Background The first successful local resection of a periampullary tumor was performed by Halsted in 1898. Kausch performed the first regional resection in 1909, and the operation was popularized by ...Whipple in 1935. The operation was infrequently performed until the 1980s and 1990s. Study Design Two thousand consecutive pancreaticoduodenectomies performed by 1 surgeon (JLC) from the 1960s to the 2000s were retrospectively reviewed from a prospectively maintained database. The first 1,000 were performed over a period of 34 years, the second 1,000 over a period of 9 years. Results The most common indication throughout was adenocarcinoma of the head of the pancreas (PDAC, 46%). Benign intraductal papillary mutinous neoplasm (IPMN) increased from 1% (1990s) to 8% (2000s) (p = 0.002). Age range was 13 years to 103 years. Mean age increased from 59 years (1980s) to 66 (2000s) (p = 0.001), as did those older than 80 (3% to 12%, p = 0.002). Thirty-day mortality was 1.4%; hospital mortality was 1.7%. Delayed gastric emptying (23%), pancreatic fistulas (16%), and wound infections (11%), were the most frequent morbidity, and have not decreased. The median number of blood transfusions decreased from 2 (1980s) to 0 (1990s and 2000s) (p = 0.004). Length of stay decreased from 21 days (1980s) to 13 (1990s) days to 10 days (2000s) (p = 0.002). Five-year survival for PDAC increased from 19% (1990s) to 24% (2000s) (p = 0.02), and 5-year survival for node-negative, margin-negative PDAC patients was 39%. Conclusions The volume of pancreatic pathology has attracted 22 basic and clinical scientists to Hopkins, which has $28.5 million of direct support and more than $30 million in endowments, to support research in pancreatic cancer. The volume of clinical material has also supported the training of many young surgeons, 15 of whom have become department chairmen, and more than 20 have become division chiefs.
OBJECTIVE:To describe accurately the pattern, timing, and predictors of disease recurrence after a potentially curative resection for pancreatic ductal adenocarcinoma (PDAC).
SUMMARY BACKGROUND ...DATA:After surgery for PDAC, most patients will develop disease recurrence. Understanding the patterns and timing of disease failure can help guide improvements in therapy.
METHODS:Patients who underwent pancreatectomy for PDAC at the Johns Hopkins Hospital between 2000 and 2010 were included. Exclusion criteria were incomplete follow-up records, follow-up <24 months, and neoadjuvant therapy. The first recurrence site was recorded and recurrence-free survival (RFS) was estimated using Kaplan–Meier curves. Predictive factors for specific recurrence patterns were assessed by univariate and multivariate analyses using Cox-proportional hazard regression models.
RESULTS:From the identified cohort of 1103 patients, 692 patients had comprehensive and detailed follow-up data available. At a median follow-up of 25.3 months, 531 (76.7%) of the 692 had recurred after a median RFS of 11.7 months. Most patients recurred at isolated distant sites (n = 307, 57.8%), while isolated local recurrence was seen in 126 patients (23.7%). Liver-only recurrence (n = 134, 25.2%) tended to occur early (median 6.9 mo), while lung-only recurrence (n = 78, 14.7%) occurred later (median 18.6 mo). A positive lymph node ratio >0.2 was a strong predictor for all distant disease recurrence. Patients receiving adjuvant chemotherapy or chemoradiotherapy had fewer recurrences and a longer RFS of 18.0 and 17.2 months, respectively.
CONCLUSIONS:Specific recurrence locations have different predictive factors and possess distinct RFS curves, supporting the hypothesis that unique biological differences exist among tumors leading to distinct patterns of recurrence.
OBJECTIVE:The aim of the study was to identify the survival of patients with locally advanced pancreatic cancer (LAPC) and assess the effect of surgical resection after neoadjuvant therapy on patient ...outcomes.
BACKGROUND:An increasing number of LAPC patients who respond favorably to neoadjuvant therapy undergo surgical resection. The impact of surgery on patient survival is largely unknown.
MATERIALS AND METHODS:All LAPC patients who presented to the institutional pancreatic multidisciplinary clinic (PMDC) from January 2013 to September 2017 were included in the study. Demographics and clinical data on neoadjuvant treatment and surgical resection were documented. Primary tumor resection rates after neoadjuvant therapy and overall survival (OS) were the primary study endpoints.
RESULTS:A total of 415 LAPC patients were included in the study. Stratification of neoadjuvant therapy in FOLFIRINOX-based, gemcitabine-based, and combination of the two, and subsequent outcome comparison did not demonstrate significant differences in OS of 331 non-resected LAPC patients (P = 0.134). Eighty-four patients underwent resection of the primary tumor (20%), after a median duration of 5 months of neoadjuvant therapy. FOLFIRINOX-based therapy and stereotactic body radiation therapy correlated with increased probability of resection (P = 0.006). Resected patients had better performance status, smaller median tumor size (P = 0.029), and lower median CA19-9 values (P < 0.001) at PMDC. Patients who underwent surgical resection had significant higher median OS compared with those who did not (35.3 vs 16.3 mo, P < 0.001). The difference remained significant when non-resected patients were matched for time of neoadjuvant therapy (19.9 mo, P < 0.001).
CONCLUSIONS:Surgical resection of LAPC after neoadjuvant therapy is feasible in a highly selected cohort of patients (20%) and is associated with significantly longer median overall survival.
OBJECTIVE:The purpose of this study is to determine preoperative factors that are predictive of malignancy in patients undergoing pancreatic resection for intraductal papillary mucinous neoplasms ...(IPMN).
SUMMARY BACKGROUND DATA:IPMN of the pancreas may be precursor lesions to pancreatic cancer (PC) and represent a target for early diagnosis or prevention. While there has been much effort to define preoperative risk factors for malignant pathology, guidelines are ever-changing and controversy remains surrounding which patients would benefit most from resection.
METHODS:We performed a retrospective analysis of 901 consecutive patients obtained from two tertiary referral centers who underwent pancreatic resection for histologically proven IPMN between 2004 and 2017. Collected data included patient demographic characteristics, preoperative symptoms, radiological findings, and laboratory data.
RESULTS:Main pancreatic duct (MPD) dilatation was the only variable that was significantly associated with increased probability of malignancy (defined high-dysplasia or invasion) on both univariate and multivariate analysis. Even middle-range MPD dilatation from 5 mm to 9.9 mm (n = 286) was associated with increased odds of HG-IPMN (OR = 2.74; 95% CI = 1.80–4.16) and invasion (OR = 4.42; 95% CI = 2.55–7.66). MPD dilatation >10 mm (n = 150) had even greater odds of HG-IPMN (OR = 6.57; 95% CI = 3.94–10.98) and invasion (OR = 15.07; 95% CI = 8.21–27.65). A cutoff of 5 to 7 mm MPD diameter was determined to be the best predictor to discriminate between malignant and benign lesions.
CONCLUSIONS:In agreement with current IPMN management guidelines, we found MPD dilatation, even low levels from 5 mm to 9.9 mm, to be the single best predictor of HG-IPMN or invasion, highlighting the critical role that MPD plays in the selection of surgical candidates.
Background Data on readmission as well as the potential impact of length of stay (LOS) after colectomy for colon cancer remain poorly defined. The objective of the current study was to evaluate risk ...factors associated with readmission among a nationwide cohort of patients after colorectal surgery. Study Design We identified 149,622 unique individuals from the Surveillance, Epidemiology, and End Results–Medicare dataset with a diagnosis of primary colorectal cancer who underwent colectomy between 1986 and 2005. In-hospital morbidity, mortality, LOS, and 30-day readmission were examined using univariate and multivariate logistic regression models. Results Primary surgical treatment consisted of right (37.4%), transverse (4.9%), left (10.5%), sigmoid (22.8%), abdominoperineal resection (7.3%), low anterior resection (5.6%), total colectomy (1.2%), or other/unspecified (10.3%). Mean patient age was 76.5 years and more patients were female (52.9%). The number of patients with multiple preoperative comorbidities increased over time (Charlson comorbidity score ≥3: 1986 to 1990, 52.5% vs 2001 to 2005, 63.1%; p < 0.001). Mean LOS was 11.7 days and morbidity and mortality were 36.5% and 4.2%, respectively. LOS decreased over time (1986 to 1990, 14.0 days; 1991 to 1995, 12.0 days; 1996 to 2000, 10.4 days; 2001 to 2005, 10.6 days; p < 0.001). In contrast, 30-day readmission rates increased (1986 to 1990, 10.2%; 1991 to 1995, 10.9%; 1996 to 2000, 12.4%; 2001 to 2005, 13.7%; p < 0.001). Factors associated with increased risk of readmission included LOS (odds ratio = 1.02), Charlson comorbidities ≥3 (odds ratio = 1.27), and postoperative complications (odds ratio = 1.17) (all p < 0.01). Conclusions Readmission rates after colectomies have increased during the past 2 decades and mean LOS after this operation has declined. More research is needed to understand the balance and possible trade off between these hospital performance measures for all surgical procedures.
Introduction
Assessing patient-specific risk factors for long-term mortality following resection of pancreatic adenocarcinoma can be difficult. Sarcopenia—the measurement of muscle wasting—may be a ...more objective and comprehensive patient-specific factor associated with long-term survival.
Methods
Total psoas area (TPA) was measured on preoperative cross-sectional imaging in 557 patients undergoing resection of pancreatic adenocarcinoma between 1996 and 2010. Sarcopenia was defined as the presence of a TPA in the lowest sex-specific quartile. The impact of sarcopenia on 90-day, 1-year, and 3-year mortality was assessed relative to other clinicopathological factors.
Results
Mean patient age was 65.7 years and 53.1 % was male. Mean TPA among men (611 mm
2
/m
2
) was greater than among women (454 mm
2
/m
2
). Surgery involved pancreaticoduodenectomy (86.0 %) or distal pancreatectomy (14.0 %). Mean tumor size was 3.4 cm; 49.9 % and 88.5 % of patients had vascular and perineural invasion, respectively. Margin status was R0 (59.0 %) and 77.7 % patients had lymph node metastasis. Overall 90-day mortality was 3.1 % and overall 1- and 3-year survival was 67.9 % and 35.7 %, respectively. Sarcopenia was associated with increased risk of 3-year mortality (HR = 1.68;
P
< 0.001). Tumor-specific factors such as poor differentiation on histology (HR = 1.75), margin status (HR = 1.66), and lymph node metastasis (HR = 2.06) were associated with risk of death at 3-years (all
P
< 0.001). After controlling for these factors, sarcopenia remained independently associated with an increased risk of death at 3 years (HR = 1.63;
P
< 0.001).
Conclusions
Sarcopenia was a predictor of survival following pancreatic surgery, with sarcopenic patients having a 63 % increased risk of death at 3 years. Sarcopenia was an objective measure of patient frailty that was strongly associated with long-term outcome independent of tumor-specific factors.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
OBJECTIVE:We assessed circulating tumor cells (CTCs) with epithelial and mesenchymal phenotypes as a potential prognostic biomarker for patients with pancreatic adenocarcinoma (PDAC).
BACKGROUND:PDAC ...is the fourth leading cause of cancer death in the United States. There is an urgent need to develop biomarkers that predict patient prognosis and allow for better treatment stratification.
METHODS:Peripheral and portal blood samples were obtained from 50 patients with PDAC before surgical resection and filtered using the Isolation by Size of Epithelial Tumor cells method. CTCs were identified by immunofluorescence using commercially available antibodies to cytokeratin, vimentin, and CD45.
RESULTS:Thirty-nine patients (78%) had epithelial CTCs that expressed cytokeratin but not CD45. Twenty-six (67%) of the 39 patients had CTCs which also expressed vimentin, a mesenchymal marker. No patients had cytokeratin-negative and vimentin-positive CTCs. The presence of cytokeratin-positive CTCs (P < 0.01), but not mesenchymal-like CTCs (P = 0.39), was associated with poorer survival. The presence of cytokeratin-positive CTCs remained a significant independent predictor of survival by multivariable analysis after accounting for other prognostic factors (P < 0.01). The detection of CTCs expressing both vimentin and cytokeratin was predictive of recurrence (P = 0.01). Among patients with cancer recurrence, those with vimentin-positive and cytokeratin-expressing CTCs had decreased median time to recurrence compared with patients without CTCs (P = 0.02).
CONCLUSIONS:CTCs are an exciting potential strategy for understanding the biology of metastases, and provide prognostic utility for PDAC patients. CTCs exist as heterogeneous populations, and assessment should include phenotypic identification tailored to characterize cells based on epithelial and mesenchymal markers.
OBJECTIVE:To evaluate the correlation between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values, and the presence of invasive carcinoma in patients with intraductal ...papillary mucinous neoplasm (IPMN).
BACKGROUND:NLR and (PLR) are inflammatory markers that have been associated with overall survival in patients with invasive malignancies, including pancreatic cancer.
METHODS:We retrospectively reviewed 272 patients who underwent surgical resection for histologically confirmed IPMN from January 1997 to July 2015. NLR and PLR were calculated and coevaluated with additional demographic, clinical, and imaging data for possible correlation with IPMN-associated carcinoma in the form of a predictive nomogram.
RESULTS:NLR and PLR were significantly elevated in patients with IPMN-associated invasive carcinoma (P < 0.001). In the multivariate analysis, NLR value higher than 4 (P < 0.001), IPMN cyst of size more than 3 cm (P < 0.001), presence of enhanced solid component (P = 0.014), main pancreatic duct dilatation of more than 5 mm (P < 0.001), and jaundice (P < 0.001) were statistically significant variables. The developed statistical model has a c-index of 0.895. Implementation of the statistically significant variables in a predictive nomogram provided a reliable point system for estimating the presence of IPMN-associated invasive carcinoma.
CONCLUSIONS:NLR is an independent predictive marker for the presence of IPMN-associated invasive carcinoma. Further prospective studies are needed to assess the predictive ability of NLR and how it can be applied in the clinical setting.
The outcomes of sporadic pancreatic ductal adenocarcinoma (PDAC) patients with germline mutations of BRCA1/BRCA2 remains unclear. The prognostic significance of BRCA1/BRCA2 mutations on survival is ...not well established.
We performed targeted next-generation sequencing (NGS) to identify BRCA1/BRCA2 germline mutations in resected sporadic PDAC cases from 2000 to 2015. Germline BRCA mutation carriers were matched by age and tumor location to those with BRCA1/BRCA2 wild-type genes from our institutional database. Demographics, clinicopathologic features, overall survival (OS), and disease-free survival (DFS) were abstracted from medical records and compared between the 2 cohorts.
Twenty-two patients with sporadic cancer and BRCA1 (n = 4) or BRCA2 (n = 18) germline mutations and 105 wild-type patients were identified for this case-control study. The BRCA1/BRCA2 mutations were associated with inferior median OS (20.2 vs 27.8 months, p = 0.034) and DFS (8.4 vs 16.7 months, p < 0.001) when compared with the matched wild-type controls. On multivariable analyses, a BRCA1/BRCA2 mutation (hazard ratio HR 2.10, p < 0.001), positive margin status (HR 1.72, p = 0.021), and lack of adjuvant therapy (HR 2.38, p < 0.001), were all independently associated with worse survival. Within the BRCA1/BRCA2 mutated group, having had platinum-based adjuvant chemotherapy (n = 10) was associated with better survival than alternative chemotherapy (n = 8) or no adjuvant therapy (n = 4) (31.0 vs 17.8 vs 9.3 months, respectively, p < 0.001).
Carriers of BRCA1/BRCA2 mutation with sporadic PDAC had a worse survival after pancreatectomy than their BRCA wild-type counterparts. However, platinum-based chemotherapy regimens were associated with markedly improved survival in patients with BRCA1/BRCA2 mutations, with survival differences no longer appreciated with wild-type patients.
OBJECTIVE:The aim of this study was to characterize patterns of local progression following resection for pancreatic intraductal papillary mucinous neoplasms (IPMN) using targeted next-generation ...sequencing (NGS).
BACKGROUND:Progression of neoplastic disease in the remnant pancreas following resection of IPMN may include development of a new IPMN or ductal adenocarcinoma (PDAC). However, it is not clear whether this progression represents recurrence of the same neoplasm or an independent second neoplasm.
METHODS:Targeted-NGS on genes commonly mutated in IPMN and PDAC was performed on tumors from (1) 13 patients who developed disease progression in the remnant pancreas following resection of IPMN; and (2) 10 patients who underwent a resection for PDAC and had a concomitant IPMN. Mutations in the tumors were compared in order to determine the relationship between neoplasms. In parallel, clinical and pathological characteristics of 260 patients who underwent resection of noninvasive IPMN were reviewed to identify risk factors associated with local progression.
RESULTS:We identified 3 mechanisms underlying local progression in the remnant pancreas(1) residual microscopic disease at the resection margin, (2) intraparenchymal spread of neoplastic cells, leading to an anatomically separate but genetically related recurrence, and (3) multifocal disease with genetically distinct lesions. Analysis of the 260 patients with noninvasive IPMNs showed that family history of pancreatic cancer (P = 0.027) and high-grade dysplasia (HGD) (P = 0.003) were independent risk factors for the development of an IPMN with HGD or an invasive carcinoma in the remnant pancreas.
CONCLUSIONS:Using NGS, we identify distinct mechanisms for development of metachronous or synchronous neoplasms in patients with IPMN. Patients with a primary IPMN with HGD or with positive family history are at an increased risk to develop subsequent high-risk neoplasms in the remnant pancreas.
PDF
