 Vol.46 n° 4 |
Atualização Científica
Esta seção tem por objetivo divulgar os resumos dos
mais recentes artigos publicados na literatura mundial a respeito da
epidemiologia, prevenção, diagnóstico,
estadiamento, tratamento e prognóstico do câncer.
Caso o colega deseje receber separatas dos artigos referidos
(máximo cinco), imprima nosso
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Quality of life in patients with metastatic breast cancer receiving either
docetaxel or sequential methotrexate and 5-fluorouracil.
The purpose of this study was to evaluate the effects of two alternative chemotherapy regimes
on the quality of life (QoL) of patients with advanced breast cancer. In a multicentre trial, 283
patients were randomised to receive either docetaxel (T) or sequential methotrexate and
5-fluorouracil (MF). QoL was assessed at baseline and before each treatment using the European
Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire
(QLQ-C30). Initial compliance in the QoL study was 96% and the overall compliance 82%.
QoL data were available for 245 patients (T 130 and 115 MF). Both treatment groups showed
some improvement in emotional functioning during treatment, with a significant difference
favouring the MF group at treatment cycles 5 and 6. In the T group, the scores on the other
functional scales remained stable throughout the first six cycles. There were significant
differences favouring the MF group on the social functioning scale at treatment cycle 6 and on
the Global QoL scale at treatment cycles 5 and 6. On most symptom and single-item scales
there were no statistically significant differences between the groups. However, at baseline,
the T patients reported more appetite loss, at treatment cycles 2-4, the MF patients reported
more nausea/vomiting, and at treatment cycle 6, the T patients reported more symptoms of
fatigue, dyspnoea and insomnia. There were no statistically significant differences between
the groups in the mean change scores of the functional and symptom scales. Interindividual
variance was, however, larger in the T group. Differences in QoL between the two treatment
groups were minor. Hence, given the expectancy of comparable QoL outcomes, the choice of
treatment should be made on the basis of the expected clinical effect.
Key words: Quality of life; Advanced breast cancer; Chemotherapy; Docetaxel; Sequential methotrexate; 5-Fluorouracil.
Morbidity of adjuvant brachytherapy in soft tissue sarcoma of the extremity
and superficial trunk
Purpose: We have previously shown that adjuvant brachytherapy (BRT) improves local control
in soft tissue sarcoma (STS) of the extremity and superficial trunk. A detailed assessment of
the morbidity of this approach has not been examined. The purpose of this study was to
evaluate the toxicity associated with adjuvant BRT in terms of wound complications, bone
fracture, and peripheral nerve damage.
Methods and Materials: Between July 1982 and June 1992, 164 adult patients with STS of the
extremity or superficial trunk were randomized intraoperatively to receive or not to receive
BRT after complete resection. BRT was delivered with 192Ir to a total dose of 42-45 Gy. The
BRT and no-BRT arms were balanced with regard to age, sex, presentation (primary vs.
recurrent), site, grade, size, and depth. Morbidity was assessed in terms of significant wound
complication, bone fracture, and peripheral nerve damage (grade z 3). The significant wound
complications were defined as those wound problems requiring operative revision for coverage
or threatened limb loss, persistent seroma requiring repeated aspirations and/or drainage,
wound separation > 2 cm, hematoma > 25 ml, and/or purulent wound discharge. The median
follow-up was 100 months.
Results: The significant wound complication rate was 24% in the BRT group and 14% in the
no-BRT group, (p = 0.13). The rate of wound reoperation, however, was significantly higher
in the BRT arm (10% vs. 0%;p = 0.006). Examination of other covariables that may have
contributed to wound reoperation revealed the width of the excised skin (WES) to be a significant
factor [1% (WES 5 4 cm) vs. 10% (WES > 4 cm), p = 0.02]. Bone fracture only occurred in
patients receiving BRT (n = 3, 4%), although this was not statistically significant (p = 0.2). The
rate of peripheral nerve damage, however, was similar in both arms (7% vs. 7%).
Conclusion: The overall morbidity associated with adjuvant BRT was not significantly higher
than that with surgery alone. However, BRT and WES > 4 cm were associated with significantly
higher wound reoperation rate. This has significant implications for strategies designed to
maximize wound coverage in patients who receive BRT.
Key words: Sarcoma; Brachytherapy; Complications.
The influence of the radicality of resection and dose of postoperative
radiation therapy on local control and survival in carcinomas of the upper
aerodigestive tract
Purpose: To evaluate dose concepts in postoperative irradiation of carcinomas of the upper
aerodigestive tract according to the radicality of resection.
Patients and Methods: In a retrospective analysis, the charts of 257 patients with
histologically-proven carcinoma of the upper aerodigestive tract (40 TI, 80 T2, 53 T3, 84 T4
tumors, with nodal involvement in 181 cases) were reviewed according to the radicality of
resection and dose of irradiation administered. Sixty-four patients had tumor-free resection
margins (> 3 mm), 66 patients had close resection margins (< 3 mm), and 101 patients had RI
resections, and 26 patients had R2 resections. A median dose of 56 Gy was applied to the
primary tumor bed and the cervical lymphatics (2 Gy/fraction, 5 fractions/week). In cases of
Rl or R2 resection, or of close margins (< 3 mm), the tumor bed or, respectively, tumor
residuals were boosted with doses up to a median of 66 Gy. Locoregional tumor control and
survival was investigated by uni- and multivariate analyses according to T-, N-stage, grade of
resection, total dose of radiation, and presence or absence of extracapsular tumor spread and
lymphangiosis carcinomatosa.
Results: An overall 3- and 5-year survival rate of 60% and 45%, respectively, was achieved.
Rates for freedom from locoregional recurrence were 77% and 72% at 3 and 5 years,
respectively. The survival rates according to the grade of resection at 5 years were 67% for
patients resected with tumor-free margins, 59% for patients resected with close margins, 26%
for patients with RI resection, and 27% for patients with R2 resection. Within a median
follow-up period of 4.7 years for living patients, a total of 67 recurrences (26%) were observed
(in 9% of patients resected with tumor-free margins, in 27%a with close margins, in 37% of
R1 resected, and in 19% of R2 resected patients). Freedom from locoregional recurrence at 3
years was achieved in 100% of the patients resected with tumor-free margins, in 92% of
patients resected with close surgical margins, in 87% of R1 and 69% of R2 resected patients.
In multivariate Cox-regression analysis, the variables grade of resection (p = 0.00031) and
total dose of irradiation (p = 0.0046) were found as factors influencing locoregional control.
Variables influencing survival according to multivariate analysis are T-stage (p = 0.0057),
N-stage (p = 0.024), grade of resection (p = 0.000015), total dose of irradiation (p < 0.000000).
Extracapsular tumor spread and lymphangiosis carcinomatosa are factors of borderline
significance (p = 0.055, p = 0.066).
Conclusion: In postoperative radiotherapy of head and neck carcinomas, doses adapted to
the risk of locoregional recurrent disease should be applied. Patients with R1 and R2 resections
should be treated with doses of more than 68 Gy (2 Gy/fraction, 5 fractions/week) (with close
margins [< 3 mm] more than 66 Gy) to achieve an improvement in locoregional control and
survival.
Key words: Head and neck cancer; Postoperative radiotherapy; Resection margins; Radiation dose.
Prognosis and clinical presentation of BRCA2-associated breast cancer
54 female breast cancer patients from 22 families with BRCA2 germ line mutations from Sweden and Denmark were compared with 214 ageand date of diagnosis-matched controls identified among breast cancer patients from South Sweden. At diagnosis, BRCA2-associated cases were more often node-positive (N+). OR= 1.9 (95% confidence interval (CI) = 1.0-3.6; P=0.036), and were more often clinical stage IV: OR=4.6 (95% CI=1.3-17; P=0.021) than the controls. Bilateral disease was also more common among the BRCA2-associated cases: OR=2.4 (95°/a CI=1.1-5.3; P=0.027). Breast cancer-specific survival (BCSS) was significantly worse among the BRCA2-associated cases: RR 2.0 (95% CI=1.2-3.4; P=0.010). When stage was corrected for in a multivariate analysis, BCSS was no longer significantly worse for the BRCA2-associated cases: RR=1.6 (95% CI=0.85-3.1). The corresponding effect after correction for bilateral disease was: RR=1.8 (95% CI=1.0-3.1; P=0.034). The unfavourable prognosis in BRC A 2-associated breast cancer seems, to a great extent, to be a consequence of the higher clinical
stage at diagnosis. The increased presence of bilateral cancers appears to have less impact on survival in this group of hereditary breast cancer. Data presented here needs to be taken into account when counselling healthy carriers of BRC A2 germ line mutations.
Key words: Breast cancer; BRC A2; Hereditary: Prognosis; Stage.
Efficacy of adjuvant chemotherapy after curative resection for gastric cancer:
A meta-analysis of published randomised trials
Background: Several studies have investigated the possible role of the adjuvant chemotherapy
after curative resection for gastric cancer failing to show a clear indication; previous
meta-analyses suggested small survival benefit of adjuvant chemotherapy, but the statistical
methods used were open to criticisms.
Materials and methods: Randomised trials were identified by means of Medline and CancerLit
and by selecting references from relevant articles. Systematic review of all randomised clinical
trials of adjuvant chemotherapy for gastric cancer compared with surgery alone, published
before January 2000, were considered. Pooling of data was performed using the fixed effect
model. Death for any cause was the study endpoint. The hazard ratio and its 95% confidence
intervals (95% CI), derived according to the method of Parmar, were the statistics chosen for
summarising the relative benefit of chemotherapy versos control.
Results: Overall 20 articles (21 comparisons) were considered for analysis. Three studies used
single agent chemotherapy, seven combination of 5-fluorouracil (5-FU) with anthracyclin, ten
combination of 5-FU without anthracyclines. Information on 3658 patients, 2180 deaths, was collected. Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82, 95% CI: 0.75-0.89, P <0.001). Association of Anthracyclines to 5-FU did not show a statistically significant
improvement when compared with the effect of the other regimens.
Conclusions: Chemotherapy produces a small survival benefit in patients with curatively resected
gastric cancer. However, taking into account the limitations of literature based meta-analyses,
adjuvant chemotherapy is still to be considered as an investigational approach.
Key words: Adjuvant; Chemotherapy; Gastric cancer; Metaanalysis; Randomised clinical trial.
Biopsy confirmed benign breast disease, postmenopausal use of exogenous
female hormones, and breast carcinoma risk
Background: A history of proliferative benign breast disease has been shown to increase the
risk of developing breast carcinoma, but, to the authors’ knowledge, how postmenopausal
exogenous female hormone use, in general, has affected breast carcinoma risk among women
with a history of proliferative breast disease with or without atypia has not been well established.
Methods: In the current case-control study, nested within the Nurses’ Health Study, benign
breast biopsy slides of 133 postmenopausal breast carcinoma cases and 610 controls with a
history of benign breast disease, were reviewed. Reviewers had no knowledge of case status.
Results: Women with proliferative disease without atypia had a relative risk for postmenopausal
breast carcinoma of 1.8 (95%, confidence interval [CI]: 1.1 to 2.8), and women with atypical
hyperplasia had a relative risk of 3.6 (95%, CI: 2.0 to 6.4) compared with women who had
nonproliferative benign histology. Neither current postmenopausal use of exogenous female
hormones nor long term use for 5 or more years further increased the risk of breast carcinoma
in the study population beyond that already associated with their benign histology.
Conclusion: Women who had proliferative benign breast disease, with or without atypia,
were at moderately to substantially increased risk of developing postmenopausal breast carcinoma
compared with women who had nonproliferative benign conditions. In the current study,
postmenopausal exogenous female hormone use in general did not further increase the breast
carcinoma risk for women with proliferative benign breast disease. However, the analysis did
not exclude the possibility of increased risk with a particular hormone combination or dosage.
Key words: Breast carcinoma risk; Benign breast disease; Postmenopausal exogenous female hormones; Epidemiology.
Granulocyte-colony stimulating factor and multiple cycles of strongly
myelosuppressive alkylator-based combination chemotherapy in children with
neuroblastoma
Background: The authors assessed key effects of granulocyte-colony stimulating factor (G-CSF)
used prophylactically with multiple cycles of strongly myelosuppressive alkylator-based
combination chemotherapy. To the authors’ knowledge, no large study has focused on G-CSF
in this setting, yet this kind of treatment has recently become standard for poor risk pediatric
solid tumors such as neuroblastoma.
Patients and Methods: Children with neuroblastoma received cyclophosphamide 140mg/kg (i.e., 4200mg/m²), doxorubicin 75mg/m², and vincristine (CAV) in cycles 1, 2, 4, and 6 and cisplatin 200mg/m² and etoposide 600mg/m² (P/VP) in cycles 3, 5, and 7. To maximize dose intensity, chemotherapy was begun as soon as the absolute neutrophil count (ANC) was > 500/µL and platelet count was > 100,000/µL. No cytokines were used during 1990-1994 (control group; n = 28), but G-CSF was used from 1995 to 1998 (G-CSF group; n = 30) at 5µg/Kg/day subcutaneously from 1 day after chemotherapy until the ANC was > 500/µL on 2 successive days or was > 1000/µL.
Results: Each cycle of CAV decreased ANCs to < 200/µL in all 58 patients; recovery to 200/µL and to 500/µL was significantly sooner with G-CSF. In contrast, P/VP did not invariably cause severe neutropenia: similar numbers of patients in each group maintained ANCs > 200/µL and > 500/µL; recovery to 500/µL (but not to 200/µL) was significantly faster in the G-CSF group. G-CSF had no impact on rates of febrile episodes. Bacterial/ fungal infections were slightly less frequent in the G-CSF group with CAV (P = 0.11) but not with P/VP. Dose intensity through cycle 4 was the same in both groups. Beginning with cycle 3, G-CSF patients had slower recovery to platelet counts > 100,000/µL. Response rates were similar in the two groups.
Conclusion: With multiple cycles of strongly myelosuppressive alkylator-based combination
chemotherapy, prophylactic use of G-CSF hastened ANC recovery but did not reduce the
incidence of febrile episodes, had little impact on infection rates, did not yield augmented
dose intensity, was associated with prolonged thrombocytopenia, and had no effect on response
rates of neuroblastoma. The data support more limited use of G-CSF.
Key words: Granulocyte-colony stimulating factor (G-CSF); Neuroblastoma; Doseintensive chemotherapy.
Carcinoma of the fallopian tube
Background: The objective of the current study was to increase insight into the biology of
fallopian tube carcinoma through an analysis of possible clinical and pathologic determinants
of prognosis and to formulate recommendations with regard to a more optimal therapeutic approach for patients with this rare disease.
Methods: A study was performed of the pathology specimens and clinical case records from
151 patients with fallopian tube carcinoma who were treated consecutively. Both univariate
and multivariate analyses of possible prognostic factors were performed for the whole group
and for the subgroup of 41 patients with Stage I disease. The possible significance of serum
CA-125 levels as a tumor marker and a marker of response to platinum-containing chemotherapy
was evaluated.
Results: In multivariate analysis, disease stage, the presence of residual tumor, and a
hydrosalpinx-like appearance of the fallopian tube were of independent prognostic significance
for the whole cohort. For patients with Stage I disease, the depth of infiltration in the tubal
wall and intraoperative tumor rupture were of independent prognostic significance. The marked
tendency of this disease for extraperitoneal spread, even in apparently early stages, was
confirmed. In 37 evaluable, platinum-naïve patients, an overall response rate of 70% was
obtained with platinum-based chemotherapy, with a median response duration of 12.5 months.
In view of its low efficacy and high rate of serious complications, the use of postoperative
radiotherapy in the treatment of patients with fallopian tube carcinoma is no longer
recommended. Serum CA-125 level measurements in fallopian tube carcinoma patients have
the same significance as tumor and surrogate markers of response as in ovarian carcinoma
patients.
Conclusions: Prognostic factors in patients with early stage (Stages 0 and I) fallopian tube
carcinoma seem to differ from those in patients with early stage ovarian carcinoma. For
patients with more advanced stage disease, due to the striking similarities in prognostic and
clinical characteristics between the two diseases, the authors recommend that the treatment
and follow-up strategies for patients with ovarian carcinoma be adopted in the management of
patients with fallopian tube carcinoma.
Key words: Fallopian tube carcinoma; Prognosis; Chemotherapy; Surgery; CA 125.
Incidence of p 14ARF gene deletion in high-grade adult and pediatric
astrocytomas
The INK4a-ARF locus encodes 2 separate proteins through differential splicing of alternative first exons to produce p16INK4a (exon a) and p14ARF (exon 1ß) products in human cells. The
p16INK4a protein inhibits the cyclin D-dependent kinases (CDK) that control the phosphorylation of the Rb protein and cell proliferation. The p14ARF gene product can complex with and sequester the MDM2 protein within the nucleus, thus modulating the activity of the p53 protein. Loss of p16INK4a expression would disrupt the retinoblastoma (Rb)/p16INK4a /cyclin
D-dependent kinase (CDK4) pathway, whereas loss of p14ARF expression would inactivate both the Rb and p53/MDM2/p14ARF pathways through MDM2, which can complex with either Rb or p53. Loss of the p16INK4a gene on 9p21 has been documented in a wide range of human tumors, including one third of glioblastomas. However, in tumors showing homozygous loss of exon 2 of the p161NK4a gene, loss of exon 1ß of the p14ARF gene has not been established. In this study, we have assessed deletion of the p14ARF gene in 29 pediatric and 107 adult high-grade astrocytomas and 9 glioma cell lines, using multiplex PCR analysis for exon 1ß. We found homozygous deletions for exon 1a and exon 1ß in 3 of 29 (10%) of the pediatric cases (2 grade III, 1 grade IV), 25 of 107 (23%) of the adult cases (6 grade III and 19 grade IV), and 8 of 9 (89%) of the glioma cell lines. Therefore, loss of the INK4a-ARF locus in high-grade astrocytomas may contribute to the highly malignant behavior and treatment resistance of these tumors through elimination of multiple checkpoint cell cycle control proteins.
Key words: Astrocytoma; Glioblastoma; p16INK4a; p14ARF; INK4a-ARF locus.
Abbreviations: CDK, cyclin-dependent kinase; DMSO, dimethylsulfoxide; PCP, polymerase chain reaction; PBL, peripheral blood lymphocytes.
Preoperative portal vein embolization improves prognosis after right
hepatectomy for hepatocellular carcinoma in patients with impaired hepatic
function
Background: Percutaneous transhepatic portal vein embolization (PTPE) increases the safety
of subsequent major hepatectomy. The aim of this study was to determine the effect of PTPE
on longterm prognosis after hepatectomy in patients with hepatocellular carcinoma (HCC).
Methods: Seventy-one patients with HCC underwent right hepatectomy between 1984 and
1998. Preoperative PTPE was performed in 33 patients (group 1) and was not used in 38
patients (group 2). Outcome after operation was compared between the groups. The patients
were further divided according to the median tumour diameter (cut-off 6cm) and indocyanine
green retention rate at 15 min (INGR15) (cut-off 13 percent).
Results: The cumulative survival rate was significantly higher in group 1 than in group 2 in
patients with an ICGR15 of at least 13 per cent. Tumour-free survival rates were similar in both
groups. Of patients with tumour recurrence after right hepatectomy, those in group 1 were
more frequently subjected to further treatment.
Conclusion: Preoperative PTPE improves the prognosis after right hepatectomy for HCC in
patients with impaired hepatic function, although it does not prevent tumour recurrence.
Clinical classification and staging
For clinicians and researchers to make meaningful comparisons across patient populations, a
cancer staging system must be standardized, uniformly accepted, and widely applied. It must
be simple, practical, and must accurately reflect the prognosis of patients. Developing a staging
system for melanoma is particularly difficult, however, because its biologic behavior is so
often unpredictable. Nevertheless, researchers have modified the cutaneous melanoma staging
system several times over the past five decades as a direct result of the identification of increasingly powerful prognostic determinants. The current staging is based on today’s
well-established prognostic factors, but future changes are inevitable as the understanding of
the clinical progression of melanoma metastasis is refined.
This article provides a brief historical perspective and critical review of the staging systems
for cutaneous melanoma. Recent advances in the surgical staging of patients with primary
melanoma are introduced (e.g., sentinel lymphadenectomy, and future directions are discussed.
The article emphasizes the details of the current staging system and makes practical recommendations for stage-specific evaluation according to patient presentation.
Resource use in women completing treatment for breast cancer
Objective: To explore resources used by women completing treatment for breast cancer, how
they learned about them, and the psychological factors that predicted their use.
Design: A questionnaire on resource use was administered as part of a randomized clinical trial which assessed subjects' psychosocial characteristics and tested the outcomes of a psychosocial intervention.
Setting: Women completing treatment for breast cancer were recruited from the oncology
departments of three university-teaching hospitals in Montreal. A questionnaire gathered data
on the resources used by the subjects, how they learned about them, and the role of the health
care team in their decision-making. Emotional distress, dimensions of coping effort, a sense
of control and optimism were also measured.
Results: Five categories of resources were explored; professional services, informal support
networks, informational resources, support organizations and complementary therapies. Most
women found out about the last two resources by themselves. Women who used cancer support
organizations or complementary therapies scored high on the use of problem-solving coping
and low on the use of escape/avoidance coping. In addition they were moderately optimistic,
had a slightly lower sense of personal control and were somewhat more distressed than the
non-users. The use of support organizations and complementary therapies appears to represent
a thoughtful approach to dealing with the distress of cancer. The opinion of the oncologist
regarding resource use was valued by nearly half of the sample.
Recent advances - Palliative care
Palliative care is defined as comprehensive, interdisciplinary care of patients and families
facing a terminal illness, focusing primarily on comfort and support.’ Key aspects include
meticulous symptom control; psychosocial and spiritual care; a personalised management
plan that maximises patient-determined quality of life; family oriented care that extends through
the time of bereavement; and delivery of coordinated services, especially in the home but also
in hospital, extended care facilities, day care centres, and specialised units. In this article I
introduce current concepts about palliative care and review advances in this subject over the
past five years, highlighting developments of particular interest to generalists.
Methods: My choice of topics derives from my familiarity with patterns of medical practice, particularly in the United States; presentations at meetings; review of current textbooks; and monitoring of general medical journals, selected specialty journals on pain and cancer, and nine palliative care journals (see extra box on the BMJ's website).
Impact of laparoscopic staging in the treatment of pancreatic cancer
Hypothesis: Staging laparoscopy in patients with pancreatic cancer identifies unsuspected
metastases, allows treatment selection, and helps predict survival.
Design: Inception cohort.
Setting: Tertiary referral center.
Patients: A total of 125 consecutive patients with radiographic stage II to III pancreatic ductal
adenocarcinoma who underwent staging laparoscopy with peritoneal cytologic examination
between July 1994 and November 1998. Seventy-eight proximal tumors and 47 distal tumors
were localized.
Interventions: Based on the findings of spiral computed tomography (CT) and laparoscopy,
patients were stratified into 3 groups. Group 1 patients had unsuspected metastases found at
laparoscopy and were palliated without further operation. Group 2 patients had no demonstrable
metastases, but CT indicated unresectability due to vessel invasion. This group underwent
external beam radiation with fluorouracil chemotherapy followed in selected cases by
intraoperative radiation. Patients in group 3 had no metastases or definitive vessel invasion
and were resection candidates.
Main Outcome Measure: Survival.
Results: Staging laparoscopy revealed unsuspected metastases in 39 patients (31.2%), with 9
having positive cytologic test results as the only evidence of metastatic disease (group 1).
Fifty-five patients (44.0%) had localized but unresectable carcinoma (group 2), of whom 2
(3.6%) did not tolerate treatment, 20 (36.4%) developed metastatic disease during treatment,
and 21 (38.2%) received intraoperative radiation. Of 31 patients with potentially resectable
tumors (group 3), resection for cure was performed in 23 (resectability rate, 74.2%). Median
survival was 7.5 months for patients with metastatic disease, 10.5 months for those receiving
chemoradiation, and 14.5 months for those who underwent tumor resection (P = .01 for
group 2 vs group 1; P<.001 for group 3 vs group 1).
Conclusions: Staging laparoscopy, combined with spiral CT, allowed stratification of patients
into 3 treatment groups that correlated with treatment opportunity and subsequent survival. Among the 125 patients, laparoscopy obviated 39 unnecessary operations and irradiation in
patients with metastatic disease not detectable by CT. Laparoscopic staging can help focus
aggressive treatment on patients with pancreatic cancer who might benefit.
Routine chest roentgenography is unnecessary in the work-up of stage I and
II breast cancer
Purpose: Clinical practice guidelines of many professional societies call for routine staging
chest x-rays (SCXR) for all patients with invasive cancer. Given the estimated 157,000 patients
annually for whom this recommendation pertains, this screening examination represents a
considerable health care expenditure. If it were shown that SCXR rarely changed the management
of low-risk subsets of this population, it might be possible to selectively omit this practice
from the care of these patients with substantial resultant cost savings.
Patients and Methods: All patients with clinical stage I and 11 breast cancer presenting to the
Baystate Medical Center from 1989 through 1997 were identified through the Tumor Registry.
Their hospital records were reviewed for clinical presentation and documentation of SCXR.
Results: One thousand four hundred ninety-four patients were identified with clinical stage I and 11 disease. SCXR were available for review on 1,003 patients. Only one asymptomatic patient was upstaged to stage IV based on a SCXR. Two patients with primary lung tumors were also identified. These data demonstrate an asymptomatic pulmonary metastasis detection rate of 0.099%
(95% confidence interval, 0.0% to 0.6%). The total charges of SCXR for this group approached $180,000.
Conclusion: These data demonstrate the low diagnostic yield and high cost of routine SCXR
in the management of asymptomatic patients with clinical stage I and stage II breast cancer.
Because other studies have shown that SCXR changes neither quality of life nor overall survival,
SCXR should be limited to symptomatic patients in whom metastatic disease is suspected.
Survival benefit of D2 lymphadenectomy in patients with gastric
adenocarcinoma
Background: A definite resolution to the controversy on the optimal extension of lymph node
dissection (LND) in gastric cancer has not been achieved. Surgical morbidity and survival of
D1 and D2 LND are compared by multivariate analysis.
Methods: A retrospective cohort study of 219 patients with gastric cancer and curative resection performed according to Japanese rules. D1 dissection was performed in 106 cases and D2 in
113. The logistic regression model was used to define risk factors for surgical morbidity and
the Cox model to determine prognostic factors.
Results: Surgical morbidity occurs in 16.9% and 19.5% in D1 and D2 LND, respectively (P
= .7). The morbidity determinants were operation blood loss, splenectomy,
pancreaticosplenectomy, antrum location, low serum albumin, total gastrectomy, and metastatic
nodal ratio (P < .0001), but not D2 LND. Five-year survival was 35.1 % for D 1 and 64% for
D2 LND (P < .039). The prognostic factors were T stage, N stage, serum albumin level, total
gastrectomy, D2 LND, and comorbidity (P < .0001).
Conclusions: The increment of surgical morbidity and mortality rates attributed to D2 LND
is largely caused by the effect of splenectomy and pancreaticosplenectomy. A significant survival
benefit because of D2 LND was found. The results support the value of extended LND in the
surgical treatment of gastric cancer.
Key words: Gastric adenocarcinoma; Lymphadenectomy; Surgical morbidity; Prognostic factors; Splenectomy and pancreatectomy.
Relation between thymidylate synthase expression and survival in colon
carcinoma, and determination of appropriate application of 5-fluorouracil by
immunohistochemical method
Background: Thymidylate synthase (TS) is regarded as a parameter of 5-fluorouracil (5-FU)
chemosensitivity for colorectal carcinoma. Recent researchers indicate that the chemosensitivity
of 5-FU for colorectal carcinoma with low expression of TS is better than tumors with high
expression of TS. But the relation between TS expression and overall survival of curatively
resected colorectal cancer patients has been less studied.
Methods: Specimens of curatively resected colon carcinoma from 148 patients were included
in this study. TS expression in the tumor was assessed by immunohistochemical staining
technique, and the patients were categorized into TS-(+) and TS-(-) groups. First, the relation
between TS expression and survival of patients was examined. Next, for each group, we
compared survival between the chemotherapy-(+) and the chemotherapy-(-) subgroup.
Results: Overall survival was significantly better in the TS-(-) group (n = 107) than in the
TS-(+) group (n = 41) (P = .0003). In the TS-(-) group, there was little difference between the
chemotherapy-(+) and the chemotherapy-(-) subgroup. In the TS-(+) group, the survival of the
chemotherapy-(+) subgroup was significantly better than the chemotherapy-(-) subgroup (P = .0439).
Conclusions: TS, itself, may be a prognostic factor for colon carcinoma; and 5-FU adjuvant
chemotherapy may be appropriate for colon carcinoma with high expression of TS.
Key words: Thymidylate synthase; Colon carcinoma; 5-Fluorouracil; Immunohistochemistry.
Should internal mammary nodes be sampled in the sentinel lymph node era?
Background: Controversy exists regarding internal mammary lymph nodes (IMNs) in the
staging and treatment of breast cancer. Sentinel lymph node identification with radiocolloid
can map drainage to IMNs and directed biopsy can be performed with minimal morbidity.
Furthermore, recent studies suggest that IMN drainage of breast tumors may be underestimated.
To gain further insight into the prognostic value of IMNs, we reviewed the outcome of patients
in whom the IMN status was routinely assessed.
Methods: A retrospective review of 286 patients with breast cancer who underwent IMN dissection between 1956 and 1987 was conducted.
Results: Median follow-up is 186 months, age was 52 years (range, 21-85 years), tumor size was 2.5cm, and number of IMNs removed was 5 (range, 1-22); 44% received chemotherapy, 16% endocrine therapy, and 5% radiotherapy. Presence of IMN metastases correlated with primary tumor size (P < .0001) and number of positive axillary nodes (P < .0001) but did not
correlate with primary tumor location or age. Overall, the 20-year disease-free survival is significantly worse for the 25% of patients with IMN metastases (P < .0001). In patients with positive axillary nodes and tumors smaller than 2 cm, there was a significantly worse survival (P < .0001) in the patients with IMN metastases. This difference in survival was not seen in women with tumors larger than 2cm.
Conclusions: Patients with IMN metastases, regardless of axillary node status, have a highly
significant decrease in 20-year disease-free survival. Treatment strategies based on knowledge
of sentinel IMN status may lead to improvement in survival, especially for patients with small
tumors. At present, sentinel IMN biopsies should be performed in a clinical trial setting.
Key words: Breast cancer; Internal mammary lymph nodes; Sentinel lymph node.
Significance of multiple nodal basin drainage in truncal melanoma patients
undergoing sentinel lymph node biopsy
Background: Although previous studies have demonstrated that truncal site is associated with an adverse prognosis, explanations for such risk are lacking. In addition, the number of nodal basins as well as the number of lymph nodes containing regional metastases are important prognostic factors in these patients. Because the lymphatic drainage pattern of truncal melanoma often includes more than one basin, we designed a study to evaluate (1) whether patients with multiple nodal basin drainage (MNBD) were at an increased risk of lymph node metastases identified by sentinel lymph node (SLN) biopsy, and (2) whether the histological status of an individual basin reliably predicted the status of the other draining basins in patients with MNBD.
Methods: The records of 295 consecutive truncal melanoma patients who were managed
primarily with intraoperative lymphatic mapping and SLN biopsy, between 1991 and 1997,
were reviewed. All patients underwent preoperative lymphoscintigraphy, which established
the number and location of draining nodal basins. Univariate and multivariate analyses of
relevant clinicopathological factors were performed to assess which factors may predict the presence of a pathologically positive SLN.
Results: At least one SLN was identified in 281 patients. MNBD was present in 86 (31%)
patients, and a pathologically positive SLN was found in 56 (20%) patients. By multivariate
analysis, the presence of MNBD (relative risk = 1.9; P = .03), tumor thickness (P = .007), and
tumor ulceration (relative risk = 2.4; P = .01) were significant independent risk factors for the
presence of at least one pathologically positive SLN. SLN pathology in one basin did not
predict the histology of other basins in 19 (22%) of 86 patients with MNBD.
Conclusions: MNBD is independently associated with an increased risk of nodal metastases
in truncal melanoma patients. Because the histological status of an individual basin did not
reliably predict the status of the other draining basins in patients with MNBD, it is important
to adequately identify and completely assess all nodal basins at risk, as defined by
lymphoscintigraphy, in truncal melanoma patients.
Key words: Melanoma; Lymphoscintigraphy; Sentinel lymph node.
Human papillomavirus testing and the management of women with mildly
abnormal cervical smears: an observational study
Following publication of a report in Health Technology Assessment the NHS is running a pilot scheme screening women for human papillomavirus if they have a mildly dyskaryotic or borderline smear. How reliable is testing for human papillomavirus as a marker for high grade disease in those with mildly abnormal smears?
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Revista Brasileira de Cancerologia - Volume 46 n°4 Out/Nov/Dez 2000