hopkins Hospital between 1996 and 2012 was conducted. Clinicopathologic factors associated with lymph nodal involvement and clinical outcomes were evaluated. RESULTS: A total of 101 patients were identified. Eighty (79.2%) tumors arose from the duodenum and 21 (20.8%) from the periampullary area. Thirty-five (34.7%) patients underwent pancreaticoduodenectomy (PD), 12 (11.9%) local resection, 38 (37.6%) endoscopic excision, and 16 (15.8%) patients harbored incidental tumors identified in the specimen after PD for another indication. Lymph node (LN) pathologic evaluation was done in 56 patients, among which 27 (48%) had positive LN. Specifically, LN positivity (LN+) for tumors <1 cm in size was 4.5% (1/22), for tumors 1-2 cm 72% (13/18), and for tumors >2 cm 81% (13/16). Tumor size was the only factor associated with LN+ (p = 0.029). CONCLUSION: Lymph nodal involvement is common for duodenal and periampullary carcinoid tumors, particularly among those >1 cm in size; therefore, resection with lymphadenectomyfor these larger tumors is recommended.

The tail of neuroendocrine tumors from lung to pancreas: Two rare case reports.

INTRODUCTION: Primary pancreatic neuroendocrine tumors are a well-established disease entity, however, neuroendocrine metastases to the pancreas from other sites have been scarcely documented. Specifically, pancreatic metastases from a pulmonary carcinoid tumor have only previously been described in a single case report. PRESENTATION OF CASE: We sought to outline our institutional experience of two patients with pulmonary neuroendocrine tumors that developed metastases to the pancreas, confirmed by gross pathology and immunohistochemistry. In both cases, the pancreatic metastases were surgically resected and their pulmonary origin were discovered post-operatively. DISCUSSION: Our findings should raise awareness to the possibility of metastatic disease when evaluating a pancreatic mass in a patient with a clinical history of pulmonary carcinoid tumor. Expert opinion on immunohistochemically differentiating a primary pancreatic neuroendocrine malignancy from a metastasis should be employed in these cases. CONCLUSION: Establishing this diagnosis pre-operatively could affect the decision to proceed with surgical resection, given the morbidity of pancreatectomy and the unknown long-term clinical outcome of patients with pulmonary carcinoid tumors metastatic to the pancreas.

Alternative lengthening of telomeres predicts site of origin in neuroendocrine tumor liver metastases.

BACKGROUND: The determination of the primary tumor origin in patients with neuroendocrine tumor liver metastases (NELM) can pose a considerable management challenge. Recent studies have shown that the alternative lengthening of telomeres (ALT) is prevalent in some human tumors, including pancreatic neuroendocrine tumors (PanNET), and can be useful in predicting tumor biology. In this study, we aimed to evaluate the use of ALT as a biomarker in patients with NELM, in particular to predict the site of origin of metastases. METHODS: Tissue microarrays (TMAs) were constructed using tumor tissue from NELM patients undergoing liver resection between 1998 and 2010. These included 43 PanNET and 47 gastrointestinal carcinoid tumors. The TMAs were tested for ALT using telomere-specific fluorescent in situ hybridization. The association between ALT positivity and clinicopathologic features and long-term outcomes was investigated. RESULTS: Alternative lengthening of telomeres was positive (ALT+) in 26 (29%) of the 90 tumors included in the TMAs. Pancreatic neuroendocrine tumors were ALT+ in 56% of patients, compared with only 4% ALT+ among gastrointestinal carcinoid tumors (p < 0.001). The specificity of ALT for detecting pancreatic origin was 96% and the positive predictive value was 92%, and sensitivity was 56% and the negative predictive value was 70%. Additionally, ALT was associated with the pattern of metastatic disease: ALT+ NELM were more likely to have oligometastases (p = 0.001) and less likely to be bilateral in distribution (p = 0.05) than were ALT tumors. In addition, ALT+ was associated with improved prognosis in the PanNET patient population. CONCLUSIONS: Alternative lengthening of telomeres was found to be a useful biomarker in patients with NELM. This marker can be helpful in guiding therapy by identifying the site of origin in patients in whom the primary site is unknown.