$500 Reward
I am still looking at a "blind spot" in my data that is needed for clinical decisions. I have no data that shows that the results of clinical care are related to histologically positive and
negative biopsies of spontaneous endometriotic lesions in humans in the absence of the other finding like those covered below.
The $500 reward is for a citation to a peer reviewed, published article abstracted in PubMed that is not listed below. There will be as many rewards as there are different papers.
This excludes histology that is positive for other pathologies such as cancer, low malignant potential tumor, ectopic pregnancy, carcinoid tumor, psammoma bodies, endosalpingiosis, Walthard Rests,
mesothelial proliferation, lymphoid aggregates, and granulation tissue.
I need peer reviewed, published articles that are abstracted in PubMed. These need to show a statistically significant difference in outcomes (pain, tenderness, or fertility) of surgery or
medical therapy based on lesion histology that is positive (any two of the following: glands, stroma, hemorrhage, CD10, Ber-EP4, or pan-cytokeratin) as compared with histology that is negative for endometriosis.
The citation for the articles and the name(s) of those who win the money will be posted at this page. Permission to post your name is a requirement to win the money.
If the article is not in English, MS Word has a standard translation module for most languages. If the applicable translation module is not in MS Word, I will need an English translation of the
abstract and of the statistical analysis.
I also need, with only my gratitude,
1) PubMed articles, not listed below, that include data on differences in outcomes based on positive versus negative histology lesions, but did not show significant differences.
2) PubMed articles, not listed below that include data on endometriosis histology compared with other lesions such as cancer, low malignant potential tumor, ectopic pregnancy, carcinoid tumor,
psammoma bodies, endosalpingiosis, Walthard Rests, mesothelial proliferation, lymphoid aggregates, and granulation tissue.
Problems
Concentrating on biopsy positive patients implies that we can ignore or discount patients who have a laparoscopic diagnosis of endometriosis but have histologically negative biopsies.
My data showed a decreased confirmation from 99% using a 25-step research protocol that excluded residents to 88% with residents doing biopsies and excisions with a clinically limited protocol.
My conclusion is that if it looks like endometriosis, treat it like endometriosis unless histology has a different specific finding. Note: Do not accept "no evidnce of endometriosis" or
"no pathology" as diagnoses if a lesion was seen.
Martin DC, Ahmic R, El-Zeky FA, Vander Zwaag R, Pickens MT, Cherry K. Increased histologic confirmation of endometriosis. J Gynecol Surg 1990, 6(4):275-279. doi: 10.1089/gyn.1990.6.275
Martin D. Biopsy of endometriosis may have more risk than benefit. Fertil Steril. 2006;86 (suppl 2):s269-270-s.
There is a large body of literature on accuracy of confirmation of endometriosis but no corresponding literature on histologic diagnosis of other peritoneal and pelvic abnormalities.
Decisions on endometriosis therapy are based on different definitions. This can lead to data based on "any appearance," "a dark, scarred appearance,” "surgical diagnosis," “clinical diagnosis”
or others. Although this may be reasonable in clinical care, it is not adequate for research.
"Inflammed granulation tissue" needs investigation of pathogens including chlamydia, gonorrhea, and other STDs.
Endometriosis can have significant coexistent pathology. That can be anticipated in up to 30% of cases based on epidemiological data.
Psammoma bodies, endosalpingiosis, low malignant potential tumor, ovarian cancer, metastatic breast cancer, ectopic pregnancy, carcinoid tumor, Walthard Rests, low malignant potential tumor,
mesothelial proliferation, lymphoid aggregates, nonspecific inclusions, granulation tissue and other pathologies can look like endometriosis. Biopsies are need for subtle, atypical, and
typical appearances to rule out other pathology.
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Papers that analyzed positive and negative histology but have no statistically significant differences in clinical outcomes
Chapron C, Dubuisson J-B, Tardif D, Fritel X, Lacroix S, Kinkel K, et al. Retroperitoneal endometriosis and pelvic pain: Results of laparoscopic uterosacral ligament resection according to the rAFS classification and histopathologic results. J Gynecol Surg. 1998;14:51-8.
All 95 patients had possible retroperitoneal endometriosis infiltrating the uterosacral ligaments and underwent bilateral (14%) or unilateral (86%) uterosacral resection. Ureterolysis was necessary in 63% of cases. 89% had additional laparoscopic procedures.
All (100%) patients had positive endometriosis from some site (ovarian cysts, biopsy from the peritoneum or adhesions, uterosacral ligaments, etc.). Excellent response to deep dyspareunia and dysmenorrhea. Dysmenorrhea response was better when the histologic results of the uterosacrals were positive but this was not statistically significant. (81.6% vs 58.3%). For deep dyspareunia, there was no obvious difference (82.3% vs 76.5%).
Damario MA, Horowitz IR and Rock JA. The role of uterosacral ligament resection in conservative operation for recurrent endometriosis. J Gynecol Surg. 1994;10:57-61.
This was a retrospective review of 15 patients over 3 years.
All patients had extensive resection of endometriosis including ureterolysis and deep dissection. 12 (80%) also had pre-sacral neurectomy. He looked at relief comparing histologically positive and negative uterosacral ligaments and drew no statistical conclusions.
Jenkins TR, Liu CY, White J. Does Response to Hormonal Therapy Predict Presence or Absence of Endometriosis? J Minim Invasive Gynecol. 2008, 15:82–86
Endometriosis was identified at laparoscopy in 41 (87%) of 47 patients who responded to hormonal therapy and 46 (81%) of 57 patients who failed to respond (p=0.37). Using final pathology as the basis of diagnosis,
31 (67%) of 46 responders and 39 (68%) of 57 non-responders had endometriosis (p=0.91). When the data was analyzed by anatomic site of endometriosis, no significant difference was noted in response to preoperative hormonal therapy. Relief of chronic pelvic pain symptoms with preoperative hormonal therapy is not an accurate predictor of the presence or absence of histologically confirmed endometriosis at laparoscopy. Jenkins et al. adds histology and confirms Ling et al.'s 1999 paper on leuprolide in which had documented that 82% of women with endometriosis and 73% of those with none had pain relief on a GnRH agonist. Although that study was initially touted as indicating that Lupron could be used to diagnosis endometriosis, close examination of the data shows that inclusion in the study was more predictive of endometriosis than a response to the medication at 82% and 78% respectively. (
Ling FW for the Pelvic Pain Study Group. Randomized controlled trial of depot leuprolide in patients with chronic pelvic pain and clinically suspected endometriosis. Obstet Gynecol. 1999;93(1):51-8.)
Miller PB, Savaris RF, Forstein DA, Likes CE, Nichols C, Cooper LJ, Lessey BA. Laparoscopic surgery improves pregnancy outcomes in women with suspected endometriosis with or without pathological confirmation. Clin Exp Obstet Gynecol. 2016;43(1):31-6
Women with histological confirmation (n = 74) did not differ from those not confirmed (n = 29) in age, body mass index, gravidity, parity, ovulation induction protocol, or past duration of infertility. Pregnancy outcome was similar in both groups (39/74 vs. 15/29-p = 0.9--Chi-square) and there was no statistical difference in time to conceive/deliver (p = 0.7) between the groups.
Walter AJ, Hentz JG, Magtibay PM, Cornella JL, Magrina JF. Endometriosis: correlation between histologic and visual findings at laparoscopy. Am J Obstet Gynecol. 2001 Jun;184(7):1407-11; discussion 1411-3. doi: 10.1067/mob.2001.115747. PMID: 11408860.
The most common other finding was endosalpingiosis with
no data on that. Patients in this and other studies also had
"normal peritoneum, mesothelial hyperplasia, fibrosis, hemosiderin deposition
(not hemosiderin-laden macrophages), hemangiomas, suture granulomas, adrenal rests, malignancies (breast or ovarian), residual carbon from previous ablations, reaction to oil-based hysterosalpingogram dye,
inflammatory changes, and splenosis."