Bits and Pieces From DDW 2013
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Hi,everyone,
If you don’t have time, read #4 and #5 first.
1.A Combined Bile and Urine Proteomic Test Increases Diagnostic Accuracy of Cholangiocarcinoma in Patients With Biliary Strictures of Unknown Origin 10 | 626 | Jochen Metzger2, et.al
Results: Receiver operating characteristics analysis of proteomic CC-classification of the 87 study patients revealed AUC values of 0.85 . A logistic regression model composed of the bile and urine proteomic classification factors lead to an AUC of 0.96, and 92% sensitivity and 84% specificity at the best cut-off. Most notably only three of the 36 CC patients were false negative and two of the 33 PSC patients were false positive classified. Inclusion of CA19-9 and bilirubin values to the logistic regression model was of minor benefit as indicated by small correlation coefficients and insignificant P values for these serological markers.Conclusion: A logistic regression model combining the classification factors of bile and urine proteome analysis enables CC-diagnosis with an accuracy > 90% most applicable for patients with biliary strictures of unknown origin referred to endoscopy.
This model substantially improves the diagnosis of CC and may lead to early therapy and improved prognosis.2. Malignancy in Biliary Strictures 10:15 | 627 | Tamas A. Gonda1, Khushboo Munot1, Amrita Sethi1, John M. Poneros1, et.al
Results: 43% of cases were malignant, and 70% of these were distal biliary strictures. Positive cytology diagnoses were made in 16% of cases, excluding them from second-line testing in clinical practice. Negative cytology diagnoses were made in 72% of cases, and no cytologic diagnoses were made in 13% of cases due to paucity of cells. In all cases where cytology was negative or accellular (85%), second-line molecular testing yielded an assessable diagnosis. A diagnosis was assessable in 88% of FISH cases, in 95% mutational profiling cases, and in 100% of cases analyzed with all three tests. FISH identified 1 additional malignancy beyond cytology. Mutational profiling identified 2 additional malignancies beyond cytology and FISH testing. Mutational profiling was ∼30% more sensitive than FISH for detecting malignancy. There was no brush-to-brush variability when DNA from the supernatant of the first or second brushing was analyzed.
Conclusions: Normally discarded, cell-free supernatant fluid collected from cytology brushing of biliary strictures provides sufficient DNA for reproducible mutational profiling. The addition of second-line molecular testing increases the diagnostic yield and sensitivity for detecting malignancy in biliary strictures. Mutational profiling of DNA in cell-free supernatants may help to increase these characteristics in cases where cells are too limited to establish reliable results from cell-based assays, even in our population where a large percentage of distal biliary strictures were evaluated, making sampling especially challenging.
Molecular Analysis Increases the Diagnostic Yield and Sensitivity for
Results .3. Higher Survival Rate of Patients With Intrahepatic Cholangiocarcinoma Compared to Patients With Extrahepatic Cholangiocarcinoma: a Large Series From Thailand .
10:30 | 628 | Sittikorn Linlawan1, Parkpoom Phatharacharukul2, Suebpong Tanasanvimon1 et.alThree hundred and eighty two males and 258 females at a mean age of 59.8±12.1 years were diagnosed with cholangiocarcinoma. In this study, 216 of 640 patients (33.8%) were diagnosed ICC. We found that ECC patients presented with painless jaundice and cholangitis more often than ICC patients, significantly (80% vs. 4.6%, p<0.001). Demographic data of both groups were not statistically different (Table 1). Baseline serum TB, DB and ALP of ICC patients were statistically lower than those of ECC (TB 1.7±4.6 vs. 16.8±12.2mg/dl, DB 1.0±3.6 vs. 12.8±8.9 mg/dl, ALP 282.5±216.1 vs. 487.3±334.1 U/L, respectively; p<0.01). Serum CEA and AFP were higher in ICC patients than those of ECC patients (CEA 107.3±609.3 vs. 28.7±84.5ng/ml, respectively; p=0.11, AFP 31.5±102.1 vs. 10.2±31.3ng/ml, respectively; p<0.01), in contrast to CA19-9 which was statistically lower in ICC patients (473.5±475.4 vs. 558.5±422.7ng/ml, respectively; p=0.04). Supportive care and selection of treatment were based on clinicians' decision and 20% of them underwent curative surgery. The median survival of patients with ICC and ECC were 51 and 18 months, respectively (Figure 1). Predictors of mortality for the overall group of patients with cholangiocarcinoma were underlying of cirrhosis and HIV infection (hazard ratio, 2.3; 95% CI, 1.2 to 4.3 and 8.0; 95% CI, 2.5 to 26.3; p <0.01, respectively).
Conclusion
Higher survival rate was observed in ICC patients compared to those with ECC and the predictors of mortality were underlying of cirrhosis and HIV infection.4. A New Staging System for Perihilar Cholangiocarcinoma.
10:45 | 629 | Roongruedee Chaiteerakij1, Carlos Romero-Marrero2, Joseph Kaiya1, William S. Harmsen1, Terry M. Therneau1, William Sanchez1, Lewis R. Roberts1, Gregory J. Gores1
CONCLUSIONS: Clinical trials for potential targeted therapies are hampered by the lack of an accurate, non-operative staging system that predicts survival of patients with pCCA. We have developed a staging system based upon clinical and radiologic findings for pCCA which divides patients into four discrete, prognostic stages and should be useful to clinicians and design of clinical trials.Proposed staging system for perihilar cholangiocarcinoma.
Stage I: No mass lesion(ML) or unicentricmass (UCM) Stage II: NA ; no mets; and YES to LA and /or VC; ECOG PS=0-1.
Stage III: UCM> 3cm; Has perihilar Lymph Nodes ; NA of LA and/or VC; ECOG PS=0-1.
Stage IV: Has multcentricmass ; has distant lymph node and/or peritonealmetastatsis ; NA of LA and/or VC; and ECOG PS>/=2.NA, not applicable; ECOG, Eastern Cooperative Oncology Group; LN, lymph node
5. —Circulating Tumor Cells(CTC) Are Associated With More Advanced Disease in Cholangiocarcinoma.
11:15 | 631 | Ju Dong Yang1, Michael B. Campion et.alResults: The mean age of patients was 61 and 29 (64%) patients were male. CTC were detected in 13 (28%) patients. Patients with CTC tended to have larger tumor size, more tumor nodules, a higher CA19-9 level, increased CEA, lymph node involvement, and metastatic disease compared to patients without CTC. (Table) There was no significant association between CTC and demography (age, gender, and race) or underlying liver dysfunction . There was a trend towards poorer survival in patients with CTC compared to patients without CTC (p=0.09).
Conclusion: CTC are detectable in patients with cholangiocarcinoma. The presence of CTC was associated with tumor burden and metastatic cancer. The prognostic implications of CTC in patients with CCA need further validation in a larger patient group.
Table: CTC positive(N=13) CTC negative(N=32)
Tumor size: 10.1(6.6-13.6) 2.8(1.6-9.0)
# of Nodules: 3 1
Bilober disease: 69% 34%
CA 19-9: 1521(71-6098) 74(34-337)
CEA : 2.8(4.8-55.4) 2.7(1.8-3.1)
Lymph node 68% 31%
involvement:
Metastasis : 46% 6%God bless.
Hi, everyone,
Something I have learnt from DDW 2013. 5/23/20913 page 1.
—There are two primary bile acids in human: cholic acid and chenoceoxycholic acid.
—The concentration of the bile acids decrease from 10nM in the jejunum to 0.2 mM in the stool; and the PH increases from 6.5 to 7 likewise.
—bile acids mal- absorption can be resulted in persistent diarrhea.
— In the hepatocyte(liver cell), LDL facilitated cholesterol to form bile acids, which through the bile canaliculus circulation into the Ileal enterocyte for digestion of fats in the small intestines and the majority of the daily production ( about 12-18gms and the amount is meal dependent) will absorb (recycle) back through the portal circulation into the liver cells for the next enterohepatic circulation of bile acids. The usage of the bile acids is about 2-3gm each time and fecal excretion is about 0.5gm. In that sense ,that means the daily production of bile acids can be recycle 3-6 times/day. —[Bile manufacture ,consumption and transport at the cellular level ].
(from Wikipedia: The path of bile flow is as follows: Bile canaliculi → Canals of Hering → interlobular bile ducts → intrahepatic bile ducts → left and right hepatic ducts merge to form → common hepatic duct exits liver and joins → cystic duct (from gall bladder) forming → common bile duct → joins with pancreatic duct → forming ampulla of Vater → enters duodenum.)
— In other lecture, there are 25 different kinds of bile acids;DHA(a bile acid) decreases ALK phos. in PSC patients and the use of treatment of omega 3 fatty acid for 6 weeks TENDS to decrease the toxicity of the bile acids.
— I talked one of the lecture presenter from Thailand about whether he thinks the inflammation process caused by the liver worms and ultimately resulted in CCA is the same as in the western part of the world. He said no, he believed the process is different but the outcome is the same.
—On the lighter side, I did discuss one of my ideas with two stent manufacturers (Medi-Globe from Germany and Nanking Medical from China); I suggest to them the molecular structure of the skin of the shark is one of the least liquid flow resistant structure in nature. If the stent manufacturer can coat the inside of either the metal or the plastic stents with such material, and at each end of the stent coated with antibiotics to digest or prevent the micro fiber sludge forming, it will substantially prolong the usage of the stents and patients of CCA will require less stent replacements and improve the quality of life of the patients. The research and development adviser for the Medi-Globe from Achenmuhle ,Germany shows good interest in my design suggestion but the Chinese Nanking Medical may not fully understand what I said in English .
— I talked to one GI doctor who practice in Dallas and treat a lot of patients who have hepatitis B, I questioned him how long should the patient be on antiviral therapy . he said is between 2-5 years.
—Coffee drinking may contribute to the decrease of fibrosis formation in the liver.
—Aspirin, even in low dose(ie:81mg/day) in relatively long term of treatment( 6-8 years) can prevent many types of cancer including colon CA; aspirin reduces the risk of recurrent ADENOMA in both stage I and II of colon cancer and mets. Vitamin D, and omega 3 Fatty acid have the same effects too in reduction of CRC growth due to their effects as COX-2 inhibitor.–Dr. Andrew Chen from Mass General. Since CCA is also belonging to the class of tumor called Adenoma, therefore aspirin and other NSAID may be of value to try them too. Side effects of aspirin: GI bleeding.—Using electrostimulation acupuncture pads between the acupuncture point PC-6 in the forearm rather than using the actual acupuncture needles is effective in treating chemotherapy-induced nausea and motion sickness. patient can do it at home 3-4 times a day and will be more effective in treatment than just once a day. Ask your acupuncturist to elect the proper dose for you after buying the device from the internet.(dose is individualized)
Will be continue…
God bless.
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