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Interstitial iodine-125 radiation without adjuvant therapy in the treatment of clinically localized prostate carcinoma

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Author Reply
e are pleased to respond to the comments of Drs.
Zauber and Berman in regard to our article,1
which described an additional metachronous case of
gastric lymphoma preceding adenocarcinoma.
Although ‘‘stump’’ adenocarcinoma arising from
the gastric remnant is relatively common, the development of gastric carcinoma after treatment of primary
gastric lymphoma is very rare. Only 19 patients (including the patient in Drs. Zauber and Berman’s comment) with such metachronous tumors have been reported (mean interval between the onset of the 2 tumors, 12.9 years), 17 of whom developed stump
adenocarcinoma after gastric lymphoma.2 In our previous large study analyzing the clinicopathologic features of 233 patients with resected primary gastric
lymphoma,3 134 patients had undergone partial resection of the stomach (subtotal gastrectomy or fundic
resection), 88 of whom were followed for ¢5 years
after surgery. However, none of these patients developed stump adenocarcinoma in the gastric remnant
during the follow-up period (range, 5 – 22.5 years;
mean, 11.8 years). None of the 88 patients had ever
received radiotherapy; 16 patients were treated with
chemotherapy after surgery, and 72 were treated with
gastrectomy alone. In contrast, of the 17 patients reported to have stump adenocarcinoma after gastric
lymphoma, 13 patients (76%) had received radiotherapy with or without chemotherapy, whereas only 6
patients (35%) had received chemotherapy for the preceding lymphoma.2 Based on these observations, we
speculate that radiation treatment may play a more
important role than chemotherapy in carcinogenesis
in the gastric remnant in these metachronous cases.4
Because the long term effect of radiotherapy after
surgery on the prognosis of patients with gastric
lymphoma remains controversial,5,6 we normally do not
perform radiotherapy after gastrectomy for patients with
primary gastric lymphoma, except in patients with unresectable or recurrent disease. We believe that the eradication of Helicobacter pylori, rather than radiotherapy, may
be more useful in preventing the development of adenocarcinoma7 as well as that of mucosa-associated
lymphoid tissue lymphoma8 in the stomach.
Nakamura S, Aoyagi K, Iwanaga S, Yao T, Tsuneyoshi M,
Fujishima M. Synchronous and metachronous primary gastric lymphoma and adenocarcinoma: a clinicopathologic
study of 12 patients. Cancer 1997;79:1077–85.
Zorlu AF, Atahan IL, Gedikoglu G, Ruacan S, Sayek I, Tekuzman G. Does gastric adenocarcinoma develop after the treatment of gastric lymphoma? J Surg Oncol 1993;54:126–31.
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Nakamura S, Akazawa K, Yao T, Tsuneyoshi M. Primary gastric lymphoma: a clinicopathologic study of 233 cases with
special reference to evaluation with the MIB-1 index. Cancer
Brumback RA, Gerber JE, Hicks DG, Strauchen JA. Adenocarcinoma of the stomach following irradiation and chemotherapy for lymphoma in young patients. Cancer 1984;54:
Azab MB, Henry-Amar M, Rougier P, Bognel C, Theodore C,
Carde P, et al. Prognositic factors in primary gastrointestinal
non-Hodgkin’s lymphoma: a multivariate analysis, report of
106 cases, and review of the literature. Cancer 1989;64:1208–
Gobbi PG, Dionigi P, Barbieri F, Corbella F, Bertoloni D,
Grignani G, et al. The role of surgery in the multimodal
treatment of primary gastric non-Hodgkin’s lymphomas: a
report of 76 cases and review of the literature. Cancer
Uemura N, Mukai T, Okamoto S, Yamaguchi S, Mashiba H,
Taniyama K, et al. Helicobacter pylori eradication inhibits
the growth of intestinal type of gastric cancer in initial stage.
Gastroenterology 1996;110:A282.
Boot H, de Jong D, van Heerde P, Taal B. Role of Helicobacter
pylori eradication in high grade MALT lymphoma. Lancet
Shotaro Nakamura, M.D.
Second Department of Internal Medicine
Faculty of Medicine
Kyushu University
Fukuoka, Japan
Masazumi Tsuneyoshi, M.D.
Second Department of Pathology
Faculty of Medicine
Kyushu University
Fukuoka, Japan
Use of Primary Breast Carcinoma
Characteristics to Predict Lymph
Node Metastases—Reply
rs. Silverstein and Barth1 conclude their Editorial:
Reply to Counterpoint with an anecdote of a patient with ductal carcinoma in situ (DCIS) and a sentinel lymph node with a ‘‘micrometastasis’’ detected by
immunohistochemistry only. They ask, ‘‘What do we
do now?’’
Lymph nodes actually do have a function to
pick up garbage; therefore, it should be no surprise
that after the multiple traumatic acts of dye and
isotope injections and surgical manipulation of
mastectomy, some benign and malignant cell clusters would be dislodged and accompany the dye
and isotopes to the sentinel lymph node. Lymphatic
and vascular showers of tumor cells have been rec-
W: Cancer
CANCER January 1, 1998 / Volume 82 / Number 1
ognized for many years during surgical procedures.
Epithelial displacement by needle biopsy and needle localization, benign or malignant, has been a
more recently recognized event,2 and cell clusters
could travel to lymph nodes in this manner. Benign
epithelial inclusions are normally found in lymph
The presence of the immunohistochemically
detected epithelial cell clusters beg the question of
whether they are malignant cells or benign cells
and, if malignant, whether they have the ability to
establish a secondary tumor.
The problems that Drs. Silverstein and Barth
face have to do with test sensitivity, specificity, and
prevalence. As with any laboratory test, a low specificity test (i.e., one that detects epithelial cells but
is not specific for metastasizing carcinoma cells) of
very high sensitivity (i.e., immunohistochemistry)
used in a very, very low prevalence setting (DCIS
in lymph nodes) will yield many, many more falsepositive than true-positive results. The answer to
the question posed by the authors is therefore clear:
‘‘Don’t ask the question (i.e., don’t order the test).’’
As similar or even more sensitive methods (i.e.,
polymerase chain reaction) are applied in similar
settings, the adage ‘‘Don’t ask’’ will be increasingly
Silverstein MJ, Barth A. Use of Primary Breast Carcinoma
Characteristics to Predict Lymph Node Metastases—Reply
[Editorial: Reply to Counterpoint]. Cancer 1997;79:1862–4.
Youngson BJ, Liberman L, Rosen PP. Displacement of carcinomatous epithelium in surgical breast specimens following
stereotaxic core biopsy. Am J Clin Pathol 1995;103:598–602.
Robert J. Rosser, M.D.
Department of Pathology
Desert Hospital
Palm Springs, California
Author Reply
r. Rosser points out an important problem: the accuracy of immunohistochemistry with keratin stains
when it is used to evaluate the status of axillary lymph
nodes thought to be negative by routine hematoxylin
and eosin (H & E) staining. A key problem that arises,
in some cases, is distinguishing a true metastasis from
iatrogenic needle debris that has migrated to a lymph
node. Making the distinction can be exceptionally difficult because some malignant cells, such as invasive lobular carcinoma cells, may appear to be benign. In addi-
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tion, if a group of cells within a lymph node are clearly
malignant cells, we have no way of being certain whether
or not they were destined to be destroyed by that lymph
node or whether they had the molecular genetic abilities
required to become a metastasis.
The Ludwig trial,1 in which negative axillary lymph
nodes were serially sectioned at 6 levels and stained with
H & E, revealed a 9% incidence of previously undetected
micrometastasis. Patients who were converted to lymph
node positive status by this technique had a 16% decrease in 5-year disease free survival and a 9% decrease
in overall survival. Moreover, these data held up over 10
years of follow-up (R. Gelber, personal communication,
December 1995). However, step sectioning of axillary
lymph nodes is a tedious, time-consuming, and expensive process. Our hope is that immunohistochemical
analysis will be as accurate as step sectioning in identifying these patients. Our concern, and clearly Dr. Rosser’s concern, is that it may be ‘‘too accurate.’’
The impact of ‘‘immunochemically only’’ positive
lymph nodes has been examined for years (Table 1). In
one of the largest series,2 12% of 343 routinely studied
lymph node negative patients were found to have positive lymph nodes by immunohistochemical analysis.
There was a 28% decrease in 5-year disease free survival
but no statistically significant effect on overall survival.
On the other hand, Trojani et al.3 demonstrated a 25%
decrease in overall mortality among patients with immunochemically positive axillary lymph nodes.
The harder one looks for positive lymph nodes, the
more will be found. Current technology using polymerase chain reaction (PCR) may yield an even higher percentage of lymph node positivity4,5 than immunohistochemistry. Clearly, patients with lymph nodes that are
shown to be positive by one of these techniques and
negative by standard H & E staining are not the same
as patients with lymph nodes that are shown to be positive by standard pathology. In all likelihood, they have a
better prognosis. Therefore, as these techniques become
more widely used, lymph node positivity must be described by the method used to determine it. For example, a patient may be N0 (H & E) and N1 (immunohistochemistry). At this point in the evolution of our knowledge, we cannot be sure whether this patient has Stage
I or Stage IIA disease. As even more sensitive techniques,
such as polymerase chain reaction (PCR), become more
widely available, we will have patients that are N0 (H &
E), N0 (immunohistochemistry), N1 (PCR). As these new
data accrue, they will have to be equated with outcome
to determine the proper stage; in all likelihood, the current staging system will have to be amended to reflect
Although we understand Dr. Rosser’s point completely, ‘‘Don’t ask, don’t tell’’ is not acceptable for those
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without, adjuvant, carcinoma, radiation, treatment, clinical, interstitial, 125, iodine, localized, therapy, prostate
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