Tuesday, May 27, 2014

The case of Urothelial Cancer

Greater east cancer center was referred a case of a 42 year old man with history of previous admission for Peptic Ulcer disease who had reported to the hospital for indigestion, fatigue, 20 lbs weight loss and abdominal epigastric pains.
The patient underwent an EGD which suggested a non raised ulcer. Biopsy at the Stomach revealed an undifferentiated cancer.   A subsequent Colonoscopy revealed the same lesion in the Sigmoid and rectal areas with signet ring characteristics but clearly the same lesion.  Given the suspicion of a Urothelial cancer with plasmacytoid differentiation based on immunochemistry and flow, presence of CD138, it was decided to perform a Cystoscopy which indeed revealed a positive biopsy by the same malignancy.  There was evidence of a significant penetration of the Detrusor.  There was extensive retroperitoneal node invasion with clear evidence of obstructive Uropathy.  Aside for a port placement, bilateral nephrostomies were placed.
It was decided this was a stage IV disease.
Of interest, the patient had history of recurrent folliculitis or abcesses on the skin or infected cysts removed.
(the question is the gene (s) involved may be linked to this abnormality)

The case  brings to genetic studies many questions that remain unanswered in the current state of treatment
1.Should we just proceed with Gemzar-Cisplatin (the Bladder regimen theory in Urothelial cancer treatment)
2 does Carboplatin has a role in the Metastatic setting (the creatinine was 6.0 on admission)
issue of dialysis was raised. But does reduced Cisplatin on a 5 day regimen better in this setting or is-it better to give Oxaliplatin.
3.The literature suggest response to gastric regimen such as EOX (Epirubicin, Oxaliplatin, and Xeloda-propsed by NIH)
frankly the idea of protracted exposure to Xeloda was attractive.
4. The peculiar nature of this disease raise the issue of whether BEP would be a better regimen and not MVAC, and a secondary role of Ifosfamide, Etoposide?
5.Is this cancer related to testicular cancer given the eventual secretion of Beta-HCG (germ cell cancers)
6.The production of CA 19-9, and the response to GI chemotherapy regimens raised many related questions
on whether genetic basis in this disease process mimic the pancreatic cancer process. role of protein 14-3-3,
and related cascade that uses the chaperon HSP-90.  Role of anti-MEK?
and that Cytoplasmic concentration of CDC25 could be a relevant bio-marker,
and activities of the SCHOC-2 and RAF-1 are relevant in this disease,
or Cyclin B1 for that matter (AS DEMONSTRATED IN OUR LUNG CANCER STUDY)!  COULD PREMETREX BE TRIED IN THIS DISEASE?  (REMEMBER THE MVAC -HAS METHOTREXATE!)

9.Cyclin B could serve an initial event.  Can Cyclin B level be followed by immuno?
10. Could cyclin B  and the HSP chaperon role play into the global elevation play into GI susceptibility to metastasize or to initiate in multiple level of GI tract
11 what is the role of STUB1 and Parkins?

IS CYCLIN B ------RAF1  THE MAIN CANCER ROUTE?

COULD THE SUSCEPTIBILITY TO TREATMENT THE SAME AS DISUSSED IN PANCREATIC CANCERS?  SEE NOTES FROM LAS VEGAS?   WHAT THE LINK WITH EMBRYONAL CANCERS OR SARCOMA---IS RAF 1/CDC25 STILL THE CULPRIT?

ROLE OF VELCADE IF UBIQUTYLATION IS INTO PLAY AS EXPECTED! It is plasmacytoid isn't it!

THE CRBCM WILL NOT HAVE THE MONEY TO ADVANCE THESE QUESTION GIVEN THE CURRENT NATURE OF LOCAL AFFAIRS!  YOU WHO CAN PLEASE CHALLENGE US! 
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