本帖最後由 lsc0019 於 2009-4-4 13:45 編輯
作者：Zosia Chustecka
出處：WebMD醫學新聞
March 19, 2009 — 根據三月號外科檔案期刊上一篇胰臟癌病患研究報告，肥胖大幅增加胰臟癌轉移、復發與死亡的風險。
在285名接受可能治癒性手術的病患中，發現其中身體質量指數(BMI)大於35 kg/m2的一小組肥胖病患，相較於其他病患，淋巴結轉移風險高達12倍，癌症復發與死亡風險幾乎兩倍。
全部病患所接受的手術相似，研究者認為，肥胖是影響腫瘤的一個主要因素，與肥胖病患的腫瘤照護難度無關。
主要研究者、德州大學安德森癌症中心的Jason Fleming醫師向Medscape Oncology表示，本研究與其他新興證據顯示，實質腫瘤在肥胖病患與非肥胖病患之間有不一樣的表現；他指出，已知肥胖與增加乳癌復發及不佳存活有關，認為是與淋巴結轉移陽性有關。
不過，當被問到這些研究發現是否會對實務有任何影響時，Fleming醫師表示，還不清楚減輕體重或者飲食調整策略是否有助於診斷癌症病患；於治療期間或者手術前後嘗試減輕體重，也可能是不安全的。
他表示，我們目前發展出「事先適格計畫（prehabilitation program）」，讓病患開始監督飲食調整、物理治療以及術前諮商；我們希望這可以讓給予的癌症治療獲致實際改善，最終達到讓病患存活的目標。
【差異並非手術造成】
所有參與者都是胰臟腺瘤病患，大多數病患接受「胰十二指腸切除術(262名病患，89%)」，有些是接受「次全胰末端切除術(31名病患，10%)」，另有3名病患(1%)接受「全胰臟切除術」。
285名病患的平均最後追蹤或死亡期間為16個月，存活病患的平均追蹤期間為19.8個月；在最後追蹤期間，133名病患存活，90人(32%)已無疾病，43人(15%)尚有疾病。
根據BMI將病患分成五組，但是結果並無顯著差異，除了最高組以外；研究者指出，BMI大於35 kg/m2的一小組、20名病患有別於其他人。
與其他病患相比，這一小組BMI大於35 kg/m2的病患，淋巴結陽性風險顯著增加(P=.02)；這一小組病患幾乎全部(95%)有淋巴結陽性，其他研究對象只有56%為陽性。
此外，這一小組肥胖病患的復發風險幾乎是其他病患的兩倍(P= .005)，死亡風險幾乎是1.95倍(P= .02)。
研究者指出，這些差異並非因為進行的手術不同；雖然肥胖會使手術複雜化，研究中，各種BMI值病患之間的淋巴結數量或者陰性切除範圍並無差異，他們指出，這兩種指標在定義胰臟腫瘤切除的完整性是相當重要的。
他們認為，這些資料顯示，BMI增加對我們在腺瘤病患進行安全的胰臟腫瘤切除並不會有不良影響。
術前放射線治療有不同之處，肥胖病患比較不會接受此治療；研究者表示，我們無法確認此一差異的原因，但是我們認為，即使控制此一差異，BMI對淋巴結轉移的影響依舊強烈。
研究者指出，就我們所知，本研究所觀察的肥胖與淋巴結轉移的關聯，是迄今文獻中最強的，且受到臨床與實驗室研究的支持，顯示肥胖與癌症惡化之間確實有關係。
【肥胖何以會增加風險？】
肥胖何以會增加癌症病患的風險，有諸多解釋，其中主要聚焦在胰島素，這在肥胖者會增加；Fleming醫師解釋，已知胰島素與類胰島素生長因素對癌細胞生長有正向刺激作用，推測是這些因素刺激肥胖病患的癌細胞生長。
最近從實驗研究中提出的另一個解釋，是過多的脂質會改變癌細胞膜，而促進它們分化與擴散的能力，這曾由Medscape Oncology報導過。
有趣的是，在這個胰臟癌病患研究中，風險增加之強烈關聯僅見於BMI大於35 kg/m2的病患，而BMI 30-35 kg/m2的病患則沒有；Fleming醫師表示，這對我們來說是個謎。他表示，BMI分組有點人工因素，因為BMI實際是連續變項，但這些資料會被解釋為類似劑量相關理論的負面效果，認為最高的BMI有最全然的負面效果。
不過，Fleming醫師也指出，多數胰臟癌的預後都不佳，與他們的BMI無關，因此難以確認一個造成預後不佳的因素。
國家健康研究中心以及Various Donor Found胰臟癌研究資金支持本研究。研究者宣告沒有相關財務關係。
Obesity Increases Risk for Metastases in Pancreatic Cancer
By Zosia Chustecka
Medscape Medical News
March 19, 2009 — Obesity greatly increased the risk for metastasis, as well as for recurrence and death, according to a study of pancreatic cancer patients reported in the March issue of the Archives of Surgery.
In a series of 285 patients who underwent potentially curative surgery, a small group of obese patients with a body mass index (BMI) of more than 35?kg/m2 was found to have a 12-fold higher risk for lymph node metastases and an almost doubled risk for cancer recurrence and death, compared with all the other patients.
The surgery was similar in all of the patients, which suggests that "obesity is a host factor affecting tumor biology, independent of the difficulties involved in delivering oncologic care in obese patients," the researchers comment.
The implication from this study, and from other emerging evidence, is that solid tumors behave differently in patients who are obese and in those who are not obese, lead author Jason Fleming, MD, from the University of Texas MD Anderson Cancer Center, in Houston, told Medscape Oncology. He noted that obesity has also been linked to increased recurrence and poor survival in breast cancer, and that a positive influence on lymph node metastasis has been suggested.
However, when asked whether there are any practical implications from these findings, Dr. Fleming said: "It is still unclear whether some weight-loss or dietary-modification strategy would help patients after they have been diagnosed with cancer. Attempts to lose weight during therapy or before or after surgery could be unsafe."
"We are currently developing a 'prehabilitation program,' in which patients embark on supervised dietary modification, physical therapy, and counseling prior to surgery," he said. "We hope that this will result in tangible improvements in cancer-therapy delivery and, ultimately, patient survival."
Differences Did Not Stem From Surgery
All of the patients had pancreatic adenocarcinoma. Most of the patients underwent a pancreaticoduodenectomy (262 patients; 89%), but some underwent subtotal distal pancreatectomy (31 patients; 10%), and 3 patients (1%) underwent a total pancreatectomy.
The median time to last follow-up or death for the entire group of 285 patients was 16 months, with surviving patients followed for a median of 19.8 months. At last follow-up, 133 patients were alive, 90 (32%) of whom had no evidence of disease and 43 (15%) of whom were living with disease.
Patients were divided into 5 different cohorts according to BMI, but there were no significant differences in outcomes among the cohorts, with the exception of the highest. The small subgroup of 20 patients with a BMI higher than 35?kg/m2 was "unique from the others," the researchers comment.
Compared with the other patients, this subgroup of patients with a BMI higher than 35?kg/m2 had a significantly increased risk of having positive lymph nodes (P?=.02). Nearly all these patients (95%) had positive lymph nodes, compared with 56% in all study patients.
In addition, this subgroup of obese patients was at approximately a 2-fold higher risk for recurrence (P?= .005) and a 1.95-fold higher risk for death (P?= .02) than the other patients.
These differences did not stem from differences in the surgery performed, the authors comment. Although obesity can complicate surgery, there were no differences among the various BMI cohorts in this study in the number of lymph nodes that were examined or in the negative resection margin — both of which are important in defining the oncologic completeness of pancreatectomy, they note.
"These data suggest that increasing BMI did not impair our ability to perform safe and oncologically sound pancreas resection in patients with adenocarcinoma," they comment.
There was a difference in preoperative radiotherapy, with obese patients being less likely to receive this treatment. "We are uncertain of the reason for this observed difference," the researchers say, but they add that even when they controlled for this difference, the influence of BMI on lymph node metastasis "remained strong."
"To our knowledge, the relationship between obesity and lymph node metastases observed in this study is the strongest reported in the literature to date, and it is supported by clinical and laboratory studies showing a relationship between obesity and cancer progression," the researchers note.
Why Does Obesity Increase Risk?
Several explanations for why obesity can increase risk in cancer patients have been proposed. One of these centers on insulin, which is increased in obese individuals. "Insulin and insulin-like growth factors are known to be positive stimulators of cancer cell growth," Dr. Fleming explained, and "it has been postulated that these factors could stimulate cancer cell growth in obese patients."
Another explanation that has been proposed recently, from an experimental study, is that excess lipids may alter cancer-cell membranes, which enhances their ability to separate and spread, as reported by Medscape Oncology.
Intriguingly, in this study of pancreatic cancer patients, the strong association with an increased risk was seen only in patients with a BMI of more than 35 kg/m2, and but not in patients with a BMI from 30 to 35 kg/m2. This finding is "a puzzle to us," Dr. Fleming said. The BMI groupings are somewhat artificial because BMI is really a continuous variable, he said, but the data could be interpreted as suggesting a "dose-dependent" negative effect, with the highest BMI having the most profound negative effect.
However, Dr. Fleming also noted that "pancreatic cancer has a poor outcome for most patients, regardless of their BMI, so identifying any 1 factor that contributes to that is difficult."
The study was supported by a grant from the National Institute of Health and by the Various Donor Found for Pancreatic Cancer Research. The researchers have disclosed no relevant financial relationships.
Arch Surg. 2009;144;216-221. |
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