Incidental appendectomy and pathologic conditions of the appendix vermiformis

LETTERS TO THE EDITORS Surgical techniques for cytoreduction in advanced ovarian malignancy To the Editors: I read with great interest the article by Rose (Rose PG. The cavitational ultrasonic surgical aspirator for cytoreduction in advanced ovarian cancer. A"l J OBSTH GYNECOL 1992 ;166: 843-6). Rose reponed that using the cavitational ultrasonic aspirator he was able to effectively achieve an optimal cytoreduction in 48% of patients (22 of 45 patients); this is without a doubt a low percentage when it is considered that the volume of postoperative residual disease significantly affects patient survival. Rose also reported that in 29 sites in which he used this technique he was not able to achieve an optimal cytoreduction and other extensive surgical procedures had to be used. Therefore it appears that this technique is of limited value, especially in removing dense fibrous tumor; this view is supported by Deppe et al. I From my experience and the experience of others," 3 it appears that electrosurgical debulking with an argon beam coagulator is a far more superior technique. The argon beam coagulator allows better visibility, hemostasis, and tumor destruction. With this technique tumors in inaccessible sites such as the diaphragm, stomach, duodenum, and liver capsule could be debulked. The argon beam coagulator can be used for larger surface areas and areas with limited tolerance to injury. I believe that the argon beam coagulator is more effective in achieving optimal cytoreduction « 0.5 em) than the neodymium-yttrium aluminum garnet (Nd:YAG) surgical laser and the Cavitron ultrasonic surgical aspirator. In conclusion, the efficacy of this modality of cytoreduction needs to be investigated further. Prospective randomized study and analysis of long-term follow-up in comparison with other methods are needed toevaluate the effectiveness of the cavitational ultrasonic aspirator. Samir A. Farghaly, MD, PhD Albert Einstein College of Medicine, Room 421, Ullman Research Bldg., 1300 Morris Park Ave., New York, NY 10461

REFERENCES I. Deppe G, Malviya VK, Malone JM . Debulking surgery for ovarian cancer with the Cavitron Ultr asonic Surgical Aspirator (CUSA): a preliminary report. Gynecol Oncol 1988 ; 3 1:223-6 . 2. Bard Electro Medical Systems, In c. System 600 argon beam coagulator tissue effects . Technical Documents, January 1988. 3. Brand E, Pearlman N. Electrosurgical debulking of ovarian cancer: a new technique using the argon beam coagulator. Gynecol On col 1990 ;39 :115- 8.

Reply To the Editors: I appreciate the opportunity to respond to the Farghaly letter. Farghaly incorrectly states that the tumors of 48 % of the patients were optimally cytoreduced with the cavitational surgical aspirator. In my study the cavitational surgical aspirator was used in

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48 % of patients with advanced ovarian carcinoma to achieve optimal cytoreduction. In fact, the rate of optimal cytoreduction in this 24-month period, including all patients seen in our institution for advanced ovarian carcinoma (stage III or IV with> 2 em of disease), was 86% (Results, page 844, line 10). Farghaly also refers to 29 sites of disease that were interpreted as being noncytoreducible. These 29 sites were actually sites other than the liver, spleen, diaphragm, or fixed adenopathy where the cavitational aspirator was used to effect optimal cytoreduction and obviate the need for more extensive su rgery. Although these sites could be managed by standard operating techniques, including intestinal resection, it is my impression that cytoreduction by cavitational surgical aspirator has less morbidity. As Farghaly points out, as is discussed in the manuscript, and as is reported by Deppe et aI., I the cavitational surgical aspirator is not very effective in dense fibrotic tumors. Recently, a number of newer surgical techniques have become available including the cavitational surgical aspirator, the carbon dioxide laser, the argon beam coagulator, and the Nd:YAG laser. Because no comparative studies of these different techniques ha ve been performed, the statements in the third paragraph of Farghaly's letter are unsupported. The references cited concerning the argon beam coagulator are not comparative studies and deal with a limited experience, a total of seven patients. The argon beam coagulator is an ablative technique and therefore does not prevent damage to underlying normal structures. In my opinion, the selective destruction of tissue is o ne of the major ad vantages of the cavitational surgical aspirator. I am in full agreement with Farghaly that objective comparative studies of these newer techniques are warranted . Peter G. Rose, MD Department ofObstetrics and Gynecology, University ofMassachusetts Medical Center, 55 Lake Ave. North, Worcester, MA 01655

REFERENCE I. Deppe G, Malviya VK, Malone .1M. Debulking surgery for ovarian cancer with the cavitron ultrasonic surgical aspirator (cusa)-a preliminary report. Gynecol Oncol 1988;31: 223-6 .

Incidental appendectomy and pathologic conditions of the appendix vermlformis To the Editors: We read with great interest the article by Nezhat and Nezhat (Nezhat C, Nezhat F. Incidental appendectomy during videolaserscopy. ful J OBSTET GYNECOL 1991;165:559-64) and would like to make some additional remarks about pathologic conditions of the vermiform appendix. The authors found the appendix to be histologically normal in 52 % of the cases in which appendectomy was performed. However, it should be noted that 12 of these " normal" appendixes were described as exhibiting focal fibrous obliteration of the lumen.

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Fig. I. Ne uro ge n ic a p p end icopa thy with formati on of central neuroma. a, Low-power ma gnifi cat ion of appendix ve rmi lo rm is with ob litera tio n of lum en , stained with antibodies again st 5-100 protein . Note staining o f myenteri c pl exu s (long arrows). C entral ar ea o f oblite ra tio n ex hibi ts, in addition to fibroblasts a nd co lla gen fibers , numerous nerv e fibers that are immunoreactive for 5-1 00 protein (short arrows) and a re shown at higher magnification in (b). (c), Are a of oblite ration a lso exh ibits numerous ex trae p ithe lia l e n d ocr ine cells, which are immunoreactive for serotonin (ar row s). (Anti-S- IOO prot ein . a, Original m agnification x 22. b, Original magnifi cation x :-\60. An ti-se ro to n in . c, Original magnification x 36 0 .

As sta te d by Nezhat a n d Nezhat, figures qu oted in th e literature for the incid e nce of pathologic findin gs in a ppendixes removed incid entally vary from 6% to 83 9',;. The histol ogic d iagnoscs include acut e a nd chro nic a ppendicitis, luminal fibr osis, mucosal hyperplasia, e ndometriosis, mucocele, a nd carcinoid , am ong others. On the basis of our own findings and data published in th e literature, we believe th at a t least som e of the cases dia gnos ed as sim p le fibrosis o r ch ro nic a p pe nd icitis in fac t represent neurogenic a p pcnd ico pa thy, which is ofte n very difli cult to d istinguish from fibrotic cha nges in co nventionally stained sect ion s. Ne uroge n ic appendicopath y is cha rac te rized by the proliferation and degeneration of neural clements a n d a n increase in extrae p irhe lial end ocrine cells .' Hofler e t al ." distinguished between a n intra mucosal form and neurogenic a p pe nd ico pa thy in which th ere is formation of a central neuroma. A rel a-

tionship be tween appendiceal fibrosis and neurogen ic appendicopath y ha s been demonstrated in two stud ies in which cha nges corresponding to neurogeni c appendicopathy were found in all cases of " fibro us obliteratio n" of the appendix investigated. "' · We have undertaken immunohistochemi cal investigations to further confirm the relationship between fibrosis and n eurogenic ap pe ndicop a thy: Twenty appendixes ex h ibiting focal submucosal fibrosis randomly selected fro m our a rchives a nd diagnosed as exhibiting "fibro sis" or "c hro nic ap p e nd icitis with fibro sis" and 10 appendixes with a typ ical central neurom a were stain ed with antibodi es against neural and endocrine markers. All th e neuroma ca ses e xh ibited prolifer at ion of neural elements im mu no reac tive I()I - 5-100 prot ein, Leu-7 , and substance P, and an inc rease in coll agen fibers in th e area of o blitera tio n (Fig. 1, a and b) and adjacent

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submucosa. There were also increased numbers of extraepithelial endocrine cells immunoreactive for chromogranin A, serotonin (Fig, 1, c) and, in some cases, somatostatin. Similar changes with proliferation of neural elements and an increase in numbers of extraepithelial endocrine cells were also seen in the fibrotic areas of 16 of the 20 appendixes with focal submucosal fibrosis." These findings and published data indicate that there is a close relationship between appendiceal fibrosis and neurogenic appendicopathy. Neurogenic appendicopathy may cause chronic lower abodminal pain suggested by some authors to be the result of increased secretion of serotonin and regulatory peptides" 6. 7; this is an argument for incidental appendectomy during laparoscopy for the investigtaion of such pain. It is interesting to note that a study of 5000 appendectomy specimens revealed that neurogenic appendicopathy is found in 14% of men but in 20% of women." If inspection of hematoxylin and eosin stained specimens leaves the diagnosis in doubt, neurogenic appendicopathy can be confirmed by immunohistochemical investigations with, for example, antibodies against S-100 protein. Johannes Dietl, MD, Peter Ruck, MD, and Edwin Kaiserling, MD Department of Obstetrics and Gynecology and the Institute of Pathology, University of Tubmgen, 7400 Tubmgen, Germany

REFERENCES 1. Aubock L, Ratzenhofer M. "Extraepithelial enterochromaffin cell-nerve fibre complexes" in the normal human appendix, and in neurogenic appendicopathy. J Pathol 1982; 136:217-26. 2. Hofler H, Kasper M, Heitz PU. The neuroendocrine system of normal human appendix, ileum and colon, and in neurogenic appendicopathy. Virchows Arch A Pathol Anat HistopathoI1983;399:127-40. 3. Stanley MW, Cherwitz D, Hagen K, Snover DC. Neuromas of the appendix: a light-microscopic, immunohistochemical and electron-microscopic study of 20 cases. Am J Surg Pathol 1986; I 0:80 1-15. 4. Olsen BS, Holck S. Neurogenous hyperplasia leading to appendiceal obliteration: an immunohistochemical study of 237 cases. Histopathology 1987;11:843-9. 5. Ruck P, Kaiserling E. Fibrosis of the appendix. Histopathology 1991;19:387-8. 6. Hofler H. Neurogene Appendikoparhie - eine haufige abel' selten diagnostizierte Krankheit. Langenbecks Arch Chir 1980;351:171-8. 7. Dhillon AP, Rode J. Serotonin and its possible role in the painful non-inflamed appendix. Diagn Histopathol 1983;6: 239-46.

Reply To the Editors: We were delighted to note the comments of Dietl et al. First, their work on neurogenic appendicopathia adds another dimension-neuroimmunoendocrinology - to refine further the pathologic assessment of the vermiform appendix. Second, we agree with Dietl et al. that a 20% incidence of neurogenic appendicopathia in female appendixes and the likely associated pain in many instances support doing incidental appendectomies routinely unless contraindicated. Third, Dietl et a1. highlighted 12 cases from our article in which the appendixes were reported "nor-

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mal," though exhibiting luminal obliteration and focal fibrosis. We have reexamined these cases and found no evidence of neural or endocrine components, but are curious as to what might be revealed if techniques more specific for neurogenic appendicopathia were used. Fourth, we are aware of the rapidly emerging role of neuroimmunoendocrinology in broadening the scope of clinical pathophysiology, 13 and we regard the work of Dietl et a1. as timely and significant. Finally, because updating the capability of surgical laboratory pathologic coverage is a periodic necessity, we have been pondering what immunoreactive and immunochemical procedures are needed and appropriate for both clinical and research use. The thoughts of Dietl et al. have been relevant and helpful, and we thank them for their discussion and references to the literature. Camran Nezhat, MD, and Farr Nezhat, MD Fertility and Endoscopy Center, Laser Endoscopy Institute ofAtlanta, 5555 Peachtree Dunwoody Road NE, Atlanta, GA 30342

REFERENCES 1. deGroat WC. Neuropeptides in pelvic afferent pathways. Experientia Suppl 1989;56:334-61. 2. Koob GF, Sandman CA, Strand FL, eds. A decade of neuropeptides. Ann N Y Acad Sci 1990;579: 1-281. 3. O'Dorisio MS, Panerai A, eds. Neuropeptides and immunopeptides: messengers in a neuroimrnune axis. Ann NY Acad Sci 1990;594:1-499.

Effect of fetal sepsis on umbilical cord blood gases To the Editors: In the article by Meyer et a1. (Meyer BA, Dickinson JE, Chambers C, et al. The effect of fetal sepsis on umbilical cord blood gases. AM J OBSTET GYNECOL 1992;166:612-7), although the umbilical arterial pH in neonates with sepsis was significantly reduced overall, the difference in the actual pH appeared small. Had the Apgar scores of the septic and control groups been shown in the report, it would have been of interest and clinical relevance to see whether the umbilical arterial pH values relate to Apgar scores, traditionally a measure of neonatal condition at birth, between these two groups of neonates. We have been reviewing the outcome of pregnancies complicated by clinical chorioamnionitis over a 2-year period (1988 through 1989) in our institution. The majority of these pregnancies ended in preterm delivery, usually after premature rupture of the membranes or spontaneous preterm labor. We have categorized the neonates into four groups: (1) a definite sepsis group and (2) a probable sepsis group, as defined previously, 1 (3) a group with neutropenia or leukocytosis but without clinical symptoms, and (4) a group of controls without evidence of sepsis. We present here the preliminary data of the 68 neonates that had umbilical arterial pH measured at birth. There was no difference in the gestational age or umbilical arterial pH among these four groups, and although the definite sepsis group had a more than threefold higher incidence of low pH ( < 7.2) compared with the controls, this difference was