SAN FRANCISCO (EGMN) – A new diagnosis of diabetes may help identify older adults who will develop pancreatic cancer while there is still time for screening and early detection, researchers reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
In an observational study of more than 20,000 older adults with pancreatic cancer, 10 antecedent diagnoses were found to be significantly associated with the cancer diagnosis. 
Of these, a diagnosis of new-onset diabetes preceded the cancer diagnosis by the greatest amount of time – more than 2 years, on average – or potentially enough time to catch the cancer early with targeted screening. A diagnosis of abdominal pain was second, at 1.5 years.
Late diagnosis is a major contributor to the generally “dismal” survival of pancreatic cancer, lead investigator Dr. Elizaveta Ragulin-Coyne said in an interview. 
“Colonoscopy screening works great, mammography works great. But those cancers are really a lot more common, so it makes sense to screen the whole population,” she commented. 
By contrast, pancreatic cancer is relatively uncommon, so population-based screening with current tests would generate many false positives. At present, only individuals from families having hereditary pancreatic cancers associated with certain mutations are screened.
The goal of the study was therefore to identify “the factors that can precede the diagnosis of pancreatic cancer, that sort of can act as red flags to identify that population at risk,” she explained. “So we are trying to identify the risk-rich population of individuals who can benefit from potential future screening.”
The investigators analyzed data from the U.S. Surveillance, Epidemiology, and End Results (SEER) database for the years 1991-2005 and the linked Medicare database for the years 1991-2007 to identify older adults with a diagnosis of pancreatic cancer and diagnoses preceding the cancer.
They evaluated 30 possible antecedent diagnoses for their association with the pancreatic cancer diagnosis, and narrowed it down to 10 that were significantly associated (P less than .05) in a stepwise logistic regression analysis: acute pancreatitis, chronic pancreatitis, cyst-pseudocyst, other pancreatic disease, bile duct obstruction, diabetes, weight loss, jaundice, abdominal pain, and hepatomegaly.
The 22,493 study patients were 77 years old on average; 55% were women and 86% were white, according to results reported in a poster session at the meeting.
The 10 antecedent diagnoses ranged in prevalence in this population from a low of 4% for hepatomegaly to a high of 76% for abdominal pain. A diagnosis of diabetes was seen in 45%.
In most cases, the median time between the antecedent diagnosis and the pancreatic cancer diagnosis was less than 3 months. The exceptions were abdominal pain, diagnosed a median of 18 months before the cancer, and diabetes, diagnosed a median of 28 months before the cancer.
The latter intervals are long enough to provide a window of opportunity for intervention, according to Dr. Ragulin-Coyne, a surgical resident and research fellow at the University of Massachusetts Medical Center in Worcester. 
“It doesn’t make sense if you have preceding diagnoses within a month before, it doesn’t really make a difference,” she explained. “But if it’s over 6 months or over a year, it is actually clinically significant because you can hypothesize that those people are potentially at an early stage and could have more interventions that give you a possibility of cure.”
The average number of antecedent diagnoses decreased with increasing stage of pancreatic cancer at diagnosis, from 3.91 among patients with stage 0 disease to 2.04 among patients with stage IV disease.
This finding initially seemed counterintuitive, Dr. Ragulin-Coyne said. But perhaps patients having more advanced cancer at diagnosis have had less contact with the health care system in general, and therefore have fewer diagnoses on record.
In a logistic regression model among just the patients with an antecedent diabetes diagnosis, the odds of the gap between that diagnosis and the pancreatic cancer diagnosis being greater than 24 months were higher for nonwhite versus white patients; for patients aged 75-84 years or aged 85 years or older, compared with those aged 65-74 years; and for patients in the Midwest versus the Northeast.
The reason pancreatic cancer is diagnosed earlier in some patients and later in others is not yet clear, but it is likely multifactorial, according to Dr. Ragulin-Coyne.
“We can make guesses, whether it is socioeconomic or cultural or there is something else in play.” For example, some patients may “l the doctor about all their symptoms and get worked up early and get their doctors concerned more,” she said. “But if they never come to the physician or they never mention what’s going on, they get diagnosed late.”
In any case, identifying the reasons will be critical to moving all patients into the early diagnosis group. “I think that will ultimay be the best thing if, when they come, we can offer them treatments and cure and options, versus just saying, unfortunay, it’s too late,” she commented.
The investigators have obtained the SEER data for all similar older adults without a pancreatic cancer diagnosis, and using a matched analysis, plan to develop and test a prediction nomogram using the information from their study. “Stay tuned for that,” she advised.
“Screening for pancreatic cancer will be a great future tool,” Dr. Ragulin-Coyne concluded, while also cautioning that there is still much work to be done before some type of population-based screening becomes a reality.
Dr. Ragulin-Coyne reported having no conflicts of interest related to the study.

愛思唯爾醫(yī)學資訊

馬薩諸塞州大學醫(yī)學中心ElizavetaRagulin-Coyne博士在美國臨床腫瘤學會主辦的胃腸系統(tǒng)腫瘤研討會上報告稱，新診斷糖尿病可能有助于早期確定將來易患胰腺癌的老年患者，從而有時間對其進行篩查和早期檢查。

由于胰腺癌并不十分常見，而以現(xiàn)行方法進行人群篩查將會產(chǎn)生許多假陽性結果，因而目前只對具有與某些突變有關的遺傳性胰腺癌家族史的個體進行篩查，但延誤診斷是胰腺癌患者普遍生存不佳的主要原因。為此，研究者對美國監(jiān)測、流行病學和zui終結果(SEER)數(shù)據(jù)庫1991~2005年資料以及相關的聯(lián)邦醫(yī)保數(shù)據(jù)庫1991~2007年資料進行了分析，旨在確認老年胰腺癌確診患者和既往病史的相關性，以便對高危人群進行針對性篩查，使之得到早期診治。

研究者分析了22,493例老年胰腺癌患者的資料，平均年齡77歲，55%為女性，86%為白種人。他們對既往確診的30種疾病與胰腺癌的可能相關性進行評估，并應用逐步Logistic回歸分析法，確定10種既往確診疾病具有顯著相關性，即急性胰腺炎、慢性胰腺炎、囊腫-假性囊腫、其他胰腺疾病、膽管梗阻、糖尿病、體重減輕、黃疸、腹痛以及肝腫大。其中發(fā)病率zui低的疾病是肝腫大(4%)，zui高為腹痛(76%)，糖尿病發(fā)病率為45%。

大部分既往診斷與胰腺癌診斷的中位間隔時間為3個月，但腹痛和糖尿病例外，前者中位間隔時間為18個月，后者為28個月，后者可以為對目標人群進行胰腺癌篩查和早期干預提供足夠的時間。

對既往診斷為糖尿病的患者進行Logistic回歸分析，結果顯示，在既往糖尿病確診與胰腺癌確診間隔超過24個月的可能性方面，非白種人>白種人，75~84歲或≥85歲患者>65~74歲患者，中西部地區(qū)患者>東北部地區(qū)患者。其原因尚不清楚，可能與社會經(jīng)濟、文化或其他多種因素有關。

此外，分析還顯示，胰腺癌確診時癌癥分期越高的患者，既往確診的疾病種數(shù)越少。胰腺癌0期和IV期患者的既往確診疾病種數(shù)分別為3.91種和2.04種。研究者認為可能與晚期癌癥確診患者平時就醫(yī)次數(shù)較少、診斷記錄較少有關。

基于上述結果，研究者還計劃對SEER數(shù)據(jù)庫中所有相似年齡段的非胰腺癌老年患者的資料進行分析，以期開發(fā)和測試一種老年胰腺癌預測列線圖，實現(xiàn)胰腺癌篩查和早期干預。

研究者無利益沖突披露。