Curative resection plus adjuvant chemotherapy for early stage primary gastric non-Hodgkin's lymphoma: A retrospective study with emphasis on prognostic factors and treatment outcome

Surgical Gastroenterology Department, Hospital do Servidor Público Estadual, São Paulo, SP, Brazil.
Arquivos de Gastroenterologia 03/2006; 43(1):30-6. DOI: 10.1590/S0004-28032006000100009
Source: PubMed
ABSTRACT
There is controversy regarding the optimal therapy for primary non-Hodgkin gastric lymphoma with some authors defending surgical extirpation either alone or in association with radiotherapy and or chemotherapy, especially in relation to the earlier stages of the disease.
To analyze the clinical-pathological features and the results of management approaches for patients with primary early-stage non-Hodgkin's lymphoma of the stomach operated in Surgical Gastroenterology Department, "Hospital do Servidor Público Estadual", São Paulo, SP, Brazil. The literature is reviewed to highlight the aspects of diagnosis, prognostic factors and role of the various treatment regimens.
Sixteen patients with primary early-stage gastric lymphoma underwent curative surgical treatment. The variables analyzed were age, sex, location, size, type of surgery, number of lesions, depth of invasion, histological type in accordance with Kiel's classification, involvement of lymph nodes, Ann Arbor stage classification modified by Musshoff and Schmidt-Vollmer, histological grade, margins, adjuvant therapy, clinical course and survival.
Ten patients (62.5%) underwent subtotal gastrectomy and six (37.5%) underwent total gastrectomy. The majority (9/56.2%) of the lesions were located in the antrum. Single lesions (10/62.5%) were more frequent than multiple lesions (6/37.5%). Thirteen patients (81.2%) were classified as stage IE and three (18.7%) as stage IIE1. Primary gastric lymphoma classified histologically as low or high grade was presented by 10 (62.5%) and 6 (37.5%) patients, respectively. The most frequent histological types were the lymphoplasmocytic cytoid (4/25.0%) and centroblastic (4/25.0%). Ten patients (62.5%) received adjuvant treatment (chemotherapy and/or radiotherapy). Nine patients (56.2%), all in stage IE, reached a survival greater than 5 years and of these eight (50.0.%) had received adjuvant therapy. Two (12.5%) patients with stage IIE1 presented peritoneal relapse and died 3.0 years and 3.5 years after their respective operations. The mean overall survival was 42.5 months.
Among the patients with primary early-stage gastric lymphoma (IE and IIE1), the gastric resection enabled an accurate clinicopathological staging, in addition to obtaining sufficient material for histopathological study and extirpation of the lesion. Furthermore, for patients with stage IE disease, the gastric resection combined with adjuvant therapy was associated with a greater than 5-year survival. Until prospective randomized studies are realized in order to evaluate the real efficacy of the different types of treatment for primary early-stage gastric lymphoma, management approaches should be individually tailored.

Full-text

Available from: Jaques Waisberg, Oct 05, 2015
30 Arq Gastroenterol v. 43 – no.1 – jan./mar. 2006
ARTIGO ORIGINAL / ORIGINAL ARTICLE
ARQGA/1204
INTRODUCTION
Primary gastric lymphoma represents more than
half of all primary gastrointestinal lymphomas in the
western world, accounting for 2% to 7% of all malignant
tumors of the stomach, and an increasing incidence has
been reported
(1, 2, 3, 4)
.
There is still controversy over the optimal treatment
in relation to the earlier stages of the disease particularly
regarding the role of surgery
(8, 11, 16, 28)
. The best treatment
for the earlier stages has not been defined due to a lack
of major prospective trials and the heterogeneity of
retrospectives series, which, in some cases, analyzed
all stages together or included patients with intestinal
CURATIVE RESECTION PLUS
ADJUVANT CHEMOTHERAPY FOR
EARLY STAGE PRIMARY GASTRIC
NON-HODGKIN’S LYMPHOMA:
a retrospective study with emphasis on
prognostic factors and treatment outcome
Jaques WAISBERG
1
, Eduardo Antonio ANDRÉ
1
, Maria Isete Fares FRANCO
2
,
Júlio Zaki ABUCHAM-NETO
1
, Daniela WICKBOLD
1
and Fábio Schmidt GOFFI
1
ABSTRACT - Background - There is controversy regarding the optimal therapy for primary non-Hodgkin gastric lymphoma with
some authors defending surgical extirpation either alone or in association with radiotherapy and or chemotherapy, especially in
relation to the earlier stages of the disease. Aim - To analyze the clinical-pathological features and the results of management
approaches for patients with primary early-stage non-Hodgkin’s lymphoma of the stomach operated in Surgical Gastroenterology
Department,Hospital do Servidorblico Estadual”, São Paulo, SP, Brazil. The literature is reviewed to highlight the aspects of
diagnosis, prognostic factors and role of the various treatment regimens. Method - Sixteen patients with primary early-stage
gastric lymphoma underwent curative surgical treatment. The variables analyzed were age, sex, location, size, type of surgery,
number of lesions, depth of invasion, histological type in accordance with Kiel’s classification, involvement of lymph nodes,
Ann Arbor stage classification modified by Musshoff and Schmidt-Vollmer, histological grade, margins, adjuvant therapy,
clinical course and survival. Results - Ten patients (62.5%) underwent subtotal gastrectomy and six (37.5%) underwent total
gastrectomy. The majority (9/56.2%) of the lesions were located in the antrum. Single lesions (10/62.5%) were more frequent
than multiple lesions (6/37.5%). Thirteen patients (81.2%) were classified as stage IE and three (18.7%) as stage IIE1. Primary
gastric lymphoma classified histologically as low or high grade was presented by 10 (62.5%) and 6 (37.5%) patients, respectively.
The most frequent histological types were the lymphoplasmocytic cytoid (4/25.0%) and centroblastic (4/25.0%). Ten patients
(62.5%) received adjuvant treatment (chemotherapy and/or radiotherapy). Nine patients (56.2%), all in stage IE, reached a survival
greater than 5 years and of these eight (50.0.%) had received adjuvant therapy. Two (12.5%) patients with stage IIE1 presented
peritoneal relapse and died 3.0 years and 3.5 years after their respective operations. The mean overall survival was 42,5 months.
Conclusions - Among the patients with primary early-stage gastric lymphoma (IE and IIE1), the gastric resection enabled an
accurate clinicopathological staging, in addition to obtaining sufficient material for histopathological study and extirpation of the
lesion. Furthermore, for patients with stage IE disease, the gastric resection combined with adjuvant therapy was associated with a
greater than 5-year survival. Until prospective randomized studies are realized in order to evaluate the real efficacy of the different
types of treatment for primary early-stage gastric lymphoma, management approaches should be individually tailored.
HEADINGS - Lymphoma. Non-Hodgkin’s lymphoma. Gastric neoplasms. Prognostic factors. Survival.
1
Surgical Gastroenterology and
2
Pathology Departments, “Hospital do Servidor Público Estadual”, São Paulo, SP, Brazil.
Address for correspondence: Dr. Jaques Waisberg - Rua das Figueiras, 550 — apt. 134 - 09080-300 - Santo André, SP, Brazil. E-mail: jaqueswaisberg@uol.com.br
Page 1
v. 43 – no.1 – jan./mar. 2006 Arq Gastroenterol 31
lymphomas, mucosa-associated lymphoid tissue (MALT) and
low-grade lymphomas
(12, 16, 27, 28, 31)
.
Due to the relative rarity of the tumor, few centers have
accumulated an adequate number of patients to generate meaningful
data and thereby develop rational treatment protocols. In addition
to this, the use of different primary gastric lymphoma staging
and histopathological classification models has made it difficult
to perform comparative analyses of their results.
Surgical resection of these tumors is important for diagnosis,
and although extirpation of the lesion is potentially curative,
it has been reported that around 50% of patients with primary
early-stage gastric lymphoma present relapse when treated by
surgery alone
(15, 16, 27, 28, 31, 32, 33)
.
Studies have predominantly included patients, whose disease
was already at a late stage, thereby making it difficult to evaluate
the potential effect on patient survival of curative extirpation of
localized primary gastric lymphoma
(2, 3, 28, 36, 37)
.
Thus, the objective of this study was to describe the clinical-
pathological features and the results of management of patients
with primary early-stage non-Hodgkin’s lymphoma of the stomach
that underwent curative surgical treatment in our Department.
In addition the literature is reviewed to highlight the various
aspects of diagnosis, prognostic factors and the role of different
treatment modalities.
METHODS
A total of 33 patients with primary gastric lymphoma confirmed
by histopathological examinations were treated in the Department
of Surgical Gastroenterology, “Hospital do Servidor Público
Estadual”, São Paulo, SP, Brazil, during the 28-year period from
1973 to 2001. Of these, 17 were excluded from the study for
the following reasons: 6 were not operated in view of serious
associated diseases; 4 patients underwent palliative operations;
7 presented advanced-stage disease. Thus, the data from this
sample represents a review of 16 patients with primary gastric
lymphoma in initial stage, which underwent curative surgical
treatment, 10/16 in association with postoperative chemotherapy
and/or radiotherapy.
The term curative surgery implied the macroscopic absence
of residual disease at the end of the surgical procedure and in the
anatomopathological exam of the resected lesion. The clinical
course of these patients was obtained from a review of the
hospital records and from interviews with the patients or their
relatives. Postoperative complications were defined as those
that occurred within 30 days after the surgical intervention. The
survival was calculated from the time of the operation until the
last follow-up or death.
Twelve (75.0%) of the patients were male and four (25.0%)
were female, resulting in a male/female ratio of 3:1. The mean
age of the patients was 62.8 years, ranging from 40 to 83 years
(Table 1). All the patients were caucasian.
The disease was staged using the Ann Arbor system for
non-Hodgkin’s lymphomas, as modified by MUSSHOFF and
SCHMIDT-VOLLMER
(21)
. Stage IE primary gastric lymphoma
was defined as the presence of lymphoma involving the stomach in
the absence of any lymph node involvement. Stage IIE1 includes
patients with lymph node involvement in the perigastric region.
Stages IE and IIE1 were considered to be the early stages. Late
stage was defined as the presence of metastases in unilateral sub-
diaphragmatic regional lymph nodes (stage IIE2), the presence of
metastases in bilateral sub-diaphragmatic regional lymph nodes
(stage IIIE), or the presence of hematogenic dissemination with
involvement of the stomach and one or more extra-lymphatic
organs (stage IVE).
The staging was done from the physical examination
findings, gastroscopy and the respective biopsy, bone marrow
biopsies, contrast radiography of the stomach, ultrasonography,
computed tomography of the thorax and abdomen, laparotomy
and histopathological examination of specimens from the surgical
extirpation. Each neoplasm was classified as primary to the
stomach in accordance with the criteria of DAWSON et al.
(7)
: an
absence of superficial palpable lymphadenopathy in the initial
clinical presentation, an absence of mediastinal lymph node
involvement in radiography of the thorax, total and differential
leukocyte count with normal values, a lesion limited to the
stomach and regional lymph nodes, and an absence of tumor in
the liver and spleen.
The original slides were reviewed by a pathologist and, whenever
necessary, new sections were cut from the paraffin blocks. The
lymphomas were histologically classified in accordance with
Kiel’s system.
With regard to the degree of malignancy, low-grade lymphomas
were considered to be those that presented proliferation of
centrocytic cells or small cells. High-grade lymphomas were
considered to be lesions that displayed centroblastic or large-
cell proliferation.
The extent of the gastric extirpation varied according to
the location of the lesion. It was total, or extended total in
association with splenectomy and caudal pancreatectomy, for
tumors located in the body or cardia, and subtotal for those
located in the antrum. The extent of the lymphadenectomy
was R1 standard until the first half of the 1990’s and then R2
standard in recent years.
The decision regarding adjuvant therapy was made in
collaboration with the consulting oncologist and often reflected
that physician’s personal preference and the drugs disposable
at the time of treatment. The chemotherapy protocols indicated
for the control of microscopic residual disease were: CHOP
(cyclophosphamide 750 mg/m
2
, doxorubicin 50 mg/m
2
, vincristine
1.4 mg/m
2
via intravenous route and prednisone 60 mg/m
2
orally,
administered on days 1 to 5), CHOP plus bleomycin 10 mg/m
2
via
intravenous route, and CHOP plus BACOP (bleomycin 10 mg/m
2
,
adriamycin 60 mg/m
2
, cyclophosphamide 750 mg/m
2
,
vincristine
1.4 mg/m
2
and prednisone 60 mg/m
2
orally, administered on days
1 to 5). Radiotherapy, when applied, was at a standard dose of
2000 to 4000 cGy.
Quantitative variables were represented by absolute
frequency (n) and relative frequency (%). Considering the
nature of the samples, the statistical models utilized were
arithmetic mean. Patients survival was analyzed using the
Kaplan-Meier method.
Waisberg J, André EA, Franco MIF, Abucham-Neto JZ, Wickbold D, Goffi FS. Curative resection plus adjuvant chemotherapy for early stage primary gastric non-Hodgkin’s lymphoma:
a retrospective study with emphasis on prognostic factors and treatment outcome
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32 Arq Gastroenterol v. 43 – no.1 – jan./mar. 2006
RESULTS
The mean time elapsed between onset of symptoms and
the surgical treatment was 11.3 months, ranging from 1.3 to
24 months. The most frequent symptoms were epigastric pain
(75.0%), upper digestive tract hemorrhage (50.0%), weight loss
(50.0%), asthenia (37.5%) and vomiting (31.2%). The mean
weight loss was 8.3 kg. Physical examination of the patients in
this study did not reveal any abnormalities.
Gastroscopy and the respective biopsy were performed on
14 patients (87.5%), i.e. an average of 1.3 examinations per
patient. In four patients (25.0%), the diagnosis was “carcinoma”
and in another three patients (18.7%) there was a suspicion of
lymphoma. Among the remaining seven (43.7%) patients, the
histopathological study revealed “chronic gastritis”, although
the endoscopic appearance suggested malignancy of the gastric
lesion. Two patients who did not undergo gastroscopy had a
diagnostic suspicion of gastric neoplasm on the basis of findings
from contrast radiology of the stomach.
Four patients (25.0%) were examined using computed
tomography, which revealed thickening of the gastric wall in
one patient and no anomalies in the remainder. Four patients
(25.0%) underwent bone marrow biopsy and the results were
all normal. All the patients had their definitive diagnosis
established by the histopathological study of the product from
the gastric extirpation.
Ten patients (62.5%) underwent subtotal gastrectomy and
six (37.5%) underwent total gastrectomy, in association with
removal of the spleen and the tail of the pancreas in two (12.5%)
cases (Table 1).
Five patients (31.2%) presented one or more of the following
postoperative complications: anastomotic stula in three,
bronchopneumonia in three, acute respiratory insufficiency
in two, and stenosis of the esophageal-jejunal anastomosis,
peritonitis, pleural empyema and acute renal insufficiency in
one case each. The patient who presented late stenosis of the
esophageal-jejunal anastomosis was successfully treated with
endoscopic dilatation. Four patients (25.0%) died because of
postoperative complications: respiratory insufficiency in three
and septic shock in one patient.
The lesion was located in the antrum in nine patients (56.2%),
in the gastric body in six cases (37.5%) and in the cardia in one
case (6.2%) (Table 1).
The mean of the largest dimension of the tumor was 4.8 cm,
ranging from 1.0 to 10.0 cm (Table 2). The lesions located more
proximally in the stomach (cardia and gastric body) presented a
greater mean diameter (5.9 cm) than those located more distally
(3.9 cm). There was a single lesion in 10 patients (62.5%) and
multiple lesions (two or more) in 6 patients (37.5%) (Table 2).
The predominant macroscopic appearance of the neoplasm
was ulcerative in nine cases (56.2%), followed by infiltrative-
ulcerative in three cases (18.7%), vegetative-ulcerative in two
cases (12.5%) and infiltrative in one patient (6.2%).
The neoplasm invaded the tunica muscularis of the stomach
in eight patients (50.0%), the serous membrane in five cases
(31.2%) and reached the adjacent adipose tissue in three cases
(18.7%) (Table 2). The surgical margin was involved by the
neoplasm in one patient (6.2%) (Case 4).
In accordance with Kiel’s classification, the most frequent
histological types were lymphoplasmocytic cytoid (4/25.0%) and
centroblastic (4/25.0%), followed by lymphocytic (3/18.7%),
centrocytic-centroblastic (2/12.5%), centrocytic (2/12.5%) and
immunoblastic (1/6.2%) (Table 2). Eleven patients (68.7%)
presented histological low-grade primary gastric lymphoma,
while another five patients (31.2%) presented histological high-
grade primary gastric lymphoma (Table 2).
Thirteen patients (81.2%) were classified as stage IE and three
patients (18.7%) as stage IIE1 (Table 2). All nine patients (56.2%)
who achieved a survival greater than 5 years and one with 1 year
of disease free survival did not present involvement of the lymph
nodes (stage IE). On the other hand, two patients (16.6%) with
involvement of the lymph nodes (stage IIE1) presented peritoneal
relapse and died after 3.0 years and 3.5 years after their operations,
in both cases due to carcinomatosis (Table 1).
TABLE 1 – Main clinical aspects, morphological features and treatment modalities of the cases of early-stage primary gastric lymphoma
Case Age Sex Location Size (cm) Surgery Adj ther No. lesions
1 69 Male Cardia 10 Total None Single
2 40 Female Antrum 1.2 Subtotal CHTP Multiple
3 48 Female Antrum 6.0 Subtotal CHTP Single
4 74 Female Antrum 1.8 Subtotal RDTP Multiple
5 59 Male Body 7.5 Subtotal CHTP+RDTP Single
6 77 Male Antrum 6.0 Subtotal CHTP Single
7 53 Male Antrum 2.5 Subtotal CHTP Multiple
8 53 Male Antrum 2.0 Total CHTP Multiple
9 79 Male Body 8.0 Total None Single
10 67 Male Antrum 7.0 Subtotal None Single
11 43 Male Body 1.2 Subtotal None Single
12 63 Male Body 7.5 Total CHTP Multiple
13 73 Male Body 6.0 Total None Single
14 54 Male Antrum 8.0 Subtotal CHTP Single
15 83 Male Antrum 1.0 Subtotal None Multiple
16 70 Female Body 1.3 Total CHTP Single
Adj ther = adjuvant therapy; CHTP = chemotherapy; RDTP = radiotherapy; No. lesions = number of lesions
Waisberg J, André EA, Franco MIF, Abucham-Neto JZ, Wickbold D, Goffi FS. Curative resection plus adjuvant chemotherapy for early stage primary gastric non-Hodgkin’s lymphoma:
a retrospective study with emphasis on prognostic factors and treatment outcome
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v. 43 – no.1 – jan./mar. 2006 Arq Gastroenterol 33
Out of the 12 patients that survived more than 1 month, 10
(83.3%) received adjuvant treatment: 8/10 (50.0%) chemotherapy,
1/10 (6.2%) radiotherapy and 1/10 (6.2%) received both chemotherapy
and radiotherapy. The remaining two patients (12.5%) refused
adjuvant treatment (Table 1). One of them (case 1), submitted to
the total gastrectomy, presented a voluminous neoplasia in cardia
that penetrated until the serosa of the organ, with perigastric lymph
nodes involvement (stage IIE2). It presented peritoneal relapse
and died with carcinomatosis 3.5 years after the operation. Case
11, submitted to subtotal gastrectomy, presented a small lesion
in the gastric body that penetrated until the muscular layer of
the wall of the organ, without lymph nodes involvement (stage
IE). He survived more than 5 years, without active disease. The
mean global survival was 42.5 months.
DISCUSSION
Primary gastric lymphoma arises from the mucosal or
submucosal layer and spreads diffusely into the mucosa and
submucosa, and the tumor extends along the surface of the
gastric wall, usually without lymph node involvement
(6, 17, 35)
.
In this situation, gastroscopy may not be capable of detecting
the lesion, due to the lack of suggestive alterations, such as
polypoid or ulcerated lesions or also diffuse thickening of gastric
folds
(14, 30)
. Initial gross finding of gastric lymphoma may mimic
various gastric lesions, such as peptic ulcer diseases, gastritis
and primary gastric carcinoma. Although a dense lymphoid
infiltrate is the most consistent feature of gastric lymphomas, it
is not reliable as a marker of lymphoma
(30)
. In the present study,
these characteristics of primary gastric lymphoma may explain
the absence of endoscopic and histopathological detection of
primary gastric lymphoma in an initial stage in the majority of
cases during the preoperative period.
Endoscopic ultrasonography has become the tool to evaluate
the depth of the tumor in gastric cancer or lymphoma. However,
sensitivity or specificity of the enlarged lymph node varies from
one study to another
(5)
.
The ideal treatment for primary early-stage gastric lymphoma
continues to be controversial
(3, 9, 15, 16, 19, 28)
. Surgical extirpation,
chemotherapy and radiotherapy have been utilized in association
or alone
(2, 3, 13, 24, 25)
. Surgical treatment is preferred for the following
reasons: (i) more representative samples for histological diagnosis
and consequent classification can be obtained; (ii) the risk of
serious hemorrhages or perforation of the gastric wall during
chemotherapy or radiotherapy treatment of non-removed tumors
is eliminated; (iii) more accurate staging; (iv) the possibility of
removing lesions before initiating adjuvant chemotherapy and/or
radiotherapy increases the chances of success of the treatment; and
(v) relief of symptoms
(2, 4, 15, 16, 28)
. One of the principal advantages
of staging via laparotomy with gastrectomy is the capability of
accurately discriminating between stage IE, IIE1 and IIE2 lesions,
as lymph nodes adjacent to the stomach cannot generally be
accurately visualized by non-invasive methods
(2, 8, 15,16)
.
The extent of surgical extirpation utilized in the cases of
this series involved total or subtotal gastrectomy, with regional
lymphadenectomy
(2, 3, 4, 15, 16)
. With regard to splenectomy, this was
done in association with total gastrectomy in cases of lesions of
the gastric cardia and gastric body involving the serous membrane
because of the high incidence of metastases in the lymph nodes of
the hilum of spleen
(4, 15, 16)
. On the other hand, in cases of primary
gastric lymphoma located in the lower third of the stomach, the spleen
was spared, provided that it was not grossly involved
(2, 3, 4, 15)
.
Debulking of advanced disease was associated with high
morbidity and mortality and low response rates of 6%-40%
(1, 15, 16,
28)
. Operative mortality was between 3%-25% with higher rates
for palliative procedures, which were performed for symptomatic
relief, removal of tumor mass and avoidance of hemorrhage or
perforation related to other modes of therapy
(1, 2, 3, 4, 15, 16)
.
The morbidity, mortality and impairment of life quality
generated by gastric resection have led some investigators to avoid
gastrectomy, opting instead to treat patients with a conservative
approach
(10, 19, 20, 24, 25, 26, 29)
.
A prospective study
(26)
has found that in stages IE and IIE,
the complete response, survival rate and disease free survival
Waisberg J, André EA, Franco MIF, Abucham-Neto JZ, Wickbold D, Goffi FS. Curative resection plus adjuvant chemotherapy for early stage primary gastric non-Hodgkin’s lymphoma:
a retrospective study with emphasis on prognostic factors and treatment outcome
TABLE 2 – Main morphological features, outcome and survival of the cases of early-stage primary gastric lymphoma
Case Depth Histological Type LN Staging Margins Grade Outcome Survival
1 Serosa Lymphocytic Compr IIE1 Free Low Death 3.5 years
2 Muscle Lymphopl/cytd Free IE Free Low Alive > 5 years
3 Muscle Centroblastic Free IE Free High Alive > 5 years
4 Serosa Centrobl/ccytc Free IE Compr Low Alive > 5 years
5 Muscle Lymphopl/cytd Free IE Free Low Alive > 5 years
6 Serosa Centrocytic Compr IIE1 Free Low Death 3 years
7 Fatty tissue Lymphocytic Free IE Free Low Alive > 5 years
8 Fatty tissue Lymphopl/cytd Free IE Free Low Alive > 5 years
9 Serosa Centrocytic Compr IIE1 Free Low Death 18 days
10 Serosa Centroblastic Free IE Free High Death 18 days
11 Muscle Centroblastic Free IE Free Low Alive > 5 years
12 Muscle Immunoblastic Free IE Free High Alive > 5 years
13 Muscle Lymphopl/cytd Free IE Free Low Death 1 month
14 Fatty tissue Centrobl/ccytc Free IE Free High Alive > 5 years
15 Muscle Lymphocytic Free IE Free Low Death 12 days
16 Muscle Centroblastic Free IE Free High Alive > 5 years
LN = lymph nodes; Compr = compromised; Centrobl/ccytc = centroblastic/centrocytic; Lymphopl/cytd = lymphoplasmocytic/cytoid
Page 4
34 Arq Gastroenterol v. 43 – no.1 – jan./mar. 2006
rates were similar to those who underwent complete resection
and partial or no surgery prior to administration of chemotherapy.
Survival rates of 60% with surgery alone compared to 85% if
adjuvant chemotherapy was used have been reported
(26)
. In other
studies
(10, 19, 20, 34)
, the mortality and morbidity related to surgery
were similar if not greater than those related to non-surgical
treatment for stage I and II. In patients with comorbid factors
and increased risk of surgery-related morbidity and mortality,
chemotherapy offered an effective or equally effective mode of
treatment to surgical resection
(24, 25, 26)
. Series have shown the
superiority of combined surgery and chemotherapy to single
mode with survival rates reaching 86%-94% for stages IE and
IIE
(13, 31, 34)
. In these series, the survival rates were higher for
those who underwent complete resection; thus resection was
the most important variable and major determinant of prolonged
complete remission.
Surgery can be performed with a low complication rate, and
result in satisfactory patient survival in stage I disease
(2, 15, 31, 33)
. In
stage II disease, surgical curability did not affect the survival,
implying the necessity for randomized studies to evaluate
treatment strategies
(2, 3, 28, 31, 33)
. However, considering the stage
migration after histological examination and possible inaccuracy
of preoperative staging, the choice of non-surgical treatment
must be considered with care
(31)
.
Studies have recommended adjuvant therapy (chemotherapy
and/or radiotherapy) for patients with primary gastric lymphoma
invading the serous membrane, with involvement of the surgical
margins or infiltrated lymph nodes
(4, 15, 16, 28, 34)
. Although there have
been reports of apparent cure of primary gastric lymphoma with
a single resection, these should be considered with caution, since
initial dissemination may be undetectable despite an exhaustive
staging
(2, 8, 16, 29)
. Thus, postoperative chemotherapy may be used
to inhibit recurrence of neoplasm in the remaining stomach and
eradicate microscopic residual disease
(16, 23, 29)
.
Radiotherapy directed towards the framework supporting the
stomach and the para-aortic lymph nodes has been demonstrated
to be beneficial for patients with involvement of lymph nodes
and disease that is locally advanced or cannot be extirpated
(13, 17)
.
Radiation was used post-operatively in high- and low-grade
lymphomas, for any residual tumors in stages I and II in order
to improve the disease free survival
(17)
. Nevertheless, the use
of radiotherapy in the treatment of primary gastric lymphoma
remains controversial, given the absence of randomized and
prospective studies evaluating its efficacy, especially as an
isolated treatment.
In general, the decision regarding the adjuvant therapy
reflected the personal preference of the oncologist. Case 4, an
elderly patient with comorbidity that did not allow the patient to
receive adjuvant chemotherapy, was submitted to the adjuvant
radiotherapy due to the compromised surgical margin. Case 5
presented a large lesion in the gastric body and was submitted
to subtotal gastrectomy associated with adjuvant chemotherapy
and radiotherapy. Nowadays, in the patients submitted to the
curative resection of the primary gastric lymphoma in initial stage,
we indicated adjuvant chemotherapy to eradicate microscopic
residual disease.
Helicobacter pylori (H. pylori) infection has been documented
in up to 90% of patients with low-grade MALT lymphoma
(11,
18, 22)
. The discovery of a causative role for H. pylori in the
development of gastric marginal zone lymphoma of the MALT
type has dramatically altered the therapeutic approach to patients
with early stage disease. Durable complete remission might be
achieved in up to 80% in patients with early stage MALT lymphoma
following eradication of the bacteria
(11, 18)
. Conservative anti-H.
pylori therapy may regress early-stage gastric lymphoma to some
degree, but not completely
(11)
. The effect is considered insufficient
in the case of lymphoma invasion beyond the submucosa of the
stomach and a pretreatment diagnosis of the depth of lymphoma
invasion is difficult
(18)
. Besides which, the duration of this response
remains unknown and long-term follow-up studies are needed
for cases treated without surgery. Radiotherapy, chemotherapy
or surgery has been tried in patients that failed to respond to
H. pylori eradication, or that had a low grade of gastric MALT
lymphoma without H. pylori infection
(11, 15, 18)
.
In most series, the poor prognostic factors for primary gastric
lymphoma are considered to be high histological grade, involvement
of lymph nodes, incomplete extirpation of the neoplasm, primary
lesion greater than 10 cm in diameter and invasion of the serous
membrane or adjacent organs
(1, 2, 4, 33)
. On the other hand, good
prognosis was associated with low-grade disease, age below 65
years, free surgical margins in cases of resection, and achievement
of initial complete remission
(1, 2, 3, 13, 27, 33, 34)
.
The overall 5-year survival for patients considered in the
present study who presented primary gastric lymphoma in
stage IE and IIE1 was 56.2%, although the 5-year survival
found in the literature range 52 to 93%
(2, 3, 4, 31, 32, 33)
. Indeed, the
survival rates reach 60% with surgery alone, 85% with surgery
plus adjuvant chemotherapy
(26)
, and 86%-94% for combined
surgery and chemotherapy in stages IE and IIE
(13, 31, 34)
. This
difference found in the present study may disclose the high rate
of postoperative complications (25%) and the patients (2/12, 5%)
with more advanced local disease whose survival less than 5
years. In the present sample, four patients, all elderly, died due to
postoperative complications. Two of them (cases 9 and 13), both
73 years of age, presented large and localized gastric lesions in
the body of the organ, which motivated the performing of total
gastrectomy associated to splenectomy and corporeal-caudal
pancreatectomy. The third patient (case 10), 67 years old and
submitted to subtotal gastrectomy, presented an extensive lesion
and high degree of neoplasia, with infiltration of the serosa of
stomach. The fourth patient (case 15), 83 years old, was submitted
to subtotal gastrectomy for multiple gastric lesions. All four
of these patients presented comorbidities, a fact that probably
influenced the unfavorable postoperative course. In addition, it
should be considered that, since this was a historical series, recent
improvements in the intra-operative care and especially in the
postoperative period could have lowered the rate of complications
and mortality in this particular series. Another two patients, both
presenting stage IIE1 and invasion of the serosa of stomach,
whose lesions reached 6.0 cm and 10 cm in the largest diameter,
died 3 years and 3.5 years, respectively, after removal of the
neoplasia, both due to peritoneal recurrence. Involvement of
Waisberg J, André EA, Franco MIF, Abucham-Neto JZ, Wickbold D, Goffi FS. Curative resection plus adjuvant chemotherapy for early stage primary gastric non-Hodgkin’s lymphoma:
a retrospective study with emphasis on prognostic factors and treatment outcome
Page 5
v. 43 – no.1 – jan./mar. 2006 Arq Gastroenterol 35
the lymph nodes and invasion of the serosa of the organ and the
expressive dimensions of the neoplasias must have contributed
to the fact that these patients developed carcinomatosis. On the
other hand, all the other patients with stage IE reached 5 years
of survival without recurrence of the neoplasia.
Involvement of the lymph nodes and absence of adjuvant
treatment signicantly diminishes patient survival
(1, 2, 3, 4, 15, 16,
31, 32, 33)
, as was observed in the present series, and probably
because of the small number of patients in each subgroup,
it was not possible to obtain definitive results regarding the
inuence of these variables on the prognosis for patients with
primary gastric lymphoma.
Because primary early-stage gastric lymphoma is only rarely
observed in each treatment center, only cooperative prospective
multicentric studies may gain sufficient statistical power to form
conclusions, regarding the best means of increasing the cure
rate and reducing side effects from the treatment while also
considering the patients’ quality of life
(33)
.
CONCLUSIONS
Among the patients with primary early-stage gastric lymphoma
(IE and IIE1), this study, albeit with a limited number of patients,
demonstrated that gastric resection permitted extirpation of the
lesion together with an accurate clinicopathological staging
and provided sufficient material for histopathological study.
For patients with localized primary gastric lymphoma in stage
IE, the gastric resection plus adjuvant therapy was associated
with a 5-year survival. However, until prospective randomized
studies are realized in order to evaluate the real efficacy of the
various treatment strategies for primary early-stage gastric
lymphoma, management programs should be individually
tailored for each patient.
ACKNOWLEDGEMENT
The authors are grateful to Dr. Marcelo Mester for his
technical support.
Waisberg J, André EA, Franco MIF, Abucham-Neto JZ, Wickbold D, Goffi FS. Ressecção curativa associada à quimioterapia adjuvante para o
linfoma gástrico primário não-Hodgkin em estádio inicial: estudo retrospectivo com ênfase nos fatores prognósticos e resultado do tratamento.
Arq Gastroenterol. 2006;43(1):30-6.
RESUMO - Racional - A terapêutica do linfoma não-Hodgkin gástrico primário é controversa, com defensores da extirpação cirúrgica,
da radioterapia e quimioterapia isoladas ou combinadas, especialmente em relação aos estádios mais iniciais. Objetivos - Analisar as
características clínico-patológicas e os resultados do tratamento nos doentes operados no Serviço de Gastroenterologia Cirúrgica do Hospital
do Servidor Público Estadual, São Paulo, SP, com linfoma gástrico primário em estádio inicial. Realizar revisão da literatura, destacando os
aspectos diagnósticos, fatores prognósticos e o papel das diferentes modalidades de tratamento. Método – Dezesseis doentes com linfoma
gástrico primário no estádio inicial foram submetidos ao tratamento cirúrgico curativo. Idade, sexo, localização, tamanho, tipo de operação,
número de lesões, profundidade da invasão, tipo histológico de acordo com a classificação de Kiel, comprometimento linfonodal, estádio
pela classificação de Ann Arbor modificada por Musshoff e Schmidt-Vollmer, grau histológico, margens, terapia adjuvante, evolução e
sobrevivência. Resultados - Dez (62,5%) doentes foram submetidos a gastrectomia subtotal e seis (37,5%) a gastrectomia total. A maioria
(9/56,2%) das lesões estava localizada no antro. Lesões únicas (10/62,5%) foram mais freqüentes que as múltiplas (6/37,5%). Treze doentes
(81,2%) foram classificados no estádio IE e três (18,7%) no estádio IIE1. Dez (62,5%) enfermos apresentaram linfoma gástrico primário de
baixo grau e seis (37,5%) de alto grau. Os tipos histológicos mais freqüentes foram o linfoplasmocítico citóide (4/25.0%) e o centroblástico
(4/25,0%). Dez doentes (62,5%) receberam tratamento adjuvante (quimioterapia e/ou radioterapia). Nove enfermos (56,2%), todos no
estádio IE, atingiram sobrevivência maior que 5 anos e oito (50,0%) receberam tratamento adjuvante. Dois (12,5%) doentes no estádio IIE1
tiveram recidiva peritonial e faleceram 3,0 anos e 3,5 anos após suas respectivas operações. A média global de sobrevivência foi de 42,5
meses. Conclusões - Nos doentes com linfoma gástrico primário em estádio inicial (IE e IIE1), a extirpação gástrica permitiu o estádio
clinico-patológico acurado, a obtenção de material para o estudo anatomopatológico, a extirpação da lesão e, para enfermos com doença
no estádio IE, a extirpação gástrica combinada com terapia adjuvante foi associada com sobrevivência maior que 5 anos. Até que estudos
prospectivos casualizados sejam realizados para avaliar a eficácia dos diferentes tipos de tratamento do linfoma gástrico primário em estádio
inicial, os protocolos de tratamento devem ser adaptados individualmente.
DESCRITORES - Linfoma não-Hodgkin. Neoplasias gástricas. Fatores prognósticos. Sobrevida.
Waisberg J, André EA, Franco MIF, Abucham-Neto JZ, Wickbold D, Goffi FS. Curative resection plus adjuvant chemotherapy for early stage primary gastric non-Hodgkin’s lymphoma:
a retrospective study with emphasis on prognostic factors and treatment outcome
Page 6
36 Arq Gastroenterol v. 43 – no.1 – jan./mar. 2006
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Recebido em 20/12/2004.
Aprovado em 8/8/2005.
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Page 7
  • Source
    • "Treatment options include chemotherapy with a short course of rituximab, radiation therapy, or, rarely, surgery in H. pylori negative gastric MALT lymphoma [6,20]. Several studies have shown more than 90% five year survival rate with surgical re-section alone in low grade gastric MALT lymphoma which is also useful to obtain accurate clinicopathological staging [21–23]. "
    [Show abstract] [Hide abstract] ABSTRACT: Patient: Female, 91 Final Diagnosis: Low-grade gastric MALT lymphoma Symptoms: Recurrent epigastric and right upper quadrant dyscomfort Medication: Rituximab Clinical Procedure: esophagogastroduodenoscopy • gastric biopsy Specialty: Gastroenterology. Unusual or unexpected effect of treatment. Mucosa associated lymphoid tissue (MALT) lymphoma can occur in any extranodal organ or tissue, stomach being the common site. Most of the gastric MALT lymphomas are related to chronic H. pylori infection. H. pylori negative gastric MALT lymphoma is relatively uncommon and usually treated with a short course of chemotherapy, radiotherapy or surgery. Herein, we present a case of an elderly female with H. pylori negative, low-grade gastric MALT lymphoma that was successfully treated with a short course of rituximab. This case report emphasizes that rituximab monotherapy can be an effective treatment for H. pylori negative low grade gastric MALT lymphoma especially in an elderly patient where surgery or radiotherapy may not be appropriate.
    Full-text · Article · Nov 2013 · American Journal of Case Reports
  • Source
    • "Treatment strategies in nodal NHL are well established, but there still remains much debate and controversy regarding the optimal approach in GI NHL, particularly in PGL. Surgery, radiotherapy and chemotherapy have been used alone or in various combinations181920212223242526. "
    [Show abstract] [Hide abstract] ABSTRACT: The study was initiated to obtain epidemiologic data and information on anatomic and histologic distribution, clinical features, prognostic factors and treatment results in patients with primary gastrointestinal non-Hodgkin's lymphomas (PGI NHL). We carried out analysis of 208 patients of PGI NHL during the time period from January 1997 to January 2007 at the Clinical Oncology Department, Tanta University Hospital to evaluate clinical features and treatment outcome. A total of 74.5% of patients had gastric NHL (PGL). Within the intestine, the small bowel and the ileocecal region were involved in 8.2% and 7.2% of the cases, respectively. Multiple gastrointestinal (MGI) involvement was in 6.3%. Approximately 84% of the PGI NHL were in stages IE/IIE. Forty percent of PGL were of low-grade mucosa-associated lymphatic tissue (MALT) type. Most intestinal NHL were of high grade NHL. The median follow-up time was 89.3 months. The site of origin, disease stage, complete resection of the tumor and histologic grade were the most important significant prognostic factors affecting disease-free (DFS) and overall survivals (OS). Numbers in intestinal lymphomas were too small for subanalyses. The OS and DFS after 5 years were 78.5% and 72.3% respectively in all patients with PGI NHL. Primary gastrointestinal non-Hodgkin's lymphomas are heterogenous diseases. The number of localized PGL allowed for detailed analyses. Larger studies are needed for stages III and IV and for intestinal NHL. Although this is a retrospective study, a stomachconserving approach may be favored. KEY WORDS: Gastrointestinal neoplasms - NHL - Gastrointestinal lymphoma - Prognostic factors - Survival.
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  • [Show abstract] [Hide abstract] ABSTRACT: Gastric mucosa-associated lymphoid tissue (MALT) lymphomas are rare in the gut, and its occurrence rate was 1% to 5% of the malignant tumors. In histological type, most of them are non-Hodgin's lymphomas, while Hodgin's lymphomas are seldom seen. There have been a lot of controversies on the optimal treatments of gastric MALT lymphomas for a long time. Surgery was traditionally considered as the most important approach to cure the disease. However, anti-H pylori therapy has been regarded as an alternative method since H pylori infection was found to be relevant with the pathogenesis of gastric MALT lymphomas. In this article, we reviewed the current status and recent advances on the treatment of this disease.
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