Early-stage Adenocarcinoma Research Articles

Does oncologic specialization influence outcomes following surgery in early stage adenocarcinoma of the endometrium?

Objective. To evaluate treatment outcomes in women with early-stage endometrial cancer (FIGO IA, IB, IC, or IIA) surgically managed by a general gynecologist (GYN) or a gynecologic oncologist (GYO). Methods and results. 349 women treated from 1990–2003 were studied. Median follow-up was 3.7 years. Ninety-five were classified as high-intermediate risk (HIR: stages IB grade III, IC grade II or III, any stage IIA). 110 women received adjuvant radiotherapy. The GYO group had more unfavorable tumor characteristics based on stage and grade ( P < 0.0001), shorter follow-up (median 3.1 vs. 5.1 years, P = 0.0002), and an absolute 12% less likelihood of receiving adjuvant radiotherapy ( P = 0.04). Local and distant failures were not significantly different. Overall survival favored GYN patients ( P = 0.02) with no difference in disease-specific survival ( P = 0.38). Multivariate analysis for disease-free survival revealed HIR disease ( P = 0.04) and GYO treatment ( P = 0.049) to be significant, with a trend for age ≤64 ( P = 0.05). Multivariate analysis for overall survival found age ≤64 ( P = 0.0001), HIR disease ( P = 0.01), and adjuvant radiotherapy ( P = 0.0055) to be significant. Conclusions. Women primarily managed by a GYO for early-stage disease were significantly less likely to receive adjuvant radiotherapy. Despite significantly more unfavorable disease characteristics among GYO-managed women, disease-free and cause-specific survival were equivalent between the two groups. Favorable disease characteristics and adjuvant radiotherapy correlated with improved survival on multivariate analysis.

Vaginal brachytherapy alone: An alternative to adjuvant whole pelvis radiation for early stage endometrial cancer

Objective. Postoperative management of early stage adenocarcinoma of the endometrium remains controversial. The use of pelvic radiation therapy as shown by the Gynecologic Oncology Group (GOG)-99 trial improves the event free interval at the cost of increased toxicity. We reviewed and compared our results treating early stage endometrial adenocarcinoma using hypofractionated high dose rate (HDR) vaginal brachytherapy (VB) alone with the results of the GOG-99. Methods. From 1992 to 2002, 243 endometrial cancer patients were treated with TAH/BSO and selective lymph node dissection followed by adjuvant radiotherapy (RT). Of these, 50 FIGO stage I–II (occult) adenocarcinoma (no clear cell or serous papillary) of the endometrium were managed with HDR hypofractionated VB as monotherapy using Iridium-192 to a dose of 30 Gy in 6 fractions twice weekly prescribed to a depth of 5 mm and median length of 4 cm. The characteristics, toxicity rates, and outcomes of our patients were compared with the results of the GOG-99. The median follow up of our patients and the GOG-99 were 3.2 years and 5.8 years, respectively. Results. Patient characteristics including age, stage, and grade were similar in our study and the GOG-99. The local recurrence rate in our study, the pelvic RT arm of the GOG-99, and the no RT arm of the GOG-99 were 4% ( n = 2), 2% ( n = 3), and 9% ( n = 18), respectively. In our study, one patient failed in the vagina alone and a second patient failed in the vagina and pelvis. In the GOG-99, the vagina as a component of locoregional failure was also the most common failure site in the no RT arm 77.8% ( n = 14) and in the RT arm 100% ( n = 3). The 2-year cumulative recurrence rate in our study was 2%, which compares favorably with the GOG-99 pelvic RT arm (3%) and observation arm (12%). Four-year survival rates of the no RT arm of the GOG-99, the RT arm of the GOG-99, and our study with HDR VB were 86%, 92%, and 97%, respectively. Chronic grade 2 toxicity rates were reduced by the use of VB compared to pelvic RT, especially GI toxicity 0% vs. 34% ( P value < 0.001), and GI obstruction 0% vs. 7% ( P value = 0.08). Conclusion. Stage I–II (occult) endometrial adenocarcinoma treated with postoperative HDR vaginal brachytherapy has similar overall survival, locoregional failure rates, and cumulative recurrence rates to standard fractionation external beam pelvic RT with the benefit of much lower toxicity rates and shorter overall treatment time.

Contemporary results of permanent prostate seed implantation (PPI) versus conformal proton beam radiotherapy (CPBRT) to 79Gy

4639 Background: A recent Phase III randomized trial demonstrated that CPBRT to 79 Gy rendered higher biochemical control (bNED) than 70 Gy (Zietman AL et al. Randomized Trial Comparing Conventional Dose (70.2GyE) and High-Dose (79.2GyE) Conformal Radiation in Early Stage Adenocarcinoma of the Prostate: Results of an Interim Analysis of PROG 95–09. Proceedings of ASTRO, 2004). Our retrospective analysis compares the bNED with PPI +/− external beam radiotherapy (EBRT) +/− short-term neoadjuvant hormonal therapy (nHT) with CPBT to 79 Gy. Methods: Between 6/96 and 12/99 251 consecutive evaluable patients (pts) were treated with PPI at UCSF. Pts were included if pretreatment PSA, Gleason Score (GS) and T stage were available. Twenty-seven percent of pts received nHT, 12% EBRT, and 18% received both prior to PPI, none received long term HT. The median PSA was 6.6 ng/ml with 5% >15, 4% had T3 disease, and 82% had a GS < 7. Biochemical failure was assessed using the ASTRO consensus definition and included the 234 pts with at least 3 follow-up (fu) PSAs. Pts on the CPBT trial were treated between 1996 and 1999 with stages limited to T1b-T2b, PSA to < 15 ng/ml and 75% had a Gleason score (GS) <7. The median PSA was 6.3 ng/ml with no pt receiving nHT. Only the results of the 196 pts treated on 79 Gy arm were compared to our PPI pts. Results: With a median fu of 60 mos the 5 yr bNED estimate for the pts treated with PPI was 91% (95% CI: 87%–95%). Sixty-eight percent of pts achieved a PSA <0.1 and 90% <0.5ng/ml. Pts treated on the CPBT (med. fu of 48 mos.) appeared to be similar to those treated with PPI. Table 1 below summarizes the outcomes. Conclusions: This non-randomized comparison suggests that pts treated with PPI +/− nHT +/− EBRT for clinically localized prostate cancer appear to have a bNED rate at least as high as pts treated with CPBT. There does not appear to be a compelling reason to recommend CPBRT as the treatment of choice unless morbidity can be proven to be substantially less. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Blue Cross Blue Shield

In response to Dr. Halperin

We appreciate the comments of Dr. Halperin about the differences in patients with localized prostate cancer treated with different modalities as reported in our study ( 1 Kupelian P.A. Potters L. Khuntia D. et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy > or =72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1–T2 prostate cancer. Int J Radiat Oncol Biol Phys. 2004; 58: 25-33 Abstract Full Text Full Text PDF PubMed Scopus (417) Google Scholar ). Specifically, the concern was that the difference in outcomes observed between patients receiving <72 Gy vs. ≥72 Gy is secondary to differences in follow-up period and/or a resultant of the ASTRO definition of biochemical failure. With respect to the failure definition, the differences observed in outcomes should be the same, because the same definition was applied to both groups. With respect to follow-up periods, there is no doubt that with the use of KM curves, some of the difference between the two dose levels is due to the difference in follow-up periods. Therefore, with analysis of subgroups that have closer follow-up periods, that difference will decrease. However, although the magnitude of the difference might vary, the dose effect is real, regardless of follow-up duration. This was demonstrated by the well-known randomized study reported by Pollack et al. ( 2 Pollack A. Zagars G.K. Starkschall G. et al. Prostate cancer radiation dose response: Results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002; 53: 1097-1105 Abstract Full Text Full Text PDF PubMed Scopus (1206) Google Scholar ), and more recently the randomized dose escalation protocol with protons reported by Zietman et al. ( 3 Zietman A. DeSilvio M. Slater J. et al. A randomized trial comparing conventional dose (70.2 GyE) and high-dose (79.2 GyE) conformal radiation in early stage adenocarcinoma of the prostate: Results of an interim analysis of PROG 95-09. Int J Radiat Oncol Biol Phys. 2004; 60: S131 Google Scholar ). In addition, in a separate multi-institutional data set that we looked at for patients treated only in 1994 and 1995, radiation therapy dose was again an independent predictor of failure ( 4 Kupelian P.A. Kuban D. Thames H. et al. Improved biochemical relapse-free survival with increased external radiation doses in patients with localized prostate cancer: The combined experience of nine institutions in patients treated in 1994 and 1995. Int J Radiat Oncol Biol Phys. 2003; 57: S271-272 Abstract Full Text Full Text PDF Google Scholar ). All these analyses were done with patient groups with identical follow-up periods. In regard to Kupelian et al.: Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seed/external beam radiotherapy for stage T1-T2 prostate cancer (Int J Radiat Oncol Biol Phys 2004;58:25–33)International Journal of Radiation Oncology, Biology, PhysicsVol. 61Issue 2PreviewKudos to Kupelian et al. for their excellent analysis describing biochemical failure rates for prostate cancer patients treated by radical prostatectomy, external beam radiotherapy, and brachytherapy (1). In this analysis, patients who received external beam radiotherapy with <72 Gy were reported to have a significantly higher biochemical failure rate than all other groups analyzed. A review of the data showed that the median follow-up duration for <72 Gy patients was 75 months, which is the longest of all of the evaluated groups by at least 9 months. Full-Text PDF

Prediction of appropriateness of local endoscopic treatment for high-grade dysplasia and early adenocarcinoma by EUS and histopathologic features

Endoscopic techniques are being developed for the local treatment of early stage esophageal cancer. However, such therapy is not appropriate for patients with lymph node metastasis. The aim of this study was to analyze the histopathologic features of high-grade dysplasia and early stage adenocarcinoma and to relate these to lymph node involvement. Pathology reports were reviewed for all 367 patients who underwent subtotal esophagectomy for high-grade dysplasia or adenocarcinoma of the esophagus or the gastroesophageal junction between January 1993 and December 2001. Patients with histopathologically confirmed high-grade dysplasia or T1 carcinoma were included (n = 77). Pre-operative EUS results were assessed. All lesions were histopathologically subdivided in 6 different stages (mucosal 1-3 and submucosal 1-3). EUS staged 61 patients as N0. EUS correctly predicted the absence of positive lymph nodes in 57 (93%) of these patients. Histopathologically, m1, m2, m3, and sm1 cancers never had lymph node metastases, whereas 3 of 13 sm2 tumors (23%) and 9 of 13 sm3 tumors (69%) had lymph node involvement. Lymphangio invasion was present exclusively in sm2 and sm3 cancers. Factors that predicted the presence of lymph node metastasis were the following: tumor diameter greater than 3 cm, infiltration of malignancy beyond sm1, poor differentiation grade, and lymphangio invasion, although only infiltration beyond sm1 remained significant in the definitive multivariate analysis. EUS and the histopathologic features of high-grade dysplasia and early stage adenocarcinoma of the esophagus or the gastroesophageal junction can predict the presence of lymph node involvement. These data can be used to identify patients for whom local endoscopic treatment may be appropriate.

A randomized trial comparing conventional dose (70.2GyE) and high-dose (79.2GyE) conformal radiation in early stage adenocarcinoma of the prostate: Results of an interim analysis of PROG 95–09

A randomized trial comparing conventional dose (70.2GyE) and high-dose (79.2GyE) conformal radiation in early stage adenocarcinoma of the prostate: Results of an interim analysis of PROG 95–09

Vaginal brachytherapy alone: An alternative to whole pelvis radiation for early stage endometrial cancer

Vaginal brachytherapy alone: An alternative to whole pelvis radiation for early stage endometrial cancer

A randomized trial comparing conventional dose (70.2GyE) and high-dose (79.2GyE) conformal radiation in early stage adenocarcinoma of the prostate: Results of an interim analysis of PROG 95–09

This trial was designed to test the hypothesis that increasing the radiation dose delivered conformally to men with early stage prostate cancer above conventional levels improves disease free outcome. From January 1996 to December 1999 393 patients with biopsy proven T1b-T2b prostate cancer and a PSA of <15ng/ml were recruited at two centers onto an IRB approved protocol. 75.3% had Gleason scores of 6 or less, 15.3% Gleason 7, and 8.4% Gleason 8–10. 61.2% had T1c tumors. The median age at diagnosis was 67 years and the median PSA was 6.3. Patients were randomized to receive an initial boost to the prostate alone using conformal protons (either lateral or perineal fields) of either 19.8 or 28.8 Gray equivalent (GyE). All patients then received 50.4Gy at 1.8Gy per fraction using 3-D conformal photons to the prostate, seminal vesicles, and peri-prostatic tissues. 197 patients were randomized to a total dose of 70.2 GyE (conventional dose) and 196 to 79.2 GyE (high dose). Of those assigned to high dose 12 received less than 77 GyE (5.6%). Of those assigned to conventional dose only 5 received doses above 71 GyE (2%). Median follow-up is 4 years. No patient received adjunctive androgen suppression therapy with their radiation. Local failure was defined using both direct and surrogate criteria: clinically through palpation, histologically after rebiopsy of a clinically benign prostate with a rising PSA, or biochemically by a PSA of >1ng/ml 2 or more years after treatment without rebiopsy. Biochemical failure was determined using the ASTRO definition. This trial originated with the Proton Radiation Oncology Group and received statistical and data management support from the American College of Radiology. The distribution of PSA nadirs of either <0.5 or <1.0ng/ml was 36.7% and 73% after 70.2 GyE and 50% and 79.9% after 79.2 GyE. The cumulative incidence estimates of the five-year local failure rate using the surrogate of a PSA >1ng/ml 2 or more years after radiation were 63.6% (95% CI = 54.5% to 72.8%) for the 70.2 GyE group and 36.3% (95% CI = 26.5% to 46.0%) for the 79.2 GyE group (p ≤ 0.0001). The five-year biochemical failure rates were 37.3% (95% CI = 28.4% to 46.3%) for the conventional dose group and 19.1% (95% CI = 11.1% to 27.1%) for the high dose group (p = 0.00001). This difference held true when only those with low risk disease were examined (T1b-2a, PSA <10, Gleason <6, n = 227, 58% of total). The 5-year biochemical failure rate was 34.9% in the conventional dose arm and only 17.2% in the high dose arm (p = 0.002). It was also significant for intermediate risk patients (39.5% vs 21.3% p = 0.01). At this time, there was no difference in the overall survival rates between the treatment arms (p = 0.83). Only 2% of patients receiving conventional dose and 1.5% receiving high dose radiation experienced acute urinary or rectal morbidity of RTOG grade >3. The respective proportions for those experiencing any grade 2 acute morbidity was 62 and 69%. So far only 1.5% and 0.5% respectively have experienced late morbidity of RTOG grade >3. This randomized controlled trial shows an advantage in terms of freedom from biochemical failure for men with low and intermediate risk prostate cancer receiving high dose versus conventional dose conformal radiation. This advantage was achieved without any associated increase in either acute or late urinary or rectal morbidity

The role of the preoperative serum carcinoembryonic antigen level in early-stage adenocarcinoma of the uterine cervix

Objective. The purpose of the study was to identify the relationship between preoperative serum levels of carcinoembryonic antigen (CEA) and clinicopathological variables in early-stage adenocarcinoma of the uterine cervix. Methods. From February 1990 to August 2002, 117 patients with surgically treated early-stage cervical adenocarcinoma that had had preoperative serum CEA evaluations were retrospectively reviewed. The cut-off value for CEA, based on the manufacturer's recommendations, was 5 ng/ml. For an evaluation of the relationship between the clinicopathological factors and increased levels of serum tumor markers, the Chi-Square/Fisher's exact test and logistic regression were used for univariate and multivariate analysis, respectively. Results. The mean age of the patients was 46 years (range, 21–78). Of the 117 patients, 28 had preoperative serum CEA levels greater than 5 ng/ml. In a univariate analysis, the increased marker was associated with a larger tumor size, presence of lymphovascular invasion, and deeper cervical wall invasion. However, in a multivariate analysis, the preoperative CEA level had a significant impact on the determination of the depth of stromal invasion (OR 4.12, 95% CI 1.97–8.68, P < 0.001). Conclusion. In early-stage cervical adenocarcinoma, preoperative serum CEA levels seem to be useful in estimating the depth of cervical stromal invasion. Assessment of tumor antigen CEA levels should be integrated with the routine examination in the work-up of patients with adenocarcinoma of the uterine cervix.

Evaluation of the cyclin-dependent kinase inhibitor p21Cip1 in epithelial ovarian tumors of low malignant potential and adenocarcinomas.

In view of the controversial information on the significance of the cyclin-dependent kinase inhibitor p21Cip1 in ovarian cancer, we conducted a retrospective investigation to clarify the relationships of this protein to proliferation rate, clinicopathological variables and prognosis of epithelial ovarian tumors. Paraffin-embedded tissue from 43 ovarian tumors of low malignant potential (LMP) and 82 primary ovarian adenocarcinomas were stained immunohistochemically for p21Cip1, p53 protein and Ki-67 antigen (a marker of cell proliferation). p21Cip1 levels were significantly higher in LMP tumors (p<0.001) as well as in early stage adenocarcinomas (p=0.021) and those associated with minimal residual disease (p=0.008). However, no relationship existed between p21Cip1 expression and the proliferation rate of adenocarcinomas or LMP tumors. In the vast majority of LMP tumors p21Cip1 expression was not accompanied by p53 accumulation. This p21Cip1-positive/p53-negative phenotype prevailed in the early stage (p=0.026), lower grade (p=0.018) adenocarcinomas as well as in those left with minimal residual disease (p=0.059). In patients with lower grade adenocarcinomas, decreased p21Cip1 expression was adversely related to poor overall survival on its own (p=0.0500) and when combined with p53 protein overexpression (p=0.0323). In multivariate analysis, only the stage remained as the independent predictor of survival. Decreased p21Cip1 expression is related to several indicators of aggressiveness in ovarian adenocarcinomas and seems to be differentially regulated in LMP tumors and adenocarcinomas. On the contrary, deregulation of p21Cip1 expression does not seem to participate in the pathogenesis of LMP tumors. Furthermore, although p21Cip1 alone or combined with p53 is of prognostic significance in lower grade adenocarcinomas, it does not appear to add to the information gained from traditional prognosticators.

Mucosal ablation with photodynamic therapy in the esophagus: Optimization of light dosimetry in the sheep model

Background: Photodynamic therapy is an attractive technique for mucosal ablation in patients with superficial squamous cell carcinoma of the esophagus, or high-grade dysplasia or early stage adenocarcinoma arising in Barrett's esophagus. Although illumination with green light is assumed to be safe, choice of the light has been empirical in clinical studies; light dose is often reduced to avoid potential complications. The present study assessed the safety of green and blue lights during photodynamic therapy in the esophagus by progressively administrating increasing doses in an attempt to standardize the dose and determine a safe upper limit. This would considerably simplify photodynamic therapy and improve therapeutic results. Methods: The sheep model was chosen because of similarities with humans regarding the thickness and histologic structure of the esophagus. Irradiation with a 180° windowed cylindrical light distributor was performed in 19 sheep 4 days after injection of 0.15 mg/kg of tetra(m-hydroxyphenyl) chlorin. Light doses ranged from 10 to 500 J/cm 2 at 514 nm (argon ion laser) and from 5 to 250 J/cm 2 at 413 nm (krypton laser). Results: Follow-up endoscopies revealed a tissue response with a fibrinous area at almost all light doses, whereas application of extremely high light doses tended to induce circumferential necrosis with subsequent stenosis. Three months after irradiation with green light, histologic examination of the resected specimens revealed transmural scarring at doses higher than 100 J/cm 2. After illumination with blue light, partial or more extensive fibrosis of the muscular layer was observed only at light doses of 175 to 250 J/cm 2. Conclusions: Application of high doses of green light after sensitization with tetra(m-hydroxyphenyl) chlorin led to severe complications in the esophagus of the sheep that are highly likely to occur in humans as well. Blue light causes significantly less damage than green light and may, therefore, be considered as an alternative for photodynamic therapy of early stage superficial esophageal cancer. (Gastrointest Endosc 2003;57:897-905.)

Results of wedge resection for focal bronchioloalveolar carcinoma showing pure ground-glass attenuation on computed tomography

Background. Focal bronchioloalveolar carcinoma (BAC) showing pure ground-glass attenuation (GGA) on thin-section computed tomography (CT), which is considered to be an early-stage adenocarcinoma, has been diagnosed with increasing frequency due to the development and spread of the helical CT scanner. We discussed the appropriateness of limited resection for this type of lesion.Methods. Between July 1996 and June 2001, 17 patients with localized BAC showing “pure GGA” (GGA without central scar formation) on thin-section CT underwent limited pulmonary resections. The mean patient age was 57.2 ± 10.5 years old. Among these patients, four tumors were detected in a CT mass-screening program and the others were incidentally detected on CT during follow-up for other diseases. Fourteen patients underwent thoracoscopic wedge resection, and 3 underwent segmentectomy because of tumor location.Results. The mean tumor diameter was 7.9 ± 1.9 mm. On pathological examination, all tumors showed a pure bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion. The median follow-up time was 32.0 months, with no cancer death or relapse to date.Conclusions. Focal BAC showing pure GGA on thin-section CT is peripheral in situ adenocarcinoma. Wedge resection by VATS is considered to be an appropriate treatment for this type of lung cancer. It can be a minimally invasive complete resection for this type of early cancer, and offer the best chance for long-term survival and good quality of life.

Factors predicting disease outcome in early stage adenocarcinoma of the uterine cervix

Context: Adenocarcinoma (AC) and adenosquamous carcinoma (ASC) comprise the second principal histological types of cervical carcinoma. As compared with the squamous cell cancer (SCC), these lesions are far less frequent, and their epidemiology, natural history and prognostic determinants are less well understood. Objective: Patients with an early stage AC of the uterine cervix diagnosed in our clinic were subjected to detailed analysis for the prognostic determinants. Study subjects: A series of 94 women with early stage (adenocarcinoma in situ (AIS) to IIB) cervical ACs or ASCs diagnosed and treated in our department during 1995–1999 and subsequently followed-up for a mean of 43.1±16.2 (S.D.) months. Main outcome measures: Patients were examined by colposcopy, Papanicolaou (PAP) smear and biopsy. The stage of the disease (FIGO) and tumour histology in operative specimens were recorded, and univariate (Kaplan–Meier) and multivariate survival analysis (Cox) were run to explore the factors predicting disease outcome. Results: Mean age of the women was 44.2±2.5 (S.D.) years (range 24–81 years), which is significantly ( P=0.000) lower than that (49.9±14.2) of 464 SCC patients in our material. Minority of the women (38.2%) reported any clinical symptoms, but these correlated with the stage ( P=0.041). Screening history was acceptable (i.e. screening interval 3 to 4 years) in 56 women, whereas 28 (29.8%) had no previous PAP smear taken. Interpretation errors were established in 17 (23.6%) and sampling errors in 6 (8.3%) of the 72 smears available for re-screening. No colposcopic lesions were found in 29 (30.9%) women. Follow-up data were available from 72 patients, of whom the disease progressed in four (one died), wheras 68 patients are alive and well at the moment. Patient’s age ( P=0.000), screening history ( P=0.0127), FIGO stage ( P=0.001), mode of therapy ( P=0.0187), and presence of co-existent squamous cell lesions ( P=0.0184) were significant prognostic indicators in univariate survival analysis. Cox’s multivariate survival analysis disclosed FIGO stage ( P=0.001) and screening history ( P=0.006) as the only significant independent predictors of the disease outcome. Conclusions: The present data emphasise the importance of early cervical AC as a disease of younger women, making early detection of its precursors (AIS) by regular PAP smear screening mandatory in prevention of disease progression. This can only be achieved by increasing the sensitivity of the PAP smear in detecting abnormal glandular cells in asymptomatic women.

Management of adenocarcinoma in situ, micro-invasive, and early stage adenocarcinoma of the cervix.

The incidence of glandular neoplasms of the uterine cervix has been steadily increasing over the past two decades. Given the fact that these lesions are more difficult to diagnosis and are relatively infrequent, less is known about them compared with their squamous counterparts. In addition, because these lesions tend to arise in women of childbearing age, there is a particular need to understand whether the in-situ and early invasive forms of adenocarcinoma are amenable to conservative treatment measures that spare fertility like their squamous counterparts. Recent publications have addressed the underlying causes of the increasing incidence, the pros and cons of conservative management, and the difficulties in definitively identifying each glandular subtype. The most difficult diagnostic lesions are adenocarcinoma in situ cases and early invasive adenocarcinomas.

Increased Expression of COX-2 in the Development of Human Lung Cancers

It is well accepted that an increase in the expression of cyclooxygenase-2 (COX-2), a key inducible enzyme involved in the production of prostaglandins and other eicosanoids, may play a significant role in carcinogenesis in addition to its well-known role in inflammatory reactions. Whereas previous studies were largely confined to colorectal tumorigenesis, we have shown that a significantly increased expression of COX-2 may also play a role in the development of lung cancer. COX-2 expression was found to be frequently elevated in lung cancer, especially in adenocarcinoma, and the proportion of lung cancer cells with marked COX-2 expression was much higher in lymph node metastases than in the corresponding primary tumors. It was also shown that early stage adenocarcinoma patients with increased COX-2 expression who were surgically treated had a shorter survival. Our studies, which used high- and low-metastatic human lung cancer cell sublines established in our laboratory, revealed an association between metastatic capabilities and COX-2 expression levels: COX-2-specific inhibitors could inhibit in vitro the invasion of the highly metastatic NCI-H460-LNM35 clone through Matrigel-containing basement membrane components as well as the spontaneous in vivo metastasis in SCID mice. Taken together, these findings suggest that an increase in COX-2 expression maybe associated with the development of lung cancer and possibly with the acquisition of an invasive and metastatic phenotype.

Fluorescence induced with 5-aminolevulinic acid for the endoscopic detection and follow-up of esophageal lesions

Background: The aim of this study was to investigate the use of orally administered 5-aminolevulinic acid (ALA) for in vivo photodynamic diagnosis and follow-up of premalignant and malignant esophageal lesions. Methods: Twenty-two patients with known or treated malignant and precancerous esophageal lesions were sensitized with orally administered ALA (15 mg/kg). Six patients had Barrett's esophagus, with or without severe dysplasia, 5 squamous cell cancer or early-stage (uT1N0M0) adenocarcinoma, 1 advanced-stage (uT3N1) adenocarcinoma, and 1 patient a lesion with an appearance that suggested esophageal cancer. Nine patients underwent photodynamic diagnosis for follow-up after treatment of esophageal cancer with curative intent; 6 had no macroscopically visible lesion and 3 a barely visible lesion under standard (white-light) endoscopy. Photodynamic diagnosis was conducted 6 to 7 hours after oral administration of ALA by using a special light source capable of delivering either white or violet-blue light. Red fluorescence was detected with a charged coupled device camera attached to a fiberoptic endoscope. Corresponding endoscopic, fluorescence, and microscopic findings were compared. Results: By using histology as the reference standard (n = 86 biopsies), 85% of the biopsy sites with premalignant or malignant histopathology exhibited red fluorescence, whereas only 25% were detected with white-light endoscopy. Conclusion: ALA-induced fluorescence might be useful for the early endoscopic detection of malignant esophageal lesions and follow-up after treatment of such lesions with curative intent. (Gastrointest Endosc 2000;54:572-8.)

Early stage adenocarcinoma of the esophagus arising in circular heterotopic gastric mucosa treated by endoscopic mucosal resection

Early stage adenocarcinoma of the esophagus arising in circular heterotopic gastric mucosa treated by endoscopic mucosal resection

Videoendoscopy with vital double dye staining (crystal violet and methylene blue) for detection of a minute focus of early stage adenocarcinoma in Barrett's esophagus: A case report

Barrett's esophagus is a condition in which the normal stratified squamous esophageal epithelium is replaced by metaplastic columnar epithelium.1 Intestinal metaplasia leads to an increased risk for adenocarcinoma2; the incidence of adenocarcinoma associated with Barrett's esophagus has increased over the last decade.3-5 Traditionally the preferred curative treatment has been esophagectomy. However, the management of early-stage adenocarcinoma in Barrett's epithelium is changing. Initial reports have appeared concerning promising results with photodynamic therapy6 and argon plasma coagulation.

Recurrent Ascites and Pleural Effusions After Surgery for Early-Stage Endometrial Adenocarcinoma

A case of massive postoperative ascites in a woman treated for endometrial cancer is reported. A workup for typical causes of ascites yielded negative results, prompting a more detailed analysis of the patient's condition. Hypothyroidism was discovered. After correction of the hypothyroidism, the ascites slowly resolved. Since myxedema is an uncommon cause of ascites, this is usually a diagnosis of exclusion. However, hypothyroidism must be ruled out to prevent unnecessary and possibly inappropriate treatments for ascites.

Recurrent Ascites and Pleural Effusions After Surgery for Early-Stage Endometrial Adenocarcinoma

Recurrent Ascites and Pleural Effusions After Surgery for Early-Stage Endometrial Adenocarcinoma