More effective therapy is needed for intrahepatic cholangiocarcinoma (ICC). The encouraging clinical results obtained with checkpoint molecule-specific monoclonal antibodies (mAb) have prompted us to ...investigate whether this type of immunotherapy may be applicable to ICC. The aims of this study were to determine whether (i) patients mount a T-cell immune response to their ICC, (ii) checkpoint molecules are expressed on both T cells and tumor cells, and (iii) tumor cells are susceptible to recognition by cognate T cells.
Twenty-seven ICC tumors were analyzed for (i) lymphocyte infiltrate, (ii) HLA class I and HLA class II expression, and (iii) PD-1 and PD-L1 expression by T cells and ICC cells, respectively. The results of this analysis were correlated with the clinicopathologic characteristics of the patients investigated.
Lymphocyte infiltrates were identified in all tumors. PD-L1 expression and HLA class I antigen expression by ICC cells was observed in 8 and 11, respectively, of the 27 tumors analyzed. HLA class I antigen expression correlated with CD8(+) T-cell infiltrate. Furthermore, positive HLA class I antigen expression in combination with negative/rare PD-L1 expression was associated with favorable clinical course of the disease.
ICC patients are likely to mount a T-cell immune response against their own tumors. Defects in HLA class I antigen expression in combination with PD-L1 expression by ICC cells provide them with an immune escape mechanism. This mechanism justifies the implementation of immunotherapy with checkpoint molecule-specific mAbs in patients bearing ICC tumors without defects in HLA class I antigen expression.
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.
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).
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.
Metastatic Tumors in the Pancreas in the Modern Era Konstantinidis, Ioannis T., MD; Dursun, Abdulmetin, MD; Zheng, Hui, PhD ...
Journal of the American College of Surgeons,
12/2010, Letnik:
211, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Background Tumors metastasizing to the pancreas are rare, and published series are limited by few patients treated for extended periods of time. Renal cell cancer (RCC) is the most common primary ...tumor metastasizing to the pancreas. Our aim was to describe the clinicopathologic characteristics and patient outcomes in a modern series of patients who underwent metastasectomy, with an emphasis on RCC. Study Design Retrospective review of all pancreatic resections between January 1993 and October 2009. Results We identified 40 patients with a median age of 62 years; 55% were female. Patients most commonly presented with abdominal pain (47.5%). Operations performed included 10 pancreaticoduodenectomies, 1 middle, 23 distal, 3 total pancreatectomies, and 3 enucleations. Primary cancers were RCC (n = 20), ovarian (n = 6), sarcoma (n = 3), colon (n = 3), melanoma (n = 2), and others (n = 6). Median survival for all patients after metastasectomy was 4.4 years. Median survival after metastasectomy for RCC was 8.7 years, and the 5-year actuarial survival was 61%. For RCCs, pancreas was the first site of an extrarenal recurrence in 85% and was synchronous with the primary in 5% of patients. There was no survival difference if the time interval to metastasis was shorter than the median (8.7 years), if tumor nodules were multiple or bigger than the median (3 cm), or if the pancreas was not the first site of metastases. Conclusions An aggressive approach to lesions metastatic to the pancreas is often warranted if the patient can be rendered free of disease. Although patients with RCC can experience long-term survival after metastasectomy, survival is less favorable for other primary tumors.
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.
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.
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).
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.
Evaluate the value of cytology relative to imaging features in risk assessment for malignancy as defined in the Sendai Guidelines.
The Sendai Guidelines list symptoms, cyst size >30 mm, dilated main ...pancreatic duct (MPD) >6 mm, mural nodule (MN) and "positive" cytology as high risk stigmata for malignancy warranting surgical triage.
We reviewed clinical, radiological and cytological data of 112 patients with histologically confirmed mucinous cysts of the pancreas evaluated in a single tertiary medical center. Cytology slides were blindly re-reviewed and epithelial cells grouped as either benign or high-grade atypia (HGA) ≥high-grade dysplasia. Histologically, neoplasms were grouped as benign (low-grade and moderate dysplasia) and malignant (in situ and invasive carcinoma). Performance characteristics of cytology relative to other risk factors were evaluated.
Dilated MPD, MN, and HGA were independent predictors of malignancy (p < 0.0001), but not symptoms (p = 0.29) or cyst size >30 mm (p = 0.51). HGA was the most sensitive predictor of malignancy in all cysts (72%) and in small (≤30 mm) branch-duct intraductal papillary mucinous neoplasm (BD IPMN; 67%), whereas also being specific (85 and 88%, respectively). MN and dilated MPD were highly specific (>90%), but insensitive (39%-44%). Cytology detected 30% more cancers in small cysts than dilated MPD or MN and half of the cancers without either of these high-risk imaging features.
Cytology adds value to the radiological assessment of predicting malignancy in mucinous cysts, particularly in small BD IPMN.
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.
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.
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